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Nathan Goodyear

Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Literature - 0 views

jaha.ahajournals.org/...e000272.full

Testosterone men male cardiovascular disease low T

shared by Nathan Goodyear on 20 Nov 13 - No Cached
  • Low endogenous bioavailable testosterone levels have been shown to be associated with higher rates of all‐cause and cardiovascular‐related mortality.39,41,46–47 Patients suffering from CAD,13–18 CHF,137 T2DM,25–26 and obesity27–28
  • have all been shown to have lower levels of endogenous testosterone compared with those in healthy controls. In addition, the severity of CAD15,17,29–30 and CHF137 correlates with the degree of testosterone deficiency
  • In patients with CHF, testosterone replacement therapy has been shown to significantly improve exercise tolerance while having no effect on LVEF
  • ...66 more annotations...
  • testosterone therapy causes a shift in the skeletal muscle of CHF patients toward a higher concentration of type I muscle fibers
  • Testosterone replacement therapy has also been shown to improve the homeostatic model of insulin resistance and hemoglobin A1c in diabetics26,68–69 and to lower the BMI in obese patients.
  • Lower levels of endogenous testosterone have been associated with longer duration of the QTc interval
  • testosterone replacement has been shown to shorten the QTc interval
  • negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries, abdominal aorta, and thoracic aorta
  • These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.
  • Current guidelines from the Endocrine Society make no recommEndations on whether patients with heart disease should be screened for hypogonadism and do not recommEnd supplementing patients with heart disease to improve survival.
  • The Massachusetts Male Aging Study also projects ≈481 000 new cases of hypogonadism annually in US men within the same age group
  • since 1993 prescriptions for testosterone, regardless of the formulation, have increased nearly 500%
  • Testosterone levels are lower in patients with chronic illnesses such as end‐stage renal disease, human immunodeficiency virus, chronic obstructive pulmonary disease, type 2 diabetes mellitus (T2DM), obesity, and several genetic conditions such as Klinefelter syndrome
  • A growing body of evidence suggests that men with lower levels of endogenous testosterone are more prone to develop CAD during their lifetimes
  • There are 2 major potential confounding factors that the older studies generally failed to account for. These factors are the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD.
  • The biologically inactive form of testosterone is tightly bound to SHBG and is therefore unable to bind to androgen receptors
  • The biologically inactive fraction of testosterone comprises nearly 68% of the total testosterone in human serum
  • The biologically active subfraction of testosterone, also referred to as bioavailable testosterone, is either loosely bound to albumin or circulates freely in the blood, the latter referred to as free testosterone
  • It is estimated that ≈30% of total serum testosterone is bound to albumin, whereas the remaining 1% to 3% circulates as free testosterone
  • it can be argued that using the biologically active form of testosterone to evaluate the association with CAD will produce the most reliable results
  • English et al14 found statistically significant lower levels of bioavailable testosterone, free testosterone, and free androgen index in patients with catheterization‐proven CAD compared with controls with normal coronary arteries
  • patients with catheterization‐proven CAD had statistically significant lower levels of bioavailable testosterone
  • In conclusion, existing evidence suggests that men with CAD have lower levels of endogenous testosterone,13–18 and more specifically lower levels of bioavailable testosterone
  • low testosterone levels are associated with risk factors for CAD such as T2DM25–26 and obesity
  • In a meta‐analysis of these 7 population‐based studies, Araujo et al41 showed a trend toward increased cardiovascular mortality associated with lower levels of total testosterone, but statistical significance was not achieved (RR, 1.25
  • the authors showed that a decrease of 2.1 standard deviations in levels of total testosterone was associated with a 25% increase in the risk of cardiovascular mortality
  • the relative risk of all‐cause mortality in men with lower levels of total testosterone was calculated to be 1.35
  • higher risk of cardiovascular mortality is associated with lower levels of bioavailable testosterone
  • Existing evidence seems to suggest that lower levels of endogenous testosterone are associated with higher rates of all‐cause mortality and cardiovascular mortality
  • studies have shown that lower levels of endogenous bioavailable testosterone are associated with higher rates of all‐cause and cardiovascular mortality
  • It may be possible that using bioavailable testosterone to perform mortality analysis will yield more accurate results because it prevents the biologically inactive subfraction of testosterone from playing a potential confounding role in the analysis
  • The earliest published material on this matter dates to the late 1930s
  • the concept that testosterone replacement therapy improves angina has yet to be proven wrong
  • In more recent studies, 3 randomized, placebo‐controlled trials demonstrated that administration of testosterone improves myocardial ischemia in men with CAD
  • The improvement in myocardial ischemia was shown to occur in response to both acute and chronic testosterone therapy and seemed to be independent of whether an intravenous or transdermal formulation of testosterone was used.
  • testosterone had no effect on endothelial nitric oxide activity
