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Nathan Goodyear

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast canc... - 1 views

www.ncbi.nlm.nih.gov/...PMC2562592

estrogen metabolism menopause post-menopause post menopause estrogen metabolite 2-OH-estrone 16-alpha-OH-estrone 2:16alpha-OH estrone breast cancer risk hormone hormones

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • 2-OH estrogens bind to the estrogen receptor (ER) with affinity equivalent to or greater than estradiol
  • previous prospective studies have not observed any significant associations with either 2-OH or 16α-OH estrone or the ratio of the two metabolites and breast cancer risk overall.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      whether that risk is increased or decreased
  • it has been hypothesized that metabolism favoring the 2-OH over the 16α-OH pathway may be inversely associated with breast cancer risk (28).
  • ...24 more annotations...
  • they may act as only weak mitogens (14, 15), or as inhibitors of proliferation
  • No significant associations have been observed between 2-OH estrone and breast cancer risk
  • While 16α-OH estrone binds to the ER with lower affinity than estradiol, it binds covalently (18-20) and once bound, fails to down-regulate the receptor (21). Thus, 16α-OH estrone stimulates cell proliferation in a manner comparable to estradiol in ER+ breast cancer cell lines
  • In this large prospective study of 2-OH and 16α-OH estrone metabolites and breast cancer risk, we did not observe any significant associations overall with either individual metabolite or with the ratio of the two metabolites
  • we observed positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with lower BMI and women with ER-/PR-tumors,
  • To date, several epidemiologic studies have examined the association between the 2-OH and 16α-OH estrogen metabolites and breast cancer risk with inconclusive results.
  • circulating estrogen levels have been associated more strongly with ER+/PR+ tumors than with ER-/PR- tumors
  • our results do not support the hypothesis that metabolism favoring the 2-OH estrone pathway is more beneficial to breast cancer risk than that favoring the 16α-OH estrone pathway
  • we observed significant positive associations of both 2-OH estrone and the 2:16α-OH estrone ratio with ER-/PR-tumors
  • Three (30, 32, 33) of four (30-33) studies observed RRs above 1 for the association between 16α-OH estrone and breast cancer risk (range of RRs=1.23-2.47); none of the point estimates was statistically significant though one trend was suggestive
  • based on animal studies, 2-OH estrone and the 2:16α-OH estrone ratio have been hypothesized to be inversely associated with breast cancer risk
  • No significant associations have been observed between 2-OH estrone, 16α-OH estrone, or the 2:16α-OH estrone ratio and breast cancer risk and the direction of the estimates is not consistent across studies.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      better worded is no consistent, significant associations.   There are some studies that point to the 16 catecholestrogen and increased cancer risk; limited studies show negative effects of 2 catecholestrogens on cancer risk and prospective studies available pretty much dispel the idea that the 2:16 ratio has an risk predictability.
  • we observed a suggestive inverse association with 16α-OH estrone and a significant positive association with the 2:16α-OH estrone ratio among lean women, suggesting possible associations in a low estrogen environment.
  • 16α-OH estrone increases unscheduled DNA synthesis in mouse mammary cells (27) and hence also may be genotoxic
  • Although 2-OH estrogens are capable of redox cycling, the semiquinones and quinones (i.e., the oxidized forms) form stable DNA adducts that are reversible without DNA destruction
  • In our population of PMH nonusers, we observed no associations with ER+/PR+ tumors, but significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      one of the few studies to find this association between 2 catecholestrogens and the 2:16 ratio and ER-/PR-tumors
  • Animal and in vitro studies have shown that hydroxy estrogens can induce DNA damage either directly, through the formation of quinones and DNA adducts, or indirectly, through redox cycling and the generation of reactive oxygen species
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      genotoxic via directe DNA adducts and indirectly via ROS; this is in addition to the proliferative effect
  • we observed a significant positive association between the 2:16α-OH estrone ratio and breast cancer risk among lean women
  • No significant associations have been observed with the 2:16α-OH estrone ratio
  • In the Danish study, no associations were observed with either ER+ or ER- tumors among PMH nonusers
  • significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio were observed among PMH users with ER+, but not ER-, tumors
  • it is possible that the genotoxicity of 2-OH estrone plays a role in hormone receptor negative tumors
  • 4-OH estrogens have a greater estrogenic potential than 2-OH estrogens, given the lower dissociation rate from estrogen receptors compared with estradiol (61), and are potentially more genotoxic since the quinones form unstable adducts, leading to depurination and mutation in vitro and in vivo
  • the balance between the catechol (i.e., 2-OH and 4-OH) and methoxy (i.e., 2-Me and 4-Me) estrogens may impact risk
  • Nathan Goodyear on 21 Aug 14
     
    The risks of estrogen metabolism are not clear cut.  Likely never will be due to the complexity of individual metabolism.  This study found no correlation between 2OH-Estrone and 2OH:16alpha-Estrone and breast cancer risk in ER+/PR+ breast cancer.  Translated: no benefit in breast cancer risk in 2OH-Estrone metabolism or increased 2OH:16alpha estrone metabolism.  There was a positive association between 2OH-Estrone and 2:16alpha-Estrone in women with ER-/PR- tumors and low BMI.
  • anonymous on 28 Oct 15
     
