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krsnaphysio1

Physiotherapist in Gurgaon - 0 views

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    Since its establishment in the year 2011, Krshna Physio Plus is aimed to provide patients with comprehensive, high quality and professional physiotherapy treatments and rehabilitation to people in need. The efficient team of three, Dr. Ravi Sahauta - A very well-known complex trauma surgeon and Orthopaedician, Dr. Dharm Pal Sharma - an ex-Air force Physio trainer and Dr. Parmila Sharma - an experienced and talented physio expert, Krshna Physio Plus is counted among the well-known Physiotherapy clinic in Gurgaon and Delhi/NCR regions.  This clinic is one of the oldest organizations which was started with a vision to help people suffering from diverse dysfunctionalities with proper guidance and treatment which encompasses mainly physical, psychological, emotional, and social well being. With 8 centers in Delhi/NCR and Bihar, we are aimed at setting over 300 centers across Asia by 2020 and become the Physiotherapy clinic in Gurgaon.  Moreover, KRSNA Physio Plus is well equipped with various advanced facilities and equipment used to treat people to assure patient satisfaction and fast recovery. We have with us Top Physiotherapist in Gurgaon and Delhi/NCR regions with us who are specialized in offering treatment in physiotherapy dealing with Orthopedic, Neurological, Pediatric, Cardio-pulmonary, and Sports Injury, etc. All the experts here put their best for providing the best results.  Our experienced team of doctors and physiotherapists in Gurgaon who would be better able to diagnose what might be making it impossible for you to crane your neck, or pick articles off the floor, or simply kneel before your deity. Sports-Related Injuries Could Happen to Anyone It could be just that badminton match on a winter evening, or an office football match. Before you realize what is happening you've pulled a back muscle or your hamstring. Playing tug-of-war in colleges and office parties is fraught with the risk of a rotator cuff injury. Cricketers diving to save
fitspresso

https://www.fitspresso-co.com/ - 0 views

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    FitSpresso™ | Official Site fitspresso-co.com FitSpresso Only $39/Bottle Limited Time Offer! FitSpresso Special Deal + Special 51% Discount Save $660 + 180 Days Money Back Guarantee FitSpresso Herpesyl Five Star A dietary product formulated to assist users in reducing weight can increase other advantages that can support overall health. This product can assist users in getting closer to the desirable body weight. Regular Price: 149/per bottle Only for: $39/per bottle Buy Now What IsFitSpresso? FitSpresso is promoted as a natural supplement that comes in the form of diet pills, and it can aid in rapid and efficient weight loss, similar to many other supplements. The term "natural supplements refers to a nutritional supplement that is made entirely of natural, chemical-free materials. You can utilize these organic ingredients to aid in natural weight loss. It can speed up your body's metabolism and assist with other crucial processes. All parts of our bodies are impacted by weight increase, and not only do we need to deal with the increased weight, but we also need to deal with the numerous problems and illnesses that come along with it. This refers to the risk of developing chronic cardiac conditions, low blood pressure, and, in some circumstances, problems with blood sugar. However, FitSpresso even with its bright and bold claims, can help you efficiently manage your weight and completely avoid these extra uncomfortable problems. FitSpresso is a supplement that comes in the form of a pill, which makes it tasty, simple to swallow, and handy. According to the manufacturer, these diet tablets are GMO-free and toxic-free, making them edible. This is why we have things such as weight loss supplements. Thanks to modern advancements, we can just take a dietary supplement pill to bring about significant weight loss in a completely healthy and natural manner. Not only this, but dietary supplements can also support healthy blood sugar levels and help with
fitspresso

