MAF precursor activity has also been lost or reduced after Gc-globulin treatment in some cancer cell lines
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Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside - 0 views
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This appears to result from the deglycosylated ɑ-N-acetylgalactosaminidase (nagalase) secreted from cancerous cells
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Studies have shown that the production of nagalase has a mutual relationship with Gc-MAF level and immunosuppression
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It has been demonstrated that serum levels of nagalase are good prognosticators of some types of cancer
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The nagalase level in serum correlates with tumor burden and it has been shown that Gc-MAF therapy progresses, nagalase activity decreases
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It has been shown that Gc-MAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1
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The effect of Gc-MAF on chemotaxis or activation of tumoricidal macrophages is likely the main mechanism against angiogenesis.
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Administration of Gc-MAF stimulates immune-cell progenitors for extensive mitogenesis, activates macrophages and produces antibodies. “This indicates that Gc-MAF is a powerful adjuvant for immunization.”
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Cancer cell lines do not develop into tumor genes in mouse models after Gc-MAF-primed immunization (29-31) and the effect of Gc-MAF has been approved for macrophage stimulation for angiogenesis, proliferation, migration and metastatic inhibition on tumors induced by MCF-7 human breast cancer cell line
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The protocol included: "a high dose of second-generation Gc-MAF (0.5 ml) administered twice a week intramuscularly for a total of 21 injections.”
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Yamamoto et al. showed that the administration of Gc-MAF to 16 patients with prostate cancer led to improvements in all patients without recurrence
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Inui et al. reported that a 74-year-old man diagnosed with prostate cancer with multiple bone metastases was in complete remission nine months after initiation of GcMAF therapy simultaneously with hyper T/NK cell, high-dose vitamin C and alpha lipoic acid therapy
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It has also been approved for non-neoplastic diseases such as autism (41), multiple sclerosis (42, 43), chronic fatigue syndrome (CFS) (40), juvenile osteoporosis (44) and systemic lupus erythematous (45).
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Gc-MAF has been verified for use in colon, thyroid (38), lung (39), liver, thymus (36), pancreatic (40), bladder and ovarian cancer and tongue squamous carcinoma
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Prostate, breast, colon, liver, stomach, lung (including mesothelioma), kidney, bladder, uterus, ovarian, head/neck and brain cancers, fibrosarcomas and melanomas are the types of cancer tested thus far
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weekly administration of 100 ng Gc-MAF to cancer at different stages and types showed curative effects at different follow-up times
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Studies have shown that weekly administration of 100 ng Gc-MAF to cancer patients had curative effects on a variety of cancers
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Because the half-life of the activated macrophages is approximately one week, it must be administered weekly
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In vivo weekly intramuscular administration of Gc-MAF (100 ng) for 16-22 weeks was used to treat patients with breast cancer
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individuals harboring different VDR genotypes had different responses to Gc-MAF and that some genotypes were more responsive than others
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Administration of Gc-MAF for cancer patients exclusively activates macrophages as an important cell in adaptive immunity
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Gc-MAF supports humoral immunity by producing, developing and releasing large quantities of antibodies against cancer. Clinical evidence from a human model of breast cancer patients supports this hypothesis
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It is likely that the best therapeutic responses will be observed when the nutritional and inflammatory aspects are taken together with stimulation of the immune system
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it should be noted that no harmful side effects of Gc-MAF treatment have been reported, even when it was successfully administered to autistic children
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The natural activation mechanism of macrophages by Gc-MAF is so natural and it should not have any side effects on humans or animal models even in cell culture
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Besides the Gc-MAF efficacy on macrophage activity, it can be a potential anti-angiogenic agent (28) and an inhibitor of the migration of cancerous cells in the absence of macrophages (47).
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Activating or modifying natural killer cells, dendritic cells, DC, CTL, INF and IL-2 have all been recommended for cancer immunotherapy
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It has been reported that nagalase cannot deglycosylate Gc-MAF as it has specificity for Gc globulin alone
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inflammation-derived macrophage activation with the participation of B and T lymphocytes is the main mechanism
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Previous clinical investigations have confirmed the efficacy of Gc-MAF. In addition to activating existing macrophages, Gc-MAF is a potent mitogenic factor that can stimulate the myeloid progenitor cells to increase systemic macrophage cell counts by 40-fold in four days
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Tricycle Manufacturers - 0 views
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Comfortable Ergonomics For Wheelchair Users lightweight frames and seats Tricycle Manufacturers increase strength and coordination durability and safety Karman Ergonomic Wheelchair upper body strength
shared by wheelchairindia9 on 13 May 15
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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
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Arch Intern Med -- Abstract: Effects of Calcium Supplementation on Clinical Fracture an... - 0 views
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Persistent sexual dysfunction after discontinuatio... [J Sex Med. 2008] - PubMed result - 0 views
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SSRIs can cause long-term effects on all aspects of the sexual response cycle that may persist after they are discontinued
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Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views
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vitamin C IV vitamin C cancer cancer stem cells milk thistle silymarin ascorbic acid bee propolis CAPE glycolytic inhibitor natural
shared by Nathan Goodyear on 08 Dec 17
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Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
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ultimately leading to treatment failure in patients with advanced disease [1-3]. They have been directly implicated mechanistically in tumor recurrence and metastasis, resulting in poor patient survival
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Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
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high levels of NAD(P)H auto-fluorescence are known to be a surrogate marker for mitochondrial “power”, high OXPHOS capacity and increased ATP production
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an intact NAD+ salvage pathway is strictly required for mammosphere formation, supporting our results using NAD(P)H auto-fluorescence, which enriched CSC activity by more than 5-fold.