  • There is growing evidence from in vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels, such as potassium and calcium channels, on the surface of vascular smooth muscle cells
  • Experimental studies suggest that the most likely mechanism of action for testosterone on vascular smooth muscle cells is via modulation of action of non‐ATP‐sensitive potassium ion channels, calcium‐activated potassium ion channels, voltage‐sensitive potassium ion channels, and finally L‐type calcium ion channels
  • Corona et al confirmed those results by demonstrating that not only total testosterone levels are lower among diabetics, but also the levels of free testosterone and SHBG are lower in diabetic patients
  • Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone, and SHBG were more likely to develop T2DM and metabolic syndrome.
  • Vikan et al followed 1454 Swedish men for 11 years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM
  • authors demonstrated a statistically significant increase in the incidence of T2DM in subjects receiving gonadotropin‐releasing hormone antagonist therapy. In addition, a significant increase in the rate of myocardial infarction, stroke, sudden cardiac death, and development of cardiovascular disease was noted in patients receiving antiandrogen therapy.67
  • Several authors have demonstrated that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c, and fasting plasma glucose
  • Existing evidence strongly suggests that the levels of total and free testosterone are lower among diabetic patients compared with those in nondiabetics
  • insulin seems to be acting as a stimulant for the hypothalamus to secret gonadotropin‐releasing hormone, which consequently results in increased testosterone production. It can be argued that decreased stimulation of the hypothalamus in diabetics secondary to insulin deficiency could result in hypogonadotropic hypogonadism
  • BMI has been shown to be inversely associated with testosterone levels
  • This interaction may be a result of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity. On the other hand, given that adipose tissue has a higher concentration of the enzyme aromatase, it could be that increased adipose tissue results in more testosterone being converted to estrogen, thereby causing hypogonadism. Third, increased abdominal obesity may cause reduced testosterone secretion by negatively affecting the hypothalamus‐pituitary‐testicular axis. Finally, testosterone may be the key factor in activating the enzyme 11‐hydroxysteroid dehydrogenase in adipose tissue, which transforms glucocorticoids into their inactive form.
  • increasing age may alter the association between testosterone and CRP. Another possible explanation for the association between testosterone level and CRP is central obesity and waist circumference
  • Bai et al have provided convincing evidence that testosterone might be able to shorten the QTc interval by augmenting the activity of slowly activating delayed rectifier potassium channels while simultaneously slowing the activity of L‐type calcium channels
  • consistent evidence that supplemental testosterone shortens the QTc interval.
  • Intima‐media thickness (IMT) of the carotid artery is considered a marker for preclinical atherosclerosis
  • Studies have shown that levels of endogenous testosterone are inversely associated with IMT of the carotid artery,126–128,32,129–130 as well as both the thoracic134 and the abdominal aorta
  • 1 study has demonstrated that lower levels of free testosterone are associated with accelerated progression of carotid artery IMT
  • another study has reported that decreased levels of total and bioavailable testosterone are associated with progression of atherosclerosis in the abdominal aorta
  • These findings suggest that normal physiologic testosterone levels may help to protect men from the development of atherosclerosis
  • Czesla et al successfully demonstrated that the muscle specimens that were exposed to metenolone had a significant shift in their composition toward type I muscle fibers
  • Type I muscle fibers, also known as slow‐twitch or oxidative fibers, are associated with enhanced strength and physical capability
  • It has been shown that those with advanced CHF have a higher percentage of type II muscle fibers, based on muscle biopsy
  • Studies have shown that men with CHF suffer from reduced levels of total and free testosterone.137 It has also been shown that reduced testosterone levels in men with CHF portends a poor prognosis and is associated with increased CHF mortality.138 Reduced testosterone has also been shown to correlate negatively with exercise capacity in CHF patients.
  • Testosterone replacement therapy has been shown to significantly improve exercise capacity, without affecting LVEF
  • the results of the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not cause an increase in the rate of adverse cardiovascular events
  • Data from 3 meta‐analyses seem to contradict the commonly held belief that testosterone administration may increase the risk of developing prostate cancer
  • One meta‐analysis reported an increase in all prostate‐related adverse events with testosterone administration.146 However, when each prostate‐related event, including prostate cancer and a rise in PSA, was analyzed separately, no differences were observed between the testosterone group and the placebo group
  • the existing data from the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not increase the risk of adverse cardiovascular events
  • the authors correctly point out the weaknesses of their study which include retrospective study design and lack of randomization, small sample size at extremes of follow‐up, lack of outcome validation by chart review and poor generalizability of the results given that only male veterans with CAD were included in this study
    • Nathan Goodyear
      Nathan Goodyear on 04 Dec 13
       
