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Risk Factors Associated With Cardiovascular Events During Testosterone Administration i... - 0 views

biomedgerontology.oxfordjournals.org/...153.abstract testosterone low T low testosterone inflammation CVD cardiovascular
shared by Nathan Goodyear on 12 Feb 13 - No Cached
  • Nathan Goodyear on 12 Feb 13
     
    This study proves the problems rampant in science today.  This study looked at older men with mobility limitations: safe to say, not optimal health.  They give 10 grams of testosterone daily to these men.  Physiologic doses are 5-10 mg.  And they are surprise that there is an increase in side effects, here in this study CVD.  They did look at cytokines, I'll give them that; but they did not look at aromatase activity and E2, E1 levels which have been shown to be the driving forces behind these inflammatory cytokines in men.  Testosterone has in fact been shown to downregulate these inflammatory cytokines.  Poor study.  No conclusion can be taken from this study.
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Top 10 home easy weight loss exercises | Health2day | www.vie2day.com - 0 views

www.vie2day.com/ome-easy-weight-loss-exercises Health tips how to lose weight gain belly fat get rid of yoga exercises
shared by vrocky on 21 Sep 16 - No Cached
  • vrocky on 21 Sep 16
     
    Top 10 Weight loss exercises at home, the weight loss can be reached with a full body exercise daily you can shelter your extra pounds
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Tynor Ankle Brace - 0 views

www.wheelchairindia.com/...Tynor-Ankle-Brace Tynor Ankle Brace ankle brace ankle braces ankle support brace best ankle brace best ankle support ankle support braces brace ankle tynor ankle braces
shared by wheelchairindia9 on 15 Mar 16 - No Cached
  • wheelchairindia9 on 15 Mar 16
     
    Tynor Ankle Brace Ankle brace is designed to support, stabilize, and limit the range-of-motion of the ankle joint. In injury, or offer protection to people who are prone to ankle injuries. It uses the triple action of straps, laces and rigid lateral natomical splints to provide optimal ankle stabilization. Rigid Splinting Fits left & right. Easy to wear Controlled compression. Comfortable sung fit. Tynor Ankle Brace Features Triple stabilization Splint ensure strong immobilization Lace offers regional tightening, firm grip and good fitting. "Figure of eight Tynor Ankle Brace Measurements Measure circumference approx 2 inches above the ankle joint. Size Chart- Size Inches CM Small 7.2-8.4 18-21 Medium 8.4-9.6 21-24 Large 9.6-10.8 24-27 XL 10.8-12 27-30
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Two-year changes in lipids and lipoproteins associa... [Obes Res. 1999] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10102254 weight loss weight loss lipids total cholesterol LDL triglycerides obesity overweight
shared by Nathan Goodyear on 30 Mar 12 - No Cached
  • Nathan Goodyear on 30 Mar 12
     
    Weight loss improves lipid profile.  Total cholesterol, LDL, and triglycerides were reduced with weight loss of 5-10%.  However, weight loss exceeding 10% resulted in greater reduction and longer maintenance of the improved lipid panel results.
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Inflammation and insulin resistance 10.1016/j.febslet.2007.11.057 : FEBS Letters | Scie... - 0 views