https://www.thefastleanpro.us/ - 0 views

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

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

Recliner Wheelchair - 0 views

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    Reclining Back Wheelchair( bed cum wheelchair ) which are suitable for indoor as well as outdoor purposes. These wheel chairs are manufactured using high quality material to ensure high strength and durability. Wheelchairs are available in foldable frames and are capable for maximum weight. Reclining wheelchairs are available in standard folding frames with extended head supports and seat widths up to 24" wide. The recline mechanism is attendant operated with levers much like a bicycle brake lever. The levers operate hydraulic (pump) mechanisms for a smooth adjustment. Using this Recliner Wheelchair mechanism, the chair back can easily and frequently be positioned to any angle. Reclining Wheelchair 609 GC: Reclining Wheelchair 609 GC is one of the multipurpose chairs which boast of features like reclining, inbuilt commode, customized armrest and footrest and foldable nature of the chair. Reclining Wheelchair 609 GC Features: The wheelchair can be folded within very easily within seconds, making it easier during travels and outings. The backrest of the chair can be easily reclined, giving the user the freedom to relax by not moving up from the chair. The footrest can be inclined and adjusted so as to make the user comfortable during reclining or otherwise. A well paded thigh support is an add-on to the footrest. The front and rear wheels of the chair are designed and placed in such a way so as to support the reclining of the user, making it a very safe and friendly wheelchair. The inbuilt commode has its seat just underneath the main seat of the chair; it can be used by just removing the main seat. The Wheelchair can also be folded from between by just removing the commode and the chair's seat. This Wheelchair's functionality gives the user total freedom. Easy to fold and unfold within seconds. Reclining Wheelchair 609 GC Measurements: Frame Style : Foldable Frame Material : MS Chrome Plated open position wheel to wheel width in : 26" (inch
Nathan Goodyear

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

  • 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
       
      The authors here present Total Testosterone as a "confounding" value
    • Nathan Goodyear
       
      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
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    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.
wheelchairindia9

Recliner Wheelchair - 0 views

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    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. 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. reclining wheelchair compensates mechanically for body positioning by automatically readjusting armrests and lateral supports.

    Recliner wheelchair is low profile allowing to comfortably fit under tables and desks. Enjoy numerous activities with increased comfort such as stretching, napping and watching television. The ability to recline also improves circulation and the ability for sore spots to heal.

    Karma Reclining Wheelchair KM 5000:
    The karma reclining wheelchair km-5000 Transport Wheelchair is an ultra lightweight folding aluminum reclining wheelchair. With full length padded armrests, an adjustable height head pillow, and more this wheelchair has added comfort for any user. This chair also features swing-away elevating footrests and adjustable length leg supports and footplates. With a weight of 33 Lbs this chair can be transported with ease.

    Karma Reclining Wheelchair KM 5000 Features:
    Folding 6061 T-6 Aircraft-grade aluminum frame in black
    powder coat finish
    Backrest Reclines 90°~163° and includes anti-tippers
    Full length padded detachable armrests with side panels
    Swing-away detachable elevating footrests
    Adjustable length leg supports & footplates
    Adjustable-height head pillow
    14" Mag wheels with flat free polyurethane tires
    7" x 1" Flat free front polyurethane casters
    Adjustab
wheelchairindia9

Karma Vip 515 - 0 views

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    Wheelchair with comfortble reclining back headrest. This wheelchair allows the user to obtain a more comfortable position, equally for those who are unable to sit at 90 degrees, but need to lie back. Options include elevating legrests and cushioning. This type of Wheelchair is a superb light weight aluminium total care chair with all the actions one would wish. All fully adjustable, tilt in space, reclining back, multi positional headrest,elevating legrests and full pressure cushioning. The reclining deluxe manual wheelchair. This wheelchair has all the features one would need in a wheelchair, fully adjustable arms, legrests, reclining back and pop off wheels. To remove the wheels simply press the button in the centre of the wheel and slide them off. Ideal for those who need to recline in the wheelchair as the back rest on this wheelchair can be adjusted to any position. With cushions, elevating legrests and other options, this wheelchair can be configured to meet most needs. This chair does not have tilt in space mechanism or pressure care cushioning, for this must look to the tilt in space chair. Comfort and positioning tilt-in-space wheelchair which is durable, modern looking and comfortable. It offers adjustable seat height and depth, back height, length adjustable armpads and infinite recline and tilt. The multifunction tilt in space wheelchair focuses heavily on the need of each individual user which is why it has many adjustments in one frame to make sure it can alter to cater individual requirements. One of the main features of this chair is its tilt in space feature, which allows a step less adjustment of the backrest and the seat angle. This is easily operated from the push handle and can be quickly adjusted when needed. The design of the backrest and seating on the wheelchair helps ensure comfort and support for the user. Wheelchair comes with elevating leg rests fitted as standard which again are step less and easily adjusted. There is also the o
wheelchairindia9

