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

  • 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.
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    To be read article on Testosterone and Metabolic Syndrome.
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Unintended effects of statins from observational studies in the general population: sys... - 0 views

  • A markedly increased risk of myopathy was observed
  • One cohort study (Women’s Health Initiative) of higher quality and larger sample size found stronger evidence of an increased risk of self-reported T2DM (OR=1.47; 95% CI 1.32 to 1.64) for the groups of women who reported statin use at baseline and three years later
  • Hippisley-Cox et al. found an increased risk of liver enzyme changes
  • ...5 more annotations...
  • weak evidence of an increased risk of type 2 diabetes mellitus (T2DM) was observed
  • Smeeth et al. found an increased risk of incident liver disease in the first year after the index date
  • The cumulative incidence of T2DM after three years of statin treatment was 6.25%, corresponding to an excess risk of 2.25%
  • We found no increased risk of peripheral neuropathy, depression, common eye diseases, renal disorders or arthritis associated with taking statins. Studies of higher quality did not show previously reported protective effects of statins on fractures, venous thrombo-embolism or pneumonia
  • There was evidence of an increase in myopathy, raised liver enzymes and diabetes.
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    Statin use associated with increased myopathy, liver dysfunction, and type II Diabetes.  The authors conclude that the absolute risk is very low, yet OR was 1.47 for type II Diabetes (translated 47% increased odds of developing Diabetes as a result of statins) and OR of 2.63 in risk of myopathy (translated 163% increased odds of developing myopathy as a result of statins).  Seems the authors "low risk" statement is just applies to those without symptoms/side effects.  Physicians need to do a better job of understanding risks and customizing therapies.
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Coleus Forskolii Manufacturers -commonly known as Indian Coleus - 0 views

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    Star Hi Herbs Pvt Ltd. With 10 years dynamic experience have developed Coleus Forskolii Manufacturers inconsistent quality products as per gmp and cgmp Guidelines. Our company is a product-development and marketing company. We are manufacturers of standardized herbal extracts of natural products, neutraceuticals, phytochemicals, oleoresins cosmetics etc.
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Effects of thyroid hormones on hu... [J Steroid Biochem Mol Biol. 2008] - PubMed - NCBI - 0 views

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    T3 may promote cancer cell proliferation says study.  Triiodothyronine was found to enhance the MCF-7 and T47-D breast cancer cell lines.  The conclusion of the abstract discusses a role of T3 in breast cancer development and progression.  This likely has more to do with progression than development through increased metabolism of the cell lines.
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Substantial contribution of extrinsic risk factors to cancer development - 0 views

  • Here we provide evidence that intrinsic risk factors contribute only modestly (<10~30%) to cancer development
  • we conclude that cancer risk is heavily influenced by extrinsic factors. These results carry immense consequences for strategizing cancer prevention
  • cancers are proposed to originate from the malignant transformation of normal tissue progenitor and stem cells
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  • “Intrinsic processes” include those that result in mutations due to random errors in DNA replication whereas “extrinsic factors” are environmental factors that affect mutagenesis rates (such as UV radiation, ionizing radiation, and carcinogens
  • intrinsic factors do not play a major causal role.
  • intrinsic cancer risk should be determined by the cancer incidence for those cancers with the least risk in the entire group controlling for total stem cell divisions
  • if one or more cancers would feature a much higher cancer incidence, for example, lung cancer among smokers vs. non-smokers, then this most likely reflects additional (and probably extrinsic) risk factors (smoking in this case)
  • Particularly, for breast and prostate cancers, it has long been observed that large international geographical variations exist in their incidences (5-fold for breast cancer, 25-fold for prostate cancer)14, and immigrants moving from countries with lower cancer incidence to countries with higher cancer rates soon acquire the higher risk of their new country
  • Colorectal cancer is another high-incidence cancer that is widely considered to be an environmental disease17, with an estimated 75% or more colorectal cancer risk attributable to diet
  • melanoma, its risk ascribed to sun exposure is around 65–86%
  • non-melanoma basal and squamous skin cancers, ~90% is attributable to UV
  • 75% of esophageal cancer, or head and neck cancer are caused by tobacco and alcohol
  • HPV may cause ~90% cases in cervical cancer23, ~90% cases in anal cancer24, and ~70% in oropharyngeal cancer
  • HBV and HCV may account for ~80% cases of hepatocellular carcinoma
  • H pylori may be responsible for 65–80% of gastric cancer
  • While a few cancers have relatively large proportions of intrinsic mutations (>50%), the majority of cancers have large proportions of extrinsic mutations, for example, ~100% for Myeloma, Lung and Thyroid cancers and ~80–90% for Bladder, Colorectal and Uterine cancers, indicating substantial contributions of carcinogen exposures in the development of most cancers
  • onsistent estimate of contribution of extrinsic factors of >70–90% in most common cancer types. This concordance lends significant credibility to the overall conclusion on the role of extrinsic factors in cancer development
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    Really great read.  Cancer is a majority lifestyle disease.
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NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond - PMC - 0 views

