androgen
deprivation therapy results in unfavorable changes in body composition, insulin resistance, and dyslipidemia and predisposes
men to develop atherosclerosis and an increased risk of cardiovascular mortality
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CA Syringe Filters Sterile and Non Sterile | Axiva - 0 views
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CA 15-3: a prognostic marker in breast CAncer. - PubMed - NCBI - 0 views
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shared by Nathan Goodyear on 08 May 13
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Beyond the male sex hormone: deciphering the metabolic and vascular actions of testoste... - 0 views
joe.endocrinology-journals.org/...C1.full
AR androgen receptors androgen receptor testosterone androgen receptors Diabetes metabolic syndrome MetS CVD cardiovascular disease men hormone hormones male
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The hypogonadal–obesity cycle hypothesis was originally proposed by Cohen in 1999 to explain the relationship between low testosterone levels and metabolic disease. It was based on the finding that obesity impairs testosterone levels by increasing the aromatization of testosterone to estradiol, while low testosterone levels promote increased fat deposition
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adipocytokines contribute to low testosterone levels as well as to the processes underlying metabolic syndromes and type 2 diabetes
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The presence of estradiol and the adipocytokines TNF-α, IL6, and leptin (as a result of leptin resistance in obesity) inhibits the hypothalamic–pituitary–testicular axis response to decreasing androgen levels
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An increasing number of studies have illustrated the potential for applying metabolomics to the field of androgen research
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As early as the 1940s, the therapeutic use of testosterone was reported to improve angina pectoris in men with coronary artery disease
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most of the epidemiological studies reported increased cardiovascular risk and mortality in men with low testosterone levels
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long-term testosterone replacement appears to be a safe and effective means of treating hypogonadal elderly men
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a recent interventional trial showed that testosterone treatment was associated with decreased mortality when compared with no testosterone treatment in an observational cohort of men with low testosterone levels
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a number of short-term studies conducted support the notion that testosterone therapy reduces the cardiovascular risk
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The majority of animal studies support the hypothesis that the actions of testosterone on vascular relaxation are both endothelium-dependent and -independent vasodilatory effects
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Endothelial-dependent actions of testosterone increase the expression or activity of endothelial nitric oxide synthase and enhance nitric oxide production, which in turn activates cyclic guanosine monophosphate to induce vasorelaxation in smooth muscle cells
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Endothelial-independent mechanisms of testosterone are believed to occur primarily via inhibition of voltage-operated Ca2+ channels and/or activation of K+ channels in smooth muscle cells
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Testosterone may also inhibit intracellular Ca2+ influx via store-operated Ca2+ channels by blocking the response to prostaglandin F2α
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testosterone has demonstrated anti-inflammatory effects to protect against atherogenesis in animal studies
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both genomic AR activation to modulate gene transcription and non-genomic activation to modulate the rapid intracellular signaling pathways of ion channels may mediate testosterone effects on vascular function and inflammation.
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Butenandt & Ruzicka first showed how testosterone is synthesized and responsible for masculine characteristics in the early 1930s
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shared by Nathan Goodyear on 13 May 13
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Testosterone: a vascular hormone in health and disease - 0 views
joe.endocrinology-journals.org/...R47.full
testosterone hormone health disease hormones men male cardiovascular disease CVD
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Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
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In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure.