      The authors here present Total Testosterone as a "confounding" value
    • Nathan Goodyear
      Nathan Goodyear on 09 Dec 13
       
      This would be HSD-II
  • the studies that failed to find an association between testosterone and CRP used an older population group
  • low testosterone may influence the severity of CAD by adversely affecting the mediators of the inflammatory response such as high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor–α
  • Nathan Goodyear on 20 Nov 13
     
    Good review of Testosterone and CHD.  Low T is associated with increased all cause mortality and cardiovascular mortality, CAD, CHF, type II diabetes, obesity, increased IMT,  increased severity of CAD and CHF.  Testosterone replacement in men with low T has been shown to improve exercise tolerance in CHF, improve insulin resistance, improve HgbA1c and lower BMI in the obese.
Nathan Goodyear

Metabolic Effects of Liothyronine Therapy in Hypothyroidism: A Randomized, Double-Blind, Crossover Trial of Liothyronine Versus Levothyroxine: The Journal of Clinical Endocrinology & Metabolism: Vol 96, No 11 - 0 views

press.endocrine.org/...jc.2011-1329

T4 T3 hypothyroid hypothyroidism thyroid lipids weight loss metabolism cholesterol hormones

shared by Nathan Goodyear on 24 Sep 14 - No Cached
  • tissue euthyroidism is the net result of multiple steps including conversion of the prohormone T4 into its active metabolite T3, which is ultimately responsible for signaling at the end-organ target level
  • The circulating and intracellular pools of T3 of treated hypothyroid patients (i.e. devoid of endogenous TH production) depend entirely on the conversion of exogenous l-T4 into T3
  • TH is the major regulator of basal metabolic rate
  • ...8 more annotations...
  • The substitution of l-T3 for l-T4 caused a significant weight loss
  • The substitution of l-T3 for l-T4 caused a significant reduction in lipid parameters
  • TH action is increased in the liver, and the SHBG increase supports this hypothesis
  • The changes in serum lipid metabolism parameters are similar to the effects observed with drugs approved for the treatment of dyslipidemia
  • This differential response appears to be limited to the lipid metabolism and SHBG, whereas no differences in indices of insulin resistance were detected. This is remarkable because hyperthyroid states are associated with an increase in hepatic gluconeogenesis (37), and overt thyrotoxicosis is a known cause of secondary diabetes.
  • Despite the increase in serum T3, the l-T3 treatment did not cause major changes in cardiovascular or musculoskeletal function, as indicated by the echocardiographic and maximal exercise tolerance tests and DXA studies.
  • Similarly, no significant differences were observed in blood pressure, heart rate, or endothelial vascular function
  • In conclusion, the results of this pharmacology, proof-of-concept study indicate that replacement therapy of hypothyroidism with l-T3, compared with l-T4 causes weight loss and favorable changes in the lipid profile without appreciable side effects
  • Nathan Goodyear on 24 Sep 14
     
    Crossover study finds T3 versus T4 results in more weight loss, improved lipid management and increased SHBG without any adverse cardiovascular effects.   The T3 was dosed 3 x daily due to its short half life compared to T4.
wheelchairindia9

S-Ergo 105 - 0 views

www.wheelchairindia.com/...Karma-S-Ergo-105-Wheelchair

Comfort Ergonomic Folding Ultralight Wheelchairs breathable anti-bacterial S-Shape Seating System ergonomic lightweight wheelchair s-ergo 105 fully propel without armrests

shared by wheelchairindia9 on 06 May 15 - No Cached
  • wheelchairindia9 on 06 May 15
     
    Ergonomic chairs are designed to confirm to a person's physical dimensions, allowing them to sit naturally and comfortably for long periods of time, while reducing the risk of pressure ulcers. Karma Wheelchair KM 7501: Karma Healthcare KM 7501 Pediatric Wheelchair is a manual wheelchair for children. It's ergonomically antelope horn-shaped handle makes it easy to steer and push the chair, and vertical footrest allow legs to be placed in the correct position. One-piece footplate increases stability. The wheelchair has a great look with a bright color and modern style. Karma Healthcare Wheelchair KM 7501 Features: Karma Healthcare Wheelchair KM-7501 Paediatric Wheelchair offers here-we-go handle Caring footrest Seat width: 11" or 13.5" Ultra lightweight and compact Outward extended front wheels 6" solid caster and 14" solid rear wheel Maximum user weight: 60Kg One Year Warranty Karma Wheelchair KM 7501 Measurements: Width 11" And 13.5" Front/Rear Wheels 6" to 14" 6" to 14" Seat Width 28cm 34cm Seat Depth 30cm 30cm Overall Width 45cm 51cm Overall Collapsed Width 34cm 34cm Armrest Height 18cm 18cm Overall Length 70W 70W Seat Height 39cm 39cm Backrest Height 36cm 36cm Overall Height 102cm 102cm Weight 9.3kg 9.3kg Ergo Wheelchair features an ergonomic "S" shaped seat that provides the perfect shape to fit the human body to relieve pressure, increase stabilization, weight distribution and lower the risk of pressure sores and scoliosis. Karma S Ergo 105 Wheelchair Karma S Ergo 105 Wheelchair Features: High strength, weighs only 12.2 kg. (w/ footrests) ¼" thick removable Aegis Anti-Bacterial Upholstery, machine washable / dryable "Tube-in Center" footplate, assures better side leg support Fixed Footrests Pouch for carrying small items attached to upholstery behind backrest 7"x1" Polyurethane front caster 24' Rear polyurethane, high profile, flat free wheels S-Style Ergonomic Seat Folding backrest/ folding seat for tra
wheelchairindia9

