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Volume 5, Problème 1 (2021)

Résumé étendu

The role of the prostaglandin PGE2 in pancreatic β- cell death in the context of type 2 diabetes

Danielle Melloul

Type 2 diabetes (T2DM) could be a complex disease characterized by β-cell failure within the setting of insulin resistance. The underlying causes of β-cell failure are complex and result from the interplay between genetic and environmental factors. Consumption of foods high in saturated fatty acids (FFAs) and also the elevation of circulating FFAs are implicated as a crucial causative link among obesity, insulin resistance and β-cell dysfunction. Moreover, cumulative evidence indicates that there's a decrease in β-cell mass thanks to β-cell death in T2DM patients. FFAs can induce β-cell death by apoptosis, even within the absence of high glucose, whereas unsaturated fatty acids are usually protective. Several mechanisms are implicated in palmitate-induced β- cell death, including ceramide formation resulting in altered lipid partitioning, oxidative stress, and inflammation. Mild inflammation has been suggested to play a job within the pathogenesis of T2DM. Another family of molecules involved in inflammation is prostaglandins, but their role within the development of T2DM is poorly understood. this research aims at understanding the impact of prostaglandins (PGE2) on β-cell death. We show that PGE2-induced apoptosis is mediated by p38MAPK. To further elucidate the downstream signaling pathway of prostaglandins in β-cells, we studied the differential expression of PGE2 receptors (EP1-EP4) and located that the EP3 receptor is differentially upregulated in islets from T2DM patients. the importance of this receptor in β-cell apoptosis was tested by using EP3 specific siRNA or EP3 antagonist, and located that they led to a big rescue of those cells from apoptosis. In comparison to the opposite PGs, the role of PGE2 in β-cell function has been studied in greatest detail. this might stem from early reports demonstrating that the AA metabolite chargeable for decreased insulin secretion was PGE2 (Robertson 1988). However, several groups have called into question the solely inhibitory effect of PGE2 on insulin secretion. There are numerous lines of evidence in support of an inhibitory role of PGE2 on β-cell function in β-cell lines, isolated islets, and in vivo. In vitro studies have demonstrated that PGE2 treatment decreases GSIS in several different β-cell lines, including the HIT-T15, βHC13, and INS-1 (832/3) lines (Kimple et al. 2013; Meng et al. 2009; Robertson et al. 1987; Seaquist et al. 1989).

Résumé étendu

Novel therapies in pediatric inflammatory bowel disease

Karen Frost

The incidence and prevalence of pediatric Inflammatory Bowel Disease (IDB) still rise. it's expected that earlier diagnosis lends to higher treatment and outcome of disease. Nearly 1 in 4 patients are diagnosed at the age of under 20 years old. There are two main tiers of IBD: Crohn???s disease and colitis. the precise cause continues to be unknown however genetics and therefore the environment do play a job. there's currently no cure for IBD, but patients are usually managed with treatment. Treatments are often approached in a very step-up or top down algorithm. within the past, patients required steroids to realize remission, or surgery was more imminent if lack of response make up my mind. At the current time, with more novel therapies in IBD, patients are able to achieve remission at a sooner time, thereby avoiding surgery. To date, there are therapies that include 5ASA, immune-modulators and biologic therapies. Biologic therapies are still seen as novel in pediatrics. The role of monoclonal antibodies (mAbs) plays an enormous role within the current IBD treatment paradigm. the main target of this subject will review pediatric armamentarium of mAbs like anti TNF, anti ILs and gut selective mAbs, watching its targeted mechanism, the dosing recommendation, safety data and current practice.

Résumé étendu

Liver stiffness predicts relapse after Direct acting antiviral therapy against chronic Hepatitis C Virus infection

Ali Abdelrahman Sayed

Background & study aim: Assessment of fibrosis in chronic hepatitis has always been considered of utmost relevance for patient care in clinical hepatology. Over the last years, multiple non-invasive methods were used for diagnosis of hepaic fibrosis, including transient Elastography additionally to clinical and biochemical parameters or combinations of both methods. Serum markers and elastography are considered useful techniques for diagnosing severe liver fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus infected patients. Also, liver stiffness may help to foretell treatment response to antiviral therapy. We aimed to judge changes of Transient elastography values further as serum fibronectin and AST to platelet ratio index in patients (APRI) treated with sofosbuvir- based treatment regimen. Methods: this can be a follow-up study including 100 chronic HCV Egyptian patients treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded still as serum fibronectin and APRI were calculated at baseline and SVR12. Results: There was a big improvement of platelets counts, ALT and AST levels, which successively cause significant improvement in APRI scores at SVR12. Liver stiffness measurements were significantly lower at SVR12 (15.40�?��8.96 vs 8.82�?��4.74 kPa, P =0.000). There was significant decline in serum fibronectin from baseline to SVR 12 (524.14�?��237.61 vs 287.48�?��137.67, P=0.000). Key words: hepatitis C Virus, Liver stiffness, Transient Elastography and Fibronectin. Conclusion: Nonpegylated interferon (IFN) or pegylated IFN (PEGIFN) together with ribavirin (RBV) were the most drugs used for the management of HCV infection . the employment of the first-generation direct acting antivirals (DAAs) boceprevir and telaprevir with PEGIFN and RBV increased the general SVR rates to 68%-75% for naive patients and to 59%-88% for treatment-experienced patients, whether or not these regimens were used just for the treatment of genotype 1 HCV infection . Despite the positive effect of HCV infection eradication on patients??? prognosis, few data about liver cirrhosis/fibrosis regression are accessible

Résumé étendu

Clostridium difficile infection and risk of colectomy in patients with inflammatory bowel disease: A biasadjusted meta-analysis

Yingxi Chen

Clostridium difficile Infection (CDI) may be a common complication of inflammatory bowel diseases (IBDs) and is related to worse outcome. Variable rates of colectomy are reported among IBD complicated by CDI. We conducted a scientific review and biasadjusted meta-analysis of studies to assess the association between CDI and colectomy among patients with IBD. Studies were limited to cohort, case???control and cross-sectional studies reporting colectomy risk stratified by CDI in patients with IBD. We estimated summary ORs and 95% CIs using the quality-effects model. Study quality was assessed using an adaptation of the Newcastle???Ottawa scale. We found that CDI was a major risk factor for colectomy among patients with IBD, mainly patients with colitis, almost doubling the chances (OR 1.90; 95% CI, 1.23???2.93). There was significant heterogeneity across studies (Q=22.02, P<0.001; I2=68%). Funnel plots were grossly asymmetrical. Results of sensitivity analysis restricting studies to those reporting inflammatory bowel disease only and studies using laboratory tests to substantiate CDI were in keeping with the result from the most analysis. CDI could be a significant risk factor for colectomy in patients with IBD. Further research is required to research the attributable risks of surgery thanks to CDI among patients with inflammatory bