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Nathan Goodyear

Interaction of 5-methyltetrahydrofolate and tetrah... [Am J Physiol Heart Circ Physiol.... - 0 views

www.ncbi.nlm.nih.gov/...12003825

5-methyltetrahydrofolate tetrahydropbiopterin NO endothelial vascular function cardiovascular disease

shared by Nathan Goodyear on 29 Apr 11 - No Cached
  • We demonstrate that 5-methyltetrahydrofolate binds the active site of nitric oxide synthase and mimics the orientation of tetrahydrobiopterin
  • 5-methyltetrahydrofolate attenuates superoxide production (induced by inhibition of tetrahydrobiopterin synthesis) and improves endothelial function
  • e suggest that 5-methyltetrahydrofolate directly interacts with nitric oxide synthase to promote nitric oxide (vs. superoxide) production and improve endothelial function
  • ...1 more annotation...
  • 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability.
  • Nathan Goodyear on 29 Apr 11
     
    5-methyltetrahydrofolate promotes NO synthase and improves endothelial vascular function;  proposed as way to increase tetrahydropbiopterin
Nathan Goodyear

Hyperhomocysteinemia, deep vein thrombosi... [J Formos Med Assoc. 2007] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17908667

vitamin B12 homocysteine DVT blood clots MS methionine synthase metformin DM diabetes insulin resistance IR

shared by Nathan Goodyear on 23 Jan 12 - No Cached
  • Nathan Goodyear on 23 Jan 12
     
    Vitamin B12 deficiency will decrease methionine synthase activity, which will result in elevated homocysteine and the risk of DVT increases as a result.  In this article, the cause of the vitamin B12 depletion was metformin.  Diabetics and those with insulin resistance are already at an increased risk of blood clots.
Nathan Goodyear

Equine Estrogens Impair Nitric Oxide Production and Endothelial Nitric Oxide ... - 0 views

hyper.ahajournals.org/...405.long

premarin estradiol HRT BHRT eNOS NO nitric oxide endothelium

shared by Nathan Goodyear on 14 Oct 13 - No Cached
  • Nathan Goodyear on 14 Oct 13
     
    This is the perfect study to compare synthetic, unnatural hormones with bioidentical hormones.  Premarin was compared with bioidentical estradiol.  Premarin reduced the endothelial NO synthase transcription and activity by 30-50% compared to Estradiol.   Thus, premarin results in a lower NO production and thus greater endothelial dysfunction compared to Estradiol.
Nathan Goodyear

Journal of Clinical Investigation -- Oxidation of tetrahydrobiopterin leads to uncoupli... - 0 views

www.jci.org/14172

tetrahydrobiopterin cardiovascular disease hypertension

shared by Nathan Goodyear on 29 Apr 11 - No Cached
  • Tetrahydrobiopterin is a critical cofactor for the NO synthases
  • at hypertension produces a cascade involving production of ROSs from the NADPH oxidase leading to oxidation of tetrahydrobiopterin and uncoupling of endothelial NO synthase (eNOS). This decreases NO production and increases ROS production from eNOS
  • Tetrahydrobiopterin oxidation may represent an important abnormality in hypertension
  • ...1 more annotation...
  • Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease.
  • Nathan Goodyear on 29 Apr 11
     
    tetrahydrobiopterin deficiency plays role in cardiovasular disease
Nathan Goodyear

Testosterone Treatment and Sexual Function in Older Men with Low Testosterone Levels: T... - 0 views

press.endocrine.org/...jc.2016-1645

low T low Testosterone Testosterone male hormones libido ED estradiol hormones

shared by Nathan Goodyear on 13 Jul 16 - No Cached
  • Nathan Goodyear on 13 Jul 16
     
    new study finds that men >65 with low libido and Testosterone levels < 275 increase sexual function with Testosterone therapy.  Only libido was improved; no benefit to erectile function was noted--note that is likely due to depleted NO.  Given time that should improve with he increase in NO synthase and thus NO.  I have a fault with on elf the comments on this study: they point out that increased free Testosterone and estradiol levels were associated with improved sexual activity.  This lacks an understanding of the physiology.  In men with low T > 65, the majority are dealing with inflammation and excess weight; all of which increase aromatase activity and thus estradiol activity.  This does not indicate that an increase in estradiol activity is associated with improved libido in men.  How can elevated estrogen levels lead to low T and then increase levels are associated with improved libido?  This is merely a reflection of the body's dysfunctional physiology.  This observation of increased estradiol by no means shows cause and effect.  Scientists need to due a better job in vetting what they write!
Nathan Goodyear

