Archive for July, 2016

See comment in PubMed Commons below N Engl J Med. 2012 Oct 18;367(16):1487-96. doi: 10.1056/NEJMoa1203517. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Couban S, Ehninger G, Johnston L, Maziarz RT, Pulsipher MA, Porter DL, Mineishi S, McCarty JM, Khan SP, Anderlini P, Bensinger WI, Leitman SF, Rowley SD, Bredeson C, Carter SL, Horowitz MM, Confer DL; Blood and Marrow Transplant Clinical Trials Network. Collaborators (182)

Horowitz MM, Carter SL, Confer DL, DiFronzo N, Wagner E, Merritt W, Wu R, Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Couban S, Anderlini P, Bensinger WI, Leitman SF, Rowley SD, Carter SL, Karanes C, Horowitz MM, Confer DL, Allen C, Colby C, Gurgol C, Knust K, Foley A, King R, Mitchell P, Couban S, Pulsipher MA, Ehninger G, Johnston L, Khan SP, Maziarz RT, McCarty JM, Mineishi S, Porter DL, Bredeson C, Anasetti C, Lee S, Waller EK, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Logan BR, Carter SL, Lee SJ, Waller EK, Anasetti C, Logan BR, Lee SJ, Stadtmauer E, Wingard J, Vose J, Lazarus H, Cowan M, Wingard J, Westervelt P, Litzow M, Wu R, Geller N, Carter S, Confer D, Horowitz M, Poland N, Krance R, Carrum G, Agura E, Nademanee A, Sahdev I, Cutler C, Horwitz ME, Kurtzberg J, Waller EK, Woolfrey A, Rowley S, Brochstein J, Leber B, Wasi P, Roy J, Jansen J, Stiff PJ, Khan S, Devine S, Maziarz R, Nemecek E, Huebsch L, Couban S, McCarthy P, Johnston L, Shaughnessy P, Savoie L, Ball E, Vaughan W, Cowan M, Horn B, Wingard J, Silverman M, Abhyankar S, McGuirk J, Yanovich S, Ferrara J, Weisdorf D, Faber E Jr, Selby G, Rooms LM, Porter D, Agha M, Anderlini P, Lipton J, Pulsipher MA, Pulsipher MA, Shepherd J, Toze C, Kassim A, Frangoul H, McCarty J, Hurd D, DiPersio J, Westervelt P, Shenoy S, Agura E, Culler E, Axelrod F, Chambers L, Senaldi E, Nguyen KA, Engelman E, Hartzman R, Sutor L, Dickson L, Nademanee A, Khalife G, Lenes BA, Eames G, Sibley D, Gale P, Antin J, Ehninger G, Newberg NR, Gammon R, Montgomery M, Mair B, Rossmann S, Wada R, Waxman D, Ranlett R, Silverman M, Herzig G, Fried M, Atkinson E, Weitekamp L, Bigelow C, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Price T, Young C, Hilbert R, Oh D, Cable C, Smith JW, Kalmin ND, Schultheiss K, Beck T, Lankiewicz MW, Sharp D.

Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.

We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).

The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.

We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

Survival after Randomization in the Intention-to-Treat Analysis

The P value is from a stratified binomial comparison at the 2-year point. The P value from a stratified log-rank test was also not significant. A total of 75 patients in each group were still alive at 36 months.

N Engl J Med. ;367(16):10.1056/NEJMoa1203517.

Outcomes after Transplantation, According to Study Group

Panel A shows the rate of overall survival, and Panel B the rate of disease-free survival. Panel C shows the incidence of death unrelated to relapse. Panel D shows the incidence of relapse. Panel E shows the incidence of neutrophil engraftment (>500 neutrophils per cubic millimeter), and Panel F the incidence of platelet engraftment (>20,000 platelets per cubic millimeter, without platelet transfusion during the prior 7 days). Panel G shows the incidence of acute graft-versus-host disease (GVHD) of grades II to IV, and Panel H the incidence of chronic GVHD. P values for the between-group differences in overall survival (Panel A) and disease-free survival (Panel B) are from a stratified binomial comparison at the 2-year point; P values from stratified log-rank tests for survival and disease-free survival were also not significant. All other P values shown are from stratified log-rank tests.

N Engl J Med. ;367(16):10.1056/NEJMoa1203517.

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Peripheral-blood stem cells versus bone marrow from ...

Abstract

Mesenchymal stem cells (MSCs) represent a promising tool for new clinical concepts in supporting cellular therapy. Bone marrow (BM) was the first source reported to contain MSCs. However, for clinical use, BM may be detrimental due to the highly invasive donation procedure and the decline in MSC number and differentiation potential with increasing age. More recently, umbilical cord blood (UCB), attainable by a less invasive method, was introduced as an alternative source for MSCs. Another promising source is adipose tissue (AT). We compared MSCs derived from these sources regarding morphology, the success rate of isolating MSCs, colony frequency, expansion potential, multiple differentiation capacity, and immune phenotype. No significant differences concerning the morphology and immune phenotype of the MSCs derived from these sources were obvious. Differences could be observed concerning the success rate of isolating MSCs, which was 100% for BM and AT, but only 63% for UCB. The colony frequency was lowest in UCB, whereas it was highest in AT. However, UCB-MSCs could be cultured longest and showed the highest proliferation capacity, whereas BM-MSCs possessed the shortest culture period and the lowest proliferation capacity. Most strikingly, UCB-MSCs showed no adipogenic differentiation capacity, in contrast to BM- and AT-MSCs. Both UCB and AT are attractive alternatives to BM in isolating MSC: AT as it contains MSCs at the highest frequency and UCB as it seems to be expandable to higher numbers.

Mesenchymal stem cells (MSCs) found in many adult tissues are an attractive stem cell source for the regeneration of damaged tissues in clinical applications because they are characterized as undifferentiated cells, able to self-renew with a high proliferative capacity, and possess a mesodermal differentiation potential [1].

Although bone marrow (BM) has been the main source for the isolation of multipotent MSCs, the harvest of BM is a highly invasive procedure and the number, differentiation potential, and maximal life span of MSCs from BM decline with increasing age [24]. Therefore, alternative sources from which to isolate MSCs are subject to intensive investigation.

One alternative source is umbilical cord blood (UCB), which can be obtained by a less invasive method, without harm for the mother or the infant [5]. However, controversy still exists whether full-term UCB can serve as a source for isolating multipotent MSCs: although some groups did not succeed in isolating MSCs [6, 7], we and other groups succeeded in isolating MSCs from full-term UCB [812].

Adipose tissue (AT) is another alternative source that can be obtained by a less invasive method and in larger quantities than BM. It has been demonstrated that AT contains stem cells similar to BM-MSCs, which are termed processed lipoaspirate (PLA) cells [13]. These cells can be isolated from cosmetic liposuctions in large numbers and grown easily under standard tissue culture conditions [13]. The multilineage differentiation capacity of PLA cells has been confirmed [13].

As BM-MSCs are best characterized, we asked whether MSCs derived from other sources share the characteristics of BM-MSCs. The aim of our study was to compare MSCs isolated from the three sources under identical in vitro conditions with respect to their morphology, frequency of colonies, expansion characteristics, multilineage differentiation capacity, immunophenotype, and success rate of isolating the cells.

We compared MSCs from BM and two alternative sources, namely UCB and AT, concerning basic MSC characteristics. All cells isolated from these three sources exhibited typical MSC characteristics: a fibroblastoid morphology, the formation of CFU-F, a multipotential differentiation capability, and the expression of a typical set of surface proteins. Whereas MSCs derived from the three sources expressed classic MSC marker proteins, but lacked hematopoietic and endothelial markers, we observed significant differences concerning the expression of CD90, CD105, and CD106. These molecules are described to be associated with hematopoiesis and cell migration [18 20]. It needs to be further investigated whether these molecules are functionally important for stroma and homing capacities. In a first approach, we created a comprehensive protein expression profile of undifferentiated UCB-MSCs, which will be extended to BM- and AT-MSCs and then correlated to functional properties [21].

Since the relevance of the observed differences of marker expression has not been properly investigated yet, differences concerning differentiation capacity seem to be more relevant for MSC quality at present. We demonstrated a multilineage differentiation capacity for BM- and AT-MSCs. Interestingly, UCB-MSCs could not be differentiated toward the adipogenic lineage, which was not related to the CFU-F origin. Actually, there are conflicting data concerning the adipogenic differentiation capacity of UCB-MSCs [9 12, 22, 23]. Nevertheless, we assume that UCB-MSCs are less sensitive toward the adipogenic differentiation (supported by results of Chang et al. [22]) which might be related to the ontogenetic age of these cells. This is further supported by the fact that adipocytes reside in adult human BM and AT but are absent in fetal BM and by the observation of an increased adipogenesis correlated with age [24]. Further comparative genomic or proteomic approaches are needed to assess the susceptibility toward adipogenesis of MSCs.

None of our UCB-MSCs showed adipogenic differentiation capacity, but all differentiated into both the chondro- and osteogenic lineages. In contrast, a tripotential differentiation capacity was observed for most AT samples but only for a few BM samples. One sample each of BM and AT was observed to undergo only the chondrogenic pathway. In accordance with this, a hierarchical or even restricted differentiation potential of MSCs has been reported [1, 13, 25].

In our study, investigations were limited to the mesodermal differentiation capacity. Based on recent reports, however, the spectrum of differentiation of MSCs does not seem to be restricted to this lineage. MSCs derived from all three tissues have been shown to differentiate into further mesodermal lineages and into endo- and ectodermal lineages as well [10 13, 26 33]. Comparative experiments need to be performed to assess responsiveness toward cardiomyogenic, endothelial, hepatic, neuronal, and pancreatic differentiation.

A high impact on clinical exploitation might be related to the abundance and expansion capacity of MSCs. Based on our results, both BM and AT are reliable sources for isolating and expanding MSCs in autologous settings since all preparations gave rise to MSCs. UCB, in contrast, had an isolation efficacy of a maximum of 63% [8]. We attribute these differences to the fact that MSCs are circulating in the prenatal organism and are residing in tissues of the adult [9]. Despite the low frequency of UCB-MSCs, the expansion potential was highest compared with other cell sources. Considering clinical applications, the resulting cell numbers may be similar to both BM and AT, which can be obtained at higher frequencies. One argument against AT might be the limited availability in some patients. However, we believe that due to the high frequency of AT-MSCs, also small fat reservoirs might be sufficient for MSC isolation. BM has been the main source for clinical application of MSCs, such as the treatment of osteogenesis imperfecta, graft versus host disease, and acute myocardial infarction [3436]. As the number, frequency, and differentiation capacity of BM-MSCs correlate negatively with age, they could be clinically inefficient when derived from elderly patients. In that case, an allogeneic approach would be required. In case a matching donor is required, BM or AT from HLA identical siblings, haplo-identical relatives, or HLA-screened donors might be best choice. Speculating on a off-the-shelf product requiring mass production, AT might be a solid starting basis due to the abundance, relatively easy harvest, and high MSCs frequency.

Transplantation of MSCs is currently a highly experimental procedure, resembling the early beginnings of hematopoietic stem cell transplantation. In the latter, BM has been replaced gradually by peripheral blood progenitor cells and umbilical cord blood. Also, in the field of MSCs, alternative sources are intensely investigated, and one day these new sources may replace BM. Taking into account all the advantages and disadvantages of the three sources discussed above, depending on the therapeutic indication, the clinical applications may be based on differentiation capacity, but more likely on the abundance, frequency, and expansion potential of the cells.

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Comparative Analysis of Mesenchymal Stem Cells from Bone ...

Embryonic stem cells seen through a microscope. The study saw a 40% reduction in the size of scarred tissue on the patients hearts. Photograph: Mauricio Lima/AFP/Getty Images

People suffering from heart disease have been offered hope by a new study that suggests damaged tissue could be regenerated through a stem cell treatment injected into the heart during surgery.

The small-scale study, published in the Journal of Cardiovascular Translational Research, followed 11 patients who during bypass surgery had stem cells injected into their hearts near the site of tissue scars caused by heart attacks.

One of the trials most dramatic results was a 40% reduction in the size of scarred tissue. Such scarring occurs during a cardiac event such as a heart attack, and can increase the chances of further heart failure. The scarring was previously thought to be permanent and irreversible.

At the time of treatment, the patients were suffering heart failure and had a very high (70%) annual mortality rate. But 36 months after receiving the stem cell treatment all are still alive, and none have suffered a further cardiac event such as a heart attack or stroke, or had any readmissions for cardiac-related reasons.

According to the British Heart Foundation, while there are several treatments to help people with heart failure, there is no known cure, and in some cases a heart transplant may be the only option.

Twenty-four months after participants were injected with the stem cell treatment there was a 30% improvement in heart function, 40% reduction in scar size, and 70% improvement in quality of life, as judged by the Minnesota living with heart failure (MLHF) score.

Related: Brain damage could be repaired by creating new nerve cells

Quite frankly it was a big surprise to find the area of scar in the damaged heart got smaller, said Prof Stephen Westaby from John Radcliffe hospital in Oxford, who undertook the research at AHEPA university hospital in Thessaloniki, Greece, with Kryiakos Anastasiadis and Polychronis Antonitsis.

Westaby began theorising about the impact of stem cells on regenerating heart tissue and reducing scarring after observing how scar tissue on the hearts of babies who have had heart attacks and undergone heart failure disappeared by the time they reached adolescence, suggesting that residual stem cells might be able to repair the damaged tissue.

Its an early study and its difficult to make large-scale predictions based on small studies, said Ajan Reginald, the founder of Celixir, the company that produces the treatment. But even in a small study you dont expect to see results this dramatic.

These are 11 patients who were in advanced heart failure, they had had a heart attack in the past, multiple heart attacks in many cases. The life expectancy for these patients is less than two years, were excited and honoured that these patients are still alive.

Related: Nearly 2m people may have undiagnosed killer disease

Jeremy Pearson, the associate medical director at the British Heart Foundation (BHF), said: This very small study suggests that targeted injection into the heart of carefully prepared cells from a healthy donor during bypass surgery, is safe. It is difficult to be sure that the cells had a beneficial effect because all patients were undergoing bypass surgery at the same time, which would usually improve heart function.

A controlled trial with substantially more patients is needed to determine whether injection of these types of cells proves any more effective than previous attempts to improve heart function in this way, which have so far largely failed.

Westaby conceded that the improvement in patients health was partly due to the heart bypass surgery those in the study were undergoing, and said the next study would include a control group who undergo bypass but do not receive stem cell treatment, to measure exactly what impact the treatment has.

These patients came out of heart failure partly due to the bypass grafts of course, but we think it was partly due to the fact that they had a smaller area of scar [as a result of the stem cell treatment]. Certainly this finding of scar being reduced is quite fascinating, he said.

Westaby will commence a large-scale controlled study later this year at the Royal Brompton hospital in London, and Celixir hopes to make the Heartcel treatment available to patients in 2018 or 2019.

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Stem cell trial suggests damaged heart tissue could be ...

Multipotent Cell-Secreted Extracellular Matrix Supports Cartilage Formation Histogen to present at International Cartilage Repair Society 2015

CHICAGO, May 8, 2015 - Histogen, Inc., a regenerative medicine company developing solutions based on the products of cells grown under simulated embryonic conditions, will present new research on its human extracellular matrix (hECM) material in the promotion of cartilage regeneration during the International Cartilage Repair Society (ICRS) 2015 Meeting, taking place May 8-11, 2015 in Chicago, IL. The orthobiologic applications of all of Histogen's products are being developed by its worldwide joint venture, PUR Biologics LLC.

Histogen has previously shown that hypoxia-induced multipotent cells produce soluble and insoluble materials that contain components associated with stem cell niches in the body and with scarless healing. These proteins include a variety of laminins, osteonectin, decorin, hyaluronic acid, collagen type IV, SPARC, CXCL12, NID1, NID2, NOTCH2, tenascin, thrombospondin, fibronectin, versican, and fibrillin-2. In vitro studies further demonstrated that the CCM and ECM promote the adhesion, proliferation and migration of bone marrow-derived human mesenchymal stem cells (MSCs).

In this latest research, in vivo studies with the hECM were undertaken to determine their potential as orthobiologics. Rabbit studies demonstrated the potential of the hECM to promote regeneration and repair of full-thickness articular cartilage defects. Eight weeks following hECM treatment of femoral osteochondral defects, mature bone and hyaline cartilage formation was seen, exemplified by the presence of a tide mark and integration into the adjacent cartilage. This work is currently being repeated in a goat cartilage defect model, with similar results to date.

"The efficacy we have seen with the multipotent cell-secreted ECM in bone and cartilage regeneration is unprecedented," said Ryan Fernan, CEO of PUR Biologics. "The preclinical work overwhelmingly supports use of the material as an orthobiologic to reduce inflammation and promote cartilage regeneration in the articulating joint and intervertebral spinal disc. We look forward to entering human trials for these indications, as well as to continuing our research on utilizing the product for soft tissue repair in a variety of sports injuries."

Histogen's cell conditioned media (CCM) and hECM were also evaluated in an ex vivo rabbit intervertebral spinal disc model to study the effects of these materials in an environment where an extensive inflammatory response was induced by thrombin injection. Compared to untreated controls, both the CCM and ECM treatment significantly down regulated the expression of the inflammatory cytokine genes IL-1, IL-6, TNF-alpha, as well as the genes encoding the extracellular matrix degrading enzymes MMP3, and ADAMTS4, while upregulating aggrecan expression in the annulus fibrosus and nucleus pulposus tissue.

Dr. Gail Naughton, CEO of Histogen, will present "Human Cell Conditioned Media and Extracellular Matrix Reduce Inflammation and Support Hyaline Cartilage Formation" at the ICRS 2015 meeting in Chicago on May 9, 2015. Following the event, the presentation will be available upon request.

About PUR Biologics PUR Biologics is dedicated to providing regenerative biologic solutions to address musculoskeletal surgical needs, including spine, dental, ligament and medical device coating applications. In addition to distribution of approved allograft and biologic products, PUR is focused on development of next-generation orthopedic products based upon human protein and growth factor materials for bone and tissue regeneration. For more information visit http://www.purbiologics.com.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's technology focuses on stimulating a patient's own stem cells by delivering a proprietary complex of multipotent human proteins that have been shown to support stem cell growth and differentiation. For more information, please visit http://www.histogen.com.

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Novel Immunomodulatory Treatment Induces Apoptosis in Melanoma Histogen to present data at 2015 Society of Investigative Dermatology Annual Meeting

ATLANTA, May 6, 2015 - Histogen, Inc., a regenerative medicine company developing solutions based on the products of cells grown under simulated embryonic conditions, will present new research on its 105F immunomodulatory treatment candidate for melanoma during the 2015 Society of Investigative Dermatology (SID) Annual Meeting, taking place May 6-9, 2015 in Atlanta, GA.