www.sciencedirect.com/...S0014579307012082 inflammation insulin resistance IR PPAR TNF-alpha IL-6 IL-10 IL-1Beta JNK GLT-4 Resistin adiponectin Gherlin NF-kapppB iNOS lkkb obesity TLR-4
shared by Nathan Goodyear on 10 Jan 12 - No Cached
  • A subsequent study by Yuan et al. showed that Tnf treatment of 3T3L1 adipocytes induces insulin resistance and that this could be prevented by pretreatment of cells with aspirin
  • Activation of the Tnf receptor results in stimulation of NFκB signaling via Ikkb
  • Insulin is a pleiotropic hormone
  • ...25 more annotations...
  • the percentage of macrophages in a given adipose tissue depot is positively correlated with adiposity and adipocyte size
  • Il-10 is an anti-inflammatory cytokine produced by macrophages and lymphocytes
  • Il-10 exerts its anti-inflammatory activity by inhibiting Tnf-induced NFκB activation by reducing IKK activity [38]
  • adipose tissue macrophages are responsible for nearly all adipose tissue Tnf expression and a significant portion of Nos2 and Il6 expression
  • One theory holds that the expansion of adipose tissue leads to adipocyte hypertrophy and hyperplasia and that large adipocytes outstrip the local oxygen supply leading to cell autonomous hypoxia with activation of cellular stress pathways
  • The use of the anti-inflammatory compounds, salicylate and its derivative aspirin, for treating symptoms of T2DM dates back over 100 years
  • elevated levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin resistant states
  • overnutrition and obesity are often accompanied by elevations in tissue and circulating FFA concentrations, and saturated FFAs can directly activate pro-inflammatory responses
  • Adipokines such as resistin, leptin and adiponectin, which are secreted by adipocytes, can also affect inflammation and insulin sensitivity
  • In skeletal muscle insulin promotes glucose uptake by stimulating translocation of the GLUT4 glucose transporter
  • macrophages are also capable of undergoing a phenotypic switch from an M1 state, which was defined as the “classically activated” pro-inflammatory macrophage, to the M2 state or the “alternatively activated” non-inflammatory cell
  • saturated fatty acids are the most potent inducers of this inflammatory response
  • Several inducers of insulin resistance, including FFAs, pro-inflammatory cytokines and oxidative stress, activate the expression of Nos2, the gene that encodes iNOS (reviewed in [33]
  • Adipose tissue insulin signaling results in decreased hormone sensitive lipase activity and this anti-lipolytic effect inhibits free fatty acid (FFA) efflux out of adipocytes.
  • In the liver, insulin inhibits the expression of key gluconeogenic enzymes and, therefore, insulin resistance in liver leads to elevated hepatic glucose production
  • elevated JNK activity in liver, adipose tissue and skeletal muscle of obese insulin resistant mice, and knockout of Jnk1 (Jnk1−/−) leads to amelioration of insulin resistance in high fat diet
  • Adipose tissue from obese mice contains proportionately more M1 macrophages, whereas, lean adipose tissue contains more M2 macrophages, and increased M1 content positively correlates with inflammation, macrophage infiltration and insulin resistance
  • C-reactive protein (CRP)
  • these studies highlight the possibility that increased iNOS activity plays a direct role in the pathogenesis of insulin resistance
  • the important role of Ikkb in the development of obesity and inflammation-induced insulin resistance.
  • It is probable that local concentrations of inflammatory mediators, such as FFAs, Tnf or other cytokines/adipokines contribute to this polarity switch
  • Tnf and other cytokines/chemokines are symptomatic of inflammation, and while they propagate and/or maintain the inflammatory state, they are not the initial cause(s) of inflammation
  • Tlr4, in particular, is stimulated by lipopolysaccharide (LPS), an endotoxin released by gram-negative bacteria
  • Tlr4 belongs to the family of Toll-like receptors that function as pattern recognition receptors that guard against microorganismal infections as part of the innate immune system.
  • Tlr4 stimulation results in the activation of both Ikkb/NFκB and JNK/AP-1 signaling, culminating in the expression and secretion of pro-inflammatory cytokines/chemokines, including, Il1b, IL-6, Tnf, Mcp1, etc. (reviewed in [57
  • Nathan Goodyear on 10 Jan 12
     
    Great review of all the known components in the inflammation, insulin resistance link
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Testosterone Deficiency, Cardiac Health, and Older Men - 0 views

www.hindawi.com/...143763 low T Testosterone obesity type II diabetes diabetes health wellness metabolic syndrome lipids cholesterol hypogonadism TDS testicular dysgenesis syndrome men male hormone hormones prostate cancer
shared by Nathan Goodyear on 12 May 14 - No Cached
  • Studies have shown pharmacological doses of testosterone to relax coronary arteries when injected intraluminally [39] and to produce modest but consistent improvement in exercise-induced angina and reverse associated ECG changes [40]. The mechanism of action is via blockade of calcium channels with effect of similar magnitude to nifedipine
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      This directly refutes the recent studies (3) that Testosterone therapy increases cardiovascular events.
    • Nathan Goodyear
      Nathan Goodyear on 13 May 14
       