Vitamin Intervention for Stroke Prevention Trial - 0 views

stroke.ahajournals.org/...2404.full

homocysteine vitamin B12 folic acid VISP stroke prevention vitamins

shared by Nathan Goodyear on 25 Jul 12 - No Cached
  • Nathan Goodyear on 25 Jul 12
     
    Vitamin B12, methyl cobalamin, is very important in lowering homocysteine levels through methionine synthase.  The VISP trial did not show efficacy in the intention to treat analysis.  However, analysis of the efficacy reveals that many clients had too low of vitamin B12 levels due to malabsorption and vitamin B12 levels should have been higher in the VISP intention to treat.
Nathan Goodyear

Lead acetate may cause erectile dysfunctio... [Cell Biol Toxicol. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23979109

ED erectile dysfunction NO Pb lead

shared by Nathan Goodyear on 17 Sep 14 - No Cached
  • Nathan Goodyear on 17 Sep 14
     
    In rat model, Pb reduced NO and contributed to ED.  Of interest, arginine masked the effects of Pb on NO synthase and vitamin C reversed it all together.
Nathan Goodyear

Cyclooxygenase inhibition reduces blood p... [Clin Exp Hypertens. 2000] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10744360

cyclooxygenase NO Hg mercury heart health COX cardiovascular disease hypertension

shared by Nathan Goodyear on 16 Sep 14 - No Cached
  • Nathan Goodyear on 16 Sep 14
     
    Inhibition of NO production will result in increased COX and thus vasoconstriction in rate model.  Hg has been shown to both inhibit NO synthase and increase COX.
Nathan Goodyear

Unveiling the Mechanisms for Decreased Glutathione in Individuals with HIV Infection - 0 views

connection.ebscohost.com/...ione-individuals-hiv-infection

glutathione GSH Nrf2 GSSG HIV inflammation oxidative Stress

shared by Nathan Goodyear on 07 Jan 15 - No Cached
  • Nathan Goodyear on 07 Jan 15
     
    men with HIV have GSH depleted macrophages.  GSH is the reduced, ready to act form of Glutathione.  In contrast, the macrophages were high in the oxidized form of Glutathione--GSSG.  In HIV, the high inflammation increased oxidative stress, likely overwhelmed Nrf2 activation and resulted in decreased GSH synthase transcription and thus decreased Glutathione production balance.
Nathan Goodyear

Nitric oxide mediated erectile activity is a testosterone dependent event: a rat erecti... - 0 views

www.ncbi.nlm.nih.gov/...8770664

low T low Testosterone NO NOS nitric oxide Testosterone ED men male hormones

shared by Nathan Goodyear on 18 Nov 15 - No Cached
  • Nathan Goodyear on 18 Nov 15
     
    Only abstract available here, but rat model finds Testosterone increased NO synthase activity in corpora cavernous. 
Nathan Goodyear

Erectile dysfunction and testosterone deficiency. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19011292

PDE5 PDE5 inhibitors PDE5I low T low Testosterone NO nitric oxide ED men hormones Testosterone

shared by Nathan Goodyear on 18 Nov 15 - No Cached
  • Nathan Goodyear on 18 Nov 15
     
    A high percentage of men that fail PDE5 therapy have low T and the addition of T therapy improves the effects of PDE5 therapy.  T provides a positive impact on NO synthase which increased NO, which PDE5 therapies must have to work.
Nathan Goodyear