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Nathan Goodyear

Association between endogenous sex steroid hormones and inflammatory biomarkers in US men - 0 views

www.ncbi.nlm.nih.gov/...PMC3812341

low Testosterone Estrogen Estradiol low T Testosterone hormone hormones CRP inflammation SHBG WBC men male

shared by Nathan Goodyear on 28 Apr 15 - No Cached
  • modest statistically significant inverse associations for total and calculated free testosterone, and modest positive associations for total and calculated free estradiol with CRP concentration
  • Estradiol concentrations were also weakly positively associated with WBC count
  • SHBG was weakly inversely associated with WBC
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  • An association between testosterone and WBC count was not observed
  • These findings are consistent with the hypothesis that in men higher androgen concentration is anti-inflammatory, and higher estrogen concentration is pro-inflammatory.
  • the probability of elevated CRP concentrations (≥ 3 mg/L) decreased with higher total and calculated free testosterone concentrations, while the probability increased with higher total and calculated free estradiol concentrations
  • there is ample evidence supporting the immunosuppressive effect of androgens
  • The incidence of autoimmune diseases is higher in androgen-deficient men
  • Studies have shown that the induction of hypogonadism in older men is followed by a significant increase in IL-6 concentrations (Khosla et al. 2002), a potent stimulator of inflammation, and that activation of the androgen receptor exerts a direct anti-inflammatory effect
  • It has been suggested that the mechanisms for the immunosuppressive effect of androgens could be either a direct effect on the expression of inflammatory genes (Bellido et al. 1995; Asirvatham et al. 2006), or an indirect effect through inhibition of nuclear factor-kB activation
  • Estradiol is the major biologically active estrogen, and about 80% is formed in adult men from the aromatization of testosterone primarily in the adipose tissue
  • estrogen can stimulate the transcription factor C/EBP-β, which is involved in CRP transcription
  • Most prior cross-sectional studies have observed inverse associations between androgen concentrations and inflammatory biomarkers
  • A recent study in Chinese men showed that lower concentrations of total and calculated free testosterone were associated with higher CRP concentration
  • Data from the Boston Area Community Health Survey also reported inverse associations between testosterone and CRP concentrations
  • Total testosterone was inversely associated with WBC count (Tang et al. 2007; Schneider et al. 2009; Brand et al. 2012), but calculated free testosterone was not associated with WBC
  • The first trial found a decrease in CRP, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNFα) but no changes in IL-6 and IL-10 concentrations between the active treatment and placebo arms
  • the majority of studies in the literature have not observed statistically significant associations between estradiol and inflammatory biomarkers in men, although several of them observed point estimates in the positive direction
  • total testosterone and estradiol compete for binding to SHBG, and seem to have opposite effects on the concentration of inflammatory biomarkers
  • A small randomized controlled trial of estrogen replacement therapy in prostate cancer patients showed an increase in CRP in the active treatment group versus the comparator group
  • Obese men are known to have lower androgen concentrations compared to their normal-weight counterparts
  • The strongest suggestion of an interaction was the inverse association between androstanediol glucuronide and CRP concentrations in obese participants, while the association was positive in the non-obese
  • A recent Chinese cross-sectional study observed stronger inverse associations between total testosterone and CRP concentrations in individuals with a BMI of 27.5 kg/m2 or greater
  • our results suggest that total and calculated free testosterone are modestly inversely associated with CRP concentrations, and that total and calculated free estradiol are modestly positively associated with CRP and WBC
  • Nathan Goodyear on 28 Apr 15
     
    Study results suggest that higher Testosterone and lower Estrogen levels provide anti-inflammatory effects in men.  The inflammatory biomarker assessed here was CRP.  Low total and calculated free Testosterone was associated with an increase in CRP.  In contrast, total and free Estrogen was associated with an increase in CRP.  Estradiol increased WBC count and SHBG was inversely related to WBC count in this study.
Nathan Goodyear

Fructose decreases physical activity and increases body fat without affecting hippocamp... - 0 views

www.nature.com/...srep09589.html

fructose obesity fat diet nutrition activity physical activity

shared by Nathan Goodyear on 03 Aug 15 - No Cached
  • the fructose animals gained significantly more weight than the glucose animals
  • The average liver mass of mice in the fructose treatment group was 20% heavier than for mice in the glucose group
  • The fat pads of mice consuming the fructose diet were 69% heavier than the fat pads of animals consuming the glucose diet
  • ...12 more annotations...
  • there are many studies showing that consumption of fructose in comparison to other monosaccharides results in increased de novo lipogenesis, dyslipidemia, insulin resistance, BW6, 7 and, most recently, impaired cognitive function
  • in the present study, the intake of fructose by mice was more similar to that of typical human consumption in comparison to previous studies
  • prolonged consumption of diets containing fructose (11 weeks) increased BW and body fat deposition
  • studies in humans confirm that fructose, but not glucose (when provided as 25% of energy requirements), in the context of an energy-balanced diet increases de novo lipogenesis and visceral adiposity along with dyslipidemia, decreases insulin sensitivity10, 12 and decreases in fat oxidation
  • we hypothesize that fructose may reduce voluntary energy expenditure in terms of physical activity.
  • significant reduction (~20%) in physical activity in the fructose-fed animals in comparison to glucose
  • a recent study reported that ingestion of fructose (25% energy intake, 10 weeks) in human volunteers also resulted in reduced energy expenditure in relation to a diet with the same glucose dose
  • There is certainly evidence to suggest that, for example, exercise is able to prevent dyslipidemia in healthy subjects fed a weight-maintenance high-fructose diet (30%)54, which strongly suggests a protective role of physical activity in metabolic regulation.
  • the potential negative effects of fructose in brain and cognitive function have been investigated, with a series of studies showing cognitive deficits in spatial memory and learning in adolescent and adult animals following access to a high fructose diet
  • access to both fructose and sucrose, but not glucose, results in a 40% reduction in hippocampal neurogenesis
  • Collectively these studies seem to suggest that fructose consumption can have a considerable impact on hippocampal function and learning, which is in direct contrast with what we observed.
  • the impact of fructose is apparent only in BW, liver mass and body fat, but not in cognitive measures or rates of neurogenesis
  • Nathan Goodyear on 03 Aug 15
     
    animal study finds that fructose increased liver mass, abdominal fat and decreased physical activity when compared to glucose.  The study groups were iso caloric, but one group was fed 18% fructose and the other 18% glucose.
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
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  • 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 & Rosano 2011) or prostate cancer (Morgentaler & 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