      Testosterone acts as a calcium channel blocker inducing vasodilation.
  • men with chronic stable angina pectoris, the ischaemic threshold increased after 4 weeks of TRT and a recent study demonstrates improvement continuing beyond 12 months [
  • Exercise capacity in men with chronic heart failure increased after 12 weeks
  • ...36 more annotations...
  • Studies have shown an inverse relationship between serum testosterone and fasting blood glucose and insulin levels
  • Medications such as chronic analgesics, anticonvulsants, 5ARIs, and androgen ablation therapy are associated with increased risk of testosterone deficiency and insulin resistance
  • Women with T2D or metabolic syndrome characteristically have low SHBG and high free testosterone
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      This stands in polar opposite of that with men.
  • Hypogonadism is a common feature of the metabolic syndrome
  • The precise interaction between insulin resistance, visceral adiposity, and hypogonadism is, as yet, unclear but the important mechanisms are through increased aromatase production, raised leptin levels, and increase in inflammatory kinins
  • levels of testosterone are reduced in proportion to degree of obesity
  • Men should be encouraged to combine aerobic exercise with strength training. As muscle increases, glucose will be burned more efficiently and insulin levels will fall. A minimum of 30 minutes exercise three times weekly should be advised
  • Testosterone increases levels of fast-twitch muscle fibres
  • By increasing testosterone, levels of type 2 fibres increase and glucose burning improves
  • Weight loss will increase levels of testosterone
  • studies now clearly show that low testosterone leads to visceral obesity and metabolic syndrome and is also a consequence of obesity
  • In the case of MMAS [43], a baseline total testosterone of less than 10.4 nmol/L was associated with a greater than 4-fold incidence of type 2 diabetes over the next 9 years
  • There is high level evidence that TRT improves insulin resistance
  • Low testosterone predicts increased mortality and testosterone therapy improves survival in 587 men with type 2 diabetes
  • A similar retrospective US study involved 1031 men with 372 on TRT. The cumulative mortality was 21% in the untreated group versus 10% ( ) in the treated group with the greatest effect in younger men and those with type 2 diabetes
  • the presence of ED has been shown to be an independent risk factor, particularly in hypogonadal men, increasing the risk of cardiac events by over 50%
  • A recent online publication on ischaemic heart disease mortality in men concluded optimal androgen levels are a biomarker for survival
  • inverse associations between low TT or FT (Table 2) and the severity of CAD
  • A recent 10 year study from Western Australia involving 3690 men followed up from 2001–2010 concluded that TT and FT levels in the normal range were associated with decreased all-cause and cardiovascular mortality, for the first time suggesting that both low and DHT are associated with all-cause mortality and higher levels of DHT reduced cardiovascular risk
  • TDS is associated with increased cardiovascular and all-cause mortality
  • The effect of treatment with TRT reduced the mortality rate of treated cohort (8.4%) to that of the eugonadal group whereas the mortality for the untreated remained high at 19.2%
  • hypogonadal men had slightly increased triglycerides and HDL
  • Men with angiographically proven CAD (coronary artery disease) have significantly lower testosterone levels [29] compared to controls ( ) and there was a significant inverse relationship between the degree of CAD and TT (total testosterone) levels
  • TRT has also been shown to reduce fibrinogen to levels similar to fibrates
  • men treated with long acting testosterone showed highly significant reductions in TC, LDL, and triglycerides with increase in HDL, associated with significant reduction in weight, BMI, and visceral fat
  • Low androgen levels are associated with an increase in inflammatory markers
  • In the Moscow study, C-reactive protein was reduced by TRT at 30 weeks versus placebo
  • In some studies, a decline in diastolic blood pressure has been observed, after 3–9 months [24, 26] and in systolic blood pressure
  • A decline was noted in IL6 and TNF-alpha
  • No studies to date show an increase in LUTS/BPH symptoms with higher serum testosterone levels
  • TRT has been shown to upregulate PDE5 [65] and enhance the effect of PDE5Is (now an accepted therapy for both ED and LUTS), it no longer seems logical to advice avoidance of TRT in men with mild to moderate BPH.
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      What about just starting with normalization of Testosterone levels first.
  • Several meta-analyses have failed to show a link between TRT and development of prostate cancer [66] but some studies have shown a tendency for more aggressive prostate cancer in men with low testosterone
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      And if one would have looked at their estrogen levels, I guarantee they would have been found to be elevated.
  • low bioavailable testosterone and high SHBG were associated with a 4.9- and 3.2-fold risk of positive biopsy
  • Current EAU, ISSAM, and BSSM guidance [1, 2] is that there is “no evidence TRT is associated with increased risk of prostate cancer or activation of subclinical cancer.”
  • Men with prostate cancer, treated with androgen deprivation, develop an increase of fat mass with an altered lipid profile
  • Erectile dysfunction is an established marker for future cardiovascular risk and the major presenting symptom leading to a diagnosis of low testosterone
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Karma KP-80 - 0 views

www.wheelchairindia.com/...Karma-KP-80-Power-Wheelchair The Electric Wheelchairs For Users narrow doorways Powered Wheelchairs for sale designed for easy improve independence Karma KP-80
shared by wheelchairindia9 on 01 May 15 - No Cached
  • wheelchairindia9 on 01 May 15
     
    Powerchair, is more compact and has a better turning radius, making it is easier to navigate narrow doorways and tight turns. Another advantage of the powerchair wheelchair is that its armchair joystick does not require an upright posture like an electric scooter's handlebars. Most powerchair wheelchairs can also be taken apart and stowed, while scooters usually can't. Powerchair wheelchairs are also usually less. Power Wheelchairs/Electric Wheelchairs is specially designed for Disabled and Handicapped People. They are recognized as the prominent manufacturer and supplier of a wide array of Power Wheelchairs. Variety of Power Wheelchairs for handicapped and disability product like: Variety of Power Wheelchairs: Karma KP 10-2 Power Wheelchair Karma KP 10-3 Power Wheelchair Karma KP 80 Power Wheelchair GM Lite Power Wheelchair Bronco Wheelchair Angel Wheelchair Bronco Wheelchair: Bronco Reclining Power Wheelchair Description: Comfort mobility is a professional Bronco Wheelchair and power scooter manufacturer established in 1978 in Taiwan. It operates with the policy of combining high quality with innovation. With dedication to research and development, Bronco wheelchair are exported around the world and earned solid reputation for its superior quality, comfort and convenience. Bronco wheelchair - comfortable, durable, designed for easy and healthy movement with full precautions. Bronco Reclining Power Wheelchair Specifications: Anchorage points Adjustable footplates LED front lights Detachable backrest Flip-back armrests Adjustable headrest Mechanic repairs Optional handbrake Power Wheelchair Features: Battery Power Wheelchair. Seat, base & battery quickly detach for easy storage and transportation Come with captain seat. With seat platform, the captain seat can be moved forward or backward using tools which is included. Adjustable armrest width and height. Footrests can be moved forward or backward for optimum placeme
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Karma Ergo 115 Wheelchair - 0 views