Histogen has previously shown that hypoxia-induced multipotent cells produce a soluble material with anti-oncologic properties, with potential benefit in the treatment of a wide range of cancers. Studies to characterize the active components of the material have identified a low molecular weight fraction (105F) which directly induces apoptosis, or controlled cell death, in 21 human cancer cell lines. In its latest research, Histogen sought to further examine the mechanism of action of 105F in melanoma through in vitro and in vivo studies.

After treatment with 105F, melanoma cells were shown to release Interleukin 6 (IL-6) and TNF a, pro-inflammatory cytokines acting as signals to the immune system. This induction of an immune "flare" in combination with tumor cell apoptosis could be critically important in recruiting immune cells to the tumor for cytotoxic attack.

"We were excited to see the dual activity of 105F, both directly inducing cancer cell death and activating an anti-tumorigenic immune response to reduce metastatic disease," said Dr. Gail Naughton, CEO and Chairman of the Board of Histogen. "These results represent a potential treatment for melanoma and other solid tumors that works through multiple channels to eliminate cancer cells, but is not toxic to the body's healthy cells."

An in vivo model of lung metastasis in C57Bl/6 mice further showed the efficacy of 105F in the treatment of melanoma. Daily intravenous injections of 105F over 14 days resulted in a significant (p=0.0049) reduction in lesions and marked immune cell infiltration as compared to controls.

Dr. Naughton will present "105F is a novel immunoadaptive treatment candidate for melanoma that induces apoptosis and the secretion of pro-inflammatory IL-6" at the 2015 SID Annual Meeting in Atlanta beginning May 6, 2015. Following the event, the presentation will be available upon request.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's technology focuses on stimulating a patient's own stem cells by delivering a proprietary complex of multipotent human proteins that have been shown to support stem cell growth and differentiation. For more information, please visit http://www.histogen.com.

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Histogen's Composition for Oncology Treatments Receives US Patent

SAN DIEGO, October 8, 2014 - Histogen Oncology, a company developing innovative cancer therapies based on Histogen's regenerative medicine technology, today announced that the United States Patent & Trademark Office has issued patent 12/363,479 entitled "Extracellular matrix compositions for the treatment of cancer" to Histogen.

The patent, which is the fifth U.S. patent issued to Histogen, covers the soluble and insoluble compositions of proteins and cofactors that are secreted by multipotent stem cells through Histogen's technology process for use in the treatment of cancer. The patent claims support of the use of the compositions alone or as a delivery system for traditional chemotherapeutic agents.

Through the recent formation and funding of the Histogen Oncology joint venture, research and development of the unique, naturally secreted compositions is progressing toward a Phase I clinical trial for end stage pancreatic cancer.

"We are pleased about the timely issuance of our U.S. patent for the treatment of cancer," said Dr. Gail K. Naughton, Histogen CEO and Chairman of the Board. "Our collaborations with top institutions continue to produce mounting evidence supporting the unique mechanism of action of our secreted material in preventing metastasis and reducing tumor load while having no toxic affect on normal cells."

Histogen's composition has shown effectiveness in inhibiting over 21 human cancer cell lines both in vitro as well as in animal models. The mechanism of action of the secreted material is through the induction of apoptosis (controlled cell death) primarily in malignant cells, so there is little to no toxicity to normal cells. Histogen Oncology is studying the efficacy of a small molecular weight fraction of the cell secreted composition as a stand alone treatment as well as in combination therapy to evaluate whether effectiveness can be demonstrated with less toxic drug doses.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's technology focuses on stimulating a patient's own stem cells by delivering a proprietary complex of multipotent human proteins that have been shown to support stem cell growth and differentiation. For more information, please visit http://www.histogen.com.

Contacts Eileen Brandt, (858) 200-9520 ebrandt@histogeninc.com

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Histogen Oncology Created to Develop Novel Biologic Cancer Treatments Histogen, Inc. and Wylde, LLC Form Joint Venture

SAN DIEGO, July 8, 2014 - Histogen Inc., a regenerative medicine company developing solutions based on the products of cells grown under simulated embryonic conditions, has partnered with Southern California medical device group Wylde, LLC to create Histogen Oncology. This joint venture will focus on the development of unique cell-derived materials for cancer applications.

Under this joint venture, Histogen Oncology has acquired exclusive rights to Histogen's human multipotent cell conditioned media (CCM) and extracellular matrix (ECM) materials, as well as their derivatives, for oncology applications throughout North America. Histogen Oncology's initial clinical focus is pancreatic cancer, a highly treatment-resistant cancer in which a sub-fraction of the CCM has shown substantial preclinical promise.

"We have been very impressed with the results of Histogen's preliminary oncology work, not only because of the significant survival benefit but also because it is a naturally-derived material that is showing no toxicity," said Christopher Wiggins of Wylde, LLC. "There are so many patients out there who are not candidates for existing therapies due to the toxic nature of available drugs. This is particularly true in pancreatic cancer, where 80% of people diagnosed already have stage four disease."

In post-resection nude mouse models, intravenous treatment with the CCM sub-fraction resulted in prolonged survival by more than three fold in a majority of treated animals. In non-resection models, more than 50% of treated mice lived twice as long as the control. These results point to a potentially significant outcome for pancreatic cancer patients, and Histogen Oncology intends to progress the material toward a Phase I clinical trial for no-option pancreatic cancer patients in the coming 18 months.

Research on the mechanism responsible for cancer cell inhibition by the CCM shows the upregulation of Caspase 9 and cleaved Caspase 3, which causes cancer cells to enter apoptosis, or programmed cell death.

"The activity of the CCM sub-fraction is unique in a number of ways. Whereas most cancer therapies target rapidly dividing cells but not cancer stem cells, the inhibitory effect of this material is seen in malignant cells and circulating tumor cells as well," said Dr. Gail Naughton, CEO and Chairman of the Board of Histogen, Inc. "In addition, the activity is selective for malignant cells, supporting the proliferation of human dermal fibroblasts, embryonic stem cells and mesenchymal stem cells, while inhibiting tumor growth."

Histogen Oncology will be supported by Histogen's research group and funded by Wylde, LLC., made up of experts from the surgery and medical device industries. The creation of this joint venture allows for dedicated development of the CCM sub-fraction as a cancer treatment, as Histogen continues to allocate resources to the Company's revenue-generating aesthetic and promising therapeutic programs.

"We are extremely excited to fuel and push the next stage of development for this innovative and potentially life-saving therapy," said Wiggins. "The next generation of cancer treatment will have cell-signaling at its core, be beneficial in combination with existing therapies as well as stand alone, and provide an option to patients who currently have none. We believe Histogen's material has all of those characteristics and more."

About Histogen Aesthetics Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's technology focuses on stimulating a patient's own stem cells by delivering a proprietary complex of multipotent human proteins that have been shown to support stem cell growth and differentiation. For more information, please visit http://www.histogen.com.

Contacts Eileen Brandt, (858) 200-9520 ebrandt@histogeninc.com

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Histogen Aesthetics Acquires CellCeuticals Biomedical Skin Treatments

SAN DIEGO, March 10, 2014 - Histogen Aesthetics, a subsidiary of regenerative medicine company Histogen, Inc. focused on skin care and cosmeceuticals, announced today that the Company has acquired the CellCeuticals Biomedical Skin Treatments line of skincare products.

Histogen Aesthetics will continue sales of the eleven existing CellCeuticals Biomedical Skin Treatments skincare products, while bringing new innovation to the line through the addition of a unique regenerative medicine technology, working to improve skin aging at a cellular level.

"We have long admired the science, clinical data and elegant formulas behind the CellCeuticals line, and see it as an ideal fit for our recently revitalized aesthetics subsidiary," said Dr. Gail K. Naughton, CEO and Chairman of Histogen, Inc. "We are very excited to begin infusing unique cell-signaling factors into the CellCeuticals regimen, to truly transform skin one cell at a time."

Dr. Naughton has spent more than 30 years in tissue engineering and regenerative medicine, and holds over 100 patents in the field. She founded Histogen in 2007, focused on developing therapies that work to stimulate the stem cells in the body to regenerate tissues and organs. Through this work, she has also seen how different compositions of human proteins can have cosmetic benefits, particularly in anti-aging and rejuvenation.

"I am pleased that the CellCeuticals Biomedical Skin Treatments will evolve, and see Histogen Aesthetics as an excellent home for this innovative product line," said Paul Scott Premo, co-founder of CellCeuticals Skin Care, Inc. "I believe the addition of this regenerative medicine technology will be the opportunity to introduce a new generation of products that are the vanguard of regenerative skin care."

The CellCeuticals system is made up of eleven distinctive products including the Extremely Gentle Skin Cleanser, CellGenesis Regenerative Skin Treatment, and PhotoDefense Color Radiance SPF55+ with proprietary and patented PhotoPlex technology. The line is currently available at retailers including QVC.com, Dermstore.com, and Nordstrom.com, as well as http://www.cellceuticalskincare.com.

About Histogen Aesthetics Histogen Aesthetics LLC, formed in 2008 as a subsidiary of Histogen, Inc., focuses on the development of innovative skin care products utilizing regenerative medicine technology. Histogen Aesthetics' technology is based on the expertise of founder Dr. Gail K. Naughton, in which fibroblasts are grown under unique conditions, producing a complex of naturally-secreted proteins and synergistic bio-products known to stimulate skin cells to regenerate and rejuvenate tissues. In 2014, Histogen Aesthetics acquired CellCeuticals Biomedical Skin Treatments, a line of scientifically-proven products that reactivate cells to help aging skin perform and look healthier and younger. For more information, visit http://www.cellceuticalskincare.com.

About Suneva Medical, Inc. Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogen's process is also being researched for oncology applications, and in orthopedics through joint venture PUR Biologics, LLC. For more information, please visit http://www.histogen.com.

Contacts Eileen Brandt, (858) 200-9520 ebrandt@histogeninc.com

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Histogen and Suneva Medical Expand License for Cell Conditioned Media-based Aesthetic Products Internationally

SAN DIEGO, CA, January 14, 2014 - Histogen, Inc., a regenerative medicine company developing solutions based on the products of cells grown under simulated embryonic conditions, today announced that they have entered into an international license agreement with Suneva Medical, Inc. for physician-dispensed aesthetic products containing Histogen's proprietary multipotent cell conditioned media (CCM).

This agreement is an amendment to the existing license between Histogen and Suneva Medical, through which Suneva has exclusively licensed the Regenica skincare line within the United States since February 2012. Under the terms of the international agreement, Suneva Medical is now the exclusive licensee for the distribution of Regenica through the physician-dispensed channel in Europe, most of Asia, South America, Canada, Australia, and the Middle East.

"Not only has Suneva had sales success, but they have generated enthusiasm around the Regenica product line and our technology here in the US," said Gail K. Naughton, Ph.D., CEO and Chairman of the Board of Histogen. "We are excited about expanding our skincare partnership internationally, and look forward to an exciting year for Regenica."

Regenica contains Histogen's proprietary Multipotent Cell Conditioned Media, made up of soluble cell-signaing proteins and growth factors which support the body's epidermal stem cells and renew skin throughout life. Through Histogen's technology process, which mimics the embryonic environment including conditions of low oxygen and suspension, cells are triggered to become multipotent, and naturally produce these proteins associated with skin renewal and scarless healing.

"We believe that Regenica truly is the next generation in growth factor technology, and we are extremely pleased that the products will now have a presence around the world," said Nicholas L. Teti, Jr., Chairman and Chief Executive Officer of Suneva Medical. "Our relationship with Histogen in the US physician market has been a valuable asset to Suneva, and has laid the groundwork for international success."

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogen's process can be found in skincare products including ReGenica, which is distributed by Suneva Medical in partnership with Obagi Medical Products. For more information, please visit http://www.histogen.com.

About Suneva Medical, Inc. Suneva Medical, Inc. is a privately-held aesthetics company focused on developing, manufacturing and commercializing novel, differentiated products for the general dermatology and aesthetic markets. The company currently markets Artefill in the US, Korea, Singapore and Vietnam; Refissa and Regenica Skincare in the U.S.; and Bellafill in Canada. For more information, visit http://www.sunevamedical.com.

Regenica is a trademark of Suneva Medical, Inc. The Multipotent Cell Conditioned Media Complex is covered by U.S. patents #8,257,947 and #8,524,494.

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Multipotent Stem Cell Proteins Support Soft Tissue Regeneration Histogen to present data at TERMIS AM Annual Conference in Atlanta

ATLANTA, November 13, 2013 - Histogen, Inc., a regenerative medicine company developing solutions based on the products of cells grown under simulated embryonic conditions, announced that Dr. Michael Zimber will give a podium presentation entitled "Human Multipotent Stem Cell Proteins Support Soft Tissue Regeneration" today at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) Americas Annual Meeting in Atlanta, GA.

Through its proprietary technology process that simulates the conditions of the embryonic environment, Histogen has developed a human extracellular matrix (hECM) material composed of stem cell-associated proteins including SPARC, decorin, collagens I,III,IV, V, fibronectin, fibrillin, laminins, and hyaluronic acid. The hECM's distinctive composition of growth factors and other proteins are known to stimulate stem cells in the body, regenerate tissues, and promote scarless healing.

Histogen sought to examine whether the hECM may promote scarless healing in full thickness wounds, similar to that seen in fetal healing, using a variety of forms of the material, including hollow spheres to maximize void fill volume. In preclinical studies, all hECM-treated wounds healed rapidly with minimum contractions, and the hECM microspheres had a statistically significant improvement in healing as compared to the controls (p<0.05) and produced a 25% thicker dermis. In addition, hECM applied topically after microneedling resulted in up to a 3X dermal thickening.

"We are very pleased that our propriety materials produced by hypoxia-induced human multipotent stem cells have shown significant healing results in both soft and hard tissues," said Dr. Gail Naughton, CEO and Chairman of the Board of Histogen. "These results open new therapeutic markets, show tremendous potential for our material in cutaneous wound care and orthopedics, as well as support the expansion of our aesthetic pipeline to include soft tissue fillers."

In addition to "Human Multipotent Stem Cell Proteins Support Soft Tissue Regeneration", Dr. Zimber will also be presenting "Human Multipotent Stem Cell Proteins Support Osteogenesis In Vitro" during the TERMIS AM Annual Meeting taking place November 10-13, 2013 in Atlanta. Following the event, these presentations will be available upon request.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogen's process can be found in skincare products including ReGenica, which is distributed by Suneva Medical in partnership with Obagi Medical Products. For more information, please visit http://www.histogen.com.

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Multipotent Stem Cell Proteins Support Rejuvenation while Inhibiting Skin Cancer Histogen to present data at TERMIS AP Annual Conference in Shanghai

San Diego, October 24, 2013 - Histogen, Inc., a regenerative medicine company developing solutions based on the products of cells grown under simulated embryonic conditions, announced that the Company's Chairman and CEO, Dr. Gail Naughton, will present today at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) Asia Pacific Annual Meeting in Shanghai, China.

Through its proprietary technology process that simulates the conditions of the embryonic environment, Histogen is uniquely able to trigger the de-differentiation of skin cells into multipotent stem cells without genetic manipulation. The cells express key stem cell markers including Oct4, Sox2 and Nanog, and secrete a distinctive composition of growth factors and other proteins known to stimulate stem cells in the body, regenerate tissues, and promote scarless healing.

It is the soluble and insoluble compositions of multipotent proteins and growth factors resulting from this process that have been shown to both promote skin regeneration and induce controlled cell death in multiple skin cancers.

"The anti-aging and rejuvenation benefits of human multipotent stem cell proteins have been shown in several clinical studies, and have resulted in the material's use as a thriving next-generation ingredient for skin care," said Dr. Naughton. "In parallel, we have also been studying the anti-cancer activity of these proteins, and have shown that, just as in the embryonic environment, they support normal tissue growth while resulting in the controlled death of cancer cells".

In vitro studies performed with Histogen's material have shown reduction in Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma, and Melanoma cell number through the mechanism of apoptosis, or controlled cell death, induced by the upregulation of Caspase in these cancer cells. In one in vivo model, melanoma load was reduced by up to 80% versus the control (p<0.05) by the addition of the insoluble multipotent stem cell proteins, and a dose response curve was seen. Similar inhibition was seen with SCC. In subcutaneous mouse experiments, tumor growth was inhibited by 70-90%.

"Human Multipotent Stem Cell Proteins Stimulate Skin Regeneration While Inducing Skin Cancer Cell Apotosis" will be presented by Dr. Naughton during the TERMIS AP Annual Meeting taking place October 23-26, 2013 in Shanghai. Further information and data on the ability of multipotent stem cell proteins to induce apoptosis in skin cancers can be found in the publication Journal of Cancer Therapy at file.scirp.org/Html/1-8901700_33923.htm.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogen's process can be found in skincare products including ReGenica, which is distributed by Suneva Medical in partnership with Obagi Medical Products. For more information, please visit http://www.histogen.com.

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Histogen to present at 2013 STEM CELL MEETING ON THE MESA

San Diego, October 11, 2013 - Histogen, Inc., a regenerative medicine company developing therapies for conditions including hair loss and cancer, announced today that Histogen CEO Gail K. Naughton, Ph.D. will give a company presentation at the 3rd Annual Regen Med Partnering Forum, part of the Stem Cell Meeting on the Mesa to be held October 14-16 in La Jolla, CA.

Histogen's solutions are based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. The technology focuses on stimulating a patient's own stem cells by delivering a proprietary complex of proteins that have been shown to support stem cell growth and differentiation.

"It is an exciting time for Histogen, as we continue to move the technology forward with expanded partnerships in skincare, compelling clinical data in both male and female hair loss, and early but exciting results in orthopedics," said Dr. Naughton. "We look forward to sharing our story during the Stem Cell Meeting on the Mesa, and to progressing our products even further through growing relationships with industry leaders and through our potential merger with Stratus Media to form publicly-traded Restorgenex."

Organized by the Alliance for Regenerative Medicine (ARM), the California Institute for Regenerative Medicine (CIRM) and the Sanford Consortium for Regenerative Medicine, the 2013 Stem Cell Meeting on the Mesa is a three-day conference aimed at bringing together senior members of the regenerative medicine industry with the scientific research community to advance stem cell science into cures. The Regen Med Partnering Forum, held October 14 &15 at the Estancia La Jolla Hotel, is the only partnering meeting organized specifically for the regenerative medicine and advanced therapies industry.

The following are specific details regarding Histogen's presentation at the conference:

Event: Regen Med Partnering Forum - 2013 Stem Cell Meeting on the Mesa Date: October 14, 2013 Time: 3:15pm Location: Estancia La Jolla Hotel & Spa, 9700 North Torrey Pines Road, La Jolla

A live video webcast of all company presentations will be available at: stemcellmeetingonthemesa.com/webcast and will also be published on ARM's website shortly after the event. Histogen will also make a copy of Dr. Naughton's presentation available at http://www.histogen.com.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogen's lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogen's process can be found in skincare products including ReGenica, which is distributed by Suneva Medical in partnership with Obagi Medical Products. For more information, please visit http://www.histogen.com.