Tynor Ankle Binder - 0 views

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    The boot type walkers can be provided in a fixed mode or with ankle joints to provide articulation. Pneumatic support is also available. The brace has a lightweight, durable, semi rigid shell that will support the limb and provide protection. Incorporated are medial and lateral uprights, heel and rocker sole. Closure is achieved with Velcro. The strapping system provides full circumferential compression of the limb. The breathable fiber liner is washable. The articulated boot allows range of motion (ROM) usually from approximately 20 degrees dorsiflexion to 40 degrees plantar flexion. Tynor Walker Boot is designed by the Tynor to rehabilitate the person after injury or fracture. It allows easy movement as well as supports the ankle and leg. This can be a great substitute for cast and also useful during early cast removal. It can also be used during sprain in the foot and this walker gives great relief to the pain. It can easily do any mild activity. It also works for the persons with a lower leg and will give an equal level of the lower feet as well as reduces the pressure. It effectively enclosed the muscles of the leg or foot during the fracture and gives comfort without disturbing the recovery process. This walker boot is made up from the good quality material. It has Aluminum lateral bars that are corrosion free. It is light in weight and provides enhanced mobility. It gives sturdy support to feet and leg. Its Hook Loop system allows to adjust it according to the comfort. It is also infused with Foam liner and Pad set that gives soft feet and also provides great support. It is available in different sizes. Tynor Walker Boot is designed for rehabilitation after injury, fracture , sprains or surgery of foot, ankle or lower leg. The boots provide support to the ankle and leg without inhibiting mobility. They can be a substitute for cast or can be used in case of early cast removal. With a wider rocker bottom, these boots promote a natural gait, reduced
Nathan Goodyear

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

  • Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
  • In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure.
  • testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
  • ...54 more annotations...
  • Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
  • there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate cancer (Morgentaler & Schulman 2009)
  • bidirectional effect between decreased testosterone concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular risk factors
  • Achieving a normal physiological testosterone concentration through the administration of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory profiles and vascular function
  • It is well known that impaired erectile function and CVD are closely related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5 years
  • no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
  • free testosterone levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated brachial artery vasodilation in men with CAD
  • Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects when testosterone is replaced within normal physiological limits in humans
  • Endothelium-independent mechanisms of testosterone are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
  • Testosterone shares the same molecular binding site as nifedipine
  • Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
  • Testosterone also inhibited the Ca2+ influx response to PGF2α
  • one of the major actions of testosterone is on NO and its signalling pathways
  • In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
  • the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult to delineate and may be dependent upon the stage of plaque development
  • Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
  • t long-term testosterone treatment reduced CIMT in men with low testosterone levels and angina
  • neither intracellular nor membrane-associated ARs are required for the rapid vasodilator effect
  • acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described, primarily in the context of vascular tone regulation via the modulation of gene transcription
  • Testosterone and DHT increased the expression of eNOS in HUVECs
  • oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
  • Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
  • non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
  • increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
  • Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
  • Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM and/or hypogonadism
  • patients with the highest IL1β concentrations had lower endogenous testosterone levels
  • TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
  • testosterone treatment to normalise levels in hypogonadal men with the MetS resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
  • parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly men
  • Higher levels of serum adiponectin have been shown to lower cardiovascular risk
  • Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ (IFNG)) in endothelial cells, can be attenuated by treatment with testosterone
  • Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types including human endothelial cells
  • decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
  • The key to unravelling the link between testosterone and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
  • testosterone functions through the AR to modulate adhesion molecule expression
  • pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
  • DHT inhibited NFκB activation
  • DHT could inhibit an LPS-induced upregulation of MCP1
  • Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
  • As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
  • prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
  • DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
  • (Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT 3β-derivative, 3β-Adiol
  • TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was significantly reduced by a pre-incubation with 3β-Adiol in HUVECs
  • 3β-Adiol also reduced LPS-induced gene expression of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
  • This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
  • The authors suggest that DHT differentially effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
  • There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated an increased risk of adverse cardiovascular events or mortality
  • The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
  • trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase in either cardiovascular events or mortality in studies up to 12 months
  • Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors, there may possibly be a cardioprotective action
  • The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
  • the majority of studies suggest that testosterone may display both acute and chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via endothelium-dependent and -independent mechanisms
  •  
    Good deep look into the testosterone and CVD link.
wheelchairindia9

