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WorkSure MedPharma knowledge partner
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WorkSure MedPharma Knowledge Partner
WorkSure MedPharma Knowledge Partner

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Methyldopa may prevent/treat type 1 diabetes by blocking disease specific Human leucocyte antigen
The Journal of clinical Investigation, February 2018
Insulin-dependent diabetes mellitus or type 1 diabetes is a metabolic disorder that arises as a result of destruction of beta-cells of pancreas by body’s own immune cells. Numerous immunotherapies have been applied for prevention/reduction of beta-cell degeneration but these shown poorer clinical benefits. Studies reported the role of Human leucocyte antigen, (HLA gene complex) in pathogenesis of various autoimmune disorders while the presence of HLA-DQ8 allele has been detected in more than 50% of type I diabetic patients. This makes the antigen DQ8 as an important therapeutic target to modify immunological response that could be helpful in treating diabetes.

Methyldopa, an established anti-hypertensive drug selected by molecular docking using crystal structure of DQ8 has shown a potential in treatment of type 1 diabetes. In a clinical study conducted on 20 DQ8 positive type 1 diabetes participants (18-46 years), with methyldopa over a 6-week period, a 40% reduction in DQ8 antigen presentation was observed. In addition, methyldopa treated patients showed reduced inflammatory insulin-specific T-cell responses with good glucose tolerance and maintained beta-cell function over 3-months. Though the results have been encouraging, a longer duration study is needed to completely evaluate the metabolic efficacy of methyldopa (DQ8 antigen blockers) in the treatment of type 1 diabetes.
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Inducing specific T cells may prevent skin infection against methicillin-resistant Staphylococcus aureus
The Journal of Clinical Investigation, February 2018
Staphylococcus aureus is one of the most common pathogen responsible for skin infections in people. In addition, the multidrug resistant strains like methicillin-resistant Staphylococcus aureus (MRSA) results in severe infections with a high recurrence rate. These infections may further lead to life-threatening conditions (like, sepsis or pneumonia) especially in immuno-compromised people. In a study conducted with immunocompromised mouse model (with impaired neutrophil recruitment and IL-17 responses), the primary S. aureus skin infection resulted in relatively large skin lesions and high bacterial burdens. However, the mice undergone reinfections were found protected. The release of γδ T cells from skin-draining LNs are responsible for restoring neutrophil recruitment. This response is mediated by release of TNF and IFN- γ as reported by the increased level of TNF (5-fold) and IFN-γ (2-fold) in reinfected mice. This phenomenon was further confirmed by the elevated level of γδ T cells in immunocompromised humans (IRAK4-deficient) with recurrent S. aureus skin infections. These findings suggest that clonotypic expansion of γδ T cells is responsible for inducing long-term immunity against recurrent bacterial skin infections. Hence, targeting specific T cells could be a novel approach for treatment of MRSA skin infections.
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WorkSure Team Wishes you a Merry Christmas and happy new year
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Excessive calcium intake for postmenopausal osteoporosis may be harmful
Maturitas, The European menopause journal, 2018 (online published)
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Excessive calcium intake for postmenopausal osteoporosis may be harmful
Maturitas, The European menopause journal, 2018 (online published)
Osteoporosis is a condition in which the bones become fragile and brittle, leading to a higher risk of fractures than in normal bone. Inadequate calcium accumulation can lead to a suboptimal bone-mass peak and low bone mineralization. EMAS has recently released clinical guidelines for health professional which will help them advice women regarding calcium intake for the prevention of postmenopausal osteoporosis. According to the guidelines the dietary levels of elemental calcium intake vary between 700 and 1200 mg throughout life and vitamin D supplementation along with calcium may reduce fractures. National osteoporosis society NOS defined 400 mg/day as a lowest amount of calcium essential for a healthy skeleton. Intake below this level may increase fragility fracture risk. The extreme intake of calcium higher than 2000 mg/day is dangerous and can lead to cardiovascular events, urolithiasis and even fractures.
Clinical studies evaluating the role of calcium for the reduction of fracture risk has shown inconsistent results. Eg. pooled results from 7 prospective cohort studies having 170,991 women, 2,954 hip fractures and 5 prospective cohort studies having 68,606 men, 214 hip fractures found that calcium intake had not significantly improved hip fracture risk both in women or men. Metanalysis of 16 randomized clinical trials by the US Preventive Services Task Force has shown benefit of combined vitamin D and calcium supplementation in reducing fracture risk.
In summary, the benefits of calcium supplementation have been shown only when it is combined with vitamin D. Excessive calcium intake seems of no benefit and could probably be unsafe.
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*Even high levels of Good cholesterol (HDL) elevates mortality risk
European Heart Journal, Apr 2017*

High density lipoproteins (HDL) are a complex mixture of lipoproteins having the protein, phospholipid, and free cholesterol on the surface, with cholesteryl ester (CE) and triglycerides (TG) in the core. HDL concentrations are inversely related with Cardiovascular (CV) disease and death across a range of concentrations.
A total of (n= 52268) men and (n=64240) women from the two prospective population-based studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, were clinically followed up for an average period of 6 years (range: 0–23), with 5.7 years
(0–11), and 19.9 years (0–23) for the CGPS and CCHS. During follow-up, 561) men and 5059 women died with unknown cause providing mortality rates of 17.1 and 12.1 per 1000 person-years.
The association between HDL concentrations and all-cause mortality was U-shaped in men and women, with both extreme high and low concentrations being associated with high all-cause mortality risk.
The men with extreme high HDL (95-115 mg/dL) and (116 mg/dL) had hazard ratios of 1.36 and 2.06 respectively when compared with men in the reference group (58–76 mg/dL). Women with extreme level of HDL (116–134 mg/dL), (135 mg/dL) and (39 mg/dL) had hazard ratios of 1.10, 1.68 and 1.78 respectively when compared with reference group (77–96 mg/dL). The findings concluded that extremely raised levels of HDL cholesterol had high all-cause mortality


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Wishing you a very happy and prosperous Diwali
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Modified pancreatic beta cell adenomas can help to fight diabetes
Nature Communications, Oct 2017
Insulinomas are very rare, small (1–2 cm), slowly proliferating adenomas. These are "pancreatic beta cell adenomas" that secretes too much of the hormone insulin. Insulinomas are benign and can be treated by laparoscopic removal. Beta cells play an essential role in the development of diabetes. These tiny cells originate in our pancreas produce insulin, and a loss of beta cells is known to be a cause of type 1 diabetes.
The integrated and organized analysis of a large human Insulinomas cohort (N=38), focused on non-MEN1, was done for whole-exome sequencing (WES) and RNA sequencing (RNAseq). Thirty-four subjects’ data was taken from The Icahn School of Medicine at Mount Sinai Bio repository; WES data for an additional four Insulinomas were taken from Cao et al. RNAseq was performed on purified beta cells from 22 donors of normal human cadaveric islets.
WES was performed on genomic DNA from insulinomas and patient-matched blood cells (as normal controls, 22 patients), with sequencing depth of 79X and 105X for the blood and tumour samples, respectively. 258 somatic single nucleotides variants and 20 non somatic variants, that altered the protein sequence, were identified. Computationally generated two molecular pictures were collected from that data, one for the Insulinomas and other for the normal beta cell, and critical differences were identified.
Mostly Insulinomas exhibited genetic mutations, copy variants and dysregulation of epigenetic factors in polycomb and trithorax families. These were collectively called as new genetic "candidates" for inducing the regeneration of beta cells. The outcomes revealed that insulinoma may be a valuable approach towards diabetes treatment.


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Health Economic Outcome Research: An aid to better therapeutic decision making
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