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Nathan Goodyear

Lowered testosterone in male obesity: Mechanisms, morbidity and management Tang Fui MN,... - 0 views

  • The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
  • Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
  • By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
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  • diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage, [10] is regulated by dihydrotestosterone, [11] suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype.
  • bariatric surgery achieves 10%-30% long-term weight loss in controlled studies
  • The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
  • Reductions in testosterone levels correlate with the severity of obesity and men
  • epidemiological data suggest that the single most powerful predictor of low testosterone is obesity, and that obesity is a major contributor of the age-associated decline in testosterone levels.
  • healthy ageing by itself is uncommonly associated with marked reductions in testosterone levels
  • obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
  • Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
  • although controversial, measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range
  • SHBG increases with age
  • marked obesity however is associated with an unequivocal reduction of free testosterone levels, where LH and follicle stimulating hormone (FSH) levels are usually low or inappropriately normal, suggesting that the dominant suppression occurs at the hypothalamic-pituitary level
  • adipose tissue, especially when in the inflamed, insulin-resistant state, expresses aromatase which converts testosterone to estradiol (E 2 ). Adipose E 2 in turn may feedback negatively to decrease pituitary gonadotropin secretion
  • diabetic obesity is associated with decreases in circulatory E 2
  • In addition to E 2 , increased visceral fat also releases increased amounts of pro-inflammatory cytokines, insulin and leptin; all of which may inhibit the activity of the HPT axis at multiple levels
  • In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
  • weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
  • fat is androgen-responsive
  • low testosterone may augment the effects of a hypercaloric diet
  • In human male ex vivo adipose tissue, testosterone decreased adipocyte differentiation by 50%.
  • Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
  • in men with prostate cancer receiving 12 months of androgen deprivation therapy, fat mass increased by 3.4 kg and abdominal VAT by 22%, with the majority of these changes established within 6 months
  • severe sex steroid deficiency can increase fat mass rapidly
  • bidirectional relationship between testosterone and obesity
  • increasing body fat suppresses the HPT axis by multiple mechanisms [30] via increased secretion of pro-inflammatory cytokines, insulin resistance and diabetes; [19],[44] while on the other hand low testosterone promotes further accumulation of total and visceral fat mass, thereby exacerbating the gonadotropin inhibition
  • androgens may play a more significant role in VAT than SAT
  • men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
    • Nathan Goodyear
       
      Interesting: low T increases VAT, yet T therapy does not reduce VAT, yet T therapy reduces SAT.
  • irisin, derived from muscle, induces brown fat-like properties in rodent white fat
  • androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
  • low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
  • pro-inflammatory cytokines released by adipose tissue may contribute to loss of muscle mass and function, leading to inactivity and further weight gain in a vicious cycle
  • Sarcopenic obesity, a phenotype recapitulated in men receiving ADT for prostate cancer, [55] may not only be associated with functional limitations, but also aggravate the metabolic risks of obesity;
  • observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
  • genuine reactivation of the HPT axis in obese men requires more substantial weight-loss
  • A number of intervention studies have confirmed that both diet- and surgically-induced weight losses are associated with increased testosterone, with the rise in testosterone generally proportional to the amount of weight lost
  • men, regardless of obesity level, can benefit from the effect of weight loss.
  • inconsistent effect of testosterone on VAT
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    to be read
Nathan Goodyear

Nature Clinical Practice Endocrinology & Metabolism | Testosterone and ill-health in ag... - 0 views