Implications of free radicals and antioxidant levels in carcinoma of the breast: A neve... - 0 views

www.indianjcancer.com/article.asp

SOD superoxide disumutase catalase antioxidants antioxidant breast cancer cancer malondialdehyde MDA lipid peroxides oxidative stress inflammation

shared by Nathan Goodyear on 10 Nov 14 - No Cached
  • Experimental investigations as well as clinical and epidemiological findings have provided evidence supporting the role of reactive oxygen metabolites or free radicals such as singlet oxygen O 2 - , superoxide anions (O 2 ), hydrogen peroxide (H­2 O2 ) and hydroxyl radical in the etiology of cancer.
  • Certain aldehydes such as Malonyldialdehyde (MDA), the end product of lipid peroxidation arising from free radical degeneration of polyunsaturated fatty acids can cause cross linking in lipids, proteins and nucleic acids leading to cellular damage.
  • In this study, patients with cancer exhibited higher levels of MDA, both in tissues and serum (p<0.001) compared to the control group [Table 1]. In tissue, the MDA level in stage IV was significantly higher as compared to stage I indicating increased free radical activity with increasing severity of cancer
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  • From these observations, it can be concluded that MDA levels play an important role in assessing the outcome of cancer
  • SOD and CAT are considered primary antioxidant enzymes, since they are involved in direct elimination of reactive oxygen metabolites. [13-16] They also act as anti-carcinogens and inhibitors at initiation and promotion/transformation stage in carcinogenesis
  • In our study, SOD and CAT levels were found to be low in all cancer patients as compared to controls
  • Fridovich and Tayarani have demonstrated in their respective studies that the reduction in SOD activity increases the toxic effects of O2 - and this might lead to severe cellular damage.
  • Mehrotra et al. in their study also observed high levels of MDA and low levels of SOD and CAT in patients of cancer cervix which is in sync with our observations.
  • strong evidence regarding the definitive role of free radicals in breast malignancy.
  • Nathan Goodyear on 10 Nov 14
     
    This study finds a strong correlation between advancing breast cancer, decreased catalase and SOD with increasing MDA.  The authors of this study conclude this is a key factor in carcinogenesis and not a by-product of cancer.  This flies in the face of traditional medicines fear of antioxidant therapy in cancer.
Nathan Goodyear

Progesterone metabolites in breast cancer - 1 views

erc.endocrinology-journals.org/...717.full

progesterone metabolism tumor tumorigenesis cancer risk growth hormone hormones 5-beta-pregnanediol 5-alpha-pregnanediol 4-pregnenediol 5-alpha reductase

shared by Nathan Goodyear on 20 Feb 12 - No Cached
  • P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
  • these P metabolites function as independent pro-or anti-cancer autocrine/paracrine hormones that regulate cell proliferation, adhesion, apoptosis and cytoskeletal, and other cell status molecules via novel receptors located in the cell membrane and intrinsically linked to cell signaling pathways
  • only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
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  • P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
  • 5α-pregnane, 5β-pregnane, and 4-pregnene metabolites of P
  • These P-metabolizing enzymes included 5α-reductase, 5β-reductase, 3α-hydroxysteroid oxido-reductase (3α-HSO), 3β-HSO, 20α-HSO, 20β-HSO, 6α(β)-, 11β-, 17-, and 21-hydroxylase, and C17–20-lyase
  • Reduction of P to 5α-pregnanes is catalyzed by 5α-reductase and the direct 5α-reduced metabolite of P is 5α-pregnane-3,20-dione (5αP). The 5α-reductase reaction is irreversible
  • The two 4-pregnenes resulting from direct P conversion are 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αHP), catalyzed by the actions of 3α-HSO and 20α-HSO respectively
  • the P-metabolizing enzyme activities identified in human breast tissues and cell lines were: 5α-reductase, 3α-HSO, 3β-HSO, 20α-HSO, and 6α-hydroxylase
  • In normal breast tissue, conversion to 4-pregnenes greatly exceeded the conversion to 5α-pregnanes, whereas in tumorous tissue, conversion to 5α-pregnanes greatly exceeded that to 4-pregnenes
  • The results indicated that P 5α-reductase activity is significantly higher, whereas P 3α-HSO and 20α-HSO activities are significantly lower in tumor than in normal tissues
  • he results showed that production of 5α-pregnanes was higher and that of 4-pregnenes was lower in tumorigenic (e.g. MCF-7) than in nontumorigenic (e.g. MCF-10A) cells (Fig. 3c⇑), while differences in ER/P status did not appear to play a role
  • The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
  • altered direction in P metabolism, and hence in metabolite ratios, was due to significantly elevated 5α-reductase and depressed 3α- and 20α-HSO activities in breast tumor tissues and tumorigenic cells. It appeared, therefore, that changes in P-metabolizing enzyme activities might be related to the shift toward mammary cell tumorigenicity and neoplasia
  • In vivo, changes in enzyme activity can result from changes in levels of the enzyme due to changes in expression of the mRNA coding for the enzyme, or from changes in the milieu in which the enzyme operates (such as temperature and pH, and concentrations of cofactors, substrates, products, competitors, ions, phospholipids, and other molecules)
  • Overall, the enzyme activity and expression studies strongly suggest that 5α-reductase stimulation and 3α- and 20α-HSO suppression are associated with the transition from normalcy to cancer of the breast
  • The level of expression of 5α-reductase is up-regulated by estradiol and P in the uterus (Minjarez et al. 2001) and by 5α-dihydrotestosterone (DHT) in the prostate
  • 3αHP inhibited whereas 5αP-stimulated proliferation
  • Stimulation in cell numbers was also observed when cells were treated with other 5α-pregnanes, such as 5α-pregnan-3α-ol-20-one, 5α-pregnan-20α-ol-3-one, and 5α-pregnane-3α,20α-diol, whereas other 4-pregnenes such as 20α-HP and 4-pregnene-3α,20α-diol resulted in suppression of cell proliferation
  • Stimulation of cell proliferation with 5αP and inhibition with 3αHP were also observed in all other breast cell lines examined, whether ER/P-negative (MCF-10A, MDA-MB-231) or ER/P-positive (T47D, ZR-75-1) and whether requiring estrogen for tumorigenicity (MCF-7, T47D) or not (MDA-MB-231), or whether they are nontumorigenic (
  • αHP resulted in significant increases in apoptosis and decreases in mitosis, leading to significant decreases in total cell numbers. In contrast, treatment with 5αP resulted in decreases in apoptosis and increases in mitosis.
  • The opposing actions of 5αP and 3αHP on both cell anchorage and proliferation strengthen the hypothesis that the direction of P metabolism in vivo toward higher 5α-pregnane and lower 4-pregnene concentrations could promote breast neoplasia and lead to malignancy.
  • he effects on proliferation and adhesion were not due to P, but due to the 5α-reduced metabolites
  • The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
  • separate high-specificity, high-affinity, low- capacity receptors for 5αP and 3αHP that are distinct from each other and from the well-studied nuclear/cytosolic P, estrogen, and androgen and corticosteroid receptors
  • The studies thus provided the first demonstration of the existence of specific P metabolite receptors
  • the receptor results suggest that the putative tumorigenic actions of 5αP may be significantly augmented by the estradiol-induced increases in 5αP binding and decreases in 3αHP binding.
  • Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
  • In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
  • The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
  • current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
  • both testosterone and DHT inhibit cell growth more or less to the same extent
  • Note that 5α-reductase reaction is not reversible
  • Nathan Goodyear on 20 Feb 12
     