  • Pneumonia is a typical symptom of COVID-19 infection, while acute respiratory distress syndrome (ARDS) and multiple organ failure are common in severe COVID-19 patients
  • NETs are important for preventing pathogen invasion, their excessive formation can result in a slew of negative consequences, such as autoimmune inflammation and tissue damage
  • SARS-CoV-2 infection has also been linked to increased neutrophil-to-lymphocyte ratios, which is associated with disease severity and clinical prognosis
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  • NETosis is a special form of programmed cell death in neutrophils, which is characterized by the extrusion of DNA, histones, and antimicrobial proteins in a web-like structure known as neutrophil extracellular traps (NETs)
    • Nathan Goodyear
       
      Definition
  • increased generation of reactive oxygen species (ROS) is a crucial intracellular process that causes NETosis
  • Another indirect route of SARS-CoV-2-induced NET production is platelet activation
  • When NETs are activated in the circulation, they can also induce hypercoagulability and thrombosis
  • In COVID-19, major NET protein cargos of NETs (i.e., NE, MPO, and histones) are significantly elevated.
  • SARS-CoV-2 can also infect host cells through noncanonical receptors such as C-type lectin receptors
  • Immunopathological manifestations, including cytokine storms and impaired adaptive immunity, are the primary drivers behind COVID-19, with neutrophil infiltration being suggested as a significant cause
  • NETosis and NETs are increasingly recognized as causes of vascular injury
  • SARS-CoV-2 and its components (e.g., spike proteins and viral RNA) attach to platelets and increase their activation and aggregation in COVID-19, resulting in vascular injury and thrombosis, both of which are linked to NET formation
    • Nathan Goodyear
       
      Connects SARS-CoV-2 to TLR on Platelets to NETosis to metastasis.
  • NET formation may be caused by activated platelets rather than SARS-CoV-2 itself
  • NETosis, leading to aberrant immunity such as cytokine storms, autoimmune disorders, and immunosuppression.
  • early bacterial coinfections were more prevalent in COVID-19 patients than those infected with other viruses
  • NETosis and NETs may also have a role in the development of post COVID-19 syndromes, including lung fibrosis, neurological disorders, tumor growth, and worsening of concomitant disease
    • Nathan Goodyear
       
      NETosis-> tumor growth
  • NETs and other by-products of NETosis have been shown to act as direct inflammation amplifiers. Hyperinflammation
  • “cytokine storm”
  • SARS-CoV-2 drives NETosis and NET formation to allow for the release of free DNA and by-products (e.g., elastases and histones). This may trigger surrounding macrophages and endothelial cells to secrete excessive proinflammatory cytokines and chemokines, which, in turn, enhance NET formation and form a positive feedback of cytokine storms in COVID-19
    • Nathan Goodyear
       
      Cycle of hyperinflammation
  • NET release enables self-antigen exposure and autoantibody production, thereby increasing the autoinflammatory response
  • patients with COVID-19 who have higher anti-NET antibodies are more likely to be detected with positive autoantibodies [e.g., antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA)]
  • COVID-19 NETs may act as potential inducers for autoimmune responses
  • have weakened adaptive immunity as well as a high level of inflammation
    • Nathan Goodyear
       