disabilityproduct.in/...Karma-S-Ergo-115-Wheelchair Ergo S-Shape Seating System For Handicapped foldable and easy to store Karma Ergo 115 Wheelchair detachable foot rest washable and dry able cushions Karma Ergo 305 Wheelchair footrest for maximum safety
shared by wheelchairindia9 on 04 Sep 15 - No Cached
  • wheelchairindia9 on 04 Sep 15
     
    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. Ergonomic wheelchair series provides users with a large selection of ultra lightweight wheelchairs that can help improve life. This series has features that include a high strength lightweight frame, foldable and easy to store, breathable anti-bacterial, anti-staining, removable and machine washable cushion. Also includes the exclusive S-Shape Seating System, which provides increased stability, better weight distribution and lowers the risk of pressure sores and spinal injury. Karma S Ergo 115 Wheelchair: This model features our S-Shape Seating System and is our number one best seller for many reasons. At a mere 11.3 kg in weight with detachable foot rest and many features such as removable machine washable and dry-able cushions treated by AEIGIS treated anti-microbial coated seating system. Karma S-Ergo 115 Wheelchair Features: Ergonomic Handrims & S-Shape Ergonomic Seating System Fixed armrest w/ wider concave armpads Swing In & Away Footrests Backrest Pouch attached to the upholstery 24" flat free polyurethane tires, high tread, flat free wheels Seat width: 16"x17" or 18"x17" or 20"x 17" Silver 1/4" Aegis Anti-Bacterial Upholstery, washable Folding backrest / folding seat for easy traveling "Tube-in Center" foot-plate, assures better side leg support High strength, starting weight at only 11.3 kg. (w/o footrests) 7×1" Polyurethane front casters Upholstery: Black breathable mesh bottom & top AEIGIS Frame Color: Pearl Silver or Rose Red Weight Capacity of 115 kg. Karma S-Ergo 115 Wheelchair Measurements: Seat Width 16 inch., 18 inch., 20 inch. Seat Depth 17 inch. Armrest Height 8 inch. Seat Height 19 inch. Back Height 17 inch. Overall Height 36 inch. Overall Open Width 23 inch., 25 inch., 27 inch
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Three Wheel Motorcycle - 0 views

www.wheelchairindia.com/...3-WHEELER-ATTACHMENT Scooters for People with Disabilities Scooter For Handicapped Person disabling conditions Compact Design Three Wheel Motorcycle
shared by wheelchairindia9 on 17 Apr 15 - No Cached
  • wheelchairindia9 on 17 Apr 15
     
    Side Wheel Attachment Hero Splendor: Frame : 38 mm 16 Gauge CR Pipe With Powder Coated Wheel Hub : Alloys Molded 2 Piece Tyre Size : 3.50 x 10 Inches 2 Piece Tube Size : 3.50 x 10 inches 2 Piece Shocks Up Heavy Duty 4 Piece ball baring 2 Piece pin bush 2 Piece mudguard chrome plated 2 Piece Disk with 4 Hole Wheel Type: Alloy Wheel Width: 40" to 48" inch Carrying Capacity: 100 -150 kg Assistive and small sit-down motor scooters provide important advantages to people with problems. A scooter is useful for persons without the stamina or arm/shoulder flexibility necessary to use a manual wheelchair. Also, swiveling the seat of an electric scooter is generally easier than moving the foot supports on most conventional wheelchairs. A mobility scooter is very helpful for persons with systemic or whole-body disabling conditions (coronary or lung issues, some forms of arthritis, obesity, etc.) who are still able to stand and walk a few steps, sit upright without torso support, and control the steering tiller. Features: Compact Design. Ease of Maintenance. Premium Product with best quality kit. Quality Suspension. Lifelong Durability. Good Wheel Balancing. Lifelong Durability.
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ScienceDirect - The American Journal of Cardiology : Relation Between C-Reactive Protei... - 0 views

www.sciencedirect.com/...S0002914909029208 homocysteine CAD cardiovascular disease
shared by Nathan Goodyear on 03 Aug 11 - No Cached
  • these findings indicate that low-grade systemic inflammation and hyperhomocysteinemia were present in participants with high 10-year risk for CAD.
  • Nathan Goodyear on 03 Aug 11
     
    elevated homocysteine helps to identify patients with high CAD over 10 years
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Long-Term Statin Use and Risk of Ductal and Lobular Breast Cancer among Women 55 to 74 ... - 0 views

cebp.aacrjournals.org/...1529.abstract statins statin therapy breast cancer invasive lobular ductal carcinoma women
shared by Nathan Goodyear on 25 Mar 14 - No Cached
  • Nathan Goodyear on 25 Mar 14
     