  • Levels of total and bioavailable testosterone and SHBG were reported to be inversely correlated with the prevalence of the metabolic syndrome in men aged 40–80 years
  • as were total testosterone and SHBG in men aged 65–96 years
  • and in a cross-sectional analysis of a large cohort of non-diabetic men aged 70–89 years
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  • In longitudinal studies, decreased levels of total testosterone and SHBG predicted an increased incidence of metabolic syndrome in nonobese men
  • Free testosterone level is not associated with the prevalence of metabolic syndrome in middle-aged and older men
  • Levels of free, bioavailable and total testosterone are lower in men with T2DM than in age-matched controls,34, 35 and decreased total testosterone level predicts incident T2DM in middle-aged men.
  • men with T2DM commonly have low total or free testosterone levels
  • Total, bioavailable and free testosterone levels are inversely correlated with fasting insulin level and insulin resistance in middle-aged men without T2DM
  • total testosterone is positively correlated with insulin sensitivity in men with normal or impaired glucose tolerance or T2DM
  • low SHBG level is more strongly associated with metabolic syndrome than low total testosterone in aging men
  • the recognized association between low SHBG level and insulin resistance
  • Low levels of SHBG are also associated with smaller, denser LDL-cholesterol molecules in nondiabetic men,58 and were found to predict increased cardiovascular disease mortality in one study of older men
  • Low levels of SHBG might reflect obesity, insulin resistance and overall poor health
  • Compared with those who have normal testosterone levels, men aged 40 years or more with total testosterone levels <9.8 nmol/l or elevated LH level have greater CIMT
  • In men aged 73–94 years, total testosterone was inversely correlated with CIMT
  • a prospective analysis of men aged 73–91 years, progression of CIMT was not related to total testosterone level, but it was inversely related to free testosterone level
  • A study of men aged 55 years or more found that those with total and bioavailable testosterone levels in the highest tertile had a lower risk of severe aortic atherosclerosis (detected by radiography as abdominal aortic calcification) than those with the lowest testosterone levels.
  • a large study of men aged 69–80 years, those with total or free testosterone in the lowest quartile had increased odds of lower-extremity peripheral arterial disease
  • the possibility of reverse causation has to be considered, as systemic illness can result in decreased testosterone levels
  • previous case–control studies and longitudinal studies have failed to identify low testosterone levels as strong predictors of clinically significant coronary disease
  • Reviews of trials on testosterone therapy in men with either low or low-to-normal testosterone levels have not shown consistent beneficial effects either on lipid profiles or on actual cardiovascular events.24, 54, 55 These trials, however, have not been designed or powered to detect treatment-related differences in cardiovascular outcome
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    Declining Testosterone or low Testosterone is clearly associated with poor health in men.   Very nice review of the association between low Testosterone and metabolic dysfunction.  Low T is associated with increased metabolic syndrome, Diabetes, weight gain, insulin resistance...
wheelchairindia9

Reclining Commode Wheelchair - 0 views

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    wheelchair category (standard, transport, power, etc.) could be classified as a reclining wheelchairs, since the product class is built around one key feature: the capability to adjust the backrest and/or footrest into a reclined position. This feature is especially important to users who find it difficult or impossible to sit in a fully upright position, and users who sleep in their chairs frequently. For those that are looking for a more portable chair, however, products from this category may not be a great fit. When compared with a similar, non-reclining chair, a reclining wheelchair tends to weigh more and - unlike other manual models - manual wheelchairs that recline typically aren't foldable. Some people use special wheelchairs to distribute pressure and thus reduce the risk of skin sores. These chairs also increase comfort and sitting tolerance. One type of chair, called "tilt in space," changes a person's orientation while maintaining fixed hip, knee, and ankle angles. The whole seat, in effect, tilts. The other chair option is called a recline system, which basically changes the seat-to-back angle, flattening out the back of the chair and in some cases raising the legs to form a flat surface. Different Types Of Reclining Wheelchairs: Reclining Wheelchair 902 GC Reclining Wheelchair 609 GC Karma Aurora 4 Reclining Wheelchair Karma Reclining Wheelchair KM 5000 Karma VIP 515 Wheelchair Reclining Wheelchair 902 GC: Reclining Wheelchair 902 GC is one of the basic models of a Reclining Wheelchair which helps transfer to bed to wheelchair easily and comes with head and neck support and Calf support for added comfort. Reclining Wheelchair 902 GC Features: The chair boast of movable armrest and elevating footrest. A well padded thigh support helps the user thigh's during reclining. The front and the rear wheels are designed and placed in such a way so as to support the users weight during reclining. The Pneumatic rear wheels help the movement
wheelchairindia9