Easy Handicap Life By Heavy Duty Wheelchair - 0 views

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    Mobility is an important part of human life. When an affordable wheelchair becomes necessary, for whatever reason, the circumstances are often not ideal. Purchasing an affordable wheelchair starts with knowing the patient and researching the types of wheelchairs available. It is a great resource on many different types of medical wheelchairs. Bariatric wheelchair, designed for users between 18 and 26 stone. It has a padded sling and backrest to ensure the comfort of the user, and the armrests can be removed to allow easy transfer into and out of the wheelchair. The Heavy User Wheelchair is self-propelled, giving the option to either push it, or have the user move themselves. The large rear wheels make the wheelchair well-suited to outdoor use, and allow the user to change the direction they face when in social situations. It has folding frame, so it is easy for storage and transport. Interchangeable frame components allow to grow and change the chairs width and depth. There are custom frame specifications available. Maximum option choices allow chair to be built to the individual's specifications. It has folding "lockout" cross-brace. Cross-brace locks to limit flex in the frame for more efficient propelling. Double cross-brace. Allows more strength and enables greater weight capacity. Wheelchair Bariatric has Adjustable back height. Ensures optimal positioning of backrest for stability and scapular movement. Stabilizer bar to minimize flex and provides a more efficient ride. Multiple footplate options ensure optimal positioning of lower extremities. Quick-release axle allows quick removal of rear wheels for easy transport. Adjustable Axle Plate Adjustments help to maximize stability and propulsion of the chair. Allows center of gravity adjustment for more efficient ride. Also makes it possible to adjust the rear frame height when it's necessary to change the caster wheels. Description: Attendant cable brake. 14" rear wheels. Detachable and washable cu
wheelchairindia9

Easy Handicap Life By Heavy Duty Wheelchair - 0 views

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    Mobility is an important part of human life. When an affordable wheelchair becomes necessary, for whatever reason, the circumstances are often not ideal. Purchasing an affordable wheelchair starts with knowing the patient and researching the types of wheelchairs available. It is a great resource on many different types of medical wheelchairs. Bariatric wheelchair, designed for users between 18 and 26 stone. It has a padded sling and backrest to ensure the comfort of the user, and the armrests can be removed to allow easy transfer into and out of the wheelchair. The Heavy User Wheelchair is self-propelled, giving the option to either push it, or have the user move themselves. The large rear wheels make the wheelchair well-suited to outdoor use, and allow the user to change the direction they face when in social situations. It has folding frame, so it is easy for storage and transport. Interchangeable frame components allow to grow and change the chairs width and depth. There are custom frame specifications available. Maximum option choices allow chair to be built to the individual's specifications. It has folding "lockout" cross-brace. Cross-brace locks to limit flex in the frame for more efficient propelling. Double cross-brace. Allows more strength and enables greater weight capacity. Wheelchair Bariatric has Adjustable back height. Ensures optimal positioning of backrest for stability and scapular movement. Stabilizer bar to minimize flex and provides a more efficient ride. Multiple footplate options ensure optimal positioning of lower extremities. Quick-release axle allows quick removal of rear wheels for easy transport. Adjustable Axle Plate Adjustments help to maximize stability and propulsion of the chair. Allows center of gravity adjustment for more efficient ride. Also makes it possible to adjust the rear frame height when it's necessary to change the caster wheels. Description: Attendant cable brake. 14" rear wheels. Detachable and washable cu
wheelchairindia9

