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Bald scalp in men with androgenetic alopecia retains hair fo

Discussion in 'Hair Loss and Alopecia Published Studies' started by squeegee, Jan 8, 2011.

  1. squeegee

    squeegee Banned

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    Here is the articleBlood stem cells grow with the flow, two new studies show.The studies, led by independent groups at Children’s Hospital Boston, report that an embryo’s heartbeat and blood circulation stimulate the growth of blood stem cells.The discovery could be a boon to researchers seeking to make blood stem cells for people with blood cancers, immune system disorders and other diseases that require bone marrow transplants. In children and adults, blood stem cells reside in the bone marrow. Only about a third of patients who require bone marrow transplants have matching donors.“Basically we cannot offer optimal therapy to two-thirds of patients,†says Leonard Zon, director of the Stem Cell Program at Children’s Hospital Boston, and a coauthor of one of the new studies, which appears online May 13 and in the May 15 Cell.Scientists can make red and white blood cells easily in the laboratory, but bone marrow patients need blood stem cells to constantly replenish their blood supply. Producing these cells, also called hematopoietic stem cells, is much more difficult, Zon says.Now, his group suggests that a little force can boost blood stem cell production in zebrafish embryos. Reporting online May 13 in Nature, a group led by George Daley, director of the Pediatric Stem Cell Transplantation Program at Children’s Hospital Boston, demonstrates that blood flow also triggers hematopoietic stem cell production in mouse embryos. Both groups found nitric oxide plays an important role.Daley’s group directly tested the ability of blood flow to turn cells into hematopoietic stem cells. The team placed mouse embryonic stem cells in a centrifuge-like device that mimics sheer stress — the frictional force blood creates when it flows over cells — in a mouse’s aorta. In early embryos, blood stem cells first form on the floor of the aorta. Later in development, they migrate to the bone marrow.Embryonic stem cells exposed to the same magnitude of sheer stress as found in the mouse aorta produced hematopoietic stem cells. Cells that were exposed to a different magnitude of sheer stress, such as that in the human aorta, did not. A nitric oxide–blocking drug reduced the number of blood stem cells induced by the sheer stress. Nitric oxide is a chemical produced naturally in the body and is known to be important in regulating blood vessel growth and elasticity.When the researchers gave the nitric oxide–blocker to pregnant mice, their embryos also had problems making blood stem cells.Zon’s team used zebrafish embryos, which are transparent, to watch the stem cells develop. He and his colleagues found that chemicals that increase blood flow in the tails of zebrafish embryos also boost activity of RUNX1, a master regulator of blood stem cells. Mutant embryos that don’t have a heartbeat because of a defect in a heart muscle protein don’t make hematopoietic stem cells in their tails.When the researchers gave a nitric oxide compound to the mutant embryos, however, the embryos produced more blood stem cells. The nitric oxide–blocker also inhibited blood stem cell production, the researchers found. Those findings suggest that blood flow may increase nitric oxide levels, which then boost stem cell production, Zon says.Intuitively, scientists might expect that mechanical forces play a role in shaping development, but few biologists have studied this due to experimental difficulties, says Ihor Lemischka, a stem cell biologist at Mount Sinai School of Medicine in New York City.“I think we’ll be seeing more of these types of studies,†Lemischka says.It’s still not clear how the cells sense sheer stress, and researchers are trying to unravel the chain of events between mechanical force and stem cell production in order to manipulate the process to make blood stem cells for transplant.
     
  2. WhitePolarBear

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  3. TravisB

    TravisB Guest

    If they never die, there must be a way to stimulate them to start growing normal hair again, and therefore reverse Norwood 6 into an Norwood 0. We need a powerful stimulator.
     
  4. WhitePolarBear

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  5. Jacob

    Jacob Senior Member

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    From that PQQ blog I posted a link to earlier:

    http://pyrroloquinoline-quinone.com/pqq-info/supplement/

    I've been using it topically as well..about a week now.

    On the glutathione...the topical/transdermal isn't working as well as the acetyl-glutathione when it comes to my skin. My digestive system seemed to have benefited from the acetyl as well. I guess I could try increasing the amount I apply...need to use it up anyway.
     
  6. squeegee

    squeegee Banned

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    Eur J Pharmacol. 2005 Mar 7;510(1-2):31-8
    Antioxidants inhibit human endothelial cell functions through down-regulation of endothelial nitric oxide synthase activity.

    Polytarchou C, Papadimitriou E.

    Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR 26504, Greece.