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Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
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we show that two other natural products that function as effective glycolysis inhibitors, also inhibited mammosphere formation. More specifically, vitamin C (ascorbic acid), which induces oxidative stress and inhibits the activity of GAPDH (a key glycolytic enzyme) [17], also inhibited mammosphere formation, with an IC-50 of 1 mM (Figure 7B). Therefore, vitamin C was ~10 times more potent than 2-DG at targeting CSC propagation
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silibinin (the major active constituent of silymarin, an extract of milk thistle seeds) [18], which specifically functions as an inhibitor of glucose uptake, blocked mammosphere formation, with an IC-50 between 200 and 400 µM
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caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
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Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
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CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
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CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
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CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
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Our data directly shows that a small fraction of the total cell population, characterized by increased PGC1α activity, high mitochondrial ROS/H2O2 and high NADH levels, has the ability to survive and grow under anchorage-independent conditions, driving mammosphere formation
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We highlight the utility of certain natural products, such as Silibinin, Vitamin C and CAPE, that could be used to therapeutically target CSCs. Silibinin is the major active component of silymarin, which is an extract prepared from milk thistle seeds.
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Previous studies have also shown that when non-CSCs and CSCs are both fed mitochondrial fuels (such as L-lactate or ketone bodies), that CSCs quantitatively produce more NADH in response to this stimulus
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The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent
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Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme.
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Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS
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Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis
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Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality
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CAPE quantitatively reduces mitochondrial oxygen consumption (OCR), while inducing a reactive increase in glycolysis (ECAR). As such, it potently inhibits mammosphere formation with an IC-50 of ~2.5 µM. Similarly, it also significantly inhibits cell migration
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we also demonstrate that 7 different inhibitors of key energetic pathways can be used to effectively block CSC propagation, including three natural products (silibinin, ascorbic acid and CAPE). Future studies will be necessary to test their potential for clinical benefit in cancer patients.
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The future of cancer therapy is cancer stem cells. Study finds that Vitamin C, silymarin, and bee propolis blocks mitochondrial energy pathways in cancer stem cells. Vitamin C is a known glycolytic inhbitor. Vitamin C was found to inhibit glycolysis via GAPDH targeting to inhibit the energy pathways of the mitochondria in CSCs. The authors propse that Vitamin C can be used as add on therapies for conventional therapies to specifically attack the CSCs and their contribution to recrurence, treatment resistance, and metastasis potential all in addition to the ability of vitamin C to reduce the side effects of chemotherapy.
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Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer ... - 0 views
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daily doses up to 400 mg of HCQ or 250 mg CQ for several years are considered to carry an acceptable risk for CQ-induced retinopathies, with the exception of individuals of short stature
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chronic CQ or HCQ therapy be monitored through regular ophthalmic examinations (3–6 month intervals), full blood counts and blood glucose level checks
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long-term HCQ exposure, skeletal muscle function and tendon reflexes should be monitored for weakness
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both CQ and HCQ, specific caution is advised in patients suffering from impaired hepatic function (especially when associated with cirrhosis), porphyria, renal disease, epilepsy, psoriasis, glucose-6-phosphate dehydrogenase deficiency and known hypersensitivity to 4-aminoquinoline compounds
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CQ can prevent the entrapment of protonated chemotherapeutic drugs by buffering the extracellular tumour environment and intracellular acidic spaces
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the expression levels of TLR9 are higher in hepatocellular carcinoma, oesophageal, lung, breast, gastric and prostate cancer cells as compared with adjacent noncancerous cells, and high expression is often linked with poor prognosis
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TLR9-mediated activation of the NF-κB signalling pathway and the associated enhanced expression of matrix metalloproteinase-2 (MMP-2), MMP-7 and cyclo-oxygenase 2 mRNA
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HCQ can activate caspase-3 and modulate the Bcl-2/Bax ratio inducing apoptosis in CLL, B-cell CLL and glioblastoma cells
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In triple-negative breast cancer, CQ was shown to eliminate cancer stem cells through reduction of the expression of Janus-activated kinase 2 and DNA methyl transferase 1 [106] or through induction of mitochondrial dysfunction, subsequently causing oxidative DNA damage and impaired repair of double-stranded DNA breaks
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Therapies used in combination with CQ or HCQ include chemotherapeutic drugs, tyrosine kinase inhibitors, various monoclonal antibodies, hormone therapies and radiotherapy
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Most studies hypothesise that CQ and HCQ could increase the efficacy of other anti-cancer drugs by blocking pro-survival autophagy.