Easy Handicap Life By Heavy Duty Wheelchair - 0 views

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    Mobility is an important part of human life. When an affordable wheelchair becomes necessary, for whatever reason, the circumstances are often not ideal. Purchasing an affordable wheelchair starts with knowing the patient and researching the types of wheelchairs available. It is a great resource on many different types of medical wheelchairs. Bariatric wheelchair, designed for users between 18 and 26 stone. It has a padded sling and backrest to ensure the comfort of the user, and the armrests can be removed to allow easy transfer into and out of the wheelchair. The Heavy User Wheelchair is self-propelled, giving the option to either push it, or have the user move themselves. The large rear wheels make the wheelchair well-suited to outdoor use, and allow the user to change the direction they face when in social situations. It has folding frame, so it is easy for storage and transport. Interchangeable frame components allow to grow and change the chairs width and depth. There are custom frame specifications available. Maximum option choices allow chair to be built to the individual's specifications. It has folding "lockout" cross-brace. Cross-brace locks to limit flex in the frame for more efficient propelling. Double cross-brace. Allows more strength and enables greater weight capacity. Wheelchair Bariatric has Adjustable back height. Ensures optimal positioning of backrest for stability and scapular movement. Stabilizer bar to minimize flex and provides a more efficient ride. Multiple footplate options ensure optimal positioning of lower extremities. Quick-release axle allows quick removal of rear wheels for easy transport. Adjustable Axle Plate Adjustments help to maximize stability and propulsion of the chair. Allows center of gravity adjustment for more efficient ride. Also makes it possible to adjust the rear frame height when it's necessary to change the caster wheels. Description: Attendant cable brake. 14" rear wheels. Detachable and washable cu
wheelchairindia9

Tricycle Manufacturers - 0 views

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    Tricycles make cycling accessible to all, whatever personal challenges. There are a wide range of disability cycles that suit people with a variety of learning and physical disabilities, as well as health issues. Tricycles have 3 wheels, which means that the rider does not need to be able to balance. This is particularly useful for people with learning disabilities, such as Dyspraxia, and those recovering from illnesses. Tricycles can be fitted with foot plates to make it easier for riders to rotate the pedals and they come in upright or recumbent (horizontal sitting position). For adults and children with balance issues, stabilisers can also be fitted to standard bikes, which makes them more like tricycles. Tricycles come in a variety of accessible styles for people of all abilities including many persons with spinal cord injury disabilities. Tricycles is a great upper body workout and can provide a great sense of freedom for persons with disabilities. While the high cost prevents many from enjoying Tricycles they are steadily growing in popularity. 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. Parts: Standard Quality. Color: Black Painted. Brake: Front Wheel liver System Drive: Rear Wheel Right Side. Hand powered cycles work along the same principle as standard cycles. The pedals are replaced with handles that also steer, and riders use their arms to push the handles around to drive the chain and wheels. Most hand cycles have 3 wheels, although some have 4 wheels. 4-wheel cycles may have power assistance instead of the rider turning handles,or they may be built for going down hill, in which case gravity powers the bike. As with tricycles, hand cycles can have upright seats or low down recumbent seats. Specialist 'clip on' cycles are also available that can be attached
wheelchairindia9

A Friendly Tricycle For The Disabled Users - 0 views

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    Those of all ages whose physical disabilities restrict their movement, affect their ability to earn a living or become valued members of society. Specially designed tricycles provide a mode of transport for the physically disabled allowing them much sought after independence and an opportunity for self support. The tricycles will enable freedom of movement and less dependency on others. Most of the people who depend on these tricycles are daily wage workers who have to travel long distances every day. The regular tricycles have no suspension and the riders are prone to spinal injuries. Most of them also cannot afford good medical care, and driving these tricycles for a long time affects. To deal with the problem, come up with a model tricycle that can be very useful to people who have a disability in their lower limbs, but a strong torso. The Handy tricycle to provide the ideal cycling experience for users advancement of upper body strength and toning for athletic events. Especially valuable to triathletes and challenged, it provides the perfect way to get in shape and stay that way. The tricycle achieves the true convenience of transportation while providing easy-to-use pedaling, steering and breaking controls. These are amongst the top selling handcycles on the market today. Handy is available in upright and recumbent versions. Hand powered front wheel drive. An internal hub-based gear shifting system is built into the front wheel.This provides ultra smooth shifting and is virtually maintenance-free. The entire front frame section is removable and connects easily, quickly and securely using a bolt-on system. The seat can be repositioned quickly and easily to allow the rider to achieve an optimally efficient distance between seat and handlebars.The rear wheels are removed using a single finger push system, allowing the bike to be broken down very quickly. Defined by two ways: Fork steer: It represent the majority of handcycles. They work well for both low
wheelchairindia9