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Stratus Media Group and Histogen Execute Letter of Intent for Biotechnology Merger

LOS ANGELES, October 07, 2013 - Stratus Media Group, Inc. (OTCQB:SMDI) announced today that it was planning to expand its entrance into the biotechnology industry with the execution of a letter of intent between the Company and Histogen, Inc., a regenerative medicine company developing innovative therapies for conditions including hair loss and cancer.

The non-binding letter of intent outlines the primary terms of a merger of San Diego-based Histogen into Stratus, to be renamed Restorgenex Corporation. The letter of intent has been approved by the board of directors of both companies, and the parties are engaged in completing a formal merger agreement.

Histogen's solutions are based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. The technology focuses on stimulating a patient's own stem cells by delivering a proprietary complex of proteins that have been shown to support stem cell growth and differentiation. Histogen's lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogen's process can be found in skincare products including ReGenica, which is distributed by Suneva Medical in partnership with Obagi Medical Products.

"Histogen's technology platform opens a spectrum of potential product opportunities in both aesthetics and therapeutics, an ideal fit with our vision for Restorgenex," said Sol J. Barer, Ph.D., who will assume the position of Chairman of the Board of Restorgenex effective November 1, 2013. "The expertise of the Histogen team in developing regenerative products from concept to market, along with the success Histogen has already found in skincare partnering, will add significant value to our Company."

Following successful completion of this proposed merger, the company's goal is to build Restorgenex into a world-class cosmeceutical and pharmaceutical company in the large and expanding fields of dermatology and hair restoration. The parties intend to move toward a formal merger agreement in which Histogen would become a wholly-owned subsidiary, Histogen founder Gail K. Naughton, Ph.D. would assume the position of Chief Executive Officer of Restorgenex, and the corporate headquarters of Restorgenex would be located in San Diego. The merger will require, among other things, the satisfaction of customary closing conditions including the approval of Histogen's shareholders.

"I am very excited about the potential of a merger between Histogen and Restorgenex, and look forward to moving into the next stage," said Dr. Naughton. "It is an honor to be working with biotechnology visionaries Dr. Sol Barer and Isaac Blech, and to have them recognize the promise of Histogen's products is a true testament to the unique and exciting nature of our technology."

Dr. Naughton has spent more than 25 years extensively researching the tissue engineering process, holds more than 95 U.S. and foreign patents, and has been honored for her pioneering work in the field by prestigious organizations including receiving the Intellectual Property Owners Association Inventor of the Year Award.

Prior to founding Histogen in 2007, Dr. Naughton oversaw the design and development of the world's first up-scaled manufacturing facility for tissue engineered products, was pivotal in raising over $350M from the public market and corporate partnerships, and brought four human cell-based products from concept through FDA approval and market launch as President of Advanced Tissue Sciences.

"I believe the potential acquisition of Histogen, and the expertise and vision Dr. Naughton will bring as Chief Executive Officer will be a tremendous asset in ushering the Company into the biotechnology industry," said Jerold Rubinstein, current Chairman and Chief Executive Officer of Stratus.

http://www.histogen.com http://www.stratusmediagroup.com

Forward-Looking Statements Statements in this press release relating to plans, strategies, projections of results, and other statements that are not descriptions of historical facts may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and the Securities Acts of 1933 and 1934. Forward-looking information is inherently subject to risks and uncertainties, and actual results could differ materially from those currently anticipated due to a number of factors. Although the company's management believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee future results, performance or achievements. The company has no obligation to update these forward-looking statements.

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Nicole Kush is the first new cannabis strain to be released by DNA Genetics in collaboration with Marimberos.

The sativa-dominant strain, Nicole, can trace it's lineage back to a carefully bred plant in Mexico's Durango desert almost ten years ago. With a pedigree that includes such classic strains as MK Ultra, Shiskaberry and Blueberry, Nicole was then crossed with DNA Genetics legendary Kosher Kush to create this exciting new strain - Nicole Kush.

DNA and Marimberos' test grows of Nicole Kush, conducted in a legal environment, showed insane, over-the-top resin production. A blanket of sticky trichomes coats the plants; Nicole Kush is ideal for extractions. Flavours and aromas are fruity like blueberries and wine or even grape jam.

A lovely new strain from DNA and Marimberos that is a certainty to be popular with connoisseur cannabis seed collectors everywhere.

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All our descriptions and images have come direct from the breeders who operate in a legal climate much different to that within the United Kingdom. Take note, you should NEVER try cultivating any cannabis plants within ANY jurisdiction where such cultivation is illegal. Our seeds are sold purely for souvenirs and should be treated as a curio or novelty item and should never be germinated. PLEASE DO NOT BREAK THE LAW!

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Nicole Kush Female Cannabis Seeds by DNA Genetics and ...

When it comes to health, hormones and gut bacteria have a much bigger effect than many people realize. In fact, these two factors can destroy health even if everything else (diet, supplements, etc.) is optimized.

Conversely, regulatinghormones and fixing gut bacteria can do a lot to boost health, even if not all the other factors are optimal. In fact, there are even studies about using certain hormone reactions to heal brain trauma.

If you doubt the very real power of hormones to affect everything from mood, to weight, to bowel health, ask the nearest pregnant woman if shes noticed any difference in these areas since becoming pregnant. Or ask the nearest 13 year old girl carefully

What factor contributes to weight gain during pregnancy? Hormone balance.

What causes weight fluctuations, bloating and other health symptoms throughout the course of a month? Hormones.

What causes men to naturally put on muscle more easily or lose weight more quickly? Hormones.

What is a huge contributing factor of growth in children? Hormones.

What controls ovulation, reproduction, pregnancy, etc? Hormones.

Yes, when it comes to losing weight or improving health, what do we focus on? Calories or micronutrients or diets. Those with symptoms likefatigue, skin issues, weight gain, weight around the middle, trouble sleeping, always sleeping, PMS, endometriosis, infertility, PCOS or other issues may find that addressing hormones is vital for recovery.

Hormones are your bodys chemical messengers. They travel in your bloodstream to tissues and organs. They work slowly, over time, and affect many different processes, including metabolism, sexual function, reproduction, mood and much more.

Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal glands and pancreas. In addition, men produce hormones in their testes and women produce them in their ovaries. (source)

Hormones are produced in a complex process, but depend on beneficialfats and cholesterol, so lack of these important dietary factors can cause hormone problems simply because the body doesnt have the building blocks to make them. Toxins containing chemicals that mimic these building blocks or that mimic the hormones themselves are also problematic because the body can attempt to create hormones using the wrong building blocks. Mutant estrogen anyone?

Ive heard so many cases lately of people who have improved diet, started exercising, etc. but are still not losing weight or improving their health markers. After talking to many of these people, it seems that the factor they all have in common is an underlying problem with hormone balance.

Ive written about Leptin and thyroid hormones before, and these are just a small piece in the complicated hormone system in the body. In a given day or month, a womans body will have fluctuations in hormones like estrogen, progesterone, cortisol, lutenizing hormone, prolactin, oxytocin, leptin, ghrelin, thyroid hormones, melatonin, serotonin and others.

The endocrine system is a complex system that we will probably never completely understand, but there are some basic things you can do to boost your bodys ability to create and balance hormones:

Ivetalked about this before, but the body is simply not meant to consume the man-made fats found in vegetable oils. The fat content of the human body is largely saturated fat, with only about 3% of thebodys fat coming from other types.

The 3% of the body made up of polyunsaturated fats contains both Omega-3 fats and Omega-6 fats in about a 50:50 balance. This ratio is extremely important for health, and it is often ignored. Seed based vegetable oils (like canola oil, soybean oil, etc.) are very high in Omega-6 fats and low in Omega-3 fats. Since the 1950s, these seed based oils have replaced many sources of saturated fats and Omega-3s in the diet. This is one of the reasons that most people are not getting enough vital Omega-3 fatty acids from their diet.

Not only are we consuming way too many omega-6 fatty acids from polyunsaturated vegetable oils, but we are not consuming enough beneficial Omega-3s and saturated fats. These types of fats are vital for proper cell function and especially for hormone function, as these are literally the building blocks for hormone production. When we dont give the body adequate amounts of these fats, it must use what is available, relying on lower quality polyunsaturated fats.

The trouble is that polyunsaturated fats are less stable and oxidize easily in the body, which can lead to inflammation and mutations within the body. Emerging evidence suggests that that this inflammation can occur in arterial cells (potentially increasing the chance of clogged arteries), skin cells (leading to skin mutations) and reproductive cells (which may be connected to PCOS and other hormone problems).

Other types of fats, especially saturated fats, are vital for hormone health and balance as the body uses fats as building blocks for hormones. As this article explains:

When these important saturated fatty acids are not readily available, certain growth factors in the cells and organs will not be properly aligned. This is because the various receptors, such as G-protein receptors, need to be coupled with lipids in order to provide localization of function.

The messages that are sent from the outside of the cell to the inner part of the cell control many functions including those activated by, for example, adrenaline in the primitive mammalian fight/flight reactions. When the adrenal gland produces adrenaline and the adrenaline (beta-adrenergic) receptor communicates with the G-protein and its signal cascade, the parts of the body are alerted to the need for action; the heart beats faster, the blood flow to the gut decreases while the blood flow to the muscles increases and the production of glucose is stimulated.

The G-proteins come in different forms; the alpha subunit is covalently linked to myristic acid and the function of this subunit is important for turning on and off the binding to an enzyme called adenylate cyclase and thus the amplification of important hormone signals.

When researchers looked at the fatty acid composition of the phospholipids in the T-cells (white blood cells), from both young and old donors, they found that a loss of saturated fatty acids in the lymphocytes was responsible for age-related declines in white blood cell function. They found that they could correct cellular deficiencies in palmitic acid and myristic acid by adding these saturated fatty acids.

For this reason,Coconut Oilis amazing for hormone health. It provides the necessary building blocks for hormone production, can assist weight loss, reduce inflammation, and even has antimicrobial and antibacterial properties.My favorite way to consume it is toblend into coffeeor tea.This is the highest quality one Ive found. Other quality sources of fats include avocados, animal fats, olive oil, grass fed meats, pastured eggs, and raw dairy (for those who tolerate it). Quality seafood is also very important, as it is natures best source of naturally occurring Omega-3s.

Bottom line: Dont eat fats like vegetable oil, peanut oil, canola oil, soybean oil, margarine, shortening, or other chemically altered fats. Choose fats like coconut oil, real butter, olive oil (dont heat it!) and animal fats (tallow, lard) from healthy sources instead and eat lots of high Omega-3 fish.

I love coffee a lot, but the truth is that too much caffeine can wreakhavocon the endocrine system, especially if there are other hormone stressors involved, like pregnancy, presence of toxins, beneficial fat imbalance or stress.

Cut down the coffee if you can, or replace with beneficial herbal teas (here are my ten favorite DIY recipes). If you cant or wont cut the coffee, use it as a way to sneak in your beneficial fats by adding 1 tablespoon coconut oil to each cup and blending in the blender to emulsify. It is like a latte but with healthy fats! Here is the recipe I use and the only way I drink coffee.

Harmful chemicalsfound in pesticides, plastics, household cleaners, and even mattresses can contain hormone disrupting chemicals that mimic hormones in the body and keep the body from producing real hormones. Things likehormonal birth control can (obviously) do the same thing.

For those with a hormone imbalance or who are struggling to get pregnant, avoiding these unnecessary chemicalsis very important! Cook in glass or non-coated metal pans (no non-stick or teflon) and avoid heating or storing foods in plastic. Find organic produce and meat whenever possible and dont use chemical pesticides or cleaners. Hereis arecipe for a natural cleaner.

Here are some additional tips for avoiding indoor toxins:

Beauty products are another source of chemical exposure for many people. There are tens of thousands of chemicals in the personal care products we encounter daily, and most of these chemicals have not been tested for long-term safety. Avoiding these products can make a tremendous difference in achieving hormone balance. Start by making simple switches like homemade deodorant, and homemade lotion and even DIY makeup if youre feeling adventurous. Check out my full index of natural beauty recipes here.

I cant emphasize this one enough!Without adequatesleep, hormones will not be in balance. Period. (This is the one I struggle with the most!)

While youre sleeping, your body is extremely active removing toxins, recharging the mind, and creating hormones. Skimping on sleep, even for one night, can have a tremendous impact on hormones and even one night of missed or shortened sleep can create the hormone levels of a pre-diabetic (source).

Try some of these tips to help improve sleep::

Unfortunately, we live in a world where the food supply is often depleted of nutrients due to over-farming, the water is often contaminated with chemicals, and even the air can contain compounds that cause havoc in the body.

Ideally, we could get all of our nutrients from food, properly hydrate from water, and get enough Vitamin D from the sun on a daily basis. Wed get magnesium from the ocean and not get deficient in the first place since wed be consuming adequate minerals from eating fresh seafood. Since this is rarely the case, supplements can sometimes be needed! Ive sharedthe basic supplements that I take before, butcertain supplements are especially helpful for hormone balance.

NOTE: Make sure to check with your doctor or health care professional before taking any new supplements, especially if you are on medications or contraceptives.

Maca A hormone boosting tuber in the radish family with a long history of use in Peru. Women who use this often see improvements in fertility, reduction in PMS and better skin/hair. It can help men with sperm production, testosterone levels and muscle composition.Maca is a good source ofminerals and essential fatty acids, which is one of the ways it supports hormone balance. It is available inpowder form(least expensive option) or incapsules. Maca should be discontinued during pregnancy.

Magnesium Magnesium is vital for hundreds of functions within the human body and many of us are deficient in this master mineral (heres how to tell if you are). There are several different ways to getMagnesium:Inpowder form with a product like Natural Calmso that you can vary your dose and work up slowly,ionic liquid formcan be added to food and drinks and dose can be worked up slowly,ortransdermal form by using Magnesium oilapplied to the skin (this is my favorite method). Topical applicationis often the most effective option for those with a damaged digestive tract or severe deficiency.

Vitamin D & Omega-3s A pre-hormone is supportive of hormone function. Bestobtained from the sunif possible, or from aD3 supplementorCod Liver Oil(a good source of Omega-3 and Vitamin D and what I do in the winter). Make sure not to get too much, and optimally, get Serum Vitamin D levels checked to monitor levels.

Gelatin or Collagen-a great source of minerals and necessary amino acids. Gelatin and collagen powderssupport hormone production and digestive healthin various ways. Gelatin powder can actually gel and is useful in recipes like homemade jello and probiotic marshmallows, while collagen protein does not gel but is easily added to soups, smoothies, coffee, tea or any other food. (I get both gelatin powder and collagen peptides from here)

Natural Progesterone Cream PMS and menstrual troubles are often linked to specific hormone imbalances. Especially for those with short cycles or short second phase of their cycle (ovulation through start of menses), progesterone can be the issue. Ive seen people add only natural progesterone cream and see symptoms greatly reduce. If you do use progesterone cream, do you own research, make sure you have a goodbrand that is soy-freeand only use for the second half of your cycle (ovulation through menses). Check with a doctor or professional before using any hormone supplement.

For those withhormone imbalance, intense extended exercise can actually make the problem worse in the short term. Sleep is muchmore important, at least during the balancing phase, so focusing on relaxing exercises like walking or swimming and avoiding the extended running, cardio, and exercise videos, can help the body in the short term.

I personally likeRebounding, which is great gentle exercise and has additional health benefits.

While extended cardio can be bad, short bursts of heavy lifting (kettlebells, deadlifts, squats, lunges) can be beneficial since they trigger a cascade of beneficial hormone reactions. Aim for a few sets (5-7) at a weight that really challenges you, but make sure to get help with form and training if you havent done these before as bad form can be harmful.

Certain herbs and plants can also help the body bring hormones into balance. Of course, it is important to talk to a doctor before taking these, especially if a person is on hormonal contraceptives or other medications. Some herbs that Ive personally used are:

Vitex/Chaste Tree Berry Nourishes the pituitary gland and helps lengthen the luteal phase. It lowers prolactin and raises progesterone. For some women, this alone will improve symptoms.

Red Raspberry LeafA well know fertility herb that is also helpful in reducing PMS and cramping. It has a high nutrient profile and is especially high in calcium and is a uterine tonic. It is available incapsuleform, but makes an excellent hot or cold tea.

Adaptogens- Herbs that help the body handle stress and support the adrenals. They are a great and natural way to work toward hormone balance for many people. This is a good primer on understanding adaptogens.

The digestive system has much more of an impact on hormones than many of us realize. Not only is the digestive tract the source of many vital neurotransmitters in the body, butan imbalance in the gut can translate to an imbalance in neurotransmitter and hormones. Serotonin, a necessary neurotransmitter for sleep/stress balance is more concentrated in the gut than even in the brain! 70% of the immune system is found in the gut and it is quite literally the motherboard of many functions in the body. Even thyroid health has been linked to gut health.

What Hippocrates knew thousands of years ago seems just as true today that all disease beginsin the gut. Those who struggle with gut problems may have trouble ever achieving hormone balance without first addressing gut health. (This is the most comprehensive program Ive ever seen for addressing gut healthissues.)

Leptin is a master hormone, and if it is out of balance or if you are resistant to it, no other hormones will balance well. Fixing leptin will also help boost fertility, make weight loss easier, improve sleep, and lower inflammation. Dr. Jack Kruse, a neurosurgeon, has a whole system for getting leptin into balance.

The infographic below is a quick overview of steps to balance your hormones. Pin it or share it to save for later!

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Source: Wellness Mama

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Lime, bearing the scientific name Citrus Aurantifolia, has been used for ages in the treatment of various ailments.The first fruit that comes to mind in terms of medicinal uses is the reliable lime. This sour citrus fruit can do what many advanced medicines cannot. Lime is consumed throughout the world in the form of sorbet, beverages, refreshing cocktails, pickles, jams, jellies, snacks, candies, sugar boiled confections and in cooking. The oil extracted from its peel or skin is extensively used in soft drink concentrates, body oils, cosmetic products, hair oils, toothpastes, toilet and beauty soaps, disinfectants, mouth washes, deodorants and innumerable other products. There are many varieties of lime found all over the world, particularly in the tropical and the Mediterranean climates. Lets take a look at the benefits and medicinal uses of lime,am sure you would be amazed. Scurvy: Lime is very well-known as a cure for scurvy, the disease which is caused from a deficiency of vitamin-C. It is characterized by frequent infections that show as normal cold symptoms, cracked lips and lip corners, ulcers on the tongue and in the mouth. You can also spot scurvy from spongy, swollen and bleeding gums. Since its cause is a deficiency of vitamin-C, its remedy is none other than vitamin-C, and lime is full of this this essential vitamin. In the past, soldiers and sailors were given lime to keep them safe from scurvy, which was a horrible and potentially fatal disease back then. Even now, it is distributed among the workers working in polluted environments like furnaces, painting shops, heat treatments, cement factories, mines, and other dangerous work environments to protect them from scurvy. Skin Care: Lime juice and its natural oils are very beneficial for skin when consumed orally or applied externally. It rejuvenates the skin, keeps it shining, protects it from infections and reduces body odor due to the presence of a large amount of vitamin-C and Flavonoids. Those are both class-1 anti oxidants, and have antibiotic and disinfectant properties. When applied externally on skin, its acids scrub out the dead cells, cures dandruff, rashes, and bruises. It can also be used to create a refreshing bathing experience if its juice or oil is mixed into your bathing water.