Standard Wheelchair - 0 views

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    Standard Manual Wheelchairs are the most commonly used type of wheelchair, if searching for a standard wheelchair with a durable frame and long-lasting support, take a look at standard wheelchairs. The Standard Wheelchair usually weighs over 35 lbs, have a seat width between 16 and 20 inches, and feature fixed or detachable armrests. Most are made with steel frames and can be an economical and consistent mobility choice. Almost all standard wheelchairs can support up to 250 lb. A standard wheelchair is designed to support longer trips, and to allow for self propulsion. These chairs almost always feature two, large, rear-mounted wheels that the user can set in motion by hand, so if need to be able to operate chair without aid from a loved one or caregiver, a standard wheelchair is an ideal option. Storage is a breeze with these units as well and every model we carry is foldable, allowing the user to fit his/her chair into a tighter spaces. Standard Wheelchairs, also known as Power Operated Vehicles (POVs), are a good choice if need assistance getting around home or apartment and don't have advanced seating or positioning needs. The right Standard Wheelchair will allow to get around home with ease and without getting tired. A Standard Wheelchair allows to go where it need, when it need, with little to no assistance. Numotion will work with it and clinicians to see if a Standard Wheelchair is the right choice. Features: Good for travel and in large outdoor spaces. Designed for mobility on the go. Easy control. Adjust for speed and comfort. Conveniently charged by simply plugging in.
wheelchairindia9

Shower Wheelchair - 0 views

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    Commode chairs are portable toilets, designed to be placed at the bedside of a disabled individual whose activity is very limited. It is typically consist of a frame and a waste receptacle that can be easily removed and emptied. Having such a device close at hand is especially helpful for those too debilitated to make the trip to the bathroom. So, if someone close to needs the support and convenience that commodes can offer, the right place. Adapted and assisted toileting systems help provide independence while being designed to be practical, versatile and comfortable, as well as, easy to clean. These adjustable toilets and commodes can be used as a freestanding commode chair, over the toilet, on the toilet, or as a shower chair. Commode Wheelchair Rainbow 6 Features: Frame Material : M.S.Chrome Plated. Single Seat with center cut commode. Both Option Available In Single Seat. Plastic Commode Seat With Pot. Cushioned Top Cover. Square Pan Commode Pan . Removable Pan. Commode Wheelchair Rainbow 6 Measurements: Frame Style : Foldable Open Position Wheel To Wheel Width In : 26" (Inches) Seat Width : 18" (Inches) Total Width in Closing Position : 11" (Inches) Rear Wheel Size : 24" (Inches) Front Wheel Size : 8" (Inches) Seat to Floor Height : 19" (Inches) Seat Depth : 18" (Inches) Total Height : 34" (Inches) Max User Weight Capacity : 110 (kgs) Net Weight : 19.5 (kgs) Armrest : Fixed Footrest : Fixed Wheel Quality : Rear Tyre Solid Tube Less Rear Wheel Lock : Yes Hand Brakes : No Drop Back Handle : No Providing a wide range of commode wheelchairs which are specially designed for aged and physically challenged people. These wheelchairs can be used for indoor toilet purposes. Fabricated using quality raw material, these wheelchairs are suitable for western as well as Indian toilets. This advanced technology involved wheelchair has a comfortable seat and made of a strong steel frame. This chair is very durable
wheelchairindia9

Wheelchair Pediatric - 0 views

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    When it comes to wheelchairs, young children have a different set of needs than adults. Aesthetically, devices designed for kids are often sleek and colorful, and functionally, they are typically lightweight and adjustable. As any parent knows, young people don't stay the same size for long and since a wheelchair is a major purchase don't want a simple growth spurt to render it useless. That's why kids wheelchair category offers models that feature seat width and depth adjustability, elevating legrests, and other versatile features. Pediatric walkers differ from adult walkers in several ways. For one, walking aids for children are usually adjustable, taking growth patterns into account; but many models also provide gait training and postural correction. Those caring for kids in their formative years must be concerned about more than just the young person's mobility, they must also consider their development. Cerebral Palsy Wheelchair: Cerebral Palsy Wheelchair Description: The model designed for cerebral palsy child only. Ultra light weight aluminium alloy frame Seat Width 38 cms (15") Net Weight: 18.5 kgs Epoxy powder coated frame Detachable arm rest & foot rest provided Elevated and swinging foot rest Elevated foot rest provided to elevate leg angle Height adjustable and detachable head rest Hydraulic reclining high back for a comfortable posture Hydraulic adjustable seat angle Detachable back and seat pad Extra cushion upholstery provided to under arm, head & calg Foldable Lever and paddle brakes provided Safety belt provided Maintenance free rear solid wheels Cloth look like water proof upholstery Anti wheels for better safety and stability Extra cushion upholstery provided to under arm, head & leg Folding action Lever and paddle brakes provided Safety belt provided Maintenance free rear solid wheels Cerebral Palsy Wheelchair Recline system: Recline system provides kids with the most comfortable resting environme
wheelchairindia9