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daily doses between 400 and 1200 mg for HCQ are safe and well tolerated, but two studies identified 600-mg HCQ daily as the MTD
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Adverse Events Associated with Testosterone Administration - NEJM - 0 views
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Anabolic steroids, acute myocardial infarction and polycythemia: A case report and revi... - 0 views
www.ncbi.nlm.nih.gov/...PMC2663437
Testosterone polycythemia side effects complications anabolic steroids
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Comparison of physical and emotional side effects ... [Menopause. 2002 Jul-Aug] - PubMe... - 0 views
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he lesser side effects of the micronized progesterone-containing regimen suggest that some women may prefer it to an MPA-containing regimen.
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Phase I Study of Human Chorionic Gonadotropin Given Subcutaneously to Patients With Acq... - 0 views
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Oral S-adenosylmethionine in depression: a randomi... [Am J Psychiatry. 1990] - PubMed ... - 0 views
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The results suggest that oral S-adenosylmethionine is a safe, effective antidepressant with few side effects and a rapid onset of action
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Ergonomic Wheelchair - 0 views
www.wheelchairindia.com/...ERGONOMIC-WHEELCHAIR
Effect of Wheelchair Design on Posture and Comfort of Users Ergonomic wheelchair for Comfort Designed to Fit Almost Everyone Lightweight Ergonomic Wheelchair Karma S Ergo 105 Wheelchair Ergonomic hand rims
shared by wheelchairindia9 on 17 Feb 16
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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. Also features companion brakes located on handles for added safety and comfort. Ergonomic Wheelchairs are ultra lightweight and have a supportive seating system to provide pressure relief and anti-slippage giving the user excellent stability and posture support. . Better Ergonomic wheelchair for Comfort: Sit for any length of time in a fixed position in a traditional transport chair and it will feel how painful bad ergonomics can be. It is fully reclined 25° angle, which minimizes slumping and sliding. And because of this can be easily adjusted with the push of a button, it can change positions frequently over time, reducing the chance of secondary conditions that may include pressure sores. Designed to Fit Almost Everyone: It is one of the most extensively researched seat profiles specifically design to accommodate users ranging in size from small women to large men, with the greatest amount of comfort and proper posture/spinal support. 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. Ergonomic Wheelchair is Right: Ergonomic Wheelchair is designed for users who will spend a large amount of time in the chair. This wheelchair'
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PF Night Splint Derotation - 0 views
www.wheelchairindia.com/...PF-Night-Splint-Derotation
Understanding The Role Of Treating Night Splints plantar fascia and intrinsic musculature Derotation foot splinting provides support to the knee multiple orthopedic problems Less slippage of product
shared by wheelchairindia9 on 21 Mar 16
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PF Night Splint (Derotation) Applications Prevention and correction of foot drop. Night splint for early healing. Ambulatory, can be used as a day splint. Perfect post-operative immobilisation and derotation. Peroneal / Peritibial nerve or muscle damage. Ankle or Plantar flexion contracture and functional alignment. Can be used to protect the diabetic/ injured ankle & foot. PF Night Splint (Derotation) Features Removable de-rotation bar. Moulded foot casing, aesthetically pleasing and durable. Effective Liner, improved comfort. Highly functional Design, customized degree of dorsiflexion. Double strapping mechanism, better grip.
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Metabolic Effects of Liothyronine Therapy in Hypothyroidism: A Randomized, Double-Blind... - 0 views
press.endocrine.org/...jc.2011-1329
T4 T3 hypothyroid hypothyroidism thyroid lipids weight loss metabolism cholesterol hormones
shared by Nathan Goodyear on 24 Sep 14
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tissue euthyroidism is the net result of multiple steps including conversion of the prohormone T4 into its active metabolite T3, which is ultimately responsible for signaling at the end-organ target level
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The circulating and intracellular pools of T3 of treated hypothyroid patients (i.e. devoid of endogenous TH production) depend entirely on the conversion of exogenous l-T4 into T3
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The changes in serum lipid metabolism parameters are similar to the effects observed with drugs approved for the treatment of dyslipidemia
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This differential response appears to be limited to the lipid metabolism and SHBG, whereas no differences in indices of insulin resistance were detected. This is remarkable because hyperthyroid states are associated with an increase in hepatic gluconeogenesis (37), and overt thyrotoxicosis is a known cause of secondary diabetes.