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testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
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Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
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there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate Cancer (Morgentaler & Schulman 2009)
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bidirectional effect between decreased testosterone concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular risk factors
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Achieving a normal physiological testosterone concentration through the administration of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory profiles and vascular function
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It is well known that impaired erectile function and CVD are closely related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5 years
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no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
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free testosterone levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated brachial artery vasodilation in men with caD
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Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects when testosterone is replaced within normal physiological limits in humans
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Endothelium-independent mechanisms of testosterone are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
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Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
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In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
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the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult to delineate and may be dependent upon the stage of plaque development
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Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
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acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described, primarily in the context of vascular tone regulation via the modulation of gene transcription
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Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
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non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
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increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
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Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
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Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM and/or hypogonadism
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TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
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testosterone treatment to normalise levels in hypogonadal men with the MetS resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
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Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ (IFNG)) in endothelial cells, CAn be attenuated by treatment with testosterone
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Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types including human endothelial cells
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decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
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The key to unravelling the link between testosterone and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
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Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
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As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
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prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
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DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
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(Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT 3β-derivative, 3β-Adiol
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TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was signifiCAntly reduced by a pre-incubation with 3β-Adiol in HUVECs
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3β-Adiol also reduced LPS-induced gene expression of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
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This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
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The authors suggest that DHT differentially effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
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There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated an increased risk of adverse cardiovascular events or mortality
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The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
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trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase in either cardiovascular events or mortality in studies up to 12 months
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Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors, there may possibly be a cardioprotective action
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The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
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the majority of studies suggest that testosterone may display both acute and chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via endothelium-dependent and -independent mechanisms
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shared by Nathan Goodyear on 14 May 13
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Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activa... - 0 views
ajpheart.physiology.org/...H1720.full
testosterone vasodilation DHT androgens calcium channels potassium channels
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shared by Nathan Goodyear on 23 Apr 13
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Testosterone: a vascular hormone in health and disease - 0 views
joe.endocrinology-journals.org/...JOE-12-0582.full.pdf+html
low T low Testosterone testosterone low cardiovascular cardiovascular disease CVD health hormone hormones men male
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testosterone therapy has tremendous cardiovascular benefit in men with low T. The key here is physiologic replacement of Testosterone. Testosterone is a vasodilator and anti-inflammatory agent in men with low T. Testosterone therapy improves cardiac function in those with DHF and angina. Testosterone is found to be a ca++ channel blocker--anyone say hypertension treatment?
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shared by Nathan Goodyear on 05 Feb 13
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Estrogen receptor-alpha expression in human meningiomas - 0 views
igitur-archive.library.uu.nl/...c8.pdf
meningioma hormone receptors hormone receptor hormones estrogen receptor ER alpha PR progesterone receptor
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This is a dissertation, but they found ER alpha expression in all meningioma samplings. This is in contrast to previous studies. As further research has come with meningiomas, more ER presence is found, likely due to improved testing techniques. What is interesting here is that Low/no PR status was associated with Increased ER alpha status. This has been shown to be a more pro-inflammatory/pro-growth picture in disease states, such as breast and prostate CA.
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shared by Nathan Goodyear on 06 Feb 12
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Red Versus White Wine as a Nutriti... [J Womens Health (Larchmt). 2011] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...22150098
wine red white aromatase inhibition premenopausal women breast cancer
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red wine does appear to have health benefits over white wine through aromatase inhibition. Aromatase inhibition reduces estrogen levels. So, if the breast cancer risk is associated with elevated estrogen, then this would logically reduce the risk. The exact amount is unknown, but aromatase inhibition is a treatment of those with breast ca.
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shared by Nathan Goodyear on 10 Mar 14
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Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-ty... - 0 views
www.ncbi.nlm.nih.gov/...PMC2700344
estrogen estradiol apoptosis neurodegeneration glutamate glutamic acid
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Estradiol inhibits glutamate mediated influx of calcium and thus cell death in cell line. Glutamate, the principle excitatory neurotransmitter, is involved in neurodegeneration through activation of calcium channels. This study of cell line cultures found that Estradiol inhibits this process. I question whether this is applicable to both men and women. Time will tell.
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17β-Estradiolid Ca influx rapid Ca2+ prostate Cancer cells - 0 views
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Intravenous vitamin C administration improve... [In Vivo. 2011 Nov-Dec] - PubMed - NCBI - 0 views
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Molecular mechanisms of calcium-dependent neurodeg... [Cell calcium. 2003 Oct-Nov] - Pu... - 0 views
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shared by Nathan Goodyear on 26 Mar 14
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Environmental Estrogen Exposure During Fetal Life: A Time Bomb for Prostate Cancer: End... - 0 views
press.endocrine.org/...en.2014-1057
environmental toxins BPA prostate cancer xenoestrogens men male hormones pregnancy exposure
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environmental toxins that have estrogenic activity, i.e. BPA alter the prostate stem cells. These and other xenoestrogens, as they are collectively called, increase the sensitivity of the prostate to estrogen. This increases the risk of prostate ca. This just sets the pattern of signal interpretation and sensitivity. Add in the continued estrogenic environment, add in the excess weight, the increased aromatase activity and resultant estrogen production and one has all the ingredients for prostate cancer.