How is the Immune System Suppressed by Cancer - 1 views

www.cancertutor.com/ancer-suppresses-immune-system

iNOS cancer immune system

shared by Nathan Goodyear on 23 May 18 - No Cached
  • nitric oxide (NO) released by tumor cells
  • Excellent work by Prof de Groot of Essen, indicated by adding exogenous xanthine oxidase ( XO) in hepatoma cells, hydrogen peroxide was produced to destroy the hepatoma cells
  • NO from eNOS in cancer cells can travel through membranes and over long distances in the body
  • ...43 more annotations...
  • NO also is co linked to VEGF which in turn increases the antiapoptotic gene bcl-2
  • The other important influence of NO is in its inhibition of the proapoptoic caspases cascade. This in turn protects the cells from intracellular preprogrammed death.
  • nitric oxide in immune suppression in relation to oxygen radicals is its inhibitory effect on the binding of leukocytes (PMN) at the endothelial surface
  • Inhibition of inducible Nitric Oxide Synthase (iNOS)
  • NO from the tumor cells actually suppresses the iNOS, and in addition it reduces oxygen radicals to stop the formation of peroxynitrite in these cells. But NO is not the only inhibitor of iNOS in cancer.
  • Spermine and spermidine, from the rate limiting enzyme for DNA synthases, ODC, also inhibit iNOS
  • tolerance in the immune system that decreases the immune response to antigens on the tumors
  • Freund’s adjuvant
  • increase in kinases in these cells which phosphorylate serine, and tyrosine
  • responsible for activation of many growth factors and enzymes
  • phosphorylated amino acids suppress iNOS activity
  • Hexokinase II
  • Prostaglandin E2, released from tumor cells is also an inhibitor of iNOS, as well as suppressing the immune system
  • Th-1 subset of T-cells. These cells are responsible for anti-viral and anti-cancer activities, via their cytokine production including Interleukin-2, (IL-2), and Interleukin-12 which stimulates T-killer cell replication and further activation and release of tumor fighting cytokines.
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      Th1 cells stimulate NK and other tumor fighting macrophages via IL-2 and IL-12; In contrast, Th2, which is stimulated in allergies and parasitic infections, produce IL-4 and IL-10.  IL-4 and IL-10 inhibit TH-1 activation and the histamine released from mast cell degranulation upregulates T suppressor cells to further immune suppression.
  • Th-2 subset of lymphocytes, on the other hand are activated in allergies and parasitic infections to release Interleukin-4 and Interleukin-10
  • These have respectively inhibitory effects on iNOS and lymphocyte Th-1 activation
  • Mast cells contain histamine which when released increases the T suppressor cells, to lower the immune system and also acts directly on many tumor Histamine receptors to stimulate tumor growth
  • Tumor cells release IL-10, and this is thought to be one of the important areas of Th-1 suppression in cancer patients
  • IL-10 is also increased in cancer causing viral diseases such as HIV, HBV, HCV, and EBV
  • IL-10 is also a central regulator of cyclooxygenase-2 expression and prostaglandin production in tumor cells stimulating their angiogenesis and NO production
  • nitric oxide in tumor cells even prevents the activation of caspases responsible for apoptosis
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      NO produced by cancer cells inhibits proapoptotic pathways such as the caspases.
  • early stages of carcinogenesis, which we call tumor promotion, one needs a strong immune system, and fewer oxygen radicals to prevent mutations but still enough to destroy the tumor cells should they develop
  • later stages of cancer development, the oxygen radicals are decreased around the tumors and in the tumor cells themselves, and the entire cancer fighting Th-1 cell replication and movement are suppressed. The results are a decrease in direct toxicity and apoptosis, which is prevented by NO, a suppression of the macrophage and leukocyte toxicity and finally, a suppression of the T-cell induced tumor toxicity
  • cGMP is increased by NO
  • NO in cancer is its ability to increase platelet-tumor cell aggregates, which enhances metastases
  • the greater the malignancies and the greater the metastatic potential of these tumors
  • The greater the NO production in many types of tumors,
  • gynecological
  • elevated lactic acid which neutralizes the toxicity and activity of Lymphocyte immune response and mobility
  • The lactic acid is also feeding fungi around tumors and that leads to elevated histamine which increases T-suppressor cells.&nbsp; Histamine alone stimulates many tumor cells.
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      The warburg effect in cancer cells results in the increase in local lactic acid production which suppresses lymphocyte activity and toxicity as well as stimulates histamine production with further stimulates tumor cell growth.
  • T-regulatory cells (formerly,T suppressor cells) down regulate the activity of Natural killer cells
  • last but not least, the Lactic acid from tumor cells and acidic diets shifts the lymphocyte activity to reduce its efficacy against cancer cells and pathogens in addition to altering the bacteria of the intestinal tract.
  • intestinal tract bacteria in cancer cells release sterols that suppress the immune system and down regulate anticancer activity from lymphocytes.
  • In addition to the lactic acid, adenosine is also released from tumors. Through IL-10, adenosine and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state
  • Adenosine up regulates the PD1 receptor in T-1 Lymphocytes and inhibits their activity
  • Adenosine is a purine nucleoside found within the interstitial fluid of solid tumors at concentrations that are able to inhibit cell-mediated immune responses to tumor cells
  • Adenosine appears to up-regulate the PD1 receptor in T-1 Lymphocytes and inhibits the immune system further
  • Mast cells with their release of histamine lower the immune system and also stimulate tumor growth and activate the metalloproteinases involved in angiogenesis and metastases
  • COX 2 inhibitors or all trans-retinoic acid
  • Cimetidine, an antihistamine has been actually shown to increase in apoptosis in MDSC via a separate mechanism than the antihistamine effect
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      cimetidine is an H2 blocker
  • interleukin-8 (IL-8), a chemokine related to invasion and angiogenesis
  • In vitro analyses revealed a striking induction of IL-8 expression in CAFs and LFs by tumor necrosis factor-alpha (TNF-alpha)
  • these data raise the possibility that the majority of CAFs in CLM originate from resident LFs. TNF-alpha-induced up-regulation of IL-8 via nuclear factor-kappaB in CAFs is an inflammatory pathway, potentially permissive for cancer invasion that may represent a novel therapeutic target
  • Nathan Goodyear on 23 May 18
     
