Skip to main content

Home/ Dr. Goodyear/ Group items tagged Attenuate

Rss Feed Group items tagged

Nathan Goodyear

Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reper... - 0 views

  • In this study, the cardioprotective effects of testosterone in testosterone-deprived rats heart with I/R injury were demonstrated
  • Prior to I/R injury, testosterone replacement provided cardioprotective effects in testosterone-deprived rats as indicated by (1) improved cardiac functions by markedly preserved %EF and %FS, and (2) attenuated cardiac sympathovagal imbalance by a markedly decreased LF/HF ratio
  • Testosterone replacement exerts cardioprotective effects by improving left ventricular function and cardiac sympathovagal balance impaired by testosterone deprivation in ORX rats
  • ...3 more annotations...
  • During the I/R period, testosterone replacement in ORX rats exerted the beneficial effects as indicated by (1) improved left ventricular pressure; (2) markedly decreased infarct size; (3) reduced fatal cardiac arrhythmias by increased time to 1st VT/VF onset and reduced arrhythmia scores; and (4) attenuated cardiac mitochondrial dysfunction caused by I/R injury by reducing ROS production, cardiac mitochondrial swelling and mitochondria membrane depolarization.
  • Chronic testosterone replacement also ameliorates left ventricular dysfunction, and reduces the infarct size and cardiac arrhythmias impaired by I/R injury under testosterone-deprived conditions
  • The mechanisms responsible for these beneficial effects of testosterone could be due to its ability to attenuate cardiac mitochondrial dysfunction and cardiomyocyte apoptosis
  •  
    animal study finds that Testosterone therapy is cardioprotective in a preventative mode and with myocardial injury.  Normalization of Testosterone in these animals with low T reduced infant injury size and improved heart function.  
Nathan Goodyear

Curcumin attenuates the development of allergic airway inflammation and hyper-responsiv... - 0 views

  •  
    curcumin shown to inhibit allergic airway inflammation, through NF-kappaB inhibition.  This has implications in asthma flares.
Nathan Goodyear

Thyroid hormone attenuates cardiac remodeling and ... [Eur J Cardiothorac Surg. 2007] -... - 0 views

  • CONCLUSIONS: Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance.
  •  
    Wow, Thyroid replacement after MI, improves heart function and reduces damage
Nathan Goodyear

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting An... - 0 views

  •  
    Artesunate found to have broad range of anti-cancer activity, such as pro-apoptosis attenuation of tumor growth, metastasis, and angiogenesis. This study primarily looked at the effect in a prostate cancer mouse model. It found that the artesunate down regulated androgen receptors. Now, there is debate about how and when AR and androgens play a role in prostate cancer as studies have also pointed to estrogen and ER in carcinogenesis of the prostate.
Nathan Goodyear

Curcumin Blocks the Activation of Androgen and Interlukin‐6 on Prostate‐Speci... - 0 views

  •  
    IL‐6 increases PSA and androgen receptor expression through a STAT3‐dependent pathway in the absence of androgen in LNCaP cells. Our results agreed with those of an earlier study that indicated that IL‐6 induced expression of the androgen receptor, which up‐regulated PSA promoter activity in the androgen‐independent pathway. Moreover, curcumin blocked stimulation of IL‐6 on the androgen receptor, which attenuated PSA gene expression in a ligand‐independent manner.
Nathan Goodyear

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity ... - 0 views

  •  
    N-acetylcysteine, also known as NAC, a precursor to glutathione, is shown to significantly reduce the incidence of flu symptoms.  NAC should be taken through out the winter months as a flu prevention?  Well, this study does not support that, but if one gets the flu, NAC will significantly reduce the flu symptoms.
Nathan Goodyear

inhibition of estradiol synthesis attenuates renal injury in male streptozotocin-induce... - 0 views

  •  
    Study finds that inhibition of aromatase activity in diabetic male rats provided renal protection. There has been debate about the effects of testosterone therapy on the renal system. However, I propose that aromatase activity and conversion to estrogen is the negative effects of Testosterone. Other than over dosing men. Though this is a rat study, this study does support the theory.
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

  • 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
  •  
    Good deep look into the testosterone and CVD link.
Nathan Goodyear

Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia s... - 0 views

  •  
    animal study finds Boswellia reduces inflammation in Inflammatory Bowel Disease.
Nathan Goodyear

11beta-hydroxysteroid dehydrogenase type 1 an... [Front Horm Res. 2008] - PubMed - NCBI - 0 views