    Fantastic read on the effects of progesterone metabolism on tumor and cancer growth.  Tumorigenesis is not just about the hormone, hormone balance, but about the metabolism of hormones.  This is why premarin is so carcinogenic: it is primarily metabolized by the 4-OH estrone pathway.
Nathan Goodyear

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet - NEJM - 0 views

www.nejm.org/...NEJMoa0708681

obesity overweight low carb diet low carbohydrate diet mediterranean diet weight weight loss DIRECT study

shared by Nathan Goodyear on 13 Jun 12 - No Cached
  • Nathan Goodyear on 13 Jun 12
     
    Nice study, the DIRECT study, found a better weight loss and longer maintenance of weight loss in low carbohydrate diet compared to low fat diet and mediterranean diet.  
Nathan Goodyear

Total Testosterone Levels and the Effect of Sildenafil on Type 2 Diabetics with Erectil... - 0 views

www.ncbi.nlm.nih.gov/...PMC3910416

low T Testosterone Diabetes sildenafil erectile dysfunction ED

shared by Nathan Goodyear on 17 Feb 14 - No Cached
  • Nathan Goodyear on 17 Feb 14
     
    Interesting study. In this study group, 36% of type II diabetes with ED had low Testosterone.  This fits with the estimated 40% of those with Diabetes have low T. What is really interesting about this study is that the degree of improvement with ED by Sildenfafil was dependent on the Testosterone level in the low T group.  Meanining that Testosterone therapy in these men would probably be more of a therapy directed at the cause and not Sildenafil.  Of course, the Testosterone therapy would benefit glucose regulation as well documented in the literature.
Nathan Goodyear

Effect of Testosterone Treatment on Glucose Metabolism in Men With Type 2 Diabetes: A R... - 0 views

care.diabetesjournals.org/...2098.abstract

Testosterone treatment low subcutaneous fat visceral fat T glucose insulin resistance metabolism obesity diabetes men male hormone hormones

shared by Nathan Goodyear on 29 Jul 14 - No Cached
  • Nathan Goodyear on 29 Jul 14
     
    Only the abstract available in this publication.  Good study design.  No improvement in insulin resistance, glycemic control or visceral adiposity in obese men with type II diabetes.  The levels of inclusion were TT < 346, which would not meet the criteria put forth by other studies.  This study appeared to look at border line "low T" men with obesity and type II diabetes and found no direct glycemic control improvement.  An increase in lean muscle mass and decrease in subcutaneous fat was found.
Nathan Goodyear

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Ath... - 0 views

www.ncbi.nlm.nih.gov/...28041602

vitamin d hormones Testosterone estradiol SHBG

shared by Nathan Goodyear on 09 Jan 17 - No Cached
  • Nathan Goodyear on 09 Jan 17
     
    cross sectional study finds low vitamin D associated with a decrease in SHBG and an increase in free Testosterone;  a decrease in estradiol and an increase in DHEA was seen in women.  No association with total Testosterone was found.  There are studies that show a direct decrease in testicular Testosterone production in men with low vitamin D and decrease in AR function.
Nathan Goodyear

Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Andro... - 0 views

press.endocrine.org/...jcem.84.10.6082

obesity leptin low T low Testosterone Testosterone low T leydig cells LH leutenizing hormone men male hormones hormone

shared by Nathan Goodyear on 04 Sep 14 - No Cached
  • in male obesity basal and LH-stimulated androgen levels are reduced and inversely correlated with circulating leptin
  • functional leptin receptors are present in rodent Leydig cells
  • it is conceivable that in males high leptin concentrations may have a direct inhibitory effect(s) on Leydig cell function.
  • ...18 more annotations...
  • insulin is an important inhibitor of the synthesis of SHBG
  • no correlation between leptin and SHBG levels
  • SHBG reduction in obesity is a minor determinant of lowered androgen levels
  • SHBG can explain only up to 3% of the correlation
  • testicular T de novo production is impaired in obese men and that leptin seems to be the best hormonal predictor of this blunted response to LH stimulation
  • The low basal 17-OH-P levels found in massively obese men are consistent with a global impairment of Leydig cell steroidogenic function in this group of subjects.
  • These findings indicate that obese men have a FM-related defect in the enzymatic conversion of 17-OH-P to T, which is revealed by hCG stimulation.
  • Other studies have investigated the adrenal function in male obesity and have shown that basal cortisol and 17-OH-progesterone levels tend to decrease with the increase in the degree of obesity
  • High E2 can inhibit the expression and activity of the 17,20-lyase and may be responsible for this steroidogenic lesion
  • However, stimulated E2 levels were not higher in the obese than in controls, excluding the fact that the lower androgen response was due to an increased aromatization of T to E2 and that estrogens have a major role in the observed defect of 17,20-lyase activity in obese men.
  • the percentage increase in the 17-OH-progesterone to T molar ratio paralleled the increase in leptin levels of obese men
  • Multiple regression analysis indicated that the best hormonal predictor of the obesity-related reduction in T and FT basal levels and androgen changes after hCG stimulation was serum leptin concentration
  • insulin has no negative influences on androgen production in obese men
  • insulin is known to have stimulatory actions on T production that have been demonstrated in obese and normal weight men (57) and in Leydig cells in culture
  • the negative correlation between insulin and basal T can be partly explained by the inhibitory action of insulin on SHBG production
  • hypogonadal men have higher circulating leptin levels compared with hypogonadal patients under effective androgen substitution therapy
  • The impaired androgen response to LH stimulus was due to a defect in the enzymatic conversion of 17-OH-progesterone to T, which was disclosed by a leptin-related increase in 17-OH-progesterone to T ratio
  • Estrogens, which are inhibitory modulators of LH pulsatility and bioactivity
  • Nathan Goodyear on 04 Sep 14
     
    Leptin appears to be a good marker of low Testosterone.  This study proposes that the mechanism of action is potentially 2 fold: first, a decrease in LH release by leptin (kisspeptin?) and 2nd, a directed decrease in Testosterone production by the leydig cells in the testes.
Nathan Goodyear

Androgen Therapy Improves Insulin Sensitivity and Decreases Leptin Level in Healthy Adu... - 0 views

care.diabetesjournals.org/...2149.extract

low T low Testosterone leptin obesity Testosterone therapy insulin resistance

shared by Nathan Goodyear on 22 Oct 14 - No Cached
  • Nathan Goodyear on 22 Oct 14
     
    Three month study of men with low T, found that Testosterone therapy improved insulin sensitivity and reduced leptin levels.  The group of men here were described as "healthy, non-obese men".   Remember, low T is a biomarker of poor health in men, so the authors statement about the study group is inaccurate.  This also points to a relatively quick metabolic effect by Testosterone and a direct effect on insulin receptor effect and adipocyte leptin release.
Nathan Goodyear