Tricycle For Disabled Children - 0 views

www.wheelchairindia.com/...Handicapped-Child-Tricycle

Tricycle For Adults And Children With Special Needs shape of a conventional bicycle leg calibers various seating and bar adjustment reduced power height adjustable backrests control poles steering restrictors

shared by wheelchairindia9 on 17 Apr 15 - No Cached
  • wheelchairindia9 on 17 Apr 15
     
    The tricycles are individually designed to meet the needs of each disabled child and help provide physiotherapy, build muscle tone and promote play. Italso help benefit growth and development in children with disabilities, enabling them to keep active and retain their independence. Disabled children get huge physical and emotional benefits from having the specially tricycles, which are each custom made to suit the individual child's needs. Riding a tricycle provides both fun and fitness, and is a therapeutic activity that allows children to exercise their lower extremities. As the muscles move through cycling motions, they are flexed, extended and stretched. This range of motion is crucial for children with disabilities, because muscles are incapable of keeping up with bone growth unless fully extended. Tricycles are provided to severely disabled children and adults and come in two sizes, 20 inch and 24 inch models. These trikes are grant funded and to qualify for one of these, an individual must suffer from a condition such as, but not limited to, Cerebral Palsy, Down Syndrome, Traumatic Brain Injury or Autism. Trunk support system is ideal for riders who have trouble remaining upright while seated. An optional headrest is available. A headrest can be purchased with either a flat or contoured headpiece, and adjusts both horizontally and vertically for optimum positioning. The Front Pulley System maintains a level pedal position for children whose extreme tone forces the front of the pedal downward. Turn the oval knob to raise and lower the handlebar. A handbrake for the conventional handlebar will arrive installed on Large tricycle. Open access combined with a low transfer step makes it easy to get on and off trikes. Tricycle Deluxe Double Hand Drive: Frame : Made by E.R.W. Tubes 38.0 mm-16 G. 25.4 mm & 22.22 mm- 18 G. Seat & Back : M S, C.R.C. Sheet. Seat Size 18"x 16" Wheel Size : Wheel Diameter 24"x 1 1/2" Tyre and Tube Standard Company. Pa
wheelchairindia9

Wheelchair Detachable Wheels - 0 views

www.wheelchairindia.com/...Detachable-Wheelchair

Wheelchair Are Detachable And Foldable detachable footrests reversible desk arms wheelchair detachable wheels swing away footrests wheelchair 4 wheel

shared by wheelchairindia9 on 13 May 15 - No Cached
  • wheelchairindia9 on 13 May 15
     
    Wheelchairs is designed for those who prefer a removable armrest wheelchair. A removable armrest allows for easy patient transfer in and out of the chair.This chair is available in a different seat width and comes complete with swingaway footrests. It also incorporates solid rubber casters for a smooth and easy roll. Both detachable and flip-back arms are designed for easier lateral transfers. Most Wheelchairs in this category have Desk-Length arms, a shorter arm that allows rolling up to a desk or table. All are folding-frame chairs and are available in different seat widths. Detachable armrest for use in conjunction with wheelchairs. The armrest is comprised of a horizontal member supported at one end by a vertical member. The horizontal and vertical members are releasably attached to the wheelchair frame, and the attachment of the horizontal member to the wheelchair frame allows rotation of the horizontal member from the normal position to a position of non-use behind the back of the wheelchair. Wheelchairs - Arm Rests: The armrests support the arms and shoulders in comfortable positions and are often used to push off of for transferring from sitting to standing or held on to for balance. Desk-length armrests are shorter than standard length rests and are often chosen so that a person can pull up to a desk or table for easier access. The shorter length of these armrests is undesirable if the wheelchair user needs to use them to assist pushing into a standing position. In this case a full-length armrest would be preferred. Wheelchairs - Footrests: The footrest and legrest support protect the lower leg and feet. If they are too high they decrease the weight carried through the back of the thighs and can cause increased pressure over the buttock region. If they are two low they can cause pressure over the posterior thighs and cause problems with clearing barriers in the environment such as incline transitions. The suggested height of the footrest from th
wheelchairindia9

Karma 8020 Wheelchair - 0 views

www.disabilityproduct.in/...a-8020-X-Heavy-Duty-Wheelchair

Heavy Duty Wheelchairs The Most Important Form Of Patient fit in an average-sized chair fold like regular wheelchairs with a small motor assisting different types of wheelchairs adjusting to the hemi height centre of gravity adjustment

shared by wheelchairindia9 on 09 Sep 15 - No Cached
  • wheelchairindia9 on 09 Sep 15
     