  • Adipose-selective 11beta -HSD1 transgenic mice exhibited elevated intra-adipose and portal, but not systemic corticosterone levels, abdominal obesity, hyperglycaemia, insulin resistance, dyslipidaemia and hypertension
  • transgenic overexpression of 11beta -HSD1 in liver yielded an attenuated metabolic syndrome with mild insulin resistance, dyslipidaemia, hypertension and fatty liver, but not obesity or glucose intolerance
  •  
    11-betaHSD1 expression and effect is site specific.
Nathan Goodyear

Accumulation of Dietary Docosahexaenoic Acid in the Brain Attenuates Acute Immune Respo... - 0 views

  •  
    DHA shown to protect against post stroke inflammation and injury.  This has implications on any head injury.
Nathan Goodyear

Hormonal Modulation in Aging Patients with Erectile Dysfunction and Metabolic Syndrome - 0 views

  • Hypogonadism and MetS are strongly associated [12, 13, 16], having even been demonstrated that with the increasing number of MetS parameters there is a proportional raise in the incidence of hypogonadism
  • increasing number of MetS components is inversely associated with T levels
  • the presence of MetS did not prove to be a significant determinant of hypogonadism, as it did not lead to a decline in T levels, in MetS patients with already established hypogonadism, the increasing number of MetS features was associated with further decline in T
  • ...15 more annotations...
  • In the setting of MetS, hypertriglyceridemia and increased WC have been reported as the most important determinants of hypogonadism
  • recent literature consistently associates obesity not only with higher risk of hypogonadism [4, 6, 27] but also with lower T levels
  • Visceral adiposity has been particularly related with reduction of T and SHBG levels (independent of other metabolic disorders)
  • WC was one of the MetS parameters with the greatest influence in T levels decrease, presenting itself as a strong risk factor for hypogonadism development
  • MetS-related T decline was not accompanied by an increase in pituitary LH levels, suggesting impairment in gonadotropin secretion
  • The molecules behind this smoothing compensatory effect of GnRH/LH are still unknown, but estrogens and insulin, as well as leptin, TNF-α, and other adipokines, were proposed candidates
  • fat stores undertake an increase aromatization of androgens, therefore raising estrogen levels [9, 15], which in turn decrease LH secretion
  • our data contradicts the concept that estradiol exerts a negative feedback on hypothalamic GnRH secretion
  • taking into account that high estradiol levels have already been described as the only abnormality in a subset of patients with ED, the hypothesis that the later might not only be caused by androgen deficiency is becoming increasingly evident
  • it has been reported that the chronic exposure to phosphodiesterase type 5 inhibitors (PDE5i), widely used for the treatment of ED, may influence serum estradiol levels
  • thyroid disorders (specially hyperthyroidism) have been related to ED and hypogonadism, and so must be considered in a sexual-dysfunction setting
  • It is clear from the current literature that collecting a more thorough hormonal panel might be a wise approach to further uncover hormonal relations
    • Nathan Goodyear
       
      outstanding point.  This hits to the point that Low T is the effect not the cause.
  • We concluded that in ED patients with hypogonadism and MetS, the attenuated response of HPG axis (normal or low LH levels) might not always be due to an underlying adiposity-dependent estrogen-raising effect.
  • our findings indicate that ED, aging, and estradiol might have a stronger connection than what is currently described in the literature.
  • this study underlines the importance of the collection of a full hormonal panel in ED men
  •  
    low T strongly associated with metabolic syndrome in men.
Nathan Goodyear

Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-ty... - 0 views

  •  
    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.
Nathan Goodyear

Curcumin attenuates aluminum-induced oxidative ... [Neurotox Res. 2011] - PubMed - NCBI - 0 views

  •  
    Curcumin shown to inhibit oxidative stress, inflammation, and mitochondrial damage caused by Aluminum in rat brain.  Aluminum's effect is not just confined to rat models.  It is well known to cause similar results in the human brain as well.  what is interesting about this article is the clear pathway disruption described as a result of Aluminum exposure.
Nathan Goodyear

Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Dis... - 0 views

  • The gut microbiota participates in the body’s metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders
  • Firmicutes and Bacteroidetes represent the two largest phyla in the human and mouse microbiota and a shift in the ratio of these phyla has been associated with many disease conditions, including obesity
  • In obese humans, there is decreased abundance of Bacteroidetes compared to lean individuals
  • ...21 more annotations...
  • weight loss in obese individuals results in an increase in the abundance of Bacteroidetes
  • there is conflicting evidence on the composition of the obese microbiota phenotype with regards to Bacteroidetes and Firmicutes ratios
  • Bifidobacteria spp. from the phyla Actinobacteria, has been shown to be depleted in both obese mice and human subjects
  • While it is not yet clear which specific microbes are inducing or preventing obesity, evidence suggests that the microbiota is a factor.
  • targeted manipulation of the microbiota results in divergent metabolic outcomes depending on the composition of the diet
  • The microbiota has been linked to insulin resistance or type 2 diabetes (T2D) via metabolic syndrome and indeed the microbiota of individuals with T2D is also characterized by an increased Bacteroidetes/Firmicutes ratio, as well as an increase in Bacillus and Lactobacillus spp
  • It was also observed that the ratio of Bacteriodes-Prevotella to C. coccoides-E. rectale positively correlated with glucose levels but did not correlate with body mass index [80]. This suggests that the microbiota may influence T2D in conjunction with or independently of obesity
  • In humans, high-fat Western-style diets fed to individuals over one month can induce a 71% increase in plasma levels of endotoxins, suggesting that endotoxemia may develop in individuals with GI barrier dyfunction connected to dysbiosis
  • LPS increases macrophage infiltration essential for systemic inflammation preceding insulin resistance, LPS alone does not impair glucose metabolism
  • early treatment of dysbiosis may slow down or prevent the epidemic of metabolic diseases and hence the corresponding lethal cardiovascular consequences
  • increased Firmicutes and decreased Bacteroidetes, which is the microbial profile found in lean phenotypes, along with an increase in Bifidobacteria spp. and Lactobacillus spp
  • mouse and rat models of T1D have been shown to have microbiota marked by decreased diversity and decreased Lactobacillus spp., as well as a decrease in the Firmicutes/Bacteroidetes ratio
  • microbial antigens through the innate immune system are involved in T1D progression
  • The microbiota appears to be essential in maintaining the Th17/Treg cell balance in intestinal tissues, mesenteric and pancreatic lymph nodes, and in developing insulitis, although progression to overt diabetes has not been shown to be controlled by the microbiota
  • There is evidence that dietary and microbial antigens independently influence T1D
  • Lactobacillus johnsonii N6.2 protects BB-rats from T1D by mediating intestinal barrier function and inflammation [101,102] and a combination probiotic VSL#3 has been shown to attenuate insulitis and diabetes in NOD mice
  • breast fed infants have higher levels of Bifidobacteria spp. while formula fed infants have higher levels of Bacteroides spp., as well as increased Clostridium coccoides and Lactobacillus spp
  • the composition of the gut microbiota strongly correlates with diet
  • In mice fed a diet high in fat, there are many key gut population changes, such as the absence of gut barrier-protecting Bifidobacteria spp
  • diet has a dominating role in shaping gut microbiota and changing key populations may transform healthy gut microbiota into a disease-inducing entity
  • “Western” diet, which is high in sugar and fat, causes dysbiosis which affects both host GI tract metabolism and immune homeostasis
  •  
    Nice discussion of how diet, induces gut bacterial change, that leads to metabolic endotoxemia and disease.
Nathan Goodyear

The ISME Journal - Modulation of gut microbiota during probiotic-mediated attenuation o... - 0 views

  •  
    Gut flora as a means to attack Metabolic syndrome?  Animal study suggests yes.
Nathan Goodyear

Thyroid hormone and "cardiac metamorphosis": poten... [Pharmacol Ther. 2008] - PubMed r... - 0 views

  •  
    thyroid hormone plays important role in heart failure and heart repair; thyroid balance critical
Nathan Goodyear

Coenzyme Q10 as a possible treatment for neurodege... [Free Radic Res. 2002] - PubMed r... - 0 views

  • CoQ10 can significantly extend survival, delay motor deficits and delay weight loss and attenuate the development of striatal atrophy in a transgenic mouse model of HD
  •  
    CoQ10 shown to shown to slow progression of the neurodegenerative disease: Huntington's disease
Nathan Goodyear

Glutamine supplementation in cancer patients. [Nutrition. 2001] - PubMed result - 0 views

  • Glutamine supplementation can attenuate loss of protein in the muscle in tumor-bearing animals and protect immune and gut-barrier function during radiochemotherapy in patients with advanced cancer.
  •  
    glutamine supplementation found to protect and support the gut in patients receiving chemo and/or radiation; no increase in tumor growth with glutamine
1 - 20 of 67 Next › Last »
Showing 20 items per page