    "We have recently shown that superoxide and hydrogen peroxide are putative inducers of angiogenesis in vivo, possibly through up regulation of inducible nitric oxide synthase (NOS) and increased production of endogenous nitric oxide (NO). The aim of the present work was to elucidate the implication of reactive oxygen species in endothelial cell functions, using cultures of human umbilical vein endothelial cells (HUVEC). Superoxide dismutase (SOD), tempol (membrane permeable SOD mimetic) and the NADPH oxidase inhibitors, 4-(2-aminoethyl)-benzenesulfonyl fluoride and apocynin, but not allopurinol, inhibited HUVEC proliferation and migration, as well as activity of endothelial NOS (eNOS). Catalase and the intracellular hydrogen peroxide scavenger sodium pyruvate decreased, while hydrogen peroxide increased HUVEC proliferation, migration and activity of eNOS. Dexamethasone induced the proliferation and migration of HUVEC and activated eNOS. Nomega-nitro-L-arginine methyl ester (L-NAME), but not Nomega-nitro-D-arginine methyl ester, decreased endothelial cell functions and reversed the effects of dexamethasone and hydrogen peroxide. N5-(1-iminoethyl)-L-ornithine dihydrochloride, but not the inducible NOS specific inhibitor N-[[3-(aminomethyl)phenyl]methyl]-ethanimidamide dihydrochloride also decreased endothelial cell functions, similarly to L-NAME. The guanylate cyclase inhibitor 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one inhibited HUVEC proliferation in a concentration-dependent manner and completely reversed hydrogen peroxide-induced proliferation, migration and cGMP accumulation. In conclusion, superoxide and hydrogen peroxide seem to play a significant role in promoting endothelial cell proliferation and migration, possibly through regulation of eNOS activity."
     
  7. squeegee

    squeegee Banned

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  8. squeegee

    squeegee Banned

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    Molecular Cardiology

    Depletion of Endothelial Progenitor Cells in the Peripheral Blood of Patients With Rheumatoid Arthritis



    From the Division of Rheumatology (J.G., D.A., C.W.S., T.K., G.S., J.S.S.), Department of Internal Medicine III; the Division of Angiology (S.S., D.S.), Department of Internal Medicine II; and the Departments of Cardiothoracic Surgery (G.W.) and of Medical and Chemical Laboratory Diagnostics (I.S.), Medical University of Vienna; the Ludwig Boltzmann Institute of Experimental Endocrinology (W.W.) and Rheumatology (G.S., J.S.S.) and the Center of Molecular Medicine (G.S., J.S.S.) of the Austrian Academy of Sciences, Vienna, Austria.

    Correspondence to Johannes Grisar, MD, Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail johannes.grisar@meduniwien.ac.at

    Abstract

    Background— Rheumatoid arthritis (RA) is characterized by increased cardiovascular morbidity and mortality that cannot be explained solely by traditional cardiovascular risk factors. Cardiovascular morbidity is related to disease activity and can be normalized by effective therapy. Because the quantity of endothelial progenitor cells (EPCs) in the peripheral blood is correlated inversely with cardiovascular risk, we studied whether such abnormalities could also be observed in patients with RA.

    Methods and Results— EPCs were determined in 52 RA patients and in 16 healthy referents (HRs) by fluorescence-activated cell-sorting (FACS) analysis. Patients were divided into groups characterized by active disease (n=36) and low disease activity (n=16). Cells that were positive by flow cytometry for CD34/KDR/AC133 within the lymphocyte population were characterized as EPCs. Furthermore, in subgroups of patients, circulating EPCs were also quantified by a colony-forming unit (CFU) and a circulating angiogenic cell (CAC) assay. EPCs were significantly decreased in RA patients suffering from active disease compared with those from HRs, as measured by FACS analysis (0.026±0.002% versus 0.045±0.008%, respectively, P<0.05), CFU assay (mean of 5±2 versus 18±5 CFU/well in HRs, P<0.05), and CAC assay (mean of 7±2 versus 52±16 positive cells/high-power field, P<0.005). In contrast, the frequency of circulating EPCs from patients with low disease activity was comparable to that of healthy individuals (0.052±0.006% by FACS analysis), CFU assay (10±5 CFU/well), and CAC assay (mean of 25±5 positive cells). Moreover, EPC quantities in peripheral blood were correlated inversely with disease activity as assessed by the disease activity score (r=?0.38, P<0.01).

    Conclusions— Our observations indicate that active RA is associated with a depletion of circulating EPCs. This might be one of several factors contributing to the increased cardiovascular risk in RA.
     
  9. squeegee

    squeegee Banned

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    Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells

    Abstract

    Background: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality attributable to accelerated atherosclerosis and cardiovascular events.

    Objective: To determine the role played by endothelial progenitor cells (EPC) in the defence system against arteriosclerosis.

    Methods: The number and function of EPC in 13 young patients with RA with low disease activity (DAS28 3.5 (0.3)) and 13 healthy control subjects was studied. Endothelial function was investigated by agonist-induced, endothelium dependent vasodilatation measured by the forearm blood flow technique. Migratory activity and adhesion of EPC to tumour necrosis factor ? (TNF?) activated mature endothelial cells and components of the extracellular matrix were tested in vitro. Putative precursor populations (CD34+, CD34+/CD133+, and CD34+/KDR+ haematopoietic stem cells) were measured by flow cytometric analysis.

    Results: Acetylcholine-induced, endothelium dependent vasodilatation was reduced by about 50% in patients with RA, indicating endothelial dysfunction, whereas endothelium-independent vasodilatation in response to glyceryl trinitrate was at control level. Significantly reduced numbers of EPC were found in the patients compared with controls. Migratory activity of EPC was decreased in patients with RA. Adhesion to mature endothelial cells after activation with TNF? was enhanced only in controls. The adhesion to matrix proteins and the number of putative precursor cell lineages was comparable in both groups.

    Conclusion: Endothelial dysfunction in patients with RA with low grade inflammation is associated with a reduced number and partial dysfunction of EPC. Further studies are needed to explore whether interventions that potentially ameliorate the number and function of EPC also improve endothelial function in these patients.
     
  10. squeegee

    squeegee Banned

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    Bone marrow progenitor cell reserve and function and stromal cell function are defective in rheumatoid arthritis: evidence for a tumor necrosis factor alpha–mediated effect

    Helen A. Papadaki,
    Heraklis D. Kritikos,
    Claudia Gemetzi,
    Helen Koutala,
    Judith C. W. Marsh,
    Dimitrios T. Boumpas, and
    George D. Eliopoulos

    + Author Affiliations

    1 From the Departments of Hematology and Rheumatology, University Hospital of Crete School of Medicine, Heraklion, Greece; and the Department of Hematology, St George's Hospital Medical School, London, United Kingdom.

    Abstract

    Based on previous reports for impaired hematopoiesis in rheumatoid arhrtitis (RA), and in view of the current interest in exploring the role of autologous stem cell transplantation (ASCT) as an alternative treatment in patients with resistant disease, we have evaluated bone marrow (BM) progenitor cell reserve and function and stromal cell function in 26 patients with active RA. BM progenitor cells were assessed using flow cytometry and clonogenic assays in short-term and long-term BM cultures (LTBMCs). BM stroma function was assessed by evaluating the capacity of preformed irradiated LTBMC stromal layers to support the growth of normal CD34+ cells. We found that RA patients exhibited low number and increased apoptosis of CD34+ cells, defective clonogenic potential of BM mononuclear and purified CD34+ cells, and low progenitor cell recovery in LTBMCs, compared with healthy controls (n?=?37). Patient LTBMC stromal layers failed to support normal hematopoiesis and produced abnormally high amounts of tumor necrosis factor alpha (TNF?). TNF? levels in LTBMC supernatants inversely correlated with the proportion of CD34+ cells and the number of colony-forming cells, and positively with the percentage of apoptotic CD34+ cells. Significant restoration of the disturbed hematopoiesis was obtained following anti-TNF? treatment in 12 patients studied. We concluded that BM progenitor cell reserve and function and BM stromal cell function are defective in RA probably due, at least in part, to a TNF?-mediated effect. The role of these abnormalities on stem cell harvesting and engraftment in RA patients undergoing ASCT remains to be clarified.
     
  11. squeegee

    squeegee Banned

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    Abstract


    Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis.
    Objective

    To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder.
    Methods

    Patients: Active seropositive RA patients (N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance.
    Results

    A significant 33.4% increase (p < 0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, (p < 0.002) while a 37.6% increase was observed in mean EPC adhesion (p < 0.001). These changes were associated with a 17.5% decrease in the DAS-28 (p < 0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs.
    Conclusion

    A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.

    Keywords: Rheumatoid arthritis; Anti-TNF?; EPC; Angiogenesis
     
  12. squeegee

    squeegee Banned

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    Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy


    Abstract

    Objectives: To study the effects of short-term intermediate dose glucocorticoid (GC) therapy in patients with active rheumatoid arthritis (RA) on circulating endothelial progenitor cells (EPC), which are known to influence cardiovascular risk, and to elucidate mechanisms potentially responsible for the reduction of EPCs in patients with active RA.

    Methods: EPCs were quantified in 29 patients with active RA by flow cytometry, colony forming unit (CFU) and circulating angiogenic cell (CAC) assays before and after 7 days of intermediate dose GC therapy. CFU from patients with RA and from healthy referents (HR) were cultured in vitro in the absence or presence of dexamethasone (Dex) and/or TNF.

    Results: After 1 week of GC therapy, EPC increased from 0.026 (SD 0.003)% to 0.053 (SD 0.010)% (p<0.01), and from 12 (SD 4) to 27 (SD 7) CFU/well (p<0.02); CAC also increased from 7 (SD 2) to 29 (SD 8) cells/high power field (p<0.05). In parallel, disease activity decreased significantly after GC treatment. TNF serum levels also decreased from 36 (SD 10) to 14 (SD 6) pg/ml (p<0.0001). Addition of Dex to the RA CFU led to a significant increase of mean CFU counts, whereas addition of TNF induced a decrease of CFU.

    Conclusions: Our data indicate that TNF may be at least partly responsible for the reduction of EPC seen in patients with RA. Intermediate doses of GCs for a short period of time, apart from reducing disease activity, significantly increase circulating EPC.
     
  13. squeegee

    squeegee Banned

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  14. squeegee

    squeegee Banned

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    Dihydrotestosterone decreases tumor necrosis factor {alpha} and
    lipopolysaccharide induced inflammatory response in human endothelial cells.

    Norata GD, Tibolla G, Seccomandi PM, Poletti A, Catapano AL.

    Department of Pharmacological Sciences, University of Milan, Italy;
    Institute of Endocrinology, Centre of Excellence on Neurodegenerative
    Diseases, University of Milan, Milan, Italy; Center for the Prevention and
    therapy of Global cardiovascular risk, Italian Society for the Study of
    Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy.

    Context. An increasing body of evidence suggests that testosterone may exert
    beneficial effects on the development of atherosclerosis. It was suggested
    that testosterone may act after conversion into estradiol and activation of
    the estrogen receptors, however a direct role of androgens on the vascular
    wall has been proposed. Objective. We investigated the effects of
    dihydrotestosterone on the pro-inflammatory response observed in human
    endothelial cells. Design. Human endothelial cells isolated from umbilical
    cords were incubated with LPS or TNFalpha in the presence or absence of DHT.
    mRNA and cellular proteins were processed for gene expression studies,
    transient transfection experiments were performed to investigate molecular
    mechanisms involved in the effects observed. Setting. These studies took
    place at the Department of Pharmacological Sciences, University of Milan,
    Italy. Results. LPS and TNFalpha induced VCAM-1, and ICAM-1 mRNA and protein
    expression, as detected by Q-real time PCR, FACS and confocal microscopy,
    but this effect was reverted when cells were incubated with DHT. In addition
    DHT inhibited mRNA expression of IL-6, MCP-1, CD40, TLR4, PAI-1 and Cox-2
    and the release of cytokines and chemokines as GRO, GM-CSF and TNF. The DHT
    effect was counteracted by bicalutamide, an antagonist of the androgen
    receptor. Furthermore when cells were co-transfected with a Cox-2 promoter
    or a 3xNF-kB luciferase reporter vector and a plasmid expressing the human
    androgen receptor, DHT treatment inhibited the increase of the luciferase
    activity observed with TNFalpha. Conclusion. Dihydrotestosterone could
    positively regulate endothelial function through the control of the
    inflammatory response mediated by NF-kB in endothelial cells.
     
  15. squeegee

    squeegee Banned

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    In summary, we have shown that DHT increases COX-2 protein levels in the absence of induced inflammation via an AR-dependent mechanism, but attenuates IL-1?-induced increases in COX-2 levels via an AR-independent mechanism, in primary HCASMC. The findings suggest that DHT may be proinflammatory, by augmenting COX-2 levels under physiological conditions, but anti-inflammatory, by attenuating COX-2 under pathophysiological conditions


    http://ajpendo.physiology.org/content/298/4/E838.full
     
  16. squeegee

    squeegee Banned

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    In summary, activation of the NF?B mediated COX-2/iNOS pathway by androgens such as DHT elicits a state of vascular inflammation independent of cytokine or any other outside inflammatory stimulus. Clinically, the effects of androgens on proinflammatory enzymes may contribute to further worsening of the detrimental influence of androgenic stimulation on ischemic brain injury. This is critical, because the impact of cerebrovascular inflammation is highly relevant during pathophysiological conditions related to endothelial dysfunction, oxidative stress, hypoxia and stroke. Taken together these data suggest that, in young adults who choose to use androgen supplementation recreationally or for performance enhancement, predisposition for the onset of inflammation may be increased, with significant possible consequences for development of both cerebral and cardiovascular disease.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658637/
     