    Heavy duty wheelchair can either be manually-operated or motorized, each with its own pros and cons. A manual heavy-duty wheelchair gives full control of motion to the user, but the added weight from the reinforcements makes pushing or propelling the wheelchair much harder than normal. A motorized heavy duty wheelchair offers a solution to this dilemma, but is often more expensive and harder to maintain than a manual wheelchair. Some designs offer a combination of both, with a small motor assisting those pushing the wheelchair. The proper choice between types of Heavy Duty wheelchair depends largely on the user's expected level of activity. Heavy duty wheelchairs typically have larger seats than conventional wheelchairs. The frames of these wheelchairs can be made from several different reinforced metals, although a titanium wheelchair is often the most popular choice. The wheels themselves are made of thicker rubber than normal, preventing any possible failure due to the greater amount of weight supported. Most makes of heavy duty wheelchairs fold like regular wheelchairs, making storage relatively easy despite the wheelchair increased size. Heavy Duty Wheelchair specialy design for disabled and handicapped persons. They are two types of Heavy Duty Wheelchair for handicapped and disability product like- Karma 8020 X Heavy Duty Wheelchair Karma 8520 Heavy Duty Wheelchair Karma 8020 X Heavy Duty Wheelchair: It comes with detachable swing away footrests. The wheel chair has flip-back armrests. It comes with centre of gravity adjustment. The wheel chair has wide profile casters. Seat Size 20'' inch & 22'' inch Total Weight 17 K.G. Designed for maximum strength & weight capacity for people over 250 lbs. These end to be heavier and wider. This heavy duty bariatric wheelchair has seat dimensions of 24 inches wide by 18 inches deep to accommodate a weight capacity of up to 400 lbs. This wheelchair is dual axle, which means that the floor to seat heigh
wheelchairindia9

Karma S-Ergo 105 Manual Wheelchair - 0 views

disabilityproduct.in/...Karma-S-Ergo-105-Wheelchair

Ergonomic Wheelchair Provides Safe Movement For People brakes at the pushing handles Karma S-Ergo 105 Manual Wheelchair maximum strength and durability Karma Ergo 125 Transit Wheelchair

shared by wheelchairindia9 on 03 Sep 15 - No Cached
  • wheelchairindia9 on 03 Sep 15
     
    Ergonomic chairs are designed to confirm to a person's physical dimensions, allowing them to sit naturally and comfortably for long periods of time, while reducing the risk of pressure ulcers. Ergonomic system (Intelligent s-shaped ergonomic seating) provides efficient pressure relief by spreading weight over a greater area, at the same time provides stabilization and reduced sliding. With their lightweight frames and seats designed to reduce or prevent pressure points, ergonomic wheelchairs provide a comfortable option for mobility impaired users who have the upper body strength to propel themselves, or a caregiver strong enough to do so. Karma Ergo Lite 2501 Wheelchair: The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features: Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane Front Casters 16" x 17" or 18" x 17" Seat Width S-Style Ergonomic Seat 14" Rear Polyurethane, High Tread, Flat Free Wheels 3-Stage handle brake: allows light to firm grip for lock Folding Backrest/ Folding Seat for Transporting in Vehicle or Travel Fixed Footrests w/ Extra Wide Footplates Frame Color: Pearl Silver Weight Capacity of 100 kg Ergonomic Transporter w/ handle brakes Karma Ergo Lite 2501 Wheelchair Measurements: Seat Width 16 inch., 18
Nathan Goodyear

Branched Chain Amino Acid Supplementation for Patients with Cirrhosis | Clinical Correlations - 0 views