Ergonomic Lightweight Wheelchair - 0 views

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    Pediatric wheelchairs enable child or teen to participate in all types of daily activities. Pediatric wheelchairs are lightweight, portable, and convenient for use at school, day programs, doctor visits, and recreation with family and friends. Pediatric wheelchairs comes in wide range of sizes and vibrant colors for every lightweight wheelchair. A variety of positioning options are also available. Pediatric wheelchairs are manufactured with unsurpassed quality and style, specializing in compact-folding, lightweight wheelchairs for children of all ages - from toddlers to teens! Custom built to child's specific needs, mobility aids offer rehabilitative benefits for physical disabilities from Cerebral Palsy to Autism. Pediatric, or child wheelchairs, are mobile aids designed for and used by children. Children require the use of a wheelchair for many different reasons, some may have suffered head injuries, some have muscular dystrophy or cerebral palsy, some are amputees, and others only have an occasional use of their wheelchairs in lieu of a walking device or crutches. Certain types of pediatric wheelchairs are built to expand in size to accommodate increased bulk and weight by altering a cross balance on the bottom of the chair. The front frames for the legs can be lengthened as child's legs grow longer. For a pediatrician seeking to prescribe a Pediatric Wheelchair, must be sure that the patient has the proper upper body strength to use one. If the patient is too weak for self movement, the practitioner would be better to consider a powered wheelchair for mobility. While Pediatric Wheelchairs are smaller and can be just as manuverable as scooters, that depends upon the patient's own abilities in steering the chair. These are factors that the doctor must think about before recommending what type of wheelchair a patient should get. Pediatric Wheelchair with a body contouring S-Shaped seat frame and contoured armrests provides the user with all day comfort an
wheelchairindia9

Folding Wheelchair - 0 views

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    Lightweight, compact-folding wheelchairs for children, teenagers, and young adults let go anywhere, while still ensuring proper positioning and support. Going to school, appointments and even on vacation is possible with the convenient, lightweight design. Just fold it up and put it in trunk. Foldable Wheelchair by features a powder coat steel frame with durable nylon upholstery and padded armrests. Composite mag wheels with maintenance-free bearings and composite handrims make for a smooth ride. As with anything with moveable parts, the folding wheelchair is not as durable as the rigid frame wheelchair. Therefore maintenance is required more frequently to keep all parts in good working order. Before purchasing a wheelchair, consider all activity level. If traveling often, and need a highly-portable option, a folding lightweight wheelchair may be. Lightweight wheelchairs provide convenience and comfort to the user and caregiver alike and are often built using materials like aluminum and titanium alloy, while foldable wheelchairs allow for easy storage and transport. Merge the two styles, and got a great mobility aid that isn't a pain to lug around. Folding wheelchairs also have removable foot rests which allow for easy folding. Most frames are made from aluminum or titanium and are heavier than the rigid frame. wheelchair is designed to fit the body of the user, while the primary design of the folding wheelchair is to fold. Folding wheelchairs are generally more "boxy" while rigid wheelchairs conform to the shape of the body. This means it can hold the users body in place by tapering the frame and seat. The folding wheelchair cannot be tapered or it would not close completely. Features: Powder coat steel frame. Durable nylon upholstery. Composite mag wheels with maintenance-free bearings. Composite footplates. Padded armrests. Composite handrims. Maximum weight capacity.
Nathan Goodyear