Complete Flexibility KM 2500 Small Wheel Wheelchair - 0 views

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    Wheelchairs are easy to push, they fold to make them easier to store and simple for a friend or relative to load into a car. A wide selection of accessories too. So customise chair to give the performance, portability, comfort and style. Lightweight portable wheelchair are designed for ease of use and are made from durable material. These wheelchair are often foldable and are easier to store than conventional or custom. They are perfect for both manual and electric wheelchairs, as well as many walking aids such as a 4 wheel scooter. Lightweight portable wheelchair are extremely lightweight and for this reason they are easier to transport and store than many other types of wheelchair. Lightweight portable are made to be ultra lightweight, compact, and user friendly. They fold up in interesting ways to collapse to the size of a suitcase when not in use and are usually large enough to cover one or two stairs when extended. It is important to consider their weight and the person who would most often be carrying the ramp and setting it up. Karma KM 2500 Small Wheel Wheelchair: Karma KM 2500 Small Wheel Wheelchair Specifications: Width 18" Front/Rear Wheels 6" to 14" Seat Width 47cm Seat Depth 40cm Overall Width 66cm Overall Collapsed Width 36cm Armrest Height 21cm Overall Length 90cm Seat Height 47cm Backrest Height 38cm Overall Height 86cm Weight 9.2 k.g. Karma KM 2500 Small Wheel Wheelchair Seat and Back: AEGIS Microbe Shield Approved by the FDA, EPA, EU, etc., bonded anti-microbial barrier upholstery protects from odor, staining and deterioration from bacteria, fungus and other microorganisms. It is a shield for your health. Karma KM 2500 Small Wheel Wheelchair Extended Armrest: By simulating the natural position of arms, the extended armrest design is ergonomic and creates bigger seating space. An Ultra lightweight wheelchair (9.2 kg) with a compact design for either attendant assisted or self propelling users. The use
wheelchairindia9

Wrist and Forearm Splints Causes and Recovery Period | Health | Article Point - 0 views

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    Wrist and forearm splints may be suggested for people with weak wrists or for those that have been previously injured, for tendonitis wrist support and even as a preventative for those who awaken in the morning with pain or numbness after sleeping on their hands at night. The best orthopedic wrist braces for carpal tunnel syndrome, occupational stabilization and relief from the pain of wrist strains and sprains. This Right hand wrist and forearm splint from tynor is meant to be used among patients suffering from any injury or sprain in these regions. The splint is meant to provide controlled compression in various orthopaedic conditions. The splint immobilizes the area that helps in a speedier recovery. It has anatomical thumb opening that allows free movement of the thumb. It provides a lot of comfort and is easily breathable. Forearm splint is the term used to describe the forearm pain similarly the pain of lower leg over the shin is known as shin splints. Forearm splint describes the painful disease of elbow or wrist joint. Continuous pain in forearm is often caused by tendonitis, joint injury or hairline fracture of forearm bones (proximal radius or ulna near elbow joint). Overstretching of the elbow joint often causes forearm injury. Symptoms consist of a dull pain in the forearm. Pain is minor initially but increases as activity continues. Often pin-pointed to the dorsal or back of the hand side of the forearm, mid-way between the wrist and elbow. The patient may experience weakness in the wrist extensor muscles and tenderness deep in the forearm. Pain may be reproduced by attempting to bend the wrist backwards against resistance. They provided wrist splints are used in different medical institutions and hospitals for management of hand fractures. Our offered wrist splints are manufactured by skilled professionals using optimum quality basic material and advanced technology as per the set norms of market. As well, these wrist splints can be availed in v
Nathan Goodyear

Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutrition & Metabolism | Full Text - 0 views