The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A... - 0 views

www.ncbi.nlm.nih.gov/...PMC9925039

COVID-19 SARS-CoV-2 COVID WBC ascorbic acid vitamin C

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • vitamins A, B, C, E, B6, B12, folate, zinc, iron, copper, and selenium
  • White blood cells, including neutrophils and monocytes, accumulate concentrations of vitamin C up to 100 times greater than that of plasma
  • Vitamin C is a crucial component of both the innate (nonspecific) and adaptive (specific) portions of the immune system
  • ...52 more annotations...
  • play a role during the initial chemotactic response of neutrophils shortly after infection
  • following vitamin C supplementation, a 20% increase in neutrophil chemotactic activity was observed
  • also contributes to the phagocytosis and killing of microbes by neutrophils
  • low levels of vitamin C occurring in high-stress situations
  • maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
  • Vitamin C has been shown to directly affect the number of Igs released from B cells
  • vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
  • effects of high-dose vitamin C on cytokine levels in cancer patients, finding decreased amounts of the cytokines Interleukin-1 alpha (IL-1 alpha), IL-2, IL-8, and tumor necrosis factor-alpha (TNF-alpha) after high-dose vitamin C infusion
  • when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
  • vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
  • vitamin C also acts as an important antioxidant to the cells of the immune system.
  • human leukocytes, neutrophils, in particular, possess the ability to transport the oxidized form of vitamin C across its membrane to use as a defense mechanism against ROS produced during an immune response
  • Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
  • vitamin C can decrease the activation of NF-kB
  • can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic&nbsp;
  • subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
  • subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
  • hydroxylating proline and lysine
  • mature and stabilize the tissue of a healing wound
  • healing
  • oral surgery
  • improved soft tissue regeneration
  • vitamin C increases the mRNA levels of type I and type III collagen in the human dermis
  • Studies have demonstrated that those with low levels of vitamin C are at a significantly higher risk of respiratory infection compared to those with normal levels
  • viral cold duration was reduced by about 8% in adults and 13.5% in children using prophylactic daily doses of 200 mg of oral vitamin C
  • prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
  • combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
  • high-dose oral supplementation of vitamin C managed to prevent or reduce symptoms if taken before or just after the onset of cold- or flu-like symptoms
  • improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
  • 8 g doses of oral vitamin C
  • there is a negative correlation between age and serum levels of vitamin C
  • Patients with COVID-19 will likely also experience depletion in serum levels of vitamin C as a direct result of the upregulation of the immune system to combat the infection
  • Colunga et al. suggested that oral vitamin C can be combined with oral Quercetin, an antiviral flavonoid, to improve Quercetin’s ability to block viral membrane fusion of SARS-CoV-2
  • high doses of 1-2 g/day of oral vitamin C could prevent other upper respiratory infections
  • It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Flawed statement. What is normal? Vitamin D. Many variables effect levels and dose, including the two compartment kinetics and absorption.
  • Hiedra et al. were able to show decreases in inflammatory biomarkers, such as D-dimer and ferritin
  • some evidence to support that prophylactic use of vitamin C helps reduce the severity of respiratory infection symptoms once a subject has already been infected
  • oral vitamin C in combination with zinc provided the largest amount of antibody titers 42 days
  • linear relationship between days of vitamin C therapy and survival duration
  • other studies were unable to find any definitive improvement concerning therapy with vitamin C
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Either these studies are designed to fail or the authors are lacking some basic understanding of pharmacokinetics and pharmacodynamics with vitamin C.
  • Fowler et al. aimed to see if a high-dose vitamin C infusion would benefit patients affected by ARDS, but they were unable to conclude that vitamin C infusion, compared to a placebo, could decrease vascular inflammation and damage in ARDS
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      At what dose, duration, frequency???
  • in a sample of 67 COVID-19-positive ICU patients, 82% of them displayed plasma vitamin C levels below 0.4 mg/dL
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      They are kind of make the point from my earlier note.
  • continuous vitamin C infusion at a rate of 60 mg/kg/day for four days decreased the need for mechanical ventilation and vasopressor use but had no significant effect on overall mortality
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Again, designed to fail or ignorance designed the study which failed
  • Carr et al. suggested that high-dose IV vitamin C is most effective when treating sepsis as septic patients receiving the normal daily recommendations through diet still showed decreased vitamin C levels
  • High-dose IV vitamin C treatment has also been shown by Kakodkar et al. to decrease syndecan-1, an endothelial glycocalyx that contributes to mortality in septic patients
  • combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA&nbsp;scores and none of the patients treated developed organ failure
  • combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA&nbsp;scores and none of the patients treated developed organ failure
  • reduced overall mortality
  • reduced overall mortality
  • propose the use for high-dose vitamin C to aid in the treatment of septic shock-induced hypotension
  • treatment of severe sepsis using a high dose (up to 200 mg/kg/day) of IV vitamin C was explored in phase I, a double-blind, randomized, placebo-controlled trial by Fowler et al. [75]. Their findings included a reduction in SOFA scores and decreased vascular injury compared to a placebo control group, all while showing minimal adverse side effects
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      High dose here is laughable. Again, duration and frequency also.
  • Maintaining a daily intake of 75 and 100 mg for men and women, respectively, as recommended by the U.S. Institute of Medicine
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      This recommendation is FRANK IGNORANCE
Nathan Goodyear

Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study - 0 views

www.direct-ms.org/...s%20and%20ketagenic%20diet.pdf

hyperketogenic diet parkinson's disease PD parkinson's ketones

shared by Nathan Goodyear on 25 Jun 12 - No Cached
  • Nathan Goodyear on 25 Jun 12
     
    Hyperketogenic diet shown to provide many therapeutic benefits in other disease states. This study, though very small, showed that symptoms did improve with a hyperketonemic diet. This was a feasibility study.
Nathan Goodyear

Review of health risks of low testosterone and testosterone administration - 0 views

www.ncbi.nlm.nih.gov/...PMC4391003

low Testosterone low T Testosterone men male hormone hormones health

shared by Nathan Goodyear on 28 Apr 15 - No Cached
  • Hypogonadism may be defined either as serum concentration of T (either total T, bioavailable T or free T) or as low T plus symptoms of hypogonadism
  • The Baltimore Longitudinal Study on Aging reported the incidence of total serum T &lt; 325 ng/dL to be 20% for men in their 60s, 30% for men in their 70s and 50% for men over 80
  • The Massachusetts Aging Male Study reported that 12.3% of men aged 40 to 70 had a total serum T of &lt; 200 ng/dL with 3 or more symptoms of hypogonadism
  • ...19 more annotations...
  • The Boston Area Community Health Study reported that 5.6% of men aged 30 to 70 were hypogonadal, as defined by total serum T &lt; 300 ng/dL; or, free serum T &lt; 5 ng/dL plus 3 or more symptoms of hypogonadism
  • In a health screening project among 819 men in Taiwan, the prevalence of hypogonadism (total serum T &lt; 300 ng/dL) ranged from 16.5% for men in their 40s, 23.0% for men in their 50s, 28.9% for men in their 60s, and 37.2% for men older than 70 years of age
  • The prevalence of hypogonadism among men in Taiwan is higher than the prevalence reported in the Massachusetts Male Aging Study
  • CAG repeat sequence, within the androgen receptor (AR). Rajender et al[12] reviewed over 30 studies on the AR trinucleotide repeat and infertility
  • suggestion that CAG repeat length may determine androgen responsiveness, this issue is not clearly settled
  • reported prevalence of low T in older men range from 5.6% to 50%
  • Those in the hypogonadal group (n = 4269) had direct health care costs, that exceeded the eugonadal group (n = 4269) by an average of $7100 over the course of the observation window
  • higher economic burden and presence of co-morbidities for hypogonadism
  • minor to moderate improvements in lean mass and muscle strength
  • increased bone mineral density
  • modest enhancement in sexual function
  • reduced adiposity
  • lessening of depressive symptoms
  • Meta-analyses of clinical TRT trials as of 2010 have identified three major adverse events resulting from TRT: (1) polycythemia; (2) an increase in prostate-related events; and (3) and a slight reduction in serum high-density lipoprotein (HDL) cholesterol
  • polycythemia (&gt; 3.5-fold increase in risk
  • TRT produced a 40% prostate enlargement in older hypogonadal male Veterans over 12 mo
  • no published analysis has reported measurable increases in prostate cancer risk or Gleason score in men undergoing TRT, or in hypogonadal men with a history of prostate cancer undergoing TRT
  • the prostate which highly expresses the type II 5α-reductase enzyme. Inhibition of this enzyme via finasteride (a type II 5α-reductase inhibitor) or dutasteride (a dual type I and II 5α-reductase inhibitor) reduces circulating DHT 50%-75% and &gt; 90%, respectively[47], and reduces prostate mass[48] and prostate cancer risk
  • Normally estradiol partially regulates testosterone levels, at the hypothalamus, blunting LH and FSH release from the pituitary. As a selective estrogen receptor modulator, CC interrupts this pathway, and consequently there is a greater stimulation for the production of testosterone in Leydig cells
    • Nathan Goodyear
      Nathan Goodyear on 28 Apr 15
       