Kent Holtorf: Long Term Weight Loss - More Than Will Power? - 0 views

  • which is a major reason for the regaining of lost weight with dieting as well being the mechanism behind stress induced weight gain (it is not due to increased cortisol).
  • f greater than 10, it demonstrates there is a degree of leptin resistance contributing to an inability to lose weight
  • that it is difficult to lose weight with leptin resistance. High carbohydrate diets and in particular high-fructose corn syrup is shown to significantly increase leptin resistance and is a likely mechanism that high fructose corn syrup is associated with obesity
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  • inactive thyroid hormone called thyroxine
  • it is problem inside the cell that the inactive T4 is not converted to T3 but rather to a mirror image of T3 called reverse T3. The reverse T3 has the opposite effect of T3, blocking the effects of T3 and lowering rather than increasing metabolism.
  • Studies are showing that stress and dieting (especially yo-yo dieting) can set this hormone into action as well as chronic illness such as diabetes, chronic fatigue syndrome and fibromyalgia.
  • As soon as the body senses a reduction in calories, the production of reverse T3 is stimulated to lower metabolism
  • With chronic dieting or stress, the body often stays in this "starvation mode" with elevated levels of reverse T3 and decreased levels of T3, which is a major reason for the regaining of lost weight with dieting as well being the mechanism behind stress induced weight gain (it is not due to increased cortisol).
  • which is a major reason for the regaining of lost weight with dieting as well being the mechanism behind stress induced weight gain (it is not due to increased cortisol).
  • which is a major reason for the regaining of lost weight with dieting as well being the mechanism behind stress induced weight gain (it is not due to increased cortisol).
  • Studies are showing that such standard testing will miss 80% of thyroid dysfunction
  • ree T3/reverse T3 ratio
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    Fantastic review by Dr. Holtorf on reverse T3, leptin, and weight loss
Nathan Goodyear

The mineral selenium proves itself as powerful anti-cancer medicine - 0 views

  • In a December 1996 article in the Journal of the American Medical Association, Dr. Larry Clark presented evidence that supplemental selenium could reduce cancer death rates by as much as 50%
  • patients receiving selenium had a 67% decrease in cancer of the prostate, a 58 percent decrease in colon or rectal cancer and a 45% decrease in lung cancer
  • An article in the Journal of the American Medical Association (JAMA) by Clark et al. (1996) showed that 200 mcg of supplemental selenium a day reduced overall cancer mortality by 50% in humans compared to a placebo group not receiving supplemental selenium
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  • In a recent five-year study of nearly 30,000 rural Chinese people, researchers from the NCI found that daily doses of these three nutrients reduced cancer deaths by 13%.
  • In a study in Cancer Letters (Evangelou et al. 1997), animals with malignant tumors given high doses of vitamins C and E and selenium manifested a significant prolongation of the mean survival time. Complete remission of tumors developed in 16.8% of the animals
  • cities and states with high selenium content in the soil also had significantly lower rates of cancer, especially of the digestive and urinary systems.
  • In one study of hundreds of men, a daily intake of 200 micrograms of selenium cut the incidence of prostate cancer by 60 percent.
  • The statistics for breast cancer are particularly striking. "The higher the selenium, the lower the breast cancer
  • In Yugoslavia, scientists studied 33 patients with breast cancer. These women had selenium levels in their bloodstream only half those of healthy volunteers.
  • The overall reduction in cancer incidence was 37% in the selenium-supplemented group; a 50% reduction in cancer mortality was observed over a 10-year period
  • The following are the site-specific reductions in cancer incidence observed in the study: colon-rectal cancers (58%), lung cancer (46%), and prostate cancer (63%)
  • A selenium deficiency appears to increase the risk of prostate cancer fourfold to fivefold
  • It was determined that, as the male population ages, selenium levels decrease, paralleling an increase in prostate cancer
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    exhaustive discussion selenium deficiency and increased cancer risk
Nathan Goodyear

Chemical toxins: a hypothesis to explain the globa... [J Altern Complement Med. 2002] -... - 0 views