Digestion: Lime has an irresistible scent which causes your mouth to water and this actually aids primary digestion (the digestive saliva floods your mouth even before you taste it). The natural acidity in lime does the rest. While they break down of the macro molecules of the food, the Flavonoids, the compounds found in the fragrant oils extracted from lime, stimulate the digestive system and increase secretion of digestive juices, bile and acids. This flood of flavonoids also stimulate the peristaltic motion. This is the reason behind lemon pickle with lunch and dinner being a traditional practice in India and various neighboring countries in that region.

Constipation: Primarily, the ample amount of acids present in lime helps clear the excretory system by washing and cleaning off the tracts, just as some acids are used to clean floors and toilets. The roughage in lime is also helpful in easing constipation, but the most beneficial element is the high acidity. An overdose of lime juice with salt also acts as an excellent purgative without any side effects, thereby providing relief from constipation.

Diabetes: According to the American Diabetes Association, limes and other citrus fruits are considered a diabetes super food for a number of reasons. Mainly, the high levels of soluble fiber found in limes make it an ideal dietary aid to help regulate the bodys absorption of sugar into the bloodstream, reducing the occurrence of blood sugar spikes that are a serious risk to to diabetic patients. Also, limes and other citrus fruits have a low glycemic index, which means that they will not cause unexpected spikes in glucose levels, in addition to the benefits of soluble fibers effect.

Heart Disease: That same soluble fiber which can help diabetics maintain their blood sugar levels can also lower blood pressure and eliminate the presence of LDL cholesterol (bad cholesterol). Furthermore, soluble fiber can cut down on inflammation of the blood vessels, which is a known preventative measure against heart disease, heart attacks, and strokes.

Peptic Ulcer:In addition to vitamin-C, lime contains special compounds called Flavonoids (Limonoids such as Limonin Glucoside) which have antioxidant, anti-carcinogenic, antibiotic and detoxifying properties that stimulate the healing process of peptic and oral ulcers.

Respiratory Disorders: The flavonoid-rich oil that is extracted from limes is extensively used in anti-congestive medicines such as balms, vaporizers, and inhalers due to the presence of Kaempferol. Just scratching the peel of a lime and inhaling it gives immediate relief for congestion and nausea.

Arthritis: One of the many causes of arthritis is an excess of uric acid that builds up in the body. Uric acid is one of the waste products that normal urination will clear out of the body, but unfortunately, when too much builds up, it can make the pain and inflammation from arthritis even worse. The citric acid found in citrus fruits like limes is a solvent in which uric acid can dissolve, increasing the amounts that are eliminated in the urine. Citrus fruits in general have anti-inflammatory properties, and can be used for a number of inflammation issues.

Eye Care: Vitamin-C again! Its anti oxidant properties protect eyes from aging and macular degeneration. On top of that, flavonoids help protect them from infections.

Fever: If someone is suffering from a fever, limes and lime juice can be of great importance. Citrus fruits in general have fever-reducing qualities, and if the fever is very high, the patients diet should be restricted to lemon juice and water. However, if the fever is mild to moderate, other fruit juices, particularly citrus juices like lime juice, can be administered in order to bring the fever back a manageable level. Vitamin-C, found in high concentrations in citrus fruits, naturally lowers the temperature of the body.

Gout: There are two main causes of gout. The first source is the accumulation of free radicals in the body, and the second is accumulation of toxins in the body, primarily uric acid. Limes can help prevent both of these causes. It is a wonderful source of antioxidants & detoxifiers (vitamin-C & Flavonoids) which reduce the number of free radicals as well as detoxifying the body.

Gums: The root cause of gum problems is a deficiency of vitamin-C (Scurvy, which gives bleeding and spongy gums) and microbial growth. Sometimes, the ulcers come from physical trauma. In all of these situations, limes can help. Its vitamin-C cures scurvy, Flavonoids inhibit microbial growth and potassium and Flavonoids help heal ulcers and wounds.

Piles: Since lime helps heal ulcers and wounds in the digestive system and excretory system while providing relief from constipation, it eradicates all the root causes of piles. Piles are a different term for hemorrhoids, an uncomfortable condition that occurs in the anal region and can result in bleeding and discomfort both during excretion and general activity. It can also lead to certain forms of cancer, and limes can help prevent their formation or recurrence.

Cholera: Although it has disappeared in many parts of the world, cholera is still a dangerous and deadly disease in some places on the planet, and luckily, limes and other citrus fruits can help defend against this often fatal condition. The lime juice, when added to potentially infected water, proved to be a very effective disinfectant, and even when it was consumed regularly after someone had been exposed to cholera-infected water, fatalities were reduced. Numerous studies were done on this application of lime juice, particularly following the horrible outbreak of cholera in Guinea-Bissau in 1994.

Weight Loss: A glass of warm water with a full limes worth of juice in it is an excellent weight reducer as well as a brilliant refresher and antioxidant drink. The citric acid present in lime is an excellent fat burner. You can consume two glasses a day and see legitimate and remarkable results within a week.

Urinary Disorders: The high potassium content of limes is very effective in removal of the toxic substances and the precipitates which get deposited in kidneys and the urinary bladder. The disinfectant properties of limes also help cure infections in the urinary system. Furthermore, it stops prostrate growth (very common in males above 40) and clears blockage of urine that can come from calcium deposits in the urinary tract.

Other Benefits: It is a good appetizer and digestive. It can help to cure rheumatism, prostate and colon cancer, cholera, arteriosclerosis, fatigue and even high fevers (contrary to popular belief). The best part of it is that it has no negative side effects!

THANKS FOR VISITING....PLEASE SHARE AFTER READING .....LEAVE YOUR COMMENTS AND QUESTIONS BELOW....

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There are several ways adult stem cells can be isolated, most of which are being actively explored by our researchers.

1) From the body itself: Scientists are discovering that many tissues and organs contain a small number of adult stem cells that help maintain them. Adult stem cells have been found in the brain, bone marrow, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, and other (although not all) organs and tissues. They are thought to live in a specific area of each tissue, where they may remain dormant for years, dividing and creating new cells only when they are activated by tissue injury, disease or anything else that makes the body need more cells.

Adult stem cells can be isolated from the body in different ways, depending on the tissue. Blood stem cells, for example, can be taken from a donors bone marrow, from blood in the umbilical cord when a baby is born, or from a persons circulating blood. Mesenchymal stem cells, which can make bone, cartilage, fat, fibrous connective tissue, and cells that support the formation of blood can also be isolated from bone marrow. Neural stem cells (which form the brains three major cell types) have been isolated from the brain and spinal cord. Research teams at Childrens, headed by leading scientists Stuart Orkin, MD and William Pu, MD, both affiliate members of the Stem Cell Program, recently isolated cardiac stem cells from the heart.

Isolating adult stem cells, however, is just the first step. The cells then need to be grown to large enough numbers to be useful for treatment purposes. The laboratory of Leonard Zon, MD, director of the Stem Cell Program, has developed a technique for boosting numbers of blood stem cells thats now in Phase I clinical testing.

2) From amniotic fluid: Amniotic fluid, which bathes the fetus in the womb, contains fetal cells including mesenchymal stem cells, which are able to make a variety of tissues. Many pregnant women elect to have amniotic fluid drawn to test for chromosome defects, the procedure known as amniocentesis. This fluid is normally discarded after testing, but Childrens Hospital Boston surgeon Dario Fauza, MD, a Principal Investigator at Childrens and an affiliate member of the Stem Cell Program, has been investigating the idea of isolating mesenchymal stem cells and using them to grow new tissues for babies who have birth defects detected while they are still in the womb, such as congenital diaphragmatic hernia. These tissues would match the baby genetically, so would not be rejected by the immune system, and could be implanted either in utero or after the baby is born.

3) From pluripotent stem cells: Because embryonic stem cells and induced pluripotent cells (iPS cells), which are functionally similar, are able to create all types of cells and tissues, scientists at Childrens and elsewhere hope to use them to produce many different kinds of adult stem cells. Laboratories around the world are testing different chemical and mechanical factors that might prod embryonic stem cells or iPS cells into forming a particular kind of adult stem cell. Adult stem cells made in this fashion would potentially match the patient genetically, eliminating both the problem of tissue rejection and the need for toxic therapies to suppress the immune system.

4) From other adult stem cells: A number of research groups have reported that certain kinds of adult stem cells can transform, or differentiate, into apparently unrelated cell types (such as brain stem cells that differentiate into blood cells or blood-forming cells that differentiate into cardiac muscle cells). This phenomenon, called transdifferentiation, has been reported in some animals. However, its still far from clear how versatile adult stem cells really are, whether transdifferentiation can occur in human cells, or whether it could be made to happen reliably in the lab.

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Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!

1. Proliferation of unproved stem cell clinics in US The biggest buzz this week was a study by @LeighGTurner and @pknoepfler on stem cell clinics in US. This is very interesting study, which Id highly recommend you to read! Forget about stem cell tourism, all you need to do now is to look across the street or open glossy magazine at airplane. They are everywhere:

Using rigorous Internet-based key word searches (see Supplemental Information for details), we found 351 U.S. businesses engaged in direct-to-consumer marketing of stem cell interventions offered at 570 clinics. For each business, we collected the company name, location(s), website address, advertised stem cell types, and diseases, injuries, and other conditions that clinics claim to treat with stem cell interventions. (Table S1 lists and describes all of the businesses we identified).

The authors did a lot of work and they are also open to suggestions for clinics database and improvements in methodology. Also read about this study on the Niche blog.

2. Failure of Phase 3 cardiac cell therapy trial This week Belgian company Celyad released headline results of their Phase 3 cardiac cell therapy pan-European trial CHART-1. It was efficacy assessment of auto- bone marrow MSC, induced in cardiac lineage, on 271 patients with chronic ischemic heart failure. Primary endpoints of the study were missed. So, study is failed. However, post-hoc analysis showed 60% of patient subgroup with significant efficacy, measured by primary endpoint. Companys press release has a positive spin and most media outlets called the results of the trial mixed or even promising. The fate of so-called C-CURE cell therapy now will depend on discussion with EMA in Europe. Company still may attempt to commercialize it and/ or continue with re-designed trial in US. In any case Celyad would not proceed with C-CURE without partner. Unfortunately for Celyad, dropping of the companys value by investors for more than a third, will make a search for potential partner very hard.

3. Stem cell professionals divided for 2 camps in best regulation debate Article in STAT nicely summarized recent debate on the best rergulatory framework for stem cell-based therapies in US. In the first camp, proponents of so-called Regrow Act and anyone else (for example, president of CIRM, Randy Mills), who supports reformation of FDA to accelerate approvals and ease regulation in general. In the second camp, professionals, who are opposing simple ease of current FDA regulation. In this camp, we can see such professional organizations as ISSCR, ARM and some patient advocacy groups. As the example of second camp, you can read Knoepflers op-ed in the San Francisco Chronicle. Very interesting debate! Let me know what do you think in comments.

4. More clinical trials updates The results of the Phase 2 ALS trial, sponsored by NeuralStem were published online in Neurology on June 29, 2016. 15 patients, divided for 5 treatments groups, underwent experimental procedures in 3 different US centers. Even though there were 2 cases of serious adverse events observed and 2 deaths (attributed to disease progression) before 270 days, procedure deemed to be safe and well tolerated in general. Important conclusion experimental treatment was not clinically beneficial. However, as it was highlighted by investigators, the trial was not designed and powered to assess efficacy.

Last year, US-based company Cytori had 2 cardiac cell therapy trials, called ATHENA 1 and 2. Both trials were terminated last year, due to safety concerns and business considerations. Recently, company published available data, generated from both trials. 31 patients were included in analysis (28 from ATHENA 1 and 3 from ATHENA 2) 17 in cell therapy group and 14 in placebo group. Patients with chronic myocardial ischemia received 40 or 80 millions of autologous adipose tissue-derived stromal vascular fraction cells, processed from lipoaspirates at point of care with Celution system. Serious adverse events in 2 patients (related to procedure, but not related to cells) triggered stopping rule and studies were suspended. FDA allowed to continue after amendment, however company decided to terminate trials. In relation to safety, ATHENA 1 did not meet primary endpoint, measured by major adverse cardiac events (MACE) 35.3% in cell therapy group versus 21.4% in placebo. Some efficacy endpoints, specified in ATHENA 2 were met at some time points. The authors concluded that studies were feasible with suggestion of benefit.

5. Caution about new gene therapy trials Two recent proposals for new gene therapy trials in US, evaluated by NIH Recombinant DNA Advisory Committee (RAC) caused concerns about safety. Nature editorial this week covered proposals of Dimension Therapeutics and University of Pennsylvania, saying it must proceed with caution. Links about proposal for the first CRISPR-based application in human, you can look in previous Cells Weekly. Here is decision on Dimensions proposal:

After some discussion, the RAC voted unanimously to approve the trial. However, that came with a long list of conditions, including that the treatment first be tested in a second animal species. The researchers disagree with most of the conditions, believing that more expensive animal trials will add nothing. They feel that they are being held to a different standard from most trials. Dimension still plans to submit an application to the US Food and Drug Administration (FDA) later this year to start a clinical trial. It is unclear how heavily the RACs recommendations weigh into FDA decisions, but Wadsworth says that the company will conduct its trials overseas if necessary. These patients have been waiting a long time, he says.

6. Is FDA really holding stem cell therapy developers? Based on the recent post on California Stem Cell Report, the answer is YES. This opinion was voiced by CIRMs president Randy Mills several times. Ive asked Jan Nolta (IND submitter) on twitter FDA request of $330k pigs experiments and she said that it makes sense to do and $330k was misquoted.

Do you guys have any good examples when FDA was unreasonably holding developers with their INDs and trials progression? Please comment!

7. MSC and cancer friends or foes? New interesting data came up this week about impact of MSC-based therapy on carcinogenesis. Researchers found that in breast tumor model coinjection and distant injection of MSC has different impact on tumor growth:

Unlike previous reports, this is the first study reporting that MSCs may exert opposite roles on tumor growth in the same animal model by modulating the host immune system, which may shed light on the potential application of MSCs as vehicles for tumor therapy and other clinical applications.

8. New methods and protocols: Osteogenic differentiation of bioprinted constructs consisting of human adipose-derived stem cells (PLoS ONE) Bone marrow is a reservoir for cardiac resident stem cells (Sci Rep) Multiple genetically engineered humanized microenvironments in a single mouse (Biomater Res) Xenotransplantation of human fetal cardiac progenitor cells is useless in porcine model of ischemic heart failure (PLoS ONE) Feeding strategies in expansion of human pluripotent stem cells in stirred tank bioreactors (Stem Cells TM)

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Stem Cell Assays Reproducible Research on Stem Cells

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Our fully personalized age management and wellness programs, incorporating Physician prescribed Hormone Replacement Therapy (HRT), wellness coaching and program monitoring will help to slow down and even reverse the signs and symptoms of aging so you can look and feel your absolute best at any age. How you look and feel as you age is entirely up to you, you can make the years to come the best years of your life. Take the first step toward a fitter, younger and healthier you. Our team of expert Physicians and wellness consultants are here to guide you every step of the way. Together, well help you to look better, feel younger and stay healthier.

Call us for a free private consultation, your call is completely confidential and no obligation is required, youll be glad you did. Prefer information via email? Submit your questions and concerns using one of our contact forms. One of our Physicians or wellness consultants will respond right away.

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Hormone Replacement Therapy Boca Raton - Hormone Doctor ...

Is hormone therapy (HRT) making a comeback?

A few years ago, the use of hormone replacement therapy (HRT) looked like a medical mess. For decades, women were told that HRT -- usually a combination of estrogen and progestin -- was good for them during and after menopause. Then the 2002 results of the Women's Health Initiative study seemed to show just the opposite: hormone replacement therapy actually had life-threatening risks such as heart attacks, strokes, and cancer.

"Women felt betrayed," says Isaac Schiff, MD, chief of obstetrics and gynecology at Massachusetts General Hospital in Boston. "They were calling their doctors, saying, 'How could you put me on this drug which causes heart attacks, strokes, and cancer?'"

Almost overnight, standard medical practice changed. Doctors stopped prescribing hormone replacement therapy and 65% of women on HRT quit, according to Schiff.

But some experts say hormone replacement therapy may be coming back. All along HRT remained an important treatment for menopause symptoms like hot flashes. And now, a number of recent studies show that hormone replacement therapy may have protective benefits for women who are early in menopause.

"I think we swung too positive on hormone therapy in the past and then we went too negative," says Schiff, who is also chair of the American College of Obstetricians and Gynecologists Task Force on Hormone Therapy. "Now we're trying to find a balance in between."

"We're definitely in a gray zone of uncertainty about hormone therapy," says Jacques Rossouw, MD, project officer for the federal Women's Health Initiative (WHI). "But when you're uncertain, you have to err on the side of safety."

While Rossouw concedes that new studies show some preventative benefit for younger women, he says any potential benefit is very slight. And, he notes, there is no evidence that any benefit would last if women kept taking hormones as they got older.

But increasing numbers of researchers say there should be a place for hormone replacement therapy as a preventive treatment for limited periods as it may help prevent disease in younger women around the age of menopause.

"We have evidence that hormone therapy can prevent heart disease, hip fractures, and osteoporosis, and that it cuts the risk of developing diabetes by 30% in younger women," says Shelley R. Salpeter, MD, a clinical professor of medicine at Stanford University's School of Medicine.