      Immunomodulation
  • tumor-associated NETosis and NETs promote an immunosuppressive environment in which anti-tumor immunity is compromised
  • NETs have also been shown to enhance macrophage pyroptosis in sepsis
  • facilitating an immunosuppressive microenvironment
  • persistent immunosuppression may result in bacterial co-infection or secondary infection
  • can enhance this process by interacting with neutrophils through toll-like receptor 4 (TLR4), platelet factor 4 (PF4), and extracellular vesicle-dependent processes
  • NET-induced immunosuppression in COVID-19 in the context of co-existing bacterial infection
  • Following initial onset of COVID-19, an estimated 50% or more of COVID-19 survivors may develop multi-organ problems (e.g., pulmonary dysfunction and neurologic impairment) or have worsening concomitant chronic illness
  • NETs in the bronchoalveolar lavage fluid of severe COVID-19 patients cause EMT in lung epithelial cells
  • decreased E-cadherin (an epithelial marker) expression
    • Nathan Goodyear
       
      Leads to emt
  • COVID-19 also has a long-term influence on tumor progression
  • Patients with tumors have been shown to be more vulnerable to SARS-CoV-2 infection and subsequent development of severe COVID-19
  • patients who have recovered from COVID-19 may have an increased risk of developing cancer or of cancer progression and metastasis
  • awaken cancer cells
  • NETs have been shown to change the tumor microenvironment
  • enhance tumor progression and metastasis
  • vitamin C has been tested in phase 2 clinical trials aimed at reducing COVID-19-associated mortality by reducing excessive activation of the inflammatory response
  • vitamin C is an antioxidant that significantly attenuates PMA-induced NETosis in healthy neutrophils by scavenging ROS
  • vitamin C may also inhibit NETosis and NET production in COVID-19
  • Metformin
  • Vitamin C
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    NETosis intimately involved in progressive COVID, long COVID, autoimmunity, and cancer
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https://www.thefastleanpro.us/ - 0 views

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    Fast Lean Pro™ (official) | weight lose Formula thefastleanpro.us · by Fast Lean Pro Fast Lean Pro Only $49/Bottle Limited Time Offer! Fast Lean Pro Special Deal + Special 51% Discount Save $300 + 180 Days Money Back Guarantee FastLeanPro The #1 Solution To natural metabolism booster helps you lose weight quickly without starving yourself. Fast Lean Pro is a natural powder supplement for weight loss that has recently been developed by Japanese scientists. Regular Price: $99/per bottle Only for: $49/per bottle What Is Fast Lean Pro? Fast Lean Pro is a powdered dietary powdery supplement designed to aid in weight loss. It contains a unique combination of ingredients that are believed to activate the body's "fasting switch" to optimize results. This product focuses not only on weight loss but also on promoting cellular rejuvenation, fasting, and a healthy metabolism. The concept behind Fast Lean Pro is that incorporating fasting into one's lifestyle can lead to positive outcomes irrespective of individual food choices and eating habits. To comprehend the mechanism of the Fast Lean Pro process, it is necessary to delve into its specific details. One of the few weight loss pills on the market that contains Fibersol is Fast Lean Pro. This safe, specialized fiber adds bulk to its weight when combined with water, curbing your appetite before it throws off your meal plan. If you're trying to lose weight or curb your appetite, Fast Lean Pro can help. Supporting substances such as niacin and chromium contribute to this. The body can further benefit from these nutrients, such as through improved metabolic regulation. Fast lean Pro is non-GMO, vegan friendly, and contains no artificial ingredients or stimulants. Fast Lean Pro is a weight loss product that promotes the body's natural self-feeding process. The body naturally removes old, damaged cells through a process known as autophagy to encourage cell regeneration and repair. Recent studies by a group
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Hope in Every Incision: The Promise of Brain Tumor Surgery - 0 views

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    The observed cost of brain tumor surgery is approximately 60% lower than in other developed Western countries. The affordability of brain tumor surgery is significantly lower when compared to developed countries, making India a preferred choice over other Western destinations for brain tumor surgery. The outstanding success rate of brain tumor surgery is attributed to the expertise of top brain tumor surgeons in the country.
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The Danger of Excessive Vaccination During Brain Development - 0 views

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    Dr. Blaylock, neurosurgeon, on the detrimental effects of excessive vaccinations in our children.  This is heavily referenced.
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Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes - 0 views

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    elevated  inflammatory markers, IL-1B, IL-6, and TNF-alpha, found to be associated with the development of type II Diabetes.
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Chronic inflammation in fat plays a crucial role in the development of obesity-related ... - 0 views

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    chronic low-grade inflammation plays role in development of insulin resistance and eventually obesity.  This occurs in White Adipose Tissue
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PLoS ONE: Influence of Milk-Feeding Type and Genetic Risk of Developing Coeliac Disease... - 0 views