  • Because the obesity epidemic occurred relatively quickly, it has been suggested that environmental causes instead of genetic factors maybe largely responsible
  • exponential production and usage of synthetic organic and inorganic chemicals. Many of these chemicals are better known for causing weight loss at high levels of exposure but much lower concentrations of these same chemicals have powerful weight-promoting actions.
  • his paper presents a hypothesis that the current level of human exposure to these chemicals may have damaged many of the body's natural weight-control mechanisms. Furthermore, it is posited here that these effects, together with a wide range of additional, possibly synergistic, factors may play a significant role in the worldwide obesity epidemic.
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    Toxins as chemical cause of obesity problem?
Nathan Goodyear

Diagnosing Growth Hormone Deficiency in Adults - 0 views

  • it is clear that serum IGF-1 and or IGFBP-3 can be normal in patients with undisputed GHD
  • Various investigators have reported normal IGF-1 values in 37–70% of GH deficient adults
  • The co-administration of arginine and GHRH (the combined test) is a powerful stimulus for GH production and has gained increasing acceptance as a useful method of diagnosing GHD [34]. This test has been advocated as a suitable alternative to ITT
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  • The glucagon stimulation test (GST) is a reliable, safe alternative to the ITT in the diagnosis of GHD
  • An intravenous infusion of arginine (0.5 g/kg body weight) together with an intravenous bolus of GHRH (1 mcg/kg body weight) is administered [30]. Serum samples for GH are then obtained every 15–30 minutes for two hours.
  • Obesity, particularly marked obesity, is associated with blunted GH secretion in response to provocative stimuli
  • It has also been suggested that that even mildly increased BMI (25–30 kg/m2) can result in diminished stimulated GH production in 13% of healthy subjects
  • Corneli et al. have defined BMI-specific cut-off points for diagnosing adult-onset GHD using GHRH + arginine—11.5 ng/mL for those with BMI < 25 kg/m2, 8.0 ng/mL for BMI 25–30 kg/m2, 4.2 ng/mL for those with BMI > 30 kg/m2
  • GH levels are higher during the luteal phase in comparison with the follicular phase of the cycle
  • Oral, in contrast to transdermal oestrogen, lowers IGF-1 levels and is associated with increased GH levels
  • Adequate pituitary replacement with thyroxine and hydrocortisone are needed for optimal GH production
  • one cannot rely on a low IGF-1 to diagnose GHD in women taking oral oestrogen preparations.
  • Numerous GH secretagogues are available with the insulin tolerance test being the gold standard and the glucagon stimulation test or the GHRH + arginine as acceptable alternatives
  • ain et al. found the GST to be at least as good as the ITT in provoking GH secretion
  • the GST is safe, with almost no contraindications, it causes nausea and sometimes vomiting in 15–20% of subjects
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    Nice, more recent analysis, of HGH testing.
Mark Bublitz

Do Emotions Affect The Structure Of Water? - 0 views

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    Do Emotions Affect The Structure Of Water? What you think, feel and speak affect your entire body and change the molecular structure of every drop of water in your body. Make sure that your thoughts, feelings and words are loving and supportive. If they are filled with anger, hate, blame and shame it may lead to toxicity.
Nathan Goodyear

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
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  • 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.
xshop69

vacum pembesar penis | alat pembesar penis | jual vakum - 0 views

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    Vacuum Penis Is A penile health or sport tube to enlarge and lengthen the male penis quickly and permanently. Vacuum penis enlarger or commonly called a therapeutic tool to enlarge and extend penis powerful.
wheelchairindia9

Large Electric Scooters LY-EW415 - 0 views

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    Large Electric Scooters LY-EW415 Large Electric Scooters LY-EW415 with CTS Suspension offers a smooth ride with performance to match. Comfort-Trac Suspension (CTS) is the next generation in mobility scooter ride comfort. Large Electric Scooters LY-EW415 first technology incorporates advanced suspension components for improved absorption over rough surfaces, and a more comfortable ride experience over various terrains. Large Electric Scooters LY-EW415 Features Comfort-Trac front and rear suspension. Feather-touch disassembly permits simple frame separation with only one hand. Delta tiller with wraparound handles. Crush Proof Front Basket. Black, non-scuffing tires. Back-lit battery gauge. Full LED lighting package that includes curb and rear lights, directional signals and courtesy light under tiller. Auto connecting front to rear harness. Easy Grip Tiller adjustment knob. Easy access tiller-mounted charger port. Storage compartment below tiller. Enhanced flush-mounted horn buttons. Large Electric Scooters LY-EW415 Specifications Large medium scooter 450W motor(Optional 550W/750W)? 50AH battery Max speed: 12 km/h Max loading: 150 kg Suspension in front and rear wheels
Nathan Goodyear