    Why has this study not received major press?  Study finds that 10+ year users of statin therapies have an 83% increased risk of invasive ductal carcinoma of the breast, a 97% increase in invasive lobular carcinoma of the breast.  In women with elevated cholesterol, the data gets worse.  There is a 204% increased risk of invasive ductal carcinoma of the breast and a 243% increased risk of invasive lobular carcinoma of the breast in women with elevated lipids and on statins 10+ years.  No matter how  you try to slice this data, this is not good news for a large sub set of women.
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Effect of resistance exercise on muscle steroidogenesis | Journal of Applied Physiology - 0 views

jap.physiology.org/...1754 resistance resistance training training exercise Testosterone male female hormone hormones muscle
shared by Nathan Goodyear on 03 Sep 14 - No Cached
  • skeletal muscle cell cultures incubated with DHEA produced testosterone in a DHEA dose-dependent manner
  • Muscle joins a growing list of tissues found to be capable of steroidogenesis
  • testosterone appears to have a role in the maintenance of muscle mass in women, although the importance of this role has not yet been fully established.
  • ...7 more annotations...
  • Circulating testosterone concentrations are generally elevated following a bout of resistance exercise in men (24, 31, 46, 52), whereas findings for the effect of resistance exercise on circulating testosterone in women are equivocal, with increases (10, 42) and no changes observed (22, 31)
  • swimming (51) and treadmill running (2) can significantly increase muscle testosterone concentrations in male and female rats
  • This upregulation of muscle testosterone in rats appears, at least in part, to be due to an increase in 3β-HSD and 17β-HSD type 1 expression
  • The primary finding in this study was that muscle steroidogenesis (i.e., testosterone production) in highly resistance-trained humans was not affected by an acute bout of heavy resistance exercise
  • A secondary finding was that the apparent molecular mass of 17β-HSD type 3 was increased following a single bout of heavy resistance exercise.
  • No differences were found for muscle testosterone or steroidogenic enzyme (17β-HSD type 3 and 3β-HSD types 1 and 2) concentrations between sexes or in response to resistance exercise
  • In conclusion, heavy resistance exercise did not induce changes in muscle steroidogenesis as measured by muscle concentrations of testosterone, 3β-HSD types 1 and 2, and 17β-HSD type 3 in highly resistance-trained young men and women.
  • Nathan Goodyear on 03 Sep 14
     
    Resistance exercise did not increase muscle concentrations of Testosterone in men or women.  The individuals in this study were actively training.  These were not sedentary individuals.
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Ergo Lite 2 - 0 views

www.wheelchairindia.com/...KM-2512-Ergo-Lite-2-Wheelchair Foldable Push Bars For Ergonomic Wheelchair Karma Ergo Wheelchair Ergo Lite 2 Karma KM 2512 Ergo Lite 2 Wheelchair Karma S Ergo 305 Wheelchair Ergonomic Wheelchair Ergo Lite 2 Wheelchair
shared by wheelchairindia9 on 20 Feb 16 - No Cached
  • wheelchairindia9 on 20 Feb 16
     
    Lightweight Ergonomic Wheelchair is designed to cradle patients in comfort while reducing risk of pressure sores, relieving pressure, dispersing weight evenly and improving stability. The Ergo Lite Wheelchair is easy to lift and its small size makes it ideal for travel. Weighing only 19.8 lbs., the chair is easy to store and transport. The chair folds down the middle like a standard wheelchair and the backrest also folds down to make the wheelchair even more compact. The Karman wheelchairs are exceptional in both their function and style. With comfort built right into the frame of a wheelchair eliminating the need for a "thick cushion" to add comfort, S-Shape seat allows the wheelchair to be "ergonomically correct" putting into a seating position and comfort conforming to natural body's curves. These chairs are built for comfort and quality to stand the test of time. Karma S Ergo 305 Wheelchair: The Karma S Ergo 305 Wheelchair weighs only 13 kg, has a 115 kg weight capacity and is available in 16" and 18" seat widths. With wheels and footrest removed this chair weighs 10 kg. Karma S Ergo 305 Wheelchair Features: Only 10 kg. (w/ wheels & footrests removed) Folding backrest, for transporting chair in car, bus, trips, ect. Swing in & away footrest for maximum safety while entering or exiting the chair 24" Quick Release rear spoke/polyurethane/high profile/flat free wheels & 7×1" front casters Seat Width: 18"x17" OR 16" x 17" Upholstery: Silver/Black mesh AEIGIS back and seat cushion Height Adjustable Armrest Factory Height Settings should be selected at time of purchase for convenience High strength, weighs only 13 kg. (w/o footrests) Anti-Bacterial Upholstery/Cushion Flip back armrests w/ wider contoured arm pads for maximum comfort "Tube-in Center" foot-plate, assures better side leg support Frame Color: Pearl Silver & Rose Red Axle Adjustable Seat Height ( 18", 19", 20") Weight Capacity: 115 kg. Karma KM 2512 Ergo Lite 2 Wheel
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Revised estimates for the number of human and bacteria cells in the body | bioRxiv - 0 views

biorxiv.org/...036103 gut flora gut gut microbiome gut microbiota
shared by Nathan Goodyear on 12 Jan 16 - No Cached
  • Nathan Goodyear on 12 Jan 16
     
    Good science always challenges established dogma.  Only abstract available here.  Study calls into question the 10:1 claim: bacteria out number human cells by 10:1.  New study finds ratio more near 1:1.  
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Low serum albumin levels and liver metastasis are powerful prognostic markers for survi... - 0 views

onlinelibrary.wiley.com/...cncr.22300 albumin cancer liver metastasis
shared by Nathan Goodyear on 09 Jul 18 - No Cached
  • poor PS,8-10 the presence of liver metastases,7, 9, 10 and elevated LDH levels10 were independent prognostic factors
  • lymphopenia (HR of, 1.89; P = .04) and hypoalbuminemia (HR of 2.7; P < .0001) were independent prognostic factors for overall survival
  • lymphopenia in cancer patients remain unclear and may reflect in part poor nutrition
  • ...2 more annotations...
  • may result in part from the destruction of lymphocytes by the tumor and/or an impaired differentiation of lymphocytes progenitors
  • presence of liver metastasis (HR of, 2.27; P = .0003) and hypoalbuminemia were the 2 most powerful adverse prognostic factors
  • Nathan Goodyear on 09 Jul 18
     
    study finds that lympohopenia and low albumin was associated with the worse prognosis in 317 patients with liver mets with unknown primary cancer. 
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In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epitheli... - 0 views

www.pnas.org/E7301 Ivermectin cancer ovarian cancer oncogene oncogenes
shared by Nathan Goodyear on 20 Mar 18 - No Cached
  • we functionally validated a potent EOC oncogene, KPNB1, and showed its clinical relevance to human EOC
  • a well-established antiparasitic drug, ivermectin, has antitumor effects on EOC through its inhibition of KPNB1
  • EOC has high intertumor and intratumor heterogeneity at the molecular and epigenetic levels
  • ...22 more annotations...
  • the mortality rate of EOC has not been significantly changed for several decades
  • Sequencing revealed that almost all tumors (96%) had mutations in TP53, which serves as a major driver of this cancer
  • Low-prevalence but statistically significant mutations in nine other genes including NF1, BRCA1, BRCA2, RB1, and CDK12 were also identified, but the majority of genes were mutated at low frequency, making it difficult to distinguish between driver and passenger mutations
  • KPNB1 inhibition via any of three KPNB1 siRNAs or importazole treatment induced apoptosis in human EOC cell lines (Fig. 3 A–F and Fig. S4), and was accompanied by an increase in the expression levels of the proapoptotic proteins BAX and cleaved caspase-3
  • Stable overexpression of KPNB1 in SKOV3 and OVCAR3 (Fig. S6) significantly accelerated cell proliferation/survival (Fig. 5 A–C), confirming that KPNB1 functions as an oncogene in EOC
  • KPNB1 overexpression significantly decreased caspase-3/7 activity (Fig. 5D), in addition to the expression levels of cleaved caspase-3 and BAX proteins (Fig. 5E). KPNB1 overexpression also decreased p21 and p27 protein levels (Fig. 5E), as opposed to their increase by KPNB1 inhibition
  • KPNB1 functions as an antiapoptotic and proproliferative oncogene in EOC.
  • Patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1
  • KPNB1 acts as an oncogene in human EOC and represents a promising therapeutic target.
  • ivermectin treatment suppressed cell proliferation/viability in a dose-dependent manner (Fig. 7A), indicating that it exerts an antitumor effect on EOC
  • ivermectin also induced apoptosis
  • ivermectin increased the expression levels of BAX, and cleaved PARP, as well as p21 and p27
  • KPNB1 inhibition is responsible for the antitumor effect of ivermectin
  • we found that ivermectin synergistically reduced cell proliferation/viability in combination with paclitaxel in human EOC cells
  • Single treatment of ivermectin or paclitaxel reduced tumor growth in nude mice, but, notably, combination treatment of ivermectin and paclitaxel almost completely suppressed tumor growth
  • ERBB2, is amplified and overexpressed in many cancers, including breast (31), ovary (31), colon (32), bladder (33), non-small-cell lung (34), and gastric cancer (35), and is a poor prognostic factor in certain cancer types
  • KPNB1 was the second-highest-ranked gene identified in our screen
  • Increased KPNB1 protein levels have been reported in several cancers, including cervical cancer (42), hepatocellular carcinoma (43), and glioma (44), suggesting KPNB1’s oncogenic potential in these tumor types
  • our findings suggest that KPNB1 might serve as a master regulator of cell cycle by regulating several cell cycle-related proteins, including p21, p27, and APC/C family members
  • higher and/or more-frequent doses of ivermectin than currently approved for humans are well tolerated in humans
  • none of the mice in this study treated with the effective dosage of ivermectin for in vivo anticancer therapy showed severe adverse event
  • we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC cell lines than either drug alone
  • Nathan Goodyear on 20 Mar 18
     