www.clinicalcorrelations.org/?p=3544

BCCA branched chain amino acids liver cirrhosis hepatitis amino acids

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • low level of BCAAs in patients with cirrhosis is hypothesized to be one of multiple factors responsible for development of hepatic encephalopathy
  • supplementation of BCAAs is thought to facilitate ammonia detoxification by supporting synthesis of glutamine, one of the non-branched chain amino acids, in skeletal muscle and in the brain as well as diminishing the influx of AAAs across the blood-brain barrier
  • oral BCAA supplementation is more useful in chronic encephalopathic patients than is parenteral BCAA supplementation in patients with acute encephalopathy
  • ...35 more annotations...
  • malnutrition progressing to cachexia is another common manifestation of cirrhosis
  • Malnutrition can be mitigated with BCAA supplementation
  • Studies show that administration of amino acid formulas enriched with BCAAs can reduce protein loss, support protein synthesis, and improve nutritional status of patients with chronic liver disease
  • Leucine has been shown to be the most effective of the BCAAs because it acts via multiple pathways to stimulate protein synthesis
  • BCAAs metabolites inhibit proteolysis
  • Patients with cirrhosis have both insulin deficiency and insulin resistance
  • BCAAs (particularly leucine) help to reverse the catabolic, hyperglucagonemic state of cirrhosis both by stimulating insulin release from the pancreatic β cells and by decreasing insulin resistance allowing for better glucose utilization
  • Coadministration of BCAAs and glucose has been found to be particularly useful
  • BCAA supplementation improves protein-energy malnutrition by improving utilization of glucose, thereby diminishing the drive for proteolysis, inhibiting protein breakdown, and stimulating protein synthesis
  • Cirrhotic patients have impaired immune defense, characterized by defective phagocytic activity and impaired intracellular killing activity
  • another effect of BCAA supplementation is improvement of phagocytic function of neutrophils and possibly improvement in natural killer T (NKT) cell lymphocyte activity
  • BCAA supplementation may reduce the risk of infection in patients with advanced cirrhosis not only through improvement in protein-energy malnutrition but also by directly improving the function of the immune cells themselves
  • BCAA administration has also been shown to have a positive effect on liver regeneration
  • A proposed mechanism for improved liver regeneration is the stimulatory effect of BCAAs (particularly leucine) on the secretion of hepatocyte growth factor by hepatic stellate cells
  • BCAAs activate rapamycin signaling pathways which promotes albumin synthesis in the liver as well as protein and glycogen synthesis in muscle tissue
  • Chemical improvement with BCAA treatment is demonstrated by recovery of serum albumin and lowering of serum bilirubin levels
  • long-term oral BCAA supplementation was useful in staving off malnutrition and improving survival by preventing end-stage fatal complications of cirrhosis such as hepatic failure and gastrointestinal bleeding
  • The incidence of death by any cause, development of liver cancer, rupture of esophageal varices, or progression to hepatic failure was decreased in the group that received BCAA supplementation
  • Patients receiving BCAA supplementation also have a lower average hospital admission rate, better nutritional status, and better liver function tests
  • patients taking BCAA supplementation report improved quality of life
  • BCAAs have been shown to mitigate hepatic encephalopathy, cachexia, and infection rates, complications associated with the progression of hepatic cirrhosis
  • BCAAs make up 20-25% of the protein content of most foods
  • Highest levels are found in casein whey protein of dairy products and vegetables, such as corn and mushrooms. Other sources include egg albumin, beans, peanuts and brown rice bran
  • In addition to BCAAs from diet, oral supplements of BCAAs can be used
  • Oral supplementation tends to provide a better hepatic supply of BCAAs for patients able to tolerate PO nutrition as compared with IV supplementation, especially when treating symptoms of hepatic encephalopathy
  • Coadministration of BCAAs with carnitine and zinc has also been shown to increase ammonia metabolism further reducing the encephalopathic symptoms
  • Cirrhotic patients benefit from eating frequent, small meals that prevent long fasts which place the patient in a catabolic state
  • the best time for BCAA supplementation is at bedtime to improve the catabolic state during starvation in early morning fasting
  • A late night nutritional snack reduces symptoms of weakness and fatigability, lowers postprandial hyperglycemia, increases skeletal muscle mass,[25] improves nitrogen balance, and increases serum albumin levels.[26] Nocturnal BCAAs even improve serum albumin in cirrhotic patients who show no improvement with daytime BCAAs
  • Protein-energy malnutrition (PEM), with low serum albumin and low muscle mass, occurs in 65-90% of cases of advanced cirrhosis
  • hyperglucagonemia results in a catabolic state eventually producing anorexia and cachexia
  • BCAAs are further depleted from the circulation due to increased uptake by skeletal muscles that use the BCAAs in the synthesis of glutamine, which is produced in order to clear the ammonia that is not cleared by the failing liver
  • patients with chronic liver disease, particularly cirrhosis, routinely have decreased BCAAs and increased aromatic amino acids (AAAs) in their circulation
  • Maintaining a higher serum albumin in patients with cirrhosis is associated with decreased mortality and improved quality of life
  • the serum BCAA concentration is strongly correlated with the serum albumin level
  • Nathan Goodyear on 05 Oct 15
     
    great review of cirrhosis and BCCA supplementation.
wheelchairindia9

Commode Wheelchair - 0 views

disabilityproduct.in/...COMMODE-WHEELCHAIR

Bariatric Designed For Maximum Strength Extra Wide Wheelchair wheelchair bariatric Adjusting to the hemi height fold-able wheelchairs commode wheelchair

shared by wheelchairindia9 on 10 Aug 15 - No Cached
  • wheelchairindia9 on 10 Aug 15
     
    This lightweight portable shower chair commode with casters is packed with features to ensure a pleasant and comfortable bathing experience. One of the greatest benefits is the ultra comfort padded seat featuring an open front design making personal hygiene easy and convenient. When the shower chair is not in use the back and 12 qt. commode bucket can be removed without tools making cleaning and storage simple. The frame is manufactured with lightweight rust resistant anodized aluminum able to withstand a 300 lb. weight capacity. Easy to operate, shower chair. Commode comes equipped with 3" non-skid casters, making transfer to and from any bathroom safe and secure. Commode/shower chair soft seat features strong and practical armrests designed to withstand a lot of load, including the sideways forces that are exerted during sideways transfers.The armrests offer comfortable support for the forearms while sitting and they are long enough to provide sustained support when standing up and sitting down. The armrests can be folded up individually, e.g. to facilitate a sideways transfers. When folded down, the armrest rests behind the backrest thereby preventing fingers, skin or hair from getting caught. Commode Wheelchair Rainbow 6: Karma commode wheelchair rainbow 6 comes with lot of exiting features for elderly or physically challenged person who want commode in wheelchair. Karma Rainbow 6 has single seat with center cut commode having cushion cover on top and removable pan or plastic commode seat with pot. 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 Whe
Nathan Goodyear

Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. - Diabetes - 0 views

diabetes.diabetesjournals.org/...1481.abstract

Alpha lipoic Acid ALA inflammation NF-KappaB

shared by Nathan Goodyear on 18 Feb 11 - No Cached
  • Nathan Goodyear on 18 Feb 11
     
    Alpha LIpoic Acid inhibits major production of inflammation: NF-KappaB
Nathan Goodyear

Arch Intern Med -- Abstract: The Progressive Cost of Complications in Type 2 Diabetes Mellitus, September 13, 1999, Brown et al. 159 (16): 1873 - 0 views

archinte.ama-assn.org/...1873

health costs healthcare

shared by Nathan Goodyear on 22 Mar 11 - No Cached
  • Per-person costs increased over baseline ($2033) by more than 50% ($1087) after initiation of cardiovascular drug therapy and/or use of a cardiologist, and by 360% ($7352) after a major cardiovascular event. Abnormal renal function increased diabetes treatment costs by 65% ($1337); advanced renal disease, by 195% ($3979); and end-stage renal disease, by 771% ($15,675)
  • Nathan Goodyear on 22 Mar 11
     
    Costs of "poor health"
Sonny Cher

Activate Party Pills: The Natural Energy Booster - 1 views

Being a full time mom, wife and career woman is never an easy feat. But after juggling heaps of tasks, at the end of the day I always feel tired and exhausted. I do not have time anymore for myself...

legal highs

started by Sonny Cher on 23 May 11 no follow-up yet
Sonny Cher

Party All You Want After Work - 1 views

My current job ends at 10 in the evening. However, it is my friend's homecoming party and he invited me to come by after work. I knew I would definitely feel exhausted after work and I am afraid I ...

stimulants

started by Sonny Cher on 17 May 11 no follow-up yet
Sonny Cher

Party All You Want After Work - 1 views

My current job ends at 10 in the evening. However, it is my friend's homecoming party and he invited me to come by after work. I knew I would definitely feel exhausted after work and I am afraid I ...

stimulants

started by Sonny Cher on 20 Apr 11 no follow-up yet
Nathan Goodyear

Occupational Lead Poisoning - February 15, 1998 - American Family Physician - 0 views

www.aafp.org/...stauding.html

occupational poisoning lead

shared by Nathan Goodyear on 05 Jul 11 - No Cached
  • The freely diffusible plasma fraction is distributed extensively throughout tissues, reaching highest concentrations in bone, teeth, liver, lungs, kidneys, brain and spleen
  • Inorganic lead does not undergo any metabolic transformation or digestion in the intestines, or detoxification in the liver.5
  • With chronic exposure over a long period of time, most absorbed lead ends up in bone
  • ...4 more annotations...
  • The total bodily content of lead is called the body burden; in a steady state, about 90 percent of the body burden is bound to bone.2
  • n general, lead is excreted quite slowly from the body (with the biologic half-life estimated at 10 years). Since excretion is slow, accumulation in the body occurs easily.2
  • hronic toxicity is an insidious illness with protean manifestations.3,6 Symptoms may include arthralgias, headache, weakness, depression, loss of libido, impotence and vague gastrointestinal difficulties.
  • Late effects may include chronic renal failure, hypertension, gout and chronic encephalopathy.6
  • Nathan Goodyear on 05 Jul 11
     
    occupational lead poisoning
star yu

Is There any Treatment for End Stage Renal Failure Without Dialysis - 0 views

www.huaxiainstitute.com/...170.html

Dialysis Renal Failure

shared by star yu on 19 Jan 16 - No Cached
  • star yu on 19 Jan 16
     
    "Hello, doctor. My father is Renal Failure patient. His creatinine is 880 and get rid of dialysis.
wheelchairindia9

Karman S-Ergo 115 - 0 views

www.wheelchairindia.com/...Karma-S-Ergo-115-Wheelchair

Ergo 115 Wheelchair Ensures Comfortable Ride Ergonomic Manual Wheelchair Ergonomic wheelchairs Karma S Ergo 115 Wheelchair Karma S Ergo 125 Wheelchair Karman S-Ergo 115 Ergonomic Transport Chair

shared by wheelchairindia9 on 17 Feb 16 - No Cached
  • wheelchairindia9 on 17 Feb 16
     