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shared by Nathan Goodyear on 02 Sep 14
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http://www.biomed.cas.cz/physiolres/pdf/prepress/932627.pdf - 0 views
www.biomed.cas.cz/...932627.pdf
resistance training exercise resistance Testosterone cortisol men obese obesity hormone hormones
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Renal Control of Calcium, Phosphate, and Magnesium Homeostasis - 0 views
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Intravenous Ascorbate as a Tumor Cytotoxic Chemotherapeutic Agent - 0 views
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Ascorbic acid and its salts (AA) are preferentially toxic to tumor cells in vitro (6 — 13) and in vivo
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Increases animal and human resistance to infectious agents by enhancing lymphocyte blastogenesis, enhancing cellular immunity, strengthening the extracellular matrix, and enhancing bactericidal activity of neutrophils and modulation of complement protein
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Strengthens the structural integrity of the extracellular matrix which is responsible for stromal resistance to malignant invasiveness
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In 1977, Bram et al reported preferential AA toxicity for several malignant melanoma cell lines, including four human-derived lines
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Noto et al reported that AA plus vitamin K3 had growth inhibiting action against three human tumor cell lines at non-toxic levels
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The AA begins to reduce cell proliferation in the tumor cell line at the lowest concentration, 1.76 mg/dl, and is completely cytotoxic to the cells at 7.04 mg/dl
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preferential toxicity of AA for tumor cells. >95% toxicity to human endometrial adenocarcinoma and pancreatic tumor cells (ATCC AN3-ca and MIA Paca-2) occurred at 20 and 30 mg/dl, respectively.
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No toxicity or inhibition was demonstrated in the normal, human skin fibroblasts (ATCC CCD 25SK) even at the highest concentration of 50 mg/dl.
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Cameron and Pauling have published extensive suggestive evidence for prolonged life in terminal Cancer patients orally supplemented (with and without initial intravenous AA therapy) with 10 g/day of AA
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the long-term, oral dosage used in those experiments (10 g/day), while substantial and capable of producing immunostimulatory and extracellular matrix modulation effects, was not high enough to achieve plasma concentrations that are generally cytotoxic to tumor cells in culture
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5 — 40 mg/dl of AA is required in vitro to kill 100% of tumor cells within 3 days. The 100% kill levels of 30 mg/dl for the endometrial carcinoma cells and 40 mg/dl for the pancreatic carcinoma cells in Figure 2 are typical
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1 h after beginning his first 8-h infusion of 115 g AA (Merit Pharmaceuticals, Los Angeles, ca), the plasma AA was 3.7 mg/dl and at 5 h was 19 mg/dl. During his fourth 8-h infusion, 8 days later, the 1 h plasma level was 158 mg/dl and 5 h was 185 mg/dl
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plasma levels of over 100 mg/dl have been maintained in 3 patients for more than 5 h using continuous intravenous infusion
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In rare instances of patients with widely disseminated and rapidly proliferating tumors, intravenous AA administration (10 — 45 g/day) precipitated widespread tumor hemorrhage and necrosis, resulting in death
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Although the outcomes were disastrous in these cases, they are similar to the description of tumor-necrosis-factor-induced hemorrhage and necrosis in mice (52) and seem to demonstrate the ability of AA to kill tumor cells in vivo.
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toxic effects of AA on one normal cell line were observed at 58.36 mg/dl and the lack of side effects in patients maintaining >100 mg/dl plasma levels
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Although it is very rare, tumor necrosis, hemorrhage, and subsequent death should be the highest priority concern for the safety of intravenous AA for cancer patients.
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CathCart (55) who describes no ill effects with doses of up to 200 g/d in patients with various pathologiCal conditions
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following circumstances: renal insufficiency, chronic hemodialysis patients, unusual forms of iron overload, and oxalate stone formers
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Screening for red cell glucose-6-phosphate dehydrogenase deficiency, which can give rise to hemolysis of red blood cells under oxidative stress (57), should also be performed
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any cancer therapy should be started at a low dosage to ensure that tumor hemorrhage does not occur.
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a scorbutic rebound effect can be avoided with oral supplementation. Because of the possibility of a rebound effect, measurement of plasma levels during the periods between infusions should be performed to ensure that no such effect takes place
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Every effort should be made to monitor plasma AA levels when a patient discontinues intravenous AA therapy.
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