  17. squeegee

    squeegee Banned

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    To examine the possible involvement of DHT in the production of inflammatory cytokines in the cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-? (TNF-?). Upregulation of IL-6 and TNF-? in immunohistochemistry, and increase in RNA amplification for IL-6 and TNF-? were observed after addition of DHT compared with the control. This study suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne.

    http://www.springerlink.com/content/g73p3kk31410613l/
     
  18. squeegee

    squeegee Banned

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    Androgens modulate the inflammatory response during acute wound healing.
    Gilliver SC, Ashworth JJ, Mills SJ, Hardman MJ, Ashcroft GS.
    Source

    Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
    Abstract

    Impaired wound healing states in the elderly lead to substantial morbidity and mortality, and a cost to the health services of over 9 billion dollars per annum. In addition to intrinsic ageing processes that per se cause delayed healing, studies have suggested marked differences in wound repair between the sexes. We have previously reported that, castration of male mice results in a striking acceleration of local cutaneous wound healing and dampens the associated inflammatory response. In this study, we report that systemic 5alpha-reductase inhibition, which blocks the conversion of testosterone to its more active metabolite 5alpha-dihydrotestosterone, mimics the effects of castration in a rat model of cutaneous wound healing. The mechanisms underlying the observed effects involve a direct, cell-specific upregulation of pro-inflammatory cytokine expression by macrophages, but not fibroblasts, in response to androgens. Androgens require the transforming growth factor beta signalling intermediate Smad3 to be present in order to influence repair and local pro-inflammatory cytokine levels. That reducing 5alpha-dihydrotestosterone levels through 5alpha-reductase antagonism markedly accelerates healing suggests a specific target for future therapeutic intervention in impaired wound healing states in elderly males.

    Interesting because you need stem cells to heal up!!!
     
  19. squeegee

    squeegee Banned

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    Androgen conversion in osteoarthritis and rheumatoid arthritis synoviocytes--androstenedione and testosterone inhibit estrogen formation and favor production of more potent 5alpha-reduced androgens.

    In synovial cells of patients with osteoarthritis (OA) and rheumatoid arthritis (RA), conversion products of major anti-inflammatory androgens are as yet unknown but may be proinflammatory. Therefore, therapy with androgens in RA could be a problem. This study was carried out in order to compare conversion products of androgens in RA and OA synoviocytes. In 26 OA and 24 RA patients, androgen conversion in synovial cells was investigated using radiolabeled substrates and analysis by thin-layer chromatography and HPLC. Aromatase expression was studied by immunohistochemistry. Dehydroepiandrosterone (DHEA) was converted into androstenediol, androstenedione (ASD), 16alphaOH-DHEA, 7alphaOH-DHEA, testosterone, estrone (E1), estradiol (E2), estriol (E3), and 16alphaOH-testosterone (similar in OA and RA). Surprisingly, levels of E2, E3, and 16alpha-hydroxylated steroids were as high as levels of testosterone. In RA and OA, 5alpha-dihydrotestosterone increased conversion of DHEA into testosterone but not into estrogens. The second androgen, ASD, was converted into 5alpha-dihydro-ASD, testosterone, and negligible amounts of E1, E2, E3, or 16alphaOH-testosterone. 5alpha-dihydro-ASD levels were higher in RA than OA. The third androgen, testosterone, was converted into ASD, 5alpha-dihydro-ASD, 5alpha-dihydrotestosterone, and negligible quantities of E1 and E2. 5alpha-dihydrotestosterone was higher in RA than OA. ASD and testosterone nearly completely blocked aromatization of androgens. In addition, density of aromatase-positive cells and concentration of released E2, E3, and free testosterone from superfused synovial tissue was similar in RA and OA but estrogens were markedly higher than free testosterone. In conclusion, ASD and testosterone might be favorable anti-inflammatory compounds because they decrease aromatization and increase anti-inflammatory 5alpha-reduced androgens. In contrast, DHEA did not block aromatization but yielded high levels of estrogens and proproliferative 16alpha-hydroxylated steroids. Androgens were differentially converted to pro- and anti-inflammatory steroid hormones via diverse pathways.
     
  20. Jacob

    Jacob Senior Member

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    Love those last two especially..
     

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