    Ivermectin found to be pro-apoptotic for the epithelial ovarian cancer oncogene, KPNB1 in in Vivo study.  This effective anti-parasitic drug inhibits the KPNB1 oncogene.
39More

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

cancerimagingjournal.biomedcentral.com/...s40644-016-0091-3 PET_CT PET scan CT cancer
shared by Nathan Goodyear on 20 Feb 18 - No Cached
  • In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
  • We contend that SUV analysis has virtually no role in this setting.
  • tumours grow as spheres, whereas inflammatory processes are typically linear
  • ...35 more annotations...
  • Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
  • Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
  • Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
  • aerobic glycolysis
  • Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
  • The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
  • When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
  • One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
  • Many benign and inflammatory processes are also associated with high glycolytic activity
  • Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
  • The intensity of uptake in metastases usually parallels that in the primary site of disease
  • For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
  • By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
  • The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
  • Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
  • The exception to this rule is tumours with a propensity for tumour heterogeneity at different sites
  • The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
  • “metabolic signature”
  • For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
  • a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
  • Warburg effect
  • There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
  • This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
  • There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
  • Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
  • patients with hereditary paraganglioma and pheochromocytoma highlight this phenomenon
  • These have intense uptake on FDG PET/CT despite often having low proliferative rate.
  • Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
  • Metabolic activity switches off rapidly following initiation of therapy
  • Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
  • It is therefore critical to perform PET staging before commencement of anti-tumour therapy
  • The potential advantage of routine diagnostic CT is improved anatomic localisation and definition
  • Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
  • If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
  • The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
  • Nathan Goodyear on 20 Feb 18
     
    good read on the PET/CT scan reading.  They mention that tumors are spheres and inflammation is linear, yet inflammation coexists with cancer; hard to simply delineate these on simple terms. I do agree aon the metabolic signature of the PET/CT scan
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Intravenous Ascorbate as a Tumor Cytotoxic Chemotherapeutic Agent - 0 views

www.seanet.com/...d_hypotheses_1995-v44-p207.htm vitamin C cancer IV vitamin C ascorbic acid
shared by Nathan Goodyear on 05 Mar 18 - No Cached
  • There is a 10 — 100-fold greater content of catalase in normal cells than in tumor cells
  • induce hydrogen peroxide generation
  • Ascorbic acid and its salts (AA) are preferentially toxic to tumor cells in vitro (6 — 13) and in vivo
  • ...36 more annotations...
  • related to intracellular hydrogen peroxide generation
  • only be obtained by intravenous administration of AA
  • Preferentially kills neoplastic cells
  • Is virtually non-toxic at any dosage
  • Does not suppress the immune system, unlike most chemotherapy agents
  • Increases animal and human resistance to infectious agents by enhancing lymphocyte blastogenesis, enhancing cellular immunity, strengthening the extracellular matrix, and enhancing bactericidal activity of neutrophils and modulation of complement protein
  • Strengthens the structural integrity of the extracellular matrix which is responsible for stromal resistance to malignant invasiveness
  • 1969, researchers at the NCI reported AA was highly toxic to Ehrlich ascites cells in vitro
  • In 1977, Bram et al reported preferential AA toxicity for several malignant melanoma cell lines, including four human-derived lines
  • Noto et al reported that AA plus vitamin K3 had growth inhibiting action against three human tumor cell lines at non-toxic levels
  • Metabolites of AA have also shown antitumor activity in vitro
  • The AA begins to reduce cell proliferation in the tumor cell line at the lowest concentration, 1.76 mg/dl, and is completely cytotoxic to the cells at 7.04 mg/dl
  • the normal cells grew at an enhanced rate at the low dosages (1.76 and 3.52 mg/dl)
  • preferential toxicity of AA for tumor cells. >95% toxicity to human endometrial adenocarcinoma and pancreatic tumor cells (ATCC AN3-CA and MIA PaCa-2) occurred at 20 and 30 mg/dl, respectively.
  • No toxicity or inhibition was demonstrated in the normal, human skin fibroblasts (ATCC CCD 25SK) even at the highest concentration of 50 mg/dl.
  • the use of very high-dose intravenous AA for the treatment of cancer was proposed as early as 1971
  • Cameron and Pauling have published extensive suggestive evidence for prolonged life in terminal cancer patients orally supplemented (with and without initial intravenous AA therapy) with 10 g/day of AA
  • AA, plasma levels during infusion were not monitored,
  • the long-term, oral dosage used in those experiments (10 g/day), while substantial and capable of producing immunostimulatory and extracellular matrix modulation effects, was not high enough to achieve plasma concentrations that are generally cytotoxic to tumor cells in culture
  • This low cytotoxic level of AA is exceedingly rare
  • 5 — 40 mg/dl of AA is required in vitro to kill 100% of tumor cells within 3 days. The 100% kill levels of 30 mg/dl for the endometrial carcinoma cells and 40 mg/dl for the pancreatic carcinoma cells in Figure 2 are typical
  • normal range (95% range) of 0.39-1.13 mg/dl
  • 1 h after beginning his first 8-h infusion of 115 g AA (Merit Pharmaceuticals, Los Angeles, CA), the plasma AA was 3.7 mg/dl and at 5 h was 19 mg/dl. During his fourth 8-h infusion, 8 days later, the 1 h plasma level was 158 mg/dl and 5 h was 185 mg/dl
  • plasma levels of over 100 mg/dl have been maintained in 3 patients for more than 5 h using continuous intravenous infusion
  • In rare instances of patients with widely disseminated and rapidly proliferating tumors, intravenous AA administration (10 — 45 g/day) precipitated widespread tumor hemorrhage and necrosis, resulting in death
  • Although the outcomes were disastrous in these cases, they are similar to the description of tumor-necrosis-factor-induced hemorrhage and necrosis in mice (52) and seem to demonstrate the ability of AA to kill tumor cells in vivo.
  • toxic effects of AA on one normal cell line were observed at 58.36 mg/dl and the lack of side effects in patients maintaining >100 mg/dl plasma levels
  • Although it is very rare, tumor necrosis, hemorrhage, and subsequent death should be the highest priority concern for the safety of intravenous AA for cancer patients.
  • Klenner, who reported no ill effects of dosages as high as 150 g intravenously over a 24-h period
  • Cathcart (55) who describes no ill effects with doses of up to 200 g/d in patients with various pathological conditions
  • following circumstances: renal insufficiency, chronic hemodialysis patients, unusual forms of iron overload, and oxalate stone formers
  • Screening for red cell glucose-6-phosphate dehydrogenase deficiency, which can give rise to hemolysis of red blood cells under oxidative stress (57), should also be performed
  • any cancer therapy should be started at a low dosage to ensure that tumor hemorrhage does not occur.
  • patient is orally supplementing between infusions
  • a scorbutic rebound effect can be avoided with oral supplementation. Because of the possibility of a rebound effect, measurement of plasma levels during the periods between infusions should be performed to ensure that no such effect takes place
  • Every effort should be made to monitor plasma AA levels when a patient discontinues intravenous AA therapy.
  • Nathan Goodyear on 05 Mar 18
     
    Older study, 1995, but shows the long-standing evidence that IVC preferentially is cytotoxic to cancer cells.`
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Interleukin-10 mediates the neuroprotection of hyperbaric oxygen therapy against trauma... - 0 views

www.ncbi.nlm.nih.gov/...24291771 hyperbaric hyperbaric therapy brain TBI traumatic brain injury IL-10
shared by Nathan Goodyear on 17 May 17 - No Cached
  • Nathan Goodyear on 17 May 17
     
    abstract of animal study finds that hyperbaric therapy provides neuroprotection via increase in IL-10; improved blood-brain barrier, improved tight junctions were about of the benefit found.
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المزيد والمزيد من الناس يختارون جراحة القلب في الهند لجراحات القلب الصعبة - 0 views

arabhealthblogs.blogspot.com/...-best-cardiac%20-surgeons.html جراحة القلب في الهند تكلفة جراحة القلب في الهند جراحة القلب منخفضة التكلفة الهند جراحة القلب بأسعار معقولة الهند أفضل سعر لجراحة القلب في الهند جراحو القلب في الهند أفضل جراحي القلب في الهند أفضل 10 جراحي قلب في الهند
shared by indian-health on 04 Oct 21 - No Cached
  • indian-health on 04 Oct 21
     
    حصل أفضل جراحي القلب في الهند أيضًا على العديد من الجوائز لمساهماتهم الرائدة وعلاجات القلب التي لا تصدق. اقرأ المزيد https://bit.ly/3isafMr اتصل بنا + 91-9371136499 راسلنا على البريد الإلكتروني contact@indianhealthguru.com "جراحة القلب في الهند" "تكلفة جراحة القلب في الهند" "جراحة القلب منخفضة التكلفة في الهند" "جراحي القلب في الهند" "أفضل جراحي القلب في الهند" "أفضل 10 جراحي قلب في الهند"
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