    Great review of the immunosuppression in cancer driven by the likes of NO.
Nathan Goodyear

American College of Cardiology Foundation | Journal of the American College of Cardiolo... - 0 views

content.onlinejacc.org/article.aspx

mitochondria oxidative stress heart failure heart

shared by Nathan Goodyear on 19 Mar 13 - No Cached
  • Although currently no drugs that specifically target mitochondrial biogenesis in HF are available, acceleration of this process through adenosine monophosphate–activated kinase (AMPK), endothelial nitric oxide synthase (eNOS), and other pathways may represent a promising therapeutic approach
  • Mitochondrial biogenesis can be enhanced therapeutically with the use of adenosine monophosphate kinase (AMPK) agonists, stimulants of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway (including phosphodiesteraes type 5 inhibitors), or resveratrol
  • metformin, a commonly used antidiabetic drug that activates AMPK signaling
  • ...10 more annotations...
  • Recent evidence suggests that the eNOS/NO/cGMP pathway is an important activator of mitochondrial biogenesis
  • BH4 (tetrahydrobiopterin) supplementation can prevent eNOS uncoupling and was found to reduce left ventricular hypertrophy
  • folic acid is known to replenish reduced BH4 and has been shown to protect the heart through increased eNOS activity
  • Both folate deficiency and inhibition of BH4 synthesis were associated with reduced mitochondrial number and function
  • Resveratrol, a polyphenol compound responsible for the cardioprotective properties of red wine, was recently identified as a potent stimulator of mitochondrial biogenesis
  • epidemiological studies reveal a reduced risk of cardiovascular disease in premenopausal, but not post-menopausal, women compared with men
  • post-menopausal women
    • Nathan Goodyear
      Nathan Goodyear on 19 Mar 13
       
      I would hypothesis that a change in the predominance of ER expression is one of ER beta to ER alpha: creating a more pro-inflammatory signal.
  • The majority of ROS in the heart appear to come from uncoupling of mitochondrial electron transport chain at the level of complexes I and III
  • Because the majority of ROS in HF comes from mitochondria, these organelles are the primary target of oxidative damage.
  • cardioprotective therapies such as angiotensin-converting enzyme inhibitors and ATII receptor blockers were shown to possess antioxidant properties, although it is not known whether they target mitochondrial ROS directly or indirectly
  • Nathan Goodyear on 19 Mar 13
     
    great review of mitochondrial biogenesis, oxidative stress and heart failure.  
Nathan Goodyear

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

shared by Nathan Goodyear on 13 May 13 - No Cached
  • Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
  • 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.
  • testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
  • ...54 more annotations...
  • Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
  • there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson &amp; Rosano 2011) or prostate cancer (Morgentaler &amp; Schulman 2009)
  • 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
  • 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
  • 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
  • no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
  • 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
  • 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
  • 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)
  • Testosterone shares the same molecular binding site as nifedipine
  • Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
  • Testosterone also inhibited the Ca2+ influx response to PGF2α
  • one of the major actions of testosterone is on NO and its signalling pathways
  • 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
  • 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
  • Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
  • t long-term testosterone treatment reduced CIMT in men with low testosterone levels and angina
  • neither intracellular nor membrane-associated ARs are required for the rapid vasodilator effect
  • 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
  • Testosterone and DHT increased the expression of eNOS in HUVECs
  • oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
  • Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
  • non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
  • increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
  • 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
  • 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
  • patients with the highest IL1β concentrations had lower endogenous testosterone levels
  • TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
  • 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
  • parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly men
  • Higher levels of serum adiponectin have been shown to lower cardiovascular risk
  • 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
  • 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
  • decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
  • 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.
  • testosterone functions through the AR to modulate adhesion molecule expression
  • pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
  • DHT inhibited NFκB activation
  • DHT could inhibit an LPS-induced upregulation of MCP1
  • Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
  • 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
  • prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
  • DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
  • (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
  • 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
  • 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)
  • This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
  • 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
  • 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
  • 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
  • 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
  • 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
  • The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
  • 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
  • Nathan Goodyear on 13 May 13
     