  • A “press” disturbance was considered a chronic environmental stress on all organisms in an ecological community
  • “pulse” disturbances were considered acute events that disrupted biological communities to produce high mortality
  • Neoplasia involving dysregulated cell growth is the biological endpoint of the disease
  • ...84 more annotations...
  • Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
  • cancer is predicted to overtake heart disease as the leading cause of death in Western societies
  • cancer can also be recognized as a metabolic disease.
  • glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
  • Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
  • persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
  • Otto Warburg first proposed that all cancers arise from damage to cellular respiration
  • The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
  • the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
  • The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
  • Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
  • Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
  • all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
  • The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
  • respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
  • data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
  • Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
  • In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival
  • Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
  • Glucose and glutamine act synergistically for driving rapid tumor cell growth
  • Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions
  • Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
  • Hif-1α stabilization enhances aerobic fermentation
  • targeting glucose and glutamine will deprive the microenvironment of fermentable fuels
  • Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
  • Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
  • Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
  • Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
  • Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
  • It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
  • Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
  • The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
  • According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
  • A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
  • Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
  • Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
  • The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
  • Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
    • Nathan Goodyear
       
      reason to eliminate glutamine in cancer patients and even GSH with cancer patients
  • It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
  • Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
  • glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
  • In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
  • Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
  • Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
  • Ketone bodies and fats are non-fermentable fuels
  • Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
  • Apoptosis under energy stress is greater in tumor cells than in normal cells
  • A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
  • . This energy stress acts as a press disturbance
  • Drugs that target availability of glucose and glutamine would act as pulse disturbances
  • Hyperbaric oxygen therapy can also be considered another pulse disturbance
  • The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
  • Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
  • Protein amino acids can be metabolized to glucose through the Cori cycle
  • The fats in KDs used clinically also contain more medium chain triglycerides
  • Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
  • Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
  • GKI values of 1.0 or below are considered therapeutic
  • The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
  • It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
  • The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
  • Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
  • Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
    • Nathan Goodyear
       
      Ketones are much more than energy adaptabilit, but actually are therapeutic.
  • ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
  • Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
  • Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
  • In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
  • Ketone supplementation has also been shown to reduce anxiety behavior in animal models
  • This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
  • lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
  • Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
    • Nathan Goodyear
       
      oxaloacetate is a glycolytic inhibitor, as is doxycycline, and IVC.
  • A synergistic interaction of the KD diet plus radiation was seen
  • It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
  • Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
  • HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro
  • The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
  • Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
  • Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
  • Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
  • GBM and use glutamine as a major fuel
  • Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
  • Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
  • Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
  • Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
  •  
    Cancer is a mitochondrial disease? So says the well published Dr Seyfried. Glucose and glutamine drive cancer growth.
umar111

Computer Science: Computer hardware - 0 views

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    Computer Science Tuesday, April 25, 2023 Computer hardware Computer hardware is the physical components that make up a computer system. It includes everything from the central processing unit (CPU) to the monitor, keyboard, and mouse. Understanding the different types of hardware and how they work together is essential for anyone who works with computers. In this article, we will explore the various components of computer hardware, including internal and external components, and the peripherals that connect to them. We will also discuss the importance of hardware maintenance, the latest advancements in computer technology, and factors to consider when choosing the right hardware for your needs. Whether you are a computer technician, a gamer, or simply someone who uses a computer for everyday tasks, this article will help you better understand the world of computer hardware. Introduction to Computer Hardware Computer hardware refers to the physical components that make up a computer system. It includes everything from the processor and memory to input/output devices such as the keyboard and monitor. In this article, we will explore the different types of computer hardware and their functions. What is Computer Hardware Computer hardware refers to the physical components of a computer system. It includes all the components that can be touched, seen, and used to interact with a computer, such as the monitor, keyboard, and mouse. Hardware is different from computer software, which refers to the programs and applications that run on a computer system. History of Computer Hardware The history of computer hardware dates back to the 1820s when Charles Babbage, an English mathematician, and inventor, designed the first analytical engine, which was considered to be the first mechanical computer. With time, more complex electronic computers were developed, including the first Intel microprocessor in 1971. Since then, computer hardware has continued to evolve, becoming
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