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    fascinating article on how the environment and genetics play a role in the development of celiac disease.  In this study, the PROFICEL study, the intestinal microbiota was influenced by breast milk.  Those children breast fed had a favorable microbiota that decreased the incidence of celiac disease.
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Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during ... - 0 views

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    randomized study finds no difference in attention, memory in children born to mothers supplementing with DHA.  Good randomized design, but several problems.  First, did these women need supplementation.  No testing was done to determine need.  They may have needed more or none at all--the standard throw a dart on the wall and hope it sticks paradigm.  Second, Neurologcial development starts from day one, so do properly determine effect, the authors need to start support at conception or even better- before.  This follows that logic that women desiring conception should start extra folic acid 3 months prior. The literature is moving in the right direction, but they are still limiting themselves.  
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Male pubertal development: are endocrine-disrupting compounds shifting the norms? - 0 views

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    Study supports the mechanism behind endocrine disruption of xenoestrogens in the pubertal development of young boys.
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V8 Pills - V8 Energy Pills Ingredients Review - 0 views

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    V8 energy pills (V8 herbal incense, V8 dietary supplement) are developed as a strong Phenylethylamine (PEA) formula that fuels and increases ...
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    V8 energy pills (V8 herbal incense, V8 dietary supplement) are developed as a strong Phenylethylamine (PEA) formula that fuels and increases ...
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A revolution in biomedical assessment: the develop... [J Dent Educ. 2001] - PubMed result - 0 views

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    A revolution in biomedical assessment: the development of salivary diagnostics.
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Endogenous fructose production and metabolism in the liver contributes to the developme... - 0 views

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    Glucose increases fructose production in the liver through unregulated polyol pathway activity.  This aids the development of metabolic syndrome.  Carb restriction is important!  It is not just about what you give the body, but what the body does with it.
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Promotion of Bladder Cancer Development and Progression by Androgen Receptor Signals - 0 views

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    Animal study finds that Androgen Receptors play role in bladder cancer development and progression in men.
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Endocrine actions of pesticides m... [Environ Sci Pollut Res Int. 2014] - PubMed - NCBI - 0 views

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    low dose pesticide (organophosphates) exposure associated with delayed sexual development in boys and girls.  In addition, there was an inverse correlation with free T4 and a positive correlation with TSH.  
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International Journal of Impotence Research - Obesity, low testosterone levels and erec... - 0 views

  • Studies have shown that ED may be an early biomarker of general endothelial dysfunction, atherosclerosis and CVD
  • testosterone treatment of hypogonadal young and older men improves sexual function, increases lean mass and decreases fat mass
  • In men with low serum testosterone (for example, <8 or 230 nmol l−1) with obesity, metabolic syndrome and diabetes mellitus, treatment with testosterone is warranted
  • ...12 more annotations...
  • In obese middle-aged men, testosterone treatment reduced visceral adipocity, insulin resistance, serum cholesterol and glucose levels
  • testosterone replacement has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure in hypogonadal men with the metabolic syndrome as well as type 2 diabetes mellitus
  • Testosterone significantly inhibits lipoprotein lipase activity, which reduces triglycerides uptake into adipocytes in the abdominal adipose tissue
  • testosterone treatment decreased endogenous inflammatory cytokines (tumor necrosis factor-α and IL-1β) and lipids (total cholesterol) and increased IL-10 in hypogonadal men
  • Testosterone treatment reduced leptin and adiponectin levels in hypogonadal type 2 diabetic men after 3 months of testosterone replacement
  • available data clearly show a relationship between obesity, low testosterone levels and ED
  • Obesity adversely affects endothelial function and lowers serum testosterone levels through the development of insulin resistance and metabolic syndrome
  • Metabolic disturbances as well as production of cytokines and adipokines by inflamed fat cells may be causal factors in the development of ED
  • The onset of ED and the associated risk of CVD may be delayed through lifestyle modifications that affect obesity, such as diet and exercise
  • Very low testosterone levels contribute to the development of ED in obesity, metabolic syndrome and type 2 diabetes mellitus
  • Obesity is associated with low total testosterone levels that can be explained at least partially by lower sex hormone-binding globulin (SHBG) in obese men
  • epidemiological studies have shown a negative correlation between BMI and total testosterone and to a lesser extent with free and bioavailable (biologically active) testosterone levels
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    Obesity is associated with low Testosterone and ED in men.
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