    Good deep look into the testosterone and CVD link.
Nathan Goodyear

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

shared by Nathan Goodyear on 08 May 13 - No Cached
  • 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
  • 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
  • adipocytokines contribute to low testosterone levels as well as to the processes underlying metabolic syndromes and type 2 diabetes
  • ...15 more annotations...
  • hypogonadal–obesity–adipocytokine hypothesis
  • 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
  • An increasing number of studies have illustrated the potential for applying metabolomics to the field of androgen research
  • As early as the 1940s, the therapeutic use of testosterone was reported to improve angina pectoris in men with coronary artery disease
  • most of the epidemiological studies reported increased cardiovascular risk and mortality in men with low testosterone levels
  • long-term testosterone replacement appears to be a safe and effective means of treating hypogonadal elderly men
  • 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
  • a number of short-term studies conducted support the notion that testosterone therapy reduces the cardiovascular risk
  • The majority of animal studies support the hypothesis that the actions of testosterone on vascular relaxation are both endothelium-dependent and -independent vasodilatory effects
  • 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
  • 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
  • Testosterone may also inhibit intracellular Ca2+ influx via store-operated Ca2+ channels by blocking the response to prostaglandin F2α
  • testosterone has demonstrated anti-inflammatory effects to protect against atherogenesis in animal studies
  • 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.
  • Butenandt &amp; Ruzicka first showed how testosterone is synthesized and responsible for masculine characteristics in the early 1930s
  • Nathan Goodyear on 08 May 13
     
    Awesome review on the current understanding of Testosterone and Diabetes, metabolic syndrome, and CVD.  This article even goes into the literature on androgen receptors.
Nathan Goodyear

Ascorbic Acid Enhances Endothelial Nitric-oxide Synthase Activity by Increasing Intrace... - 0 views

www.jbc.org/...17399.full

vitamin C NO nitric oxide eNOS

shared by Nathan Goodyear on 16 Jan 17 - No Cached
  • Nathan Goodyear on 16 Jan 17
     
    vitamin C increases eNOS activity and thus NO production.
Nathan Goodyear

The role of S-adenosyl methionine in preventing FOLFOX-induced liver toxicity: a retros... - 0 views

informahealthcare.com/...14740338.2011.562888

SAMe methylation cancer CBS cystathionine Beta-synthase glutathione GSH chemotherapy

shared by Nathan Goodyear on 27 Jun 12 - No Cached
  • Nathan Goodyear on 27 Jun 12
     
    SAMe shown to lower liver toxicity in chemotherapy treatment.  SAMe could be a powerful chemotherapeutic adjuvant.  This makes since, because cancer is known to be a hypomethylated state.  Low methyl donors will reduce CBS activity and thus lower glutathione.  This will result in increased oxidative stress and inflammation in the liver.  SAMe will open the CBS activity up and increase glutathione production.
Nathan Goodyear

S-adenosylmethionine in alcoholic liver cirrhosis:... [J Hepatol. 1999] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10406187

SAMe NAFLD GSH glutathione liver cirrhosis cirrhosis liver

shared by Nathan Goodyear on 27 Jun 12 - No Cached
  • Nathan Goodyear on 27 Jun 12
     
    SAMe, at doses of 1200 mg, shown to decrease mortality rate and prolong transplantation in those with cirrhosis.  Very likely, these individuals, if tested, had low SAMe and methyl donors as well as depleted glutathione. This is a set up for low phosphotidyl choline/ethanolamine levels resulting in fat accumulation.
Nathan Goodyear

Estradiol Enhances Recovery After Myocardial Infarction by Augmenting Incorporation of ... - 0 views

circ.ahajournals.org/...1605.long

estradiol estrogen EPCs MI CVD endothelial progenitor cells hormone hormones

shared by Nathan Goodyear on 11 Jul 12 - No Cached
  • Nathan Goodyear on 11 Jul 12
     
    Estradiol shown to increase EPC activity post MI in female MI rat model
Nathan Goodyear

Long-Term Vitamin C Treatment Increases Vascular Tetrahydrobiopterin Levels and Nitric ... - 0 views

circres.ahajournals.org/...88

Vitamin C tetrahydrobiopterin

shared by Nathan Goodyear on 29 Apr 11 - No Cached
  • beneficial effect of vitamin C on vascular endothelial function appears to be mediated in part by protection of tetrahydrobiopterin and restoration of eNOS enzymatic activity
  • Nathan Goodyear on 29 Apr 11
     
    Vitamin C helps to preserve tetrahydrobiopterin levels
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