    Ergonomic wheelchairs have been tested and proven to be effective for relieving pressure throughout the body; this is confirmed by pressure chart mapping. Feeling comfortable on a wheelchair is something every user demands out of their new wheelchair, the ergonomic cushion that is included with the ergonomic series provides a level of comfort that is unparalleled. Ergonomic Transport Wheelchair provides the perfect shape to fit the human body to relieve pressure, increase stabilization, weight distribution and lower the risk of pressure sores and scoliosis. Lightweight Ergonomic Wheelchair features wide arm pads for extra support, folding back rest, detachable swing-away footrests, and a Tube-in Center foot-plate that provides extra support for the leg muscles. This wheelchair can hold up to daily use and is excellent for traveling. Ergonomic features flip-back armrest and swing away footrests. A lightweight frame that is 25 lbs. without footrests and a folding backrest allows easy travel or storage. The chair comes equipped with a padded anti-bacterial upholstery that is comfortable and washable. Karma Ergo Lite 2501 Wheelchair: The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features: Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane
Nathan Goodyear

The implication of neuroactive steroids in Tourette syndrome pathogenesis: a role for 5α-reductase? - 0 views

www.ncbi.nlm.nih.gov/...PMC3849218

tourette's syndrome hormones 5-alpha reductase

shared by Nathan Goodyear on 08 Dec 15 - No Cached
  • The typical onset of TS occurs at 6–7 years of age and is characterized by the appearance of simple, recurrent motor tics, followed by the manifestation of phonic tics after several months [12]. In most children, TS symptoms undergo a progressive exacerbation, which reaches its zenith at the beginning of puberty (11–12 years of age), and is then followed by a gradual remission in the majority of patients
  • 30–40% of TS-affected children retain their symptoms in adulthood
  • Multiple neurotransmitters have been implicated in TS, including dopamine (DA), serotonin, norepinephrine, acetylcholine, glutamate and γ-amino-butyric acid (GABA)
  • ...11 more annotations...
  • female gender may predict greater tic severity in adulthood
  • male gender is a major risk factor for TS (with a male:female prevalence ratio estimated at ~4:1)
  • the typical age of onset coincides with adrenarche (6–7 years old); symptoms increase in severity until the beginning of puberty (12 years old) and then undergo a spontaneous amelioration, which becomes apparent with the end of puberty (at 18–19 years of age)
  • TS is diagnosed later in females than males
  • ample evidence supports the involvement of DAergic dysfunctions in TS
  • a number of clinical observations showed that tics in TS patients could be exacerbated by anabolic androgens
  • steroidogenic enzymes and androgen receptors may serve as putative therapeutic targets for this disorder
  • Unlike males, tic severity is typically increased after puberty in females
  • 26% of females were found to experience exacerbation of tics in the estrogenic phase of the menstrual cycle, and this phenomenon was found to be correlated with increased tic severity at menarche
  • biochemical hallmark of adrenarche is the acquisition of 17,20 lyase activity by cytochrome P450 C17 (CYP17A1)
  • increased synthesis of dehydroepiandrosterone (DHEA) and androstenedione, which leads to the growth of axillary and pubic hair as well as enhancement in the oiliness of the skin
  • Nathan Goodyear on 08 Dec 15
     
    interesting read on hormones and tourette's.. Proposed that 5 alpha reductase activity is involved in worsening of tics.  This makes sense as Testosterone in men with low T is known to increase dopamine and dopaminergic dysfunction is known to play a role in tourette's;  the clinical presentation of girls vs boys is very different.  The authors of this article propose that 5 alpha reductase activity controls a back door method where by progesterone is converted to androgens.
Nathan Goodyear

High D-dimer levels are associated with poor prognosis in cancer patients - 0 views

www.ncbi.nlm.nih.gov/...PMC3409812

cancer D-dimer

shared by Nathan Goodyear on 10 Jul 18 - No Cached
  • a systemic activation of blood coagulation and procoagulant changes in the hemostatic system have frequently been observed in cancer patients, even in the absence of venous thromboembolism
  • Thrombin is a pivotal enzyme in the process of blood coagulation and leads to the conversion of fibrinogen to fibrin, which is the end product of blood coagulation and finally results in the formation of a fibrin clot
  • deposition of fibrin, which has an important role in the formation of tumor stroma and hematogenous spread of tumor cells.
  • ...5 more annotations...
  • The interaction of fibrin, platelets and tumor cells leads to the formation of platelet-fibrin-tumor-cell aggregates that promote endothelial adhesion and metastatic spread, as well as tumor cell growth and tumor cell survival
  • fibrin degradation products have been shown to display strong angiogenic properties
  • D-dimer is a biomarker that globally indicates the activation of hemostasis and fibrinolysis
  • It is a degradation product of fibrin
  • high D-dimer levels were reported to be predictive of the occurrence of VTE in cancer patients
  • Nathan Goodyear on 10 Jul 18
     
    elevated D-Dimer associated with poor prognosis in cancer. Good review of cancer and ehmostasis.
Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism - 0 views

www.pnas.org/...1715035115.full

ibuprofen Testosterone epigenetics hormones low Testosterone low T

shared by Nathan Goodyear on 09 Jan 18 - No Cached
  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
  • ...27 more annotations...
  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
  • Nathan Goodyear on 09 Jan 18
     
    ibuprofen alters genetic expression that results in decreased Testosterone production.
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