      this would only apply if E1 and/or E2 levels were elevated, which the authors make no mention of.
  • Nathan Goodyear on 28 Apr 15
     
    to be read
Nathan Goodyear

Exercise-induced right ventricular dysfunction and structural remodelling in endurance ... - 0 views

eurheartj.oxfordjournals.org/...998

endurance athletes training heart health injury

shared by Nathan Goodyear on 09 Jan 15 - No Cached
  • In a cohort of well-trained athletes, we demonstrated that intense endurance exercise causes an acute reduction in RV function that increases with race duration and correlates with increases in biomarkers of myocardial injury
  • no relationship between LV function and biomarker levels
  • focal gadolinium enhancement and increased RV remodelling were more prevalent in those athletes with a longer history of competitive sport, suggesting that repetitive ultra-endurance exercise may lead to more extensive RV change and possible myocardial fibrosis
  • ...22 more annotations...
  • he cardiac impact of both acute and cumulative exercise is greatest on the RV.
  • Greater reductions in RV function occurred in those athletes competing for a longer duration, suggesting that the heart has a finite capacity to maintain the increased work demands of exercise
  • cardiac injury is greatest in the least trained
  • Previous investigators have documented reductions in RV function in less trained subjects over the marathon distance
  • We enrolled elite and subelite athletes and found a significant association between fitness (VO2max) and the reduction in post-race RVEF
  • Even after many years of detraining, cardiac dilation may not completely regress in elite athletes
  • The focus on well-trained athletes may be of particular relevance, given that they perform exercise of highest intensity and duration most frequently, and, thus, may be at a greater risk of cumulative injury.
  • The lack of correlation between increases in troponin and changes in LV function seen in this study has been previously interpreted as evidence that post-exercise elevations in cardiac biomarkers are benign.
  • a significant correlation between changes in RVEF and post-race biomarker levels and this relationship was even stronger in the athletes who completed the race of longest duration, the ultra-triathlon
  • The correlations with RVEF, but not LVEF, provide further evidence of the differential effects of intense exercise on RV and LV function
  • BNP release during intense exercise is associated with greater relative increases in RV systolic pressures, but not LV pressures
  • BNP may provide a measure of both acute RV load and the resultant fatigue which occurs when this load is sustained
  • It has been demonstrated that ventricular load increases with exercise intensity and is greater for the RV than the LV,29 thus potentially explaining why the RV is more susceptible to fatigue after prolonged exercise.
  • This study demonstrates, for the first time, an association between endurance exercise of increasing duration and structural, functional, and biochemical markers of cardiac dysfunction in highly trained athletes
  • Functional abnormalities were confined to the RV and were largely reversible 1 week following the event
  • there remained a significant minority of athletes in whom there was evidence of myocardial fibrosis in the interventricular septum
  • RV abnormalities may be acquired through cumulative bouts of intense exercise and provides direction for prospective investigations aimed at elucidating whether extreme exercise may promote arrhythmias in some athletes.
  • the acute injury and chronic remodelling of the myocardium both disproportionately affect the RV and it remains possible that the two are linked.
  • focal DGE was confined to the interventricular septum and commonly at the site of RV attachment
  • emerging evidence that intense endurance exercise may be associated with an excess in arrhythmic disorders, the mechanisms for which remain unexplained
  • RVEF (and not LVEF) was reduced in athletes with complex ventricular arrhythmias when compared with healthy athletes and non-athletes without arrhythmias
  • it is premature to conclude that these changes may represent a proarrhythmic substrate
  • Nathan Goodyear on 09 Jan 15
     
    Study finds endurance racing results in reduce Right ventricle ejection fraction even in elite athletes.  This post-race RVEF reduction is associated with VO2max.
Nathan Goodyear