Activation of NK cells by extracellular heat shock protein 70 through induction of NKG2... - 0 views

  • Heat shock proteins (HSPs) are intracellular molecular chaperones that play essential roles in facilitating protein folding
  • their ability to interact with APCs and to chaperone antigenic peptides for cross-presentation to MHC class I and class II molecules on APC
  • vaccination with HSP70 was associated with increased T cell, as well as NK cell, activity in patients with CML
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  • HSP70 did not activate NK cells directly. Instead, HSP70 induced the expression of an NKG2D ligand MICA on DCs, which then activated NK cells in an NKG2D-dependent manner.
  • DCs are the most powerful professional antigen presenting cells (APCs) that are instrumental in processing antigens and orchestrating antigen-specific adaptive immunity and tolerance
  • NK cells and DCs can functionally interact with each other both in vitro and in vivo
  • autologous HSP70 could stimulate significant IFN-γ production
  • The magnitude of the IFN-γ response was different from patient to patient and correlated with the number of functional NK cells
  • In addition, 10 out of 14 patients had significantly increased IFN-γ producing cells in the peripheral blood after HSP70 vaccinations, which is again in line with increased NK cell activity as reported in our original study in these patients
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    great review of the relationship between heat shock proteins and NK cells.
Nathan Goodyear

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical respo... - 0 views

  • We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
  • RAS, PI3K, TP53 and MYC
  • The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
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  • The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
  • The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
  • four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
  • growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
  • glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
  • blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure ​(Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure ​(Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
  • glutamine consumption associated with parallel increases in glutamate and aspartate (Figure ​(Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
  • Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
  • changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
  • lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
  • the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
  • these metabolic disturbances would be expected to remain extant after therapeutic interventions
  • accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
  • Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
  • liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
  • cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
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    Breast cancer is a metabolic disease.  Now, where have I heard that cancer is a metabolic disease?
Nathan Goodyear

How We Read Oncologic FDG PET/CT | Cancer Imaging | Full Text - 0 views

  • In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
  • We contend that SUV analysis has virtually no role in this setting.
  • tumours grow as spheres, whereas inflammatory processes are typically linear
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  • Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
  • Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
  • Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
  • aerobic glycolysis
  • Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
  • The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
  • When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
  • One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
  • Many benign and inflammatory processes are also associated with high glycolytic activity
  • Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
  • The intensity of uptake in metastases usually parallels that in the primary site of disease
  • For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
  • By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
  • The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
  • Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
  • The exception to this rule is tumours with a propensity for tumour heterogeneity at different sites
  • The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
  • “metabolic signature”
  • For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
  • a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
  • Warburg effect
  • There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
  • This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
  • There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
  • Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
  • patients with hereditary paraganglioma and pheochromocytoma highlight this phenomenon
  • These have intense uptake on FDG PET/CT despite often having low proliferative rate.
  • Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
  • Metabolic activity switches off rapidly following initiation of therapy
  • Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
  • It is therefore critical to perform PET staging before commencement of anti-tumour therapy
  • The potential advantage of routine diagnostic CT is improved anatomic localisation and definition
  • Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
  • If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
  • The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
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    good read on the PET/CT scan reading.  They mention that tumors are spheres and inflammation is linear, yet inflammation coexists with cancer; hard to simply delineate these on simple terms. I do agree aon the metabolic signature of the PET/CT scan
arunaraayala

No pay, no expenses, no laws for Venezuela opposition lawmakers - Locality News - 0 views

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    On a minor scale, congressmen say they are also being obstructed from doing their job because of lac...
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