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This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[1][2][3] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[4]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[5] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[6]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[7]

In 2014, the European Medicines Agency recommended approval of Holoclar, a treatment involving stem cells, for use in the European Union. Holoclar is used for people with severe limbal stem cell deficiency due to burns in the eye.[8]

In March 2016 GlaxoSmithKline's Strimvelis (GSK2696273) therapy for the treatment ADA-SCID was recommended for EU approval.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in a effort to make medications.[10]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease.[11][12][13] There have been preliminary studies related to multiple sclerosis.[14][15]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[16][17][18]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. A small clinical trial was underway in Scotland in 2013, in which stem cells were injected into the brains of stroke patients.[19]

Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

The pioneering work[23] by Bodo-Eckehard Strauer has now been discredited by the identification of hundreds of factual contradictions.[24] Among several clinical trials that have reported that adult stem-cell therapy is safe and effective, powerful effects have been reported from only a few laboratories, but this has covered old[25] and recent[26] infarcts as well as heart failure not arising from myocardial infarction.[27] While initial animal studies demonstrated remarkable therapeutic effects,[28][29] later clinical trials achieved only modest, though statistically significant, improvements.[30][31] Possible reasons for this discrepancy are patient age,[32] timing of treatment[33] and the recent occurrence of a myocardial infarction.[34] It appears that these obstacles may be overcome by additional treatments which increase the effectiveness of the treatment[35] or by optimizing the methodology although these too can be controversial. Current studies vary greatly in cell-procuring techniques, cell types, cell-administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone-marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[36] Adult stem cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[11]

It may be possible to have adult bone-marrow cells differentiate into heart muscle cells.[11]

The first successful integration of human embryonic stem cell derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[37]

In 2013 the pioneering reports of powerful beneficial effects of autologous bone marrow stem cells on ventricular function were found to contain "hundreds" of discrepancies.[38] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 patient observational study. Other reports required (impossible) negative standard deviations in subsets of patients, or contained fractional patients, negative NYHA classes. Overall there were many more patients published as having receiving stem cells in trials, than the number of stem cells processed in the hospital's laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[39]

One of the most promising benefits of stem cell therapy is the potential for cardiac tissue regeneration to reverse the tissue loss underlying the development of heart failure after cardiac injury.[40]

Initially, the observed improvements were attributed to a transdifferentiation of BM-MSCs into cardiomyocyte-like cells.[28] Given the apparent inadequacy of unmodified stem cells for heart tissue regeneration, a more promising modern technique involves treating these cells to create cardiac progenitor cells before implantation to the injured area.[41]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[42] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[43] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[44] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[45][46]

Research is ongoing in different fields, alligators which are polyphyodonts grow up to 50 times a successional tooth (a small replacement tooth) under each mature functional tooth for replacement once a year.[47]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[48]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[49] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[50]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[51]

In 2014, researchers demonstrated that stem cells collected as biopsies from donor human corneas can prevent scar formation without provoking a rejection response in mice with corneal damage.[52]

In January 2012, The Lancet published a paper by Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[53]

In June 2015, the Stem Cell Ophthalmology Treatment Study (SCOTS), the largest adult stem cell study in ophthalmology ( http://www.clinicaltrials.gov NCT # 01920867) published initial results on a patient with optic nerve disease who improved from 20/2000 to 20/40 following treatment with bone marrow derived stem cells.[54]

Diabetes patients lose the function of insulin-producing beta cells within the pancreas.[55] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[56]

Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[11]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[57][58] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[59]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[61] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[61] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[61]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[62]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[63] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[64] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[65] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[66]

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".[67] In 2013 biotechnology and regenerative medicine company BioTime (NYSEMKT:BTX) acquired Geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[68]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[69]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[110] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Stem-cell research and treatment was practiced in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem-cell therapy for conditions beyond those approved of in Western countries. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures.[111]

State-funded companies based in the Shenzhen Hi-Tech Industrial Zone treat the symptoms of numerous disorders with adult stem-cell therapy. Development companies are currently focused on the treatment of neurodegenerative and cardiovascular disorders. The most radical successes of Chinese adult stem cell therapy have been in treating the brain. These therapies administer stem cells directly to the brain of patients with cerebral palsy, Alzheimer's, and brain injuries.[citation needed]

Since 2008 many universities, centers and doctors tried a diversity of methods; in Lebanon proliferation for stem cell therapy, in-vivo and in-vitro techniques were used, Thus this country is considered the launching place of the Regentime[112] procedure. http://www.researchgate.net/publication/281712114_Treatment_of_Long_Standing_Multiple_Sclerosis_with_Regentime_Stem_Cell_Technique The regenerative medicine also took place in Jordan and Egypt.[citation needed]

Stem-cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. Authorized centers are found in Tijuana, Guadalajara and Cancun. Currently undergoing the approval process is Los Cabos. This permit allows the use of stem cell.[citation needed]

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[113]

As of 2013, Thailand still considers Hematopoietic stem cell transplants as experimental. Kampon Sriwatanakul began with a clinical trial in October 2013 with 20 patients. 10 are going to receive stem-cell therapy for Type-2 diabetes and the other 10 will receive stem-cell therapy for emphysema. Chotinantakul's research is on Hematopoietic cells and their role for the hematopoietic system function in homeostasis and immune response.[114]

Today, Ukraine is permitted to perform clinical trials of stem-cell treatments (Order of the MH of Ukraine 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Other countries where doctors did stem cells research, trials, manipulation, storage, therapy: Brazil, Cyprus, Germany, Italy, Israel, Japan, Pakistan, Philippines, Russia, Switzerland, Turkey, United Kingdom, India, and many others.

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Stem-cell therapy - Wikipedia, the free encyclopedia

Stem Cell 100 is formulated to rejuvenate your body and slow the aging process to help you feel and function more like a young person. This can help you feel better, look younger and improve your health. Most of the cells in your body lose function with age. Everyone has special cells called adult stem cells which are needed to rejuvenate damaged and old tissues, but adult stem cells themselves are also aging. Until now there was not much you could do about it. Stem Cell 100 rejuvenates adult stem cells and their micro-environments. Stem Cell 100+ is a more advanced and faster acting version of Stem Cell 100.

Developed by experts in the anti-aging field, patent-pending Stem Cell 100 is the only supplement proven to double maximum lifespan of an animal model. No other product or therapy including caloric restriction even comes close.

SK of Santa Fe, NM

I have been using Stem Cell 100 for about one year. Initially I noticed a boost in energy level, which now remains steady-hence not noticed I have experienced no adverse effects from taking this product. I heartily recommend Stem Cell 100 and plan to continue on it.

Leslie

Stem Cell 100 has made a noticeable difference in me, including turning my gray hair back to its original color, which supposedly is impossible. The reversal of the gray hair to original color began a couple of months after starting the pill. After about 10 months, the gray hair is mostly gone. At the current rate of improvement, I expect my hair to completely be back to its original color within 1 to 2 months. I think my beard will take longer, but it was the first to gray. Also, my skin became smoother and younger looking. The skin and hair rely heavily on stem cells, and they seem to benefit strongly from this product. I'm so excited about telling people my results because there is nothing that can reverse the graying of hair. It will give me evidence that this supplement thing is really powerful. Unfortunately, I don't have before and after pictures because I didn't read any claims that the product would affect hair color. I would just say that I'm a person who totally believes that it does me no good to imagine things or interpret tings in a way favorable to what I want to believe. When I'm convinced enough to make a statement, you can count on it.

Joey of San Diego, CA

I am a 48 year old working woman. A friend of mine introduced me to Stem Cell 100. After taking Stem Cell 100 for about 4 months my anxiety level has really been diminished. Its a great supplement and I would recommend it to everyone!

Paul of San Diego, CA

I am an active 61 year old man in excellent health, but had experienced a serious drop in my energy level at the time I enrolled in a 4-month trial of Stem Cell 100. Within a month, my energy increased noticeably and I began to take to my physical activities (running, cycling) with a renewed enthusiasm and intensity level. My mood began to elevate steadily, and soon I had even lost those few stubborn pounds that had eluded me for years. I am very enthusiastic about Stem Cell 100. I look forward to continuing with the new, improved formulation, and would not hesitate to recommend it.

Mike, Texas

After taking the Stem Cell 100 for the last month my sinuses have also cleared, unplugging my ears for the first time since mid September.

Willie, California

As I was sprinting this morning around 6:00am I noticed that I was not hurting anymore! I have been having sore knees, ankles, hamstrings and back for the last couple of years. I usually just ran through it, but I noticed since I have been taking the Stem Cell 100 capsules for about 45 days now, those nagging pains are gone away!

Tom, Australia

Only after about 2-3 weeks of taking Stem Cell 100 my eye sight returned back to a level where I did not need glasses to work on my computer monitors. My eyes had always been good but had started to deteriorate about a year ago where 50% of the time I had to wear my glasses. I was shocked to find the improvement so quick. I found I was less stressed. No other changes to lifestyle yet a measureable difference. My fingers would sometimes get stiff in the mornings after long days on the keyboard. This stiffness disappeared. Some of my hair is getting darker. I have a full body of hair that had virtually all turned grey but I noticed that some of my hair was starting regrow brown - my original colour. I had some age spots in my left leg that are disappearing. Generally, I feel great.

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Harness the Power of Your Own Stem Cells

Millions of people suffer from chronic conditions of aging and disease. Based on international scientific studies in many academic and industry laboratories, there is new hope that many of the conditions afflicting mankind can some day be cured or greatly improved using stem cell regenerative medicine. Stem Cell 100 offers a way to receive some of the benefits of stem cell therapy today by improving the activity and effectiveness of your own adult stem cells.

Stem Cell 100 Helps to Support:

The statements above have not been reviewed by the FDA. Stem Cell 100 is not a preventive or treatment for any disease.

Help Rejuvenate Your Body by Boosting Your Own Stem Cells

As a child, we are protected from the ravages of aging and can rapidly recover from injury or illness because of the ability of the young regenerative stem cells of children have a superior ability to repair and regenerate most damaged tissues. As we age, our stem cell populations become depleted and/or slowly lose their capacity to repair. Moreover, the micro-environment (i.e. niches) around stem cells becomes less nurturing with age, so cell turnover and repair are further reduced. This natural progression occurs so slowly that we are barely aware of it, but we start to notice the body changes in our 20s, 30s, 40s, and especially after 50 years of age. Stem Cell 100 helps adults regain their youthful regenerative potential by stabilizing stem cell function.

Stem Cell 100 works differently than other stem cell products on the market

You may have seen a number of products that are advertised as stimulating or enhancing the number of stem cells. Each person only has a limited number of stem cells so using them up faster may not be a good strategy. Stem Cell 100 is about improving the effectiveness and longevity of your stem cells as well as preserving the stem cell micro-environment. That should be the goal of any effective stem cell therapy and is what Stem Cell 100 is designed to do and what other stem cell products cannot do.

Stem Cell 100 Extends Drosophila (Fruit Fly) Lifespan

In extensive laboratory testing Stem Cell 100 greatly extended both the average and maximum lifespan of Drosophila fruit flies. The study (see Charts below) included three cages of Drosophila fruit flies that were treated with Stem Cell 100 (Cages T1 to T3) and three cages which were untreated controls (Cages C1 to C3). Each cage started with 500 fruit flies including 250 males and 250 females. The experiment showed that median lifespan more than doubled with a 123% increase. While fruit flies are not people they are more like us than you might think. Drosophila have a heart and circulatory system, and the most common cause of death is heart failure. Like humans and other mammals (e.g. mice), it is difficult to increase their lifespan significantly. These observed results outperform every lifespan enhancing treatment ever tested - including experiments using genetic modification and dietary restriction.

The longest living fruit fly receiving Stem Cell 100 lived 89 days compared to the longest living untreated control which lived 48 days. It is possible that the single longest living fruit fly lived longer for other reasons such as genetic mutation, however, there were many others that lived almost as long so it was not just an aberation. The oldest 5% of the treated fruit flies lived 77% longer than the oldest 5% of the control group. It is also important that the study showed an improved ability of the fruit flies to survive stress and illness at all ages not just during old age. Even after the first few days of the study there were already more of the Stem Cell 100 treated fruit flies alive that survived youth than the control group of untreated fruit flies. For additional information about the study please go to our Longevity page.

Supplement Facts

Stem Cell 100 is a Patent-Pending Life Code Nutraceutical. All Life Code products are nutraceutical grade and provide the best of science along with the balance of nature.

All Life Code products are nutraceutical grade and provide the best of science along with the balance of nature.

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Stem Cell 100 Plus+ is a more powerful and faster acting version of Stem Cell 100.

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Serving Size: One type O capsule

Servings Per Container: 60 Capsules

Recommended Use: Typical usage of Stem Cell 100 is two capsules per day, preferably at meal times. While both capsules can be taken at the same time, it is preferable to separate the two capsules by at least 4 hours. Since Stem Cell 100 is a potent formulation, do not take more than three capsules per day. One capsule per day may be sufficient for those below 110 pounds.

Recommended Users: Anyone from ages 22 and up could benefit from Stem Cell 100. Those in their 20s and 30s will like the boost in endurance during sports or exercise, while older users will notice better energy and general health with the potential for some weight loss.

Active Ingredients in Stem Cell 100: There are ten herbal components that make up the patent-pending combination in Stem Cell 100. The herbal components are highly extracted natural herbs that are standardized for active components that promote adult stem cells and lower inflammation:

1) Polysaccharides, flavonoids, and astragalosides extracted from Astragalus membranaceus, which has many positive effects on stem cells and the cardiovascular and immune systems.

2) Proprietary natural bilberry flavonoids and other compounds from a stabilized nutraceutical grade medicinal Vaccinium extract. Activate metabolic PPARS and helps produce healthy levels of cholesterol and silent inflammation. Also has anti-fungal and anti-viral activity.

3) Flavonoids and oligo-proanthocyanidins (OPCs) extracted from Pine Bark, which greatly reduce oxidative stress, DNA damage, and inflammation.

4) L-Theanine, which is a natural amino acid from Camellia sinesis that reduces mental stress and inflammation while improving cognition and protecting brain cells from ischemic or toxic injury.

5) Pterocarpus Marsupium, which contains two stable resveratrol analogs which promote stem cells, lower inflammation, and stabilized metabolism.

6) Polygonum Multiflorium stem stem is a popular Chinese herbal tonic that fights premature aging and promotes youthfulness. Polygonum is reported to enhance fertility by improving sperm count in men and egg vitality in women. Polygonum is also widely used in Asia to strengthen muscle and is thus used by many athletes as an essential tonic for providing strength and stamina to the body. Modern research has supported Polygonum multiflorium stem in that animal studies have proven that it can extend lifespan and improve the quality of life. Polygonum appears to protect the liver and brain against damage, perhaps by improving immune and cardiovascular health. The stem sections of Polygonum multiflorium are also calming to the nervous system and promote sounder sleep. Life Code uses a proprietary Polygonum multiflorium stem extract.

7) Schisandra Berry is used by many Chinese women to preserve their youthful beauty. For thousands of years, Schisandra has been prized as an antiaging tonic that increases stamina and mental clarity, while fighting stress and fatigue. In Chinese traditional medicine, Schisandra berry has been used for liver disorders and to enhance resistance to infection and promote skin health and better sleep. Schisandra berry is classified as an adaptogen, which can stimulate the central nervous system, increase brain efficiency, improve reflexes, and enhance endurance. Modern research indicates that Schisandra berry extracts have a protective effect on the liver and promote immunity. A double-blind human trial suggested that Schisandra berry may help patients with viral hepatitis, which is very prevalent in China. Recent work indicates that the liver is protected by the enhanced production of glutathione peroxidase, which helps detoxify the liver. Life Code uses a proprietary Schisandra berry extract.

8) Fo-Ti Root (aka He-Shou-Wu) is one of the most widely used Chinese herbal medicines to restore blood, kidney, liver, and cardiovascular health. Fo-Ti is claimed to have powerful rejuvenating effects on the brain, endocrine glands, the immune system, and sexual vigor. Legend has it that Professor Li Chung Yun took daily doses of Fo-Ti to live to be 256 and is said to have outlived 23 wives and spawned 11 generations of descendents before his death in 1933. While it is unlikely that he really lived to such an old age there is scientific support for Fo-Ti as beneficial for health and longevity. Like the Indian Keno bark, Fo-ti contains resveratrol analogs and likely acts by various mechanism, which includes liver detoxification and protection of skin from UVB radiation. Life CodeTM uses a proprietary Fo-Ti root extract.

9 ) Camellia sinensis has many bioactive polyphenols including the potent epigallocatechin-3-gallate (EGCG). A 2006 Japanese study published in the Journal of the American Medical Association reports that adults aged 40 to 79 years of age who drank an average of 5 or more cups of tea per day had a significantly lower risk of dying from all causes (23% lower for females and 12% lower for males). The study tracked more than 40,000 adults for up to 11 years and found dramatically lower rates of cardiovascular disease and strokes in those drinking 5 or more cups of tea. Many studies have found that adults drinking 3 or more cups of tea per day have significantly less cancer. Other studies have found that green tea helps protect against age-related cognitive decline, kidney disease, periodontal disease, and type 2 diabetes. Green tea also promotes visceral fat loss and higher endurance levels. Summarizing all of the thousands of studies on tea and tea polyphenols that have been published, it can be concluded that tea polyphenols preserve health and youth. This conclusion is backed up by gene studies showing that tea polyphenols decrease insulin-like growth factor-1 (IGF-1), which is a highly conserved genetic pathway that has been strongly linked to aging in yeast, worms, mice, and humans. If everyone could drink 4 to 5 cups of green tea each day, they could enjoy these important health benefits, but for most people drinking that much green tea can disturb their sleep patterns. Life Code uses a nutraceutical grade green tea extract that has 98% polyphenols and 50% ESCG that provides the polyphenol and ESCG equivalent of 4 to 5 cups of green tea with only 2% of the caffeine. Thus, most or all of the benefits of green tea are provided without concerns about disturbing sleep.

10) Drynaria Rhizome is used extensively in traditional Chinese medicine as an effective herb for healing bones, ligaments, tendons, and lower back problems. Eastern martial art practitioners have used Drynaria for thousands of years to help in recovering from sprains, bruises, and stress fractures. Drynaria has also helped in many cases of bleeding gums and tinnitus (ringing in the ears). The active components of Drynaria protect bone forming cells by enhancing calcium absorption and other mechanisms. Drynaria is also reported to act as a kidney tonic and to promote hair growth and wound healing. Life Code uses a proprietary Drynaria rhizome extract.

Active Ingredients in Stem Cell 100+ There are 11 herbal extracts in Stem Cell 100+ along with two nutraceutical grade vitamins Methyl Folate (5-MTHF) and Methyl B12 that are bioavailable vitamin supplements that are highly potent but rarely found. The highly extracted natural herbs are standardized for active components that promote adult stem cells and lower inflammation and have been tested as a synergistic herbal formulation with the proper dosage of each component:

1) Polysaccharides, flavonoids, and astragalosides extracted from Astragalus membranaceus, which has many positive effects on stem cells and the cardiovascular and immune systems. Astragalus has been used for thousands of years in Traditional Chinese Medicine (TCM) to promote cardiovascular and immune health. Astragalus is also known as a primary stimulator of Qi (Life Force). Life Code uses a high quality proprietary TCM extract that tested highest in our longevity experiments.

2) Proprietary natural bilberry flavonoids and other compounds from a stabilized nutraceutical grade medicinal Vaccinium extract. Activate metabolic PPARS and helps produce healthy levels of cholesterol and silent inflammation. Also has anti-fungal and anti-viral activity.

3) Flavonoids and oligo-proanthocyanidins (OPCs) extracted from Pine Bark, which promote the vascular system and reduce oxidative stress, DNA damage, and inflammation.

4) L-Theanine, which is a natural amino acid from Camellia sinesis that reduces mental stress and inflammation while improving cognition and protecting brain cells from ischemic or toxic injury. Life Code tested supplement with Mass Spec to verify high purity.

5) Genistein, which is an isoflavone phytoestrogen, activates telomerase, metabolic PPARs, autophagy (cell waste disposal), and smooth muscles. It also inhibits DNA methylation and the carbohydrate transporter GLUT1. Life Code tested supplement with Mass Spec to verify high purity.

6) Harataki Extract (aka Terminalia chebula) contains rejuvenating tannin flavonoids that have doubled human cell longevity in culture while maintaining telomere length. In Traditional Indian Medicine, Harataki has been used to treat skin disorders and heart disease, among many other uses.

7) Two stable resveratrol analogs from extracts of Pterocarpus Marsupium, which promote stem cells, less silent inflammation, and better metabolism. Life Code uses a highly purified proprietary source that is only available to Indian doctors. Life Code does not recommend taking resveratrol supplements or synthetic analogs, as these supplements are inherently unstable.

8) He-Shou-Wu is one of the most widely used Chinese herbal medicines to restore blood, kidney, liver, and cardiovascular health. He-Shou-Wu is claimed to have powerful rejuvenating effects on the brain, endocrine glands, the immune system, and sexual vigor. Legend has it that Professor Li Chung Yun took daily doses to live to 256 years and is said to have outlived 23 wives and spawned 11 generations of descendants before his death in 1933. While it is unlikely that he really lived to such an old age, there is scientific support for He-Shou-Wu as beneficial for health and longevity. Life Code uses a proprietary TCM He-Shou-Wu root extract.

9) Schisandra Berry is used by many Chinese women to preserve their youthful beauty. For thousands of years, Schisandra has been prized as an antiaging tonic that increases stamina and mental clarity, while fighting stress and fatigue. In TCM, Schisandra berry has been used for liver disorders and to enhance resistance to infection and promote skin health and better sleep. Schisandra berry is classified as an adaptogen, which can stimulate the central nervous system, increase brain efficiency, improve reflexes, and enhance endurance. Life Code uses a proprietary TCM extract.

10) Drynaria Rhizome is used extensively in TCM as an effective herb for healing bones, ligaments, tendons, and lower back problems. Eastern martial art practitioners have used Drynaria for thousands of years to help in recovering from sprains, bruises, and stress fractures. The active components of Drynaria protect bone forming cells by enhancing calcium absorption and other mechanisms. Drynaria is also reported to act as a kidney tonic and to promote hair growth and wound healing. Life Code uses a proprietary TCM Drynaria rhizome extract.

11) BioPerine is a proprietary brand of peperine extracted from black pepper. BioPerine has been shown to enhance bioavailability of herbal extracts. Piperine has been shown in rats to have cognitive enhancing effects and to help control silent inflammation.

Safety: The extracts in Stem Cell 100 and Stem Cell 100+ are nutraceutical grade and have been individually tested in both animals and humans without significant safety issues. Those with pre-existing conditions of diabetes or hypertension should coordinate this product with your doctor, as lower blood glucose or reduced blood pressure can result from taking the recommended dose of this product.

Warnings: may lower glucose and/or blood pressure in some individuals. The supplement is not recommended for pregnant, lactating, or hypoglycemic individuals.

References

1. Yu, Q., Y.S. Bai, and J. Lin, [Effect of astragalus injection combined with mesenchymal stem cells transplantation for repairing the Spinal cord injury in rats]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2010. 30(4): p. 393-7.

2. Xu, C.J., et al., [Effect of astragalus polysaccharides on the proliferation and ultrastructure of dog bone marrow stem cells induced into osteoblasts in vitro]. Hua Xi Kou Qiang Yi Xue Za Zhi, 2007. 25(5): p. 432-6.

3. Xu, C.J., et al., [Effects of astragalus polysaccharides-chitosan/polylactic acid scaffolds and bone marrow stem cells on repairing supra-alveolar periodontal defects in dogs]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2006. 31(4): p. 512-7.

4. Zhu, X. and B. Zhu, [Effect of Astragalus membranaceus injection on megakaryocyte hematopoiesis in anemic mice]. Hua Xi Yi Ke Da Xue Xue Bao, 2001. 32(4): p. 590-2.

5. Qiu, L.H., X.J. Xie, and B.Q. Zhang, Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull, 2010. 33(4): p. 641-6.

6. Araghi-Niknam, M., et al., Pine bark extract reduces platelet aggregation. Integr Med, 2000. 2(2): p. 73-77.

7. Rohdewald, P., A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther, 2002. 40(4): p. 158-68.

8. Koch, R., Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res, 2002. 16 Suppl 1: p. S1-5.

9. Rimando, A.M., et al., Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem, 2005. 53(9): p. 3403-7.

10. Manickam, M., et al., Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J Nat Prod, 1997. 60(6): p. 609-10.

11. Grover, J.K., V. Vats, and S.S. Yadav, Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. Diabetes Obes Metab, 2005. 7(4): p. 414-20.

12. Mao, X.Q., et al., Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model. Acta Pharmacol Sin, 2007. 28(12): p. 1947-56.

13. Schafer, A. and P. Hogger, Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract, 2007. 77(1): p. 41-6.

14. Kwak, C.J., et al., Antihypertensive effect of French maritime pine bark extract (Flavangenol): possible involvement of endothelial nitric oxide-dependent vasorelaxation. J Hypertens, 2009. 27(1): p. 92-101.

15. Xue, B., et al., Effect of total flavonoid fraction of Astragalus complanatus R.Brown on angiotensin II-induced portal-vein contraction in hypertensive rats. Phytomedicine, 2008.

16. Mizuno, C.S., et al., Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha. Bioorg Med Chem, 2008. 16(7): p. 3800-8.

17. Sato, M., et al., Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level. Biosci Biotechnol Biochem, 2009. 73(6): p. 1314-7.

18. Kimura, Y. and M. Sumiyoshi, French Maritime Pine Bark (Pinus maritima Lam.) Extract (Flavangenol) Prevents Chronic UVB Radiation-induced Skin Damage and Carcinogenesis in Melanin-possessing Hairless Mice. Photochem Photobiol, 2010.

19. Pavlou, P., et al., In-vivo data on the influence of tobacco smoke and UV light on murine skin. Toxicol Ind Health, 2009. 25(4-5): p. 231-9.

20. Ni, Z., Y. Mu, and O. Gulati, Treatment of melasma with Pycnogenol. Phytother Res, 2002. 16(6): p. 567-71.

21. Bito, T., et al., Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med, 2000. 28(2): p. 219-27.

22. Rihn, B., et al., From ancient remedies to modern therapeutics: pine bark uses in skin disorders revisited. Phytother Res, 2001. 15(1): p. 76-8.

23. Saliou, C., et al., Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med, 2001. 30(2): p. 154-60.

24. Van Wijk, E.P., R. Van Wijk, and S. Bosman, Using ultra-weak photon emission to determine the effect of oligomeric proanthocyanidins on oxidative stress of human skin. J Photochem Photobiol B, 2010. 98(3): p. 199-206.

25. Haskell, C.F., et al., The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol, 2008. 77(2): p. 113-22.

26. Owen, G.N., et al., The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci, 2008. 11(4): p. 193-8.

27. Yamada, T., et al., Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test. Biosci Biotechnol Biochem, 2008. 72(5): p. 1356-9.

28. Jia, R.Z., et al., [Neuroprotective effects of Astragulus membranaceus on hypoxia-ischemia brain damage in neonatal rat hippocampus]. Zhongguo Zhong Yao Za Zhi, 2003. 28(12): p. 1174-7.

29. Nathan, P.J., et al., The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother, 2006. 6(2): p. 21-30.

30. Nobre, A.C., A. Rao, and G.N. Owen, L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr, 2008. 17 Suppl 1: p. 167-8.

31. Murakami, S., et al., Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: randomized, double-blind, placebo-controlled trial. Biosci Biotechnol Biochem, 2009. 73(4): p. 817-21.

32. Kawada, S., et al., Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res, 2010. 24(3): p. 846-51.

Continue reading here:
Stem Cell 100 - Powerful Rejuvenation and Anti-Aging ...

Human chorionic gonadotropin (hCG) is a hormone produced by the embryo after implantation.[1][2] The presence of hCG is detected in some pregnancy tests (HCG pregnancy strip tests). Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant can lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes. However, it is not known whether this production is a contributing cause or an effect of carcinogenesis. The pituitary analog of hCG, known as luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages.[1][3]

Regarding endogenous forms of hCG, there are various ways to categorize and measure them, including total hCG, C-terminal peptide total hCG, intact hCG, free -subunit hCG, -core fragment hCG, hyperglycosylated hCG, nicked hCG, alpha hCG, and pituitary hCG. Regarding pharmaceutical preparations of hCG from animal or synthetic sources, there are many gonadotropin preparations, some of which are medically justified and others of which are of a quack nature. As of December 6, 2011[update], the United States FDA has prohibited the sale of "homeopathic" and over-the-counter hCG diet products and declared them fraudulent and illegal.[4][5][6]

Human chorionic gonadotropin is a glycoprotein composed of 237 amino acids with a molecular mass of 25.7 kDa.[7]

It is heterodimeric, with an (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and (beta) subunit that is unique to hCG.

The two subunits create a small hydrophobic core surrounded by a high surface area-to-volume ratio: 2.8 times that of a sphere. The vast majority of the outer amino acids are hydrophilic.[7]

Human chorionic gonadotropin interacts with the LHCG receptor of the ovary and promotes the maintenance of the corpus luteum during the beginning of pregnancy. This allows the corpus luteum to secrete the hormone progesterone during the first trimester. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus[citation needed].

Due to its highly negative charge, hCG may repel the immune cells of the mother, protecting the fetus during the first trimester[citation needed]. It has also been hypothesized that hCG may be a placental link for the development of local maternal immunotolerance[citation needed]. For example, hCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the trophoblast invasion, which is known to expedite fetal development in the endometrium.[10] It has also been suggested that hCG levels are linked to the severity of morning sickness or Hyperemesis gravidarum in pregnant women.[11]

Because of its similarity to LH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from pregnant women to extract hCG for use in fertility treatment.[12][13]

Human chorionic gonadotropin also plays a role in cellular differentiation/proliferation and may activate apoptosis.[14]

Naturally, it is produced in the human placenta by the syncytiotrophoblast.

Like other gonadotropins, it can be extracted from the urine of pregnant women or produced from cultures of genetically modified cells using recombinant DNA technology.

In Pregnyl, Follutein, Profasi, Choragon and Novarel, it is extracted from the urine of pregnant women. In Ovidrel, it is produced with recombinant DNA technology.[15]

Regarding endogenous forms of hCG, there are various ways to categorize and measure them, including total hCG, C-terminal peptide total hCG, intact hCG, free -subunit hCG, -core fragment hCG, hyperglycosylated hCG, nicked hCG, alpha hCG, and pituitary hCG.

Regarding pharmaceutical preparations of hCG from animal or synthetic sources, there are many gonadotropin preparations, some of which are medically justified and others of which are of a quack nature.

Blood or urine tests measure hCG. These can be pregnancy tests. hCG-positive indicates an implanted blastocyst and mammalian embryogenesis. These can be done to diagnose and monitor germ cell tumors and gestational trophoblastic diseases.

Concentrations are commonly reported in thousandth international units per milliliter (mIU/ml). The international unit of hCG was originally established in 1938 and has been redefined in 1964 and in 1980.[16] At the present time, 1 international unit is equal to approximately 2.351012 moles,[17] or about 6108 grams.[18]

Most tests employ a monoclonal antibody, which is specific to the -subunit of hCG (-hCG). This procedure is employed to ensure that tests do not make false positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, whereas the presence of hCG almost always indicates pregnancy.)

Many hCG immunoassays are based on the sandwich principle, which uses antibodies to hCG labeled with an enzyme or a conventional or luminescent dye. Pregnancy urine dipstick tests are based on the lateral flow technique.

The following is a list of serum hCG levels. (LMP is the last menstrual period dated from the first day of your last period.) The levels grow exponentially after conception and implantation.

The ability to quantitate the hCG level is useful in the monitoring germ cell and trophoblastic tumors, follow-up care after miscarriage, and in diagnosis of and follow-up care after treatment of ectopic pregnancy. The lack of a visible fetus on vaginal ultrasound after the hCG levels have reached 1500 mIU/ml is strongly indicative of an ectopic pregnancy.[21] Still, even an hCG over 2000 IU/l does not necessarily exclude the presence of a viable intrauterine pregnancy in such cases.[22]

As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 and 12 days after ovulation.[23] However, it must be taken into account that total hCG levels may vary in a very wide range within the first 4 weeks of gestation, leading to false results during this period.[24] A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.[22]

Gestational trophoblastic disease like hydatidiform moles ("molar pregnancy") or choriocarcinoma may produce high levels of hCG (due to the presence of syncytialtrophoblasts- part of the villi that make up the placenta) despite the absence of an embryo. This, as well as several other conditions, can lead to elevated hCG readings in the absence of pregnancy.

hCG levels are also a component of the triple test, a screening test for certain fetal chromosomal abnormalities/birth defects.

A study of 32 normal pregnancies came to the result a gestational sac of 13mm was detected at a mean hCG level of 1150 UI/l (range 800-1500), a yolk sac was detected at a mean level of 6000 UI/l (range 4500-7500) and fetal heartbeat was visible at a mean hCG level of 10,000 UI/l (range 8650-12,200).[25]

Human chorionic gonadotropin can be used as a tumor marker,[26] as its subunit is secreted by some cancers including seminoma, choriocarcinoma, germ cell tumors, hydatidiform mole formation, teratoma with elements of choriocarcinoma, and islet cell tumor. For this reason a positive result in males can be a test for testicular cancer. The normal range for men is between 0-5 mIU/mL. Combined with alpha-fetoprotein, -HCG is an excellent tumor marker for the monitoring of germ cell tumors.[citation needed]

Human chorionic gonadotropin is extensively used parenterally for final maturation induction in lieu of luteinizing hormone. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of HCG. As ovulation will happen between 38 and 40 hours after a single HCG injection,[27] procedures can be scheduled to take advantage of this time sequence,[28] such as intrauterine insemination or sexual intercourse. Also, patients that undergo IVF, in general, receive HCG to trigger the ovulation process, but have an oocyte retrieval performed at about 34 to 36 hours after injection by, a few hours before the eggs actually would be released from the ovary.

As HCG supports the corpus luteum, administration of HCG is used in certain circumstances to enhance the production of progesterone.

In the male, HCG injections are used to stimulate the Leydig cells to synthesize testosterone. The intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. Typical uses for HCG in men include hypogonadism and fertility treatment.

Several vaccines against human chorionic gonadotropin (hCG) for the prevention of pregnancy are currently in clinical trials.[29]

In the case of female patients who want to be treated with HCG Pregnyl:[30] a) Since infertile female patients who undergo medically assisted reproduction (especially those who need in vitro fertilization), are known to often be suffering from tubal abnormalities, after a treatment with this drug they might experience many more ectopic pregnancies. This is why early ultrasound confirmation at the beginning of a pregnancy (to see whether the pregnancy is intrauterine or not) is crucial. - Pregnancies that have occurred after a treatment with this medicine are submitted to a higher risk of multiplets. - Female patients who have thrombosis, severe obesity or thrombophilia should not be prescribed this medicine as they have a higher risk of arterial or venous thromboembolic events after or during a treatment with HCG Pregnyl. b)Female patients who have been treated with this medicine are usually more prone to pregnancy losses.

In the case of male patients: A prolonged treatment with HCG Pregnyl is known to regularly lead to increased production of androgen. Therefore: Patients who are suffering from overt or latent cardiac failure, hypertension, renal dysfunction, migraines or epilepsy might not be allowed to start using this medicine or may require a lower dose of HCG Pregnyl. Also this medicine should be used with extreme caution in the treatment of prepubescent teenagers in order to reduce the risk of precocious sexual development or premature epiphyseal closure. This type of patients' skeletal maturation should be closely and regularly monitored.

Both male and female patients who have the following medical conditions must not start a treatment with HCG Pregnyl: (1) Hypersensitivity to this medicine or to any of its main ingredients. (2) Known or possible androgen-dependent tumors for example male breast carcinoma or prostatic carcinoma.

In the world of performance-enhancing drugs, HCG is increasingly used in combination with various anabolic androgenic steroid (AAS) cycles. As a result, HCG is included in some sports' illegal drug lists.

When exogenous AAS are put into the male body, natural negative-feedback loops cause the body to shut down its own production of testosterone via shutdown of the hypothalamic-pituitary-gonadal axis (HPGA). This causes testicular atrophy, among other things. HCG is commonly used during and after steroid cycles to maintain and restore testicular size as well as normal testosterone production.[31]

High levels of AASs, that mimic the body's natural testosterone, trigger the hypothalamus to shut down its production of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Without GnRH, the pituitary gland stops releasing luteinizing hormone (LH). LH normally travels from the pituitary via the blood stream to the testes, where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone.[32] In males, HCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.

If HCG is used for too long and in too high a dose, the resulting rise in natural testosterone would eventually inhibit its own production via negative feedback on the hypothalamus and pituitary gland.[citation needed]

Professional athletes who have tested positive for HCG have been temporarily banned from their sport, including a 50-game ban from MLB for Manny Ramirez in 2009[33] and a 4-game ban from the NFL for Brian Cushing for a positive urine test for HCG.Mixed Martial Arts fighter Dennis Siver was fined $19,800 and suspended 9 months for being tested positive after his bout at UFC 168.[35]

British endocrinologist Albert T. W. Simeons proposed HCG as an adjunct to an ultra-low-calorie weight-loss diet (fewer than 500 calories).[36] Simeons, while studying pregnant women in India on a calorie-deficient diet, and "fat boys" with pituitary problems (Frlich's syndrome) treated with low-dose HCG, observed that both lost fat rather than lean (muscle) tissue.[36] He reasoned that HCG must be programming the hypothalamus to do this in the former cases in order to protect the developing fetus by promoting mobilization and consumption of abnormal, excessive adipose deposits. Simeons in 1954 published a book entitled Pounds and Inches, designed to combat obesity. Simeons, practicing at Salvator Mundi International Hospital in Rome, Italy, recommended low-dose daily HCG injections (125IU) in combination with a customized ultra-low-calorie (500 cal/day, high-protein, low-carbohydrate/fat) diet, which was supposed to result in a loss of adipose tissue without loss of lean tissue.[36]

Simeons' results were not reproduced by other researchers and in 1976 in response to complaints the FDA required Simeons and others to include the following disclaimer on all advertisements:[37]

These weight reduction treatments include the injection of HCG, a drug which has not been approved by the Food and Drug Administration as safe and effective in the treatment of obesity or weight control. There is no substantial evidence that HCG increases weight loss beyond that resulting from caloric restriction, that it causes a more attractive or "normal" distribution of fat, or that it decreases the hunger and discomfort associated with calorie-restrictive diets.

1976 FDA-mandated disclaimer for HCG diet advertisements

There was a resurgence of interest in the "HCG diet" following promotion by Kevin Trudeau who was later banned from making HCG diet weight-loss claims by the U.S. Federal Trade Commission and eventually jailed over such claims.[38]

While not specifically cited here, review studies refuting the HCG diet have been published in the Journal of the American Medical Association and the American Journal of Clinical Nutrition,[39] concluded that HCG is not more effective as a weight-loss aid than dietary restriction alone.[40]

A meta analysis found that studies supporting HCG for weight loss were of poor methodological quality and concluded that "there is no scientific evidence that HCG is effective in the treatment of obesity; it does not bring about weight-loss or fat-redistribution, nor does it reduce hunger or induce a feeling of well-being".[41]

There is no scientific evidence that HCG is effective in the treatment of obesity. The meta-analysis found insufficient evidence supporting the claims that HCG is effective in altering fat-distribution, hunger reduction or in inducing a feeling of well-being. The authors stated the use of HCG should be regarded as an inappropriate therapy for weight reduction In the authors opinion, Pharmacists and physicians should be alert on the use of HCG for Simeons therapy. The results of this meta-analysis support a firm standpoint against this improper indication. Restraints on physicians practicing this therapy can be based on our findings.

According to the American Society of Bariatric Physicians, no new clinical trials have been published since the definitive 1995 meta-analysis.[42]

The scientific consensus is that any weight loss reported by individuals on an "HCG diet" may be attributed entirely to the fact that such diets prescribe calorie intake of between 500 and 1,000 calories per day, substantially below recommended levels for an adult, to the point that this may risk health effects associated with malnutrition.[43]

Controversy about, and shortages[44] of, injected HCG for weight loss have led to substantial Internet promotion of "homeopathic HCG" for weight control. The ingredients in these products are often obscure, but if prepared from true HCG via homeopathic dilution, they contain either no HCG at all or only trace amounts. Moreover, it is highly unlikely that oral HCG is bioavailable due to the fact that digestive protease enzymes and hepatic metabolism renders peptide-based molecules (such as insulin and human growth hormone) biologically inert. HCG can likely only enter the bloodstream through injection.

The United States Food and Drug Administration has stated that over-the-counter products containing HCG are fraudulent and ineffective for weight loss. They are also not protected as homeopathic drugs and have been deemed illegal substances.[45][46] HCG itself is classified as a prescription drug in the United States and it has not been approved for over-the-counter sales by the FDA as a weight loss product or for any other purposes, and therefore neither HCG in its pure form nor any preparations containing HCG may be sold legally in the country except by prescription.[4] In December 2011, FDA and FTC started to take actions to pull unapproved HCG products from the market.[4] In the aftermath, some suppliers started to switch to "hormone-free" versions of their weight loss products, where the hormone is replaced with an unproven mixture of free amino acids[47] or where radionics is used to transfer the "energy" to the final product.

In order to induce a stronger immune response, some versions of human chorionic gonadotropin based anti-fertility vaccines were designed as conjugates of the subunit of HCG covalently linked to tetanus toxoid.[29][48] It has been alleged that a non-conguated tetanus vaccine used in developing countries is laced with a human chorionic gonadotropin based anti-fertility drug[49] and is distributed as a means of mass sterilization.[50] This charge has been vigorously denied by the World Health Organization (WHO) and UNICEF.[51] Others have argued that a hCG laced vaccine could not be used for sterilization since the effects of the anti-fertility vaccines are reversible (requiring booster doses to maintain immunity) and a non-conjugated vaccine is likely to be ineffective.[52][53] Finally, independent testing of the tetanus vaccine by Kenyas health authorities has revealed no traces of the human chorionic gonadotropin hormone.[54]

PDB gallery

1hcn: STRUCTURE OF HUMAN CHORIONIC GONADOTROPIN AT 2.6 ANGSTROMS RESOLUTION FROM MAD ANALYSIS OF THE SELENOMETHIONYL PROTEIN

1hrp: CRYSTAL STRUCTURE OF HUMAN CHORIONIC GONADOTROPIN

1qfw: TERNARY COMPLEX OF HUMAN CHORIONIC GONADOTROPIN WITH FV ANTI ALPHA SUBUNIT AND FV ANTI BETA SUBUNIT

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Human chorionic gonadotropin - Wikipedia, the free ...

Rev Urol. 2004; 6(Suppl 6): S3S8.

Auxilium Pharmaceuticals, Inc., Norristown, PA

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. In the postpubertal male, testosterone replacement therapy can be used to treat the signs and symptoms of low testosterone, which include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics. Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured. Absolute contraindications to testosterone replacement therapy are prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.

Key words: Hypogonadism, Testosterone replacement therapy, Serum hormone-binding globulin, Luteinizing hormone, Follicle-stimulating hormone

Hypogonadism is a lack of testosterone in male patients and can be of central (hypothalamic or pituitary) or testicular origin, or a combination of both. Hypogonadism in male patients with testicular failure due to genetic disorders (eg, Klinefelters syndrome), orchitis, trauma, radiation, chemotherapy, or undescended testes, is known as hypergonadotropic hypogonadism or primary hypogonadism. Hypogonadism in male patients with gonadotropin deficiency or dysfunction as a result of disease or damage to the hypothalamic-pituitary axis is known as hypogonadotropic hypogonadism, central hypogonadism, or secondary hypogonadism. This might be due to Kallmanns syndrome, tumor, trauma, radiation, sarcoidosis, or tuberculosis. In addition, men older than 50 years might have low testosterone levels with functional abnormalities at multiple levels of the hypothalamic-pituitary-testicular axis.1,2,3

The prevalence of hypogonadism has increased in recent years. It has been reported that 12%, 19%, 28%, and 49% of men greater than 50, 60, 70, or 80 years of age, respectively, fit the criteria of hypogonadism.4

During puberty, testosterone is required for the development of male secondary sexual characteristics, stimulation of sexual behavior and function, and initiation of sperm production.5,6 In adult males, testosterone is involved in maintaining muscle mass and strength, fat distribution, bone mass, red blood cell production, male hair pattern, libido and potency, and spermatogenesis.13,5,6

In men, the major gonadal steroid hormone is testosterone. Testosterone circulates in 3 major forms: unbound, or free, testosterone; tightly bound testosterone, which is bound to sex hormone-binding globulin (SHBG); and weakly bound testosterone, which is bound to albumin. Only free and weakly bound testosterone is bioavailable or able to bind to the androgen receptor.2,3

In males, serum testosterone levels show a circadian variation, with the highest levels in the morning and lowest levels in the late afternoon. In young men, the variation in testosterone levels is approximately 35%. Although the normal range for serum testosterone might vary between different laboratories, the normal range for early morning total testosterone in healthy adult males is approximately 300 ng/dL to 1000 ng/dL.7,8

To determine whether a patient is testosterone deficient, a clinician must consider clinical signs and symptoms in conjunction with laboratory values. The initial clinical picture will vary depending on the age of the patient at the onset of the disorder.

In the normal male, the start of puberty is apparent by enlargement of the testes and the appearance of pubic hair, followed by the appearance of auxiliary and facial hair. At puberty there is also increased penile length and the onset of spermatogenesis. If signs of puberty are not evident in boys by 14 years of age, a workup for delayed puberty is warranted.

In the prepubertal age group, hypogonadism might be either primary hypogonadism or secondary hypogonadism. To differentiate primary from secondary hypogonadism, early morning luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels must be obtained. Because LH and FSH are secreted during the early morning at the beginning of puberty, it is necessary to measure these hormones in the early morning (8:0010:00 AM). Primary hypogonadism is associated with low levels of testosterone and high-normal to high levels of LH and FSH. Secondary hypogonadism is associated with low levels of testosterone and normal to low levels of LH and FSH.5,6

The signs and symptoms of low testosterone in postpubertal adult males can be more difficult to diagnose and might include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics.13 At the initial visit, the first objective is to distinguish between primary gonadal failure, in which low testosterone is accompanied by increased FSH and increased LH, and hypothalamic-pituitary disorders (secondary hypogonadism), with low testosterone and low to normal FSH and LH levels.

Initial laboratory testing should include early morning (8:0010:00 AM) measurement of serum testosterone, prolactin, FSH, and LH levels. For the diagnosis of primary hypogonadism, FSH measurement is particularly important because FSH has a longer half life, is more sensitive, and demonstrates less variability than LH.2,3

The aging male patient can present with signs and symptoms of low testosterone, including loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, and loss of muscle mass and strength.13 At the initial visit, laboratory testing should include early morning (8:0010:00 AM) measurement of serum testosterone. In elderly men, testosterone levels decrease between 15% and 20% over the course of 24 hours.8

Total testosterone levels might be normal with hypogonadism if the SHBG levels are increased.79 Levels of SHBG increase with age, causing a decrease in bioavailable testosterone.9 If testosterone levels are low-normal but the clinical symptoms and signs indicate hypogonadism, measurement of serum total testosterone levels should be repeated and an SHBG level should be determined. With the total testosterone and SHBG levels, a bioavailable testosterone value can be calculated. A bioavailable testosterone calculator is available at http://www.issam.ch/freetesto.htm.

It is usually not necessary to determine FSH or LH levels in the aging male.

It is well accepted that testosterone levels should be measured in the early morning, when they are at their peak level. However, in community practice the choice of which testosterone parameter to measure is still debatable.

Total testosterone assay is widely available and inexpensive to perform. Although the ranges and methods vary, physicians can consult their local laboratories for the applicable values in their clinical practice. Total testosterone values, however, must be interpreted carefully in the aging male because SHBG levels might be elevated. If the total testosterone level is normal in the aging male presenting signs of hypogonadism, the clinician can measure free testosterone or measure SHBG and calculate bioavailable testosterone.9

Free testosterone can be measured by equilibrium dialysis or ultrafiltration, which are difficult to perform and largely unavailable but reliable. In contrast, the radioimmunoassay for free testosterone is widely available but unreliable. Because total testosterone and SHBG assays are readily available and cheap, calculating bioavailable testosterone might be a good compromise. Whichever method is chosen, if the early morning testosterone level is at or below the lower limit of normal for the individual laboratory, then a repeat measurement of the early morning testosterone level should be performed to confirm the result. Because testosterone is secreted in a pulsatile fashion, it is important to obtain 2 early morning testosterone levels.

In selected patients, FSH, LH, and prolactin can be measured. If the FSH and LH levels are raised, this suggests a primary testicular cause, and if levels are low or normal, a hypothalamic or pituitary cause should be considered. A raised prolactin level suggests that further investigation of the pituitary gland should be undertaken.1,2

The clinical signs and symptoms of hypogonadism will vary depending on whether the patient presents before or after puberty. Depending on the age of the patient, the degree of pubertal development is important for establishing the differential diagnosis.

Boys aged 14 years or older should be suspected of being hypogonadal if on examination they have underdeveloped testes, lack of penile enlargement, and absence of pubic, auxiliary, and facial hair.

In patients with primary hypogonadism, history might reveal the cause for primary testicular failure, such as familial autoimmune disease, physical trauma to the testes, or trauma to the testes caused by radiation, chemotherapy, or infection.

A karyotype should be obtained to diagnose chromosomal abnormalities, such as Klinefelters syndrome, and a physical examination will reveal small or absent testes resulting from anorchia, Noonans syndrome, or other testicular disorders.

Hypothalamic or pituitary deficiency might be transitory or permanent. Transient secondary hypogonadism might be related to malnutrition or stress states and can be diagnosed by physical examination and evaluation of the patients growth chart. If permanent hypothalamic or pituitary hormone deficiency is suspected, serum levels of pituitary hormones and magnetic resonance imaging of the brain and pituitary should be obtained to screen for hypothalamic or pituitary disease.

If both physical examination and serum chemistry tests are normal, then by exclusion a diagnosis of constitutional pubertal delay must be considered.

To establish a diagnosis of hypogonadism, it is important to take a careful history to determine whether there have been major medical problems, toxic exposure, concomitant drug therapy that might cause hypogonadism, or fertility problems.

Low libido, impotence, fatigue, impaired concentration, and sexual dysfunction are important clinical problems that might not be raised by the patient in the clinic. Therefore, these symptoms need to be asked about specifically if hypogonadism is suspected.13

Formal assessment of intellectual changes, mood, and cognitive changes can be performed. Changes in lean body mass will be apparent from the medical history and examination, as will changes in hair, skin, and fat distribution. Decreases in bone mineral density might be apparent from a history of recent fractures but can only be confirmed by dual energy x-ray absorptiometry (DEXA).1

Physical examination should include testicular examination, including size and consistency. The distribution and amount of body hair should also be noted. Penile size is not affected by postpubertal testosterone deficiency. An assessment of the prostate by digital rectal examination (DRE) should be performed and a prostate-specific antigen (PSA) value obtained.3

To establish a diagnosis of hypogonadism in the aging male, it is important to assess the patient carefully for signs and symptoms. Low libido, impotence, fatigue, impaired concentration, and sexual dysfunction are important clinical problems that might not be raised by the patient in the clinic, especially by an aging patient. Therefore, as with the younger postpubertal patient, these symptoms need to be asked about specifically if hypogonadism is suspected.1,2 As with the postpubertal patient (see previous section), changes in intellectual functioning; mood; lean body mass; and hair, skin, and fat distribution should all be assessed, and DEXA can be used to confirm decreases in bone mineral density.1

In older patients, an important part of the physical examination includes an assessment of the prostate by DRE and PSA assay. In addition, an assessment of prostate-related symptoms should be undertaken. The presence of gynecomastia or carcinoma of the breast are important physical findings.

In cases of primary and permanent secondary hypogonadism diagnosed in the prepubertal male, life long testosterone treatment is needed. The usual treatment is initiation of therapy with small doses of testosterone (50100 mg IM) every 3 to 4 weeks at the appropriate psychosocial stage in development. When a final adult height is thought to have been obtained, the adult dose of testosterone replacement is inaugurated.

In the postpubertal period, once the diagnosis of testosterone deficiency has been made, replacement therapy should be considered in light of the clinical signs and symptoms in conjunction with the laboratory values. The objective of testosterone replacement therapy is to normalize serum testosterone and maintain the level within the eugonadal state. In addition, treatment objectives might include improving sexual dysfunction, intellectual capacity, depression, and lethargy; maintaining bone mineral density and possibly reducing fracture risk; increasing muscle mass and strength; and enhancing the quality of life.13,9

Although the normal range for serum testosterone might vary between different laboratories, the normal range for early morning testosterone in male adults is approximately 300 ng/dL to 1000 ng/dL.7 An early morning total serum testosterone level of less than 300 ng/dL clearly indicates hypogonadism, and under most circumstances benefit will be derived from testosterone replacement therapy. A healthy male adult patient with a serum testosterone level greater than 400 ng/dL is unlikely to be testosterone deficient, and therefore clinical judgment should be exercised if he has symptoms suggestive of testosterone deficiency.

There are some absolute contraindications to testosterone replacement therapy. These include prostate cancer, which must be assessed by history and clinical examination. If on DRE the prostate is enlarged or if the PSA level is greater than 4.0 ng/mL, biopsy of the prostate should be undertaken to confirm a diagnosis of prostate cancer or benign prostatic hyperplasia (BPH).3

An existing or prior history of breast cancer is also an absolute contraindication to testosterone replacement therapy. Testosterone therapy is known to increase the hematocrit, and therefore a pre-existing hematocrit of 55% or greater is an absolute contraindication to replacement therapy.

Sensitivity to any of the ingredients in the testosterone formulation would also be an absolute contraindication. Relative contraindications include an increased hematocrit, untreated sleep apnea, severe obstructive symptoms of BPH, and advanced congestive cardiac failure.2,3

The goal of replacement therapy is to maintain testosterone in the normal physiological range; therefore, a combination of clinical and biochemical measures should be monitored 6 to 12 weeks after initiating therapy. In most cases, an early morning serum total testosterone level is adequate to determine whether dosage adjustment is necessary. However, patients receiving injections of testosterone enanthate or cypionate every 2 weeks will require an earlier measurement of serum testosterone at 1 to 2 weeks after commencement of therapy.3

Examination of the prostate should be performed routinely, although the exact frequency after initiation of testosterone replacement is still debatable. Digital rectal examination of the prostate and PSA assay should be performed before initiation of therapy, along with an assessment of prostate-related symptoms. In elderly men, a DRE and PSA assay should be performed at 3 and 6 months after commencing testosterone therapy and then annually thereafter.3 A high PSA level should be further evaluated with a highly specific PSA assay, if available. A patient should be referred to a urologist if his PSA level increases over time or if he has a PSA level greater than 4.0 ng/mL.3

It is known that testosterone stimulates bone marrow production of erythrocytes, which might result in an increased hematocrit in some men, and therefore this should be checked at the same time as the PSA level.2,3

Lipid disturbances in testosterone-treated male patients are generally not a problem because the ratio of high-density lipoprotein to total cholesterol usually remains constant. An initial lipid profile should be performed before therapy, and a follow-up profile should be obtained after 6 to 12 months of therapy and annually thereafter.3

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. It can be easily diagnosed with measurement of the early morning serum total testosterone level, which should be repeated if the value is low. Follicle-stimulating hormone, LH, and prolactin might also need to be measured. If the clinical signs and symptoms suggest hypogonadism but the serum testosterone level is near normal, then assay of serum testosterone should be repeated in conjunction with SHBG because serum testosterone might be normal in the presence of hypogonadism if the SHBG level is raised, which commonly occurs in elderly male patients.

Before initiation of testosterone replacement therapy, an examination of the prostate, including DRE, PSA assay, and assessment of prostate symptoms should be undertaken, and both the hematocrit and lipid profile should be measured. There are few absolute contraindications to testosterone replacement therapy other than prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation. Monitoring of the prostate (assessed with DRE and PSA assay) and hematocrit and lipid profile should be repeated during testosterone replacement therapy.

The benefits of testosterone replacement therapy may include restoring metabolic parameters to the eugonadal state; improving psychosexual function and intellectual capacity, including depression and lethargy; maintaining bone mineral density and reducing bone fractures; improving muscle mass and strength; and enhancing quality of life.

Hypogonadism is a lack of testosterone in male patients and can be of central (hypothalamic or pituitary) or testicular origin, or a combination of both.

Boys ages 14 years or older should be suspected of being hypogonadal if on examination they have underdeveloped testes, a lack of penile enlargement, and an absence of pubic, auxiliary, and facial hair.

In pre- and postpubertal male patients, primary hypogonadism is associated with low levels of testosterone and high-normal to high levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); secondary hypogonadism is associated with low levels of testosterone and normal to low levels of LH and FSH.

In the aging male patient, signs and symptoms of hypogonadism can include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, and loss of muscle mass and strength.

For aging men, laboratory testing should include early morning (8:0010:00 AM) measurement of serum testosterone; levels less than 300 ng/dL clearly indicate hypogonadism, and under most circumstances benefit will be derived from testosterone replacement therapy.

Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured.

There are few absolute contraindications to testosterone replacement therapy other than prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.

1. AACE Hypogonadism Task Force. Endocr Pract. 2002;8:439456.

5. Griffin JE, Wilson JD. Endocrinology & Metabolism. 15th Ed. Vol. 335. New York, NY: McGraw Hill; 2001. Disorders of the testes. Harrisons principles of internal medicine; pp. 21432154.

6. Beers MH, Berkow R, editors. The Merck Manual of Diagnosis and Therapy. 17th ed. New York, NY: John Wiley & Sons; 1999.

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Diagnosis of Hypogonadism: Clinical Assessments and ...

Some types of cancer run in certain families, but most cancers are not clearly linked to the genes we inherit from our parents. Gene changes that start in a single cell over the course of a person's life cause most cancers. In this section you can learn more about the complex links between genes and cancer.

Cancer is such a common disease that it is no surprise that many families have at least a few members who have had cancer. Sometimes, certain types of cancer seem to run in some families. But only a small portion of all cancers are inherited. This document focuses on those cancers.

Advances in genetics and molecular biology have improved our knowledge of the inner workings of cells, the basic building blocks of the body. Here we review how cells can change during a persons life to become cancer, how certain types of changes can build on inherited gene changes to speed up the development of cancer, and how this information can help us better prevent and treat cancer.

Genetic testing can be useful for people with certain types of cancer that seem to run in their families, but these tests aren't recommended for everyone. Here we offer basic information to help you understand what genetic testing is and how it is used in cancer.

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Genetics and Cancer | American Cancer Society

The directory of Innovative Doctors and Health Practitioners is a worldwide listing of anti-aging doctors and other medical professionals who practice or have expressed interest in all aspects of preventive medicine (such as heart attack and stroke prevention), hormone replacement therapy, nutrition and dietary supplements, and other areas of alternative and complementary medicine. Invariably, they welcome individuals who choose to be involved in their own health care.

Provided to you by Extension, the directory of Innovative Doctors and Health Practitioners facilitates the location of anti-aging doctors and health practitioners who are open to alternatives to allopathic medicine. Conveniently organized geographically, the listing can be used to find a doctor by areaa handy feature for those who are traveling or are simply seeking out anti-aging doctors or health practitioners at home. The directory of Innovative Doctors and Health Practitioners is especially useful for those on a life extension program that includes the use of dietary supplements and hormones, as the listed physicians and health practitioners would likely be more suited to evaluate such a program than more conventional doctors.

While prevention, nutrition and longevity are important to the physicians and health practitioners listed, each of them has their own approach to health and wellness. So be sure to clarify the reason for your visit, as well as your goals in seeking out such treatment when scheduling your appointment.

ALABAMA ALASKA AMERICAN SAMOA ARIZONA ARKANSAS ARMED FORCES AMERICAS ARMED FORCES EUROPE ARMED FORCES PACIFIC CALIFORNIA COLORADO CONNECTICUT DELAWARE DISTRICT OF COLUMBIA FLORIDA GEORGIA GUAM HAWAII IDAHO ILLINOIS INDIANA IOWA KANSAS KENTUCKY LOUISIANA MAINE MARSHALL ISLANDS MARYLAND MASSACHUSETTS MICHIGAN MICRONESIA FED STATES MINNESOTA MISSISSIPPI MISSOURI MONTANA NEBRASKA NEVADA NEW HAMPSHIRE NEW JERSEY NEW MEXICO NEW SOUTH WALES NEW YORK NORTH CAROLINA NORTH DAKOTA NORTHERN MARIANA ISLANDS OHIO OKLAHOMA OREGON PALAU PENNSYLVANIA PLEASE SELECT PUERTO RICO RHODE ISLAND SOUTH AUSTRALIA SOUTH CAROLINA SOUTH DAKOTA TASMANIA TENNESSEE TEXAS UTAH VERMONT VICTORIA VIRGIN ISLANDS VIRGINIA WASHINGTON WEST VIRGINIA WISCONSIN WYOMING

DISCLAIMER: Inclusion in the directory of Innovative Doctors and Health and Wellness Practitioners does not constitute endorsement by Life Extension, nor are these physicians or other health practitioners affiliated with Life Extension. All physicians and health practitioners who appear on this list do so on the sole basis of their own expression of interest in the fields of health and wellness, longevity, or preventive medicine. Life Extension has not verified the competence, professional credentials, business practices or validity of the expressed interests of these physicians and health practitioners. Life Extension makes no recommendation of any physician or health practitioner on this list and makes no suggestion that any such physician or health practitioner will cure or prevent any disease, reduce anyone's rate of aging or extend anyone's life. Those consulting a physician or other health practitioner on this list should approach the consultation exactly as they would with any other unknown physician or health practitioner. Listings are periodically updated. However, physicians and health practitioners are not obligated to notify Life Extension should they relocate or retire. Life Extension relies in great part on feedback, which determines the continued eligibility of the physicians and health practitioners listed. Please contact Life Extension if you have any comments concerning any of the physicians or other health practitioners on this list.

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Directory of Innovative Anti-Aging Doctors, Health And ...

RATIONALE:

Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis.

To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects.

Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness, and contractility at baseline, at 3, 6, and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LV ejection fraction (+9.4 1.7%, P=0.0002) and decreased scar mass (-47.5 8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant reduction in scar size, perfusion, and contractile improvement (concordant score: 2.93 0.07), whereas revascularized (0.5 0.21) and nontreated segments (-0.07 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected segments).

Intramyocardial injection of autologous MSCs into akinetic yet nonrevascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive because of lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications.

http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.

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Autologous mesenchymal stem cells produce concordant ...

Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.Molecular Therapy (2016); doi:10.1038/mt.2016.97.

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Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for ...

Testosterone deficiency is frequently seen in both men and women with HIV. Endocrine abnormalities, which can affect testosterone production, have long been recognized as a complication of HIV since the earliest days of the pandemic (although it has generally been associated with late stage disease).

However, recent research has shown that nearly one out of every five men with HIV has documented testosterone deficiency, irrespective of CD4 count, viral load, or treatment status.

Similarly, testosterone deficiency is seen in one in four HIV-positive women, most often in the context of severe, unexplained weight loss (HIV wasting).

Testosterone is the steroid hormone which is central to the development of the testes (testicles) and prostate in men as well as the promotion of secondary male sexual characteristics (e.g., lean muscle mass, bone mass, hair growth). Testosterone is also important to women in maintaining normal muscle and bone mass, although at levels around 10% less than men.

In both men and women, testosterone is essential to a person's overall health and well-being, contributing to an individual's strength, energy levels, and libido.

By contrast, testosterone depletion is associated with:

Testosterone deficiency in men with HIV is largely associated with an endocrine abnormality called male hypogonadism in which the function of the male gonads (testes) is impaired, resulting in the diminished production of sex hormones beyond what would be expected of a man's specific age.

In the general population, hypogonadism is known to occur in about one in 25 men between the ages of 30 and 50, increasing to one in 14 between the ages of 50 to 79. By contrast, the incidence among men with HIV is as much as five times greater.

Hypogonadism can be caused by either a defect in the testes themselves (primary) or a dysfunction occurring outside of the testes (secondary). In adult males with HIV:

Hypogonadism can also be caused by childhood mumps or the abuse of anabolic steroids. HIV medications have not been shown to contribute to hypogonadism.

Hypogonadism in adult males is characterized by low serum (blood) testosterone levels, as well as one or several of following symptoms:

Diagnosis is made by measuring the amount of testosterone in the blood, of which there are three different subtypes. When a test is performed, the results will reveal both a person's total testosterone (all subtypes) and one of the three subtypes called free testosterone.

Free testosterone is simply a type of testosterone to which no protein is attached, allowing it enter cells and activate receptors that other subtypes can't. It is considered the most accurate measure of testosterone deficiency, despite representing only 2-3% of the total population. On its own, total testosterone is considered less accurate since results can appear normal if other non-free subtypes are elevated.

Testing should be performed early in the morning since levels can fluctuate by up to 20% during the course of a day. "Normal" levels are simply those within the reference range of the lab. These ranges can vary, but, for illustrative purposes, are roughly between

However, an assessment of "normal" cannot be made by numbers alone. Testosterone levels tend to drop by about 1-2% every year after the age of 40. Therefore, what may be "normal" for a 60-year-old male won't be the same for a 30-year-old. Assessments need to be made on an individual basis with your treating doctor.

If a diagnosis of hypogonadism is confirmed, testosterone replacement therapy may be indicated. Intramuscular testosterone injections are usually recommended, which offer low side effects if physiological doses are used and adjusted by the treating doctor. FDA-approved options include Depo-testosterone (testosterone cypionate) and Delatestryl (testosterone enanthate).

On average, injections are given every two to four weeks. To avoid the effects of fluctuating testosterone levelswhich can cause sometimes dramatic swings in mood, energy, and sexual functionlower doses and shorter dosing intervals are often used.

Side effects of treatment can include:

Testosterone replacement therapy can also cause the acceleration of pre-existing prostate cancer. Because of this, a patient's prostate-specific antigen (PSA) levels will be tested and monitored during the course of therapy.

All told, intramuscular injections offer a cost-effective option for treating hypogonadism, with associative increases in alertness, well-being, libido, lean muscle mass, and erection ability. Disadvantages include regular doctor's visits and dosing administration.

Oral, transdermal, and topical gel agents are also available, and may be applicable in certain cases. Discuss these with your doctor.

In women, testosterone is produced in the ovaries and adrenal glands. As with men, it is an important hormone for maintaining normal muscle and bone mass, as well as energy, strength, and libido.

While hypogonadism is far less common in women with HIV, it can occur and is most often in the context of HIV wasting and advanced disease. The implementation of ART can reverse wasting and the hypogonadal state in many cases.

There are currently no fixed guidelines for the treatment of female hypogonadism, and treatment options are limited. Hormone replacement therapy (HRT) may be appropriate for some, while the short-term use of testosterone may improve sex drive, lean muscle mass, and energy levels.

However, data is still incomplete on the use of testosterone to treat hypogonadism in pre-menopausal women with HIV. Speak with your health care provider about possible side effects. Testosterone is not recommended for women who are pregnant or wish to become pregnant.

Rietschel, P.; Corcoran, C.; Stanley T.; et al. "Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy." Clinical Infectious Diseases. November 2, 2000; 31(5):1240-1244.

Hugh Jones, T. "Late Onset Hypogonadism." British Medical Journal. February 13, 2009; 338:b352.

Huang, J.; Wilkie, S.; Dolan, S.; et al. "Reduced testosterone levels in human immunodeficiency virus-infected women with weight loss and low weight." Clinical Infectious Diseases. January 28, 2003; 36(4):499-506.

Grinspoon, S. "The Use of Androgens in HIV-Infected Men and Women." Physicians Research Network Notebook. March 2005.

Kalyani, R.; Gavini, S.; and Dobs. A. "Male Hypogonadism in systemic disease." Endocrinology Metabolism Clinics of North America Journal. June 2007; 36(2):333-48.

Carnegie, C. "Diagnosis of Hypogonadism: Clinical Assessment and Laboratory Tests." Review in Urology. 2004; 6(6):s3-8.

Kumar, P.; Kumar, N.; Patidar, A.; et al. "Male Hypogonadism: Symptoms and treatment." Journal of Advanced Pharmacological Technology and Research. July-September 2010; 1(3): 297-302.

Mylonakis, E.; Koutkia, P.; and Grinspoon, S. "Diagnosis and treatment of androgen deficiency in human immunodeficiency virus-infected men and women." Clinical Infectious Diseases. September 15, 2001; 33(6):857-64.

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HIV and Testosterone Deficiency - verywell.com

Hypogonadism is a medical term for a defect of the reproductive system which results in lack of function of the gonads (ovaries or testes).

Hypogonadism may occur if the hypothalamic-pituitary-gonadal axis is interrupted at any level. Hypergonadotropic hypogonadism (primary hypogonadism) results if the gonad does not produce the amount of steroid sufficient to suppress secretion of LH and FSH at normal levels. Hypogonadism resulting from defects of the gonads is traditionally referred to as primary hypogonadism. Examples include Klinefelter syndrome and Turner syndrome. Hypogonadism resulting from hypothalamic or pituitary defects are termed secondary hypogonadism or central hypogonadism (referring to the central nervous system). Hypogonadism can affect men of any age, from fetal development, through puberty and adulthood. Hypogonadism is one of the main causes of male infertility. It is estimated that 13 million men in the United States alone are affected by hypogonadism. Hypogonadism is caused by deficient testosterone secretion by the testes. The two basic types of male hypogonadism are Primary and Secondary.

Hypogonadism Primary, also known as primary testicular failure, originates from an abnormality in the testicles. Hypogonadism may be induced by chronic use of anabolic/androgenic steroids (AAS). The Secondary type of hypogonadism is caused by defects in the pituitary gland connected to the brain that controls hormone production. If chemical messages from the pituitary gland to the testicles aren't sent, impaired testicular function occurs. This condition can be a result from defects in development of the pituitary gland, certain inflammatory diseases, and the use of certain drugs used in the treatment of psychiatric disorders and gastroesophageal reflux disease. Mental and emotional changes can also accompany hypogonadism. As testosterone decreases, some men may experience signs and symptoms similar to those of menopause in women. These may include hot flashes, decreased drive, irritability, depression and fatigue.

Hypogonadism is most often treated by replacement of the appropriate hormones.

Gonadotropin or GnRH replacement is offered to the patient when fertility is desired. Oral testosterone is no longer used in the U.S. because it is broken down in the liver and rendered inactive. In boys, testosterone replacement therapy (TRT) can stimulate puberty and the development of secondary characteristics, such as increased muscle mass, beard and pubic hair growth. Also available is a topical 1% testosterone gel. It is applied once daily to clean, dry skin of the shoulders, upper arms, or abdomen. Another alternative is testosterone patches. The testosterone may be mixed with the adhesive with a new patch applied daily to a different site; this system leaves a sticky residue but causes little skin irritation. Injections of pituitary hormone may be used to help male patients produce sperm. In others, surgery and radiation therapy may be needed. In adult men, TRT can restore function and muscle strength and prevent bone loss.

Treatment for Hypogonadism

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Hypogonadism - Definition, Causes, Symptoms and Treatment

Definition

Hypogonadism occurs when the body's sex glands produce little or no hormones. In men, these glands (gonads) are the testes. In women, these glands are the ovaries.

Gonadal deficiency

The cause of hypogonadism can be primary or central. In primary hypogonadism, the ovaries or testes themselves do not function properly. Causes of primary hypogonadism include:

The most common genetic disorders that cause primary hypogonadism are Turner syndrome (in women) and Klinefelter syndrome (in men).

If you already have other autoimmune disorders you may be at higher risk of autoimmune damage to the gonads. These can include disorders that affect the liver and adrenal and thyroid glands as well as type 1 diabetes.

In central hypogonadism, the centers in the brain that control the gonads (hypothalamus and pituitary) do not function properly. Causes of central hypogonadism include:

A genetic cause of central hypogonadism is Kallmann syndrome. Many people with this condition also have a decreased sense of smell.

Girls who have hypogonadism will not begin menstruating. Hypogonadism can affect their breast development and height. If hypogonadism occurs after puberty, symptoms in women include:

In boys, hypogonadism affects muscle, beard, genital and voice development. It also leads to growth problems. In men the symptoms are:

If a pituitary or other brain tumor is present (central hypogonadism), there may be:

The most common tumors affecting the pituitary are craniopharyngioma in children and prolactinoma adenomas in adults.

You may need to have tests to check:

Other tests may include:

Sometimes imaging tests are needed, such as a sonogram of the ovaries. If pituitary disease is suspected, an MRI or CT scan of the brain may be done.

You may need to take hormone-based medicines. Estrogen and progesterone are used for girls and women. The medicines comes come in the form of a pill or skin patch. Testosterone is used for boys and men. The medicine can be given as a skin patch, skin gel, a solution applied to the armpit, a patch applied to the upper gum, or by injection.

For women who have not had their uterus removed, combination treatment with estrogen and progesterone may decrease the chance of developing endometrial cancer. Women with hypogonadism who have low sex drive may also be prescribed low-dose testosterone.

In some women, injections or pills can be used to stimulate ovulation. Injections of pituitary hormone may be used to help men produce sperm. Other people may need surgery and radiation therapy.

Many forms of hypogonadism are treatable and have a good outlook.

In women, hypogonadism may cause infertility. Menopause is a form of hypogonadism that occurs naturally and can cause hot flashes, vaginal dryness, and irritability as a woman's estrogen levels fall. The risk of osteoporosis and heart disease increase after menopause.

Some women with hypogonadism take estrogen therapy, especially those who have early menopause. But long-term used of hormone therapy can increase the risk of breast cancer, blood clots and heart disease. Women should talk with their health care provider about the risks and benefits of hormone replacement therapy with your doctor.

In men, hypogonadism results in loss of sex drive and may cause:

Men normally have lower testosterone as they age. However, the decline in hormone levels is not as dramatic as it is in women.

Talk to your health care provider if you notice:

Both men and women should call their provider if they have headaches or vision problems.

Maintain normal body weight and healthy eating habits may help in some cases. Other causes may not be preventable.

Ali O, Donohoue PA. Hypofunction of the testes. In: Kliegman RM, Stanton BF, St. Geme JW III, et al., eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 577.

Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: An Endocrine Society Clinical Practice guideline. J Clin Endocrinol Metab. 2010;95:2536-59. PMID: 20525905 http://www.ncbi.nlm.nih.gov/pubmed/20525905

Kansra AR, Donohoue PA. Hypofunction of the ovaries. In: Kliegman RM, Stanton BF, St. Geme JW III, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 580.

Swerdloff RS, Wang C. The testis and male sexual function. In: Goldman L, Schafer AI. Goldman's Cecil Medicine. 24th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 242.

Review Date: 10/25/2014 Reviewed By: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.

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The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. 1997- A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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Hypogonadism - UT Medical Center

Testosterone levels in men decline with age, at a rate of about 1% per year beginning at about 40 years old.3 Epidemiological studies have determined that total testosterone follows an age-related decline with mean serum concentration at the age of 75 years approximately two thirds that at 25 years.4

According to reports, approximately 74% of chronic opioid users5, 50% of AIDS patients6, 52% of obese men7, 50% of diabetic men7,8 have low testosterone.

Other causes of lowered testosterone levels include: injury, infection, or loss of the testicles; chemotherapyor radiation treatment for cancer; genetic abnormalities such as Klinefelter's Syndrome (extra X chromosome); hemochromatosis(too much iron in the body); dysfunction of the pituitary gland; inflammatory diseases such as sarcoidosis (a condition that causes inflammation of the lungs); chronic illness; chronic kidney failure; liver cirrhosis; stress; and, alcoholism.

3Feldman HA, et al. J. Clin Endocrinol Metab 2002; 87 (2):589-98 4Myers et al. Rev Urol 2003; 5 (4) 216-226 5Daniell HW., J Pain. 2002; 3:377-384 6Dobs AS. Baillires Clin Endocrinol Metab. 1998; 12:379-390 7Mulligan T, et al. Int J Clin Pract. 2006;60:762-769 8Bodie J, et al. J Urol. 2003;169:22622264 9Jackson JA et al., AM. J. Med. Sci. 1992,304 (1) 4-8

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Lipocine - Hypogonadism

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Hypogonadism - Risks, Symptoms and Leading Causes | Treato