The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture - 0 views

www.ncbi.nlm.nih.gov/...PMC2921747

flouroquinolones ciprofloxacin levoquin tendinitis tendinopathy Tendon rupture

shared by Nathan Goodyear on 02 Aug 17 - No Cached
  • Achilles tendinitis or rupture is among the most serious side effects associated with FQ use
  • The large body of data provided by clinical reports, histopathological examination, and experimental studies provides cogent evidence supporting a direct link between FQ use and tendonitis/tendon rupture
  • Risk factors associated with FQ-induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders
  • ...17 more annotations...
  • The average age of FQ-induced tendinopathy is 64 years, with a male-to-female ratio of 2:1, and a 27-percent incidence of bilateral involvement
  • Although more than 95 percent of cases of tendinitis/rupture secondary to FQ involve the Achilles tendon, other reported sites of tendon involvement include the quadriceps, peroneus brevis, and rotator cuff
  • FQs demonstrate a 3.8-fold greater risk for development of Achilles tendinitis/rupture
  • a large population-based case control analysis, patients treated with FQs exhibited a substantially increased risk of developing tendon disorders overall (1.7-fold), tendon rupture (1.3-fold), and ATR (4.1-fold)
  • patients taking FQs with concurrent exposure to corticosteroids were found to experience a compounding effect on the risk of tendon rupture, specifically a 46-fold greater predisposition
  • Some authors have recommended that patients with a history of Achilles tendinitis and advanced age should not be prescribed FQ antibiotics
  • Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months
  • The mean latency period between the start of FQ treatment and occurrence of tendinopathy has been reported to be a few hours to months, with a median onset of 6 days
  • The exact pathophysiology of FQ-induced tendinopathy remains elusive
  • it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue
  • It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma)
  • histopathological findings are similar to those observed in overuse conditions in athletes
  • Treatment with a FQ should be discontinued and physical therapy initiated
  • treatment should include rest and decreasing the physical load on the tendon.
  • Approximately 85 percent of patients present in less than one month
  • Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop
  • FQs should be used cautiously in patients with risk factors associated with tendinitis, such as advanced age, history of tendon rupture, corticosteroid use, and/or acute or chronic renal dysfunction
  • Nathan Goodyear on 02 Aug 17
     
    Great review of the link between flouroquinolones and Tendinitis and Tendon rupture.  Yes, there is a direct link.
Nathan Goodyear

Testosterone and metabolic syndrome Cunningham GR - Asian J Androl - 0 views

www.ajandrology.com/article.asp

Testosterone metabolic syndrome MetS TT total Testosterone SHBG men male hormone hormones Estradiol insulin resistance

shared by Nathan Goodyear on 02 Mar 15 - No Cached
  • The relationship of low testosterone to MetS often is considered to be bidirectional; however, the relationships probably are not direct
  • Many of the components of the MetS are recognized risk factors for the development of cardiovascular disease (CVD)
  • Multiple cross-sectional studies have found low TT and low sex hormone binding globulin (SHBG) levels in Caucasian and African-American men with the MetS, irrespective of age
  • ...20 more annotations...
  • Low TT and SHBG levels also are prevalent in Chinese [7],[8] and Korean [9] men with the MetS
  • Normally 40%-50% of TT is bound to SHBG, so reducing SHBG levels will decrease TT.
  • Hyperinsulinism suppresses SHBG synthesis and secretion by the liver
  • significant increase in SHBG levels occurred after acutely lowering insulin levels in obese men
  • Estradiol levels are increased in men with the MetS, and they are positively correlated with the number of abnormal components of the MetS.
  • Although it is known that estrogen will increase SHBG levels, apparently the hyperinsulinism associated with obesity has a greater effect on SHBG levels
  • Estradiol also can inhibit luteinizing hormone (LH) secretion
  • Inflammatory cytokines are thought to have a direct effect on the pituitary to reduce LH secretion [15] and also a direct effect on Leydig cell secretion of testosterone
  • Low TT Levels have been shown to predict development of the MetS in men with normal BMI
  • Men in the lowest quartiles of serum TT, calculated free testosterone (cFT) and SHBG at baseline had the highest odds ratios for developing the MetS or DM during the 11 years follow-up
  • More recently, investigators conducting population-based studies have reported that only SHBG is associated with future development of the MetS
  • Additional evidence that low TT increases the risk of MetS comes from androgen deprivation treatment of prostate cancer
  • Low TT and low bioavailable testosterone (bT) were each significantly associated with elevated 20 years risk of CVD mortality in an older population in which cause-specific mortality was age, adiposity, and lifestyle-adjusted.
  • combination of low bT and ATP III-defined MetS is associated with increased cardiovascular mortality in men aged 40 years and above
  • in elderly men, testosterone may weakly protect against CVD. Alternatively, low TT may indicate poor general health
  • Muraleedharan and Jones [27] concluded that there is convincing evidence that low T is a biomarker for disease severity and mortality.
  • The evidence that TRT improves insulin sensitivity and glucose control is conflicted
  • It is widely recognized that testosterone treatment can reduce fat mass and increase lean body mass; however, until recently most reports have not been associated with much weight loss
  • Changes in body composition and weight loss are considered potential mechanisms by which testosterone treatment improves insulin sensitivity and glucose control in patients with diabetes. Effects on inflammatory cytokines [38] and changes in oxidative metabolism [39] also have been reported to improve glucose metabolism.
  • Testosterone replacement therapy has been reported to improve some or all of the components of the MetS.
  • Nathan Goodyear on 02 Mar 15
     
    To be read article on Testosterone and Metabolic Syndrome.
Nathan Goodyear

Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study - 0 views

www.eje.org/...687.full.pdf

low T testosterone CVD cardiovascular disease men CAD mortality

shared by Nathan Goodyear on 12 Nov 12 - No Cached
  • Nathan Goodyear on 12 Nov 12
     
    Good article. Discusses the association between low Testosterone and cardiovascular risk in men. The conclude that no direct cause effect relationship has been provided, but a clear association is seen. Numerous studies have shown this association.
Nathan Goodyear

The 20-Year Public Health Impact and Direct Cost of Testosterone Deficiency in U.S. Men... - 0 views

onlinelibrary.wiley.com/...48D8B444401449DB28B6867.d03t01

low T low testosterone cost costs low testosterone deficiency

shared by Nathan Goodyear on 16 Feb 13 - No Cached
  • Nathan Goodyear on 16 Feb 13
     
    This study assumes a 13% low T prevalence.  Probably too low.  This will only grow.  Low T contributes to many disease states in men. This study showed a cost of 190-525$ billion in cost from these disease states over a 20 year time period.
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