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Despite the increase in serum T3, the l-T3 treatment did not cause major changes in cardiovascular or musculoskeletal function, as indicated by the echocardiographic and maximal exercise tolerance tests and DXA studies.
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Similarly, no significant differences were observed in blood pressure, heart rate, or endothelial vascular function
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In conclusion, the results of this pharmacology, proof-of-concept study indicate that replacement therapy of hypothyroidism with l-T3, compared with l-T4 causes weight loss and favorable changes in the lipid profile without appreciable side effects
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The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A... - 0 views
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White blood cells, including neutrophils and monocytes, accumulate concentrations of vitamin C up to 100 times greater than that of plasma
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Vitamin C is a crucial component of both the innate (nonspecific) and adaptive (specific) portions of the immune system
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maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
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vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
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effects of high-dose vitamin C on cytokine levels in cancer patients, finding decreased amounts of the cytokines Interleukin-1 alpha (IL-1 alpha), IL-2, IL-8, and tumor necrosis factor-alpha (TNF-alpha) after high-dose vitamin C infusion
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when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
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vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
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human leukocytes, neutrophils, in particular, possess the ability to transport the oxidized form of vitamin C across its membrane to use as a defense mechanism against ROS produced during an immune response
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Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
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can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic
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subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
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subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
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Studies have demonstrated that those with low levels of vitamin C are at a significantly higher risk of respiratory infection compared to those with normal levels
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viral cold duration was reduced by about 8% in adults and 13.5% in children using prophylactic daily doses of 200 mg of oral vitamin C
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prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
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combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
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high-dose oral supplementation of vitamin C managed to prevent or reduce symptoms if taken before or just after the onset of cold- or flu-like symptoms
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improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
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Patients with COVID-19 will likely also experience depletion in serum levels of vitamin C as a direct result of the upregulation of the immune system to combat the infection
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Colunga et al. suggested that oral vitamin C can be combined with oral Quercetin, an antiviral flavonoid, to improve Quercetin’s ability to block viral membrane fusion of SARS-CoV-2
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It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
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some evidence to support that prophylactic use of vitamin C helps reduce the severity of respiratory infection symptoms once a subject has already been infected
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other studies were unable to find any definitive improvement concerning therapy with vitamin C
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Fowler et al. aimed to see if a high-dose vitamin C infusion would benefit patients affected by ARDS, but they were unable to conclude that vitamin C infusion, compared to a placebo, could decrease vascular inflammation and damage in ARDS
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in a sample of 67 COVID-19-positive ICU patients, 82% of them displayed plasma vitamin C levels below 0.4 mg/dL
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continuous vitamin C infusion at a rate of 60 mg/kg/day for four days decreased the need for mechanical ventilation and vasopressor use but had no significant effect on overall mortality
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Carr et al. suggested that high-dose IV vitamin C is most effective when treating sepsis as septic patients receiving the normal daily recommendations through diet still showed decreased vitamin C levels
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High-dose IV vitamin C treatment has also been shown by Kakodkar et al. to decrease syndecan-1, an endothelial glycocalyx that contributes to mortality in septic patients
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combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
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combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
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treatment of severe sepsis using a high dose (up to 200 mg/kg/day) of IV vitamin C was explored in phase I, a double-blind, randomized, placebo-controlled trial by Fowler et al. [75]. Their findings included a reduction in SOFA scores and decreased vascular injury compared to a placebo control group, all while showing minimal adverse side effects
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Maintaining a daily intake of 75 and 100 mg for men and women, respectively, as recommended by the U.S. Institute of Medicine
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Acute Effects of Triiodothyronine (T3) Replacement Therapy in Patients with Chronic Hea... - 0 views
jcem.endojournals.org/...1351.long
T3 fT3 thyroid disease low T3 syndrome T3 syndrome cardiomyopathy CHF congestive heart failure
shared by Nathan Goodyear on 03 Jul 12
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IV T3 was given to patients with chronic heart failure. What the study found may surprise you: improved heart function (ventricular), improved BNP, decrease heart rate, no side effects. T3 has been shown to be more predictive of cardiac death in those with cardiac disease, than elevated lipids or decreased ejection fraction.
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Effects of physiologic testosterone therapy on qua... [Menopause. 2014] - PubMed - NCBI - 1 views
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Effects of Ginger for Nausea and Vomiting in Early Pregnancy: A Meta-Analysis - 0 views
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PLOS ONE: Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practiti... - 0 views
www.plosone.org/...journal.pone.0011414
IV vitamin C vitamin C intravenous alternative medicine complementary alternative
shared by Nathan Goodyear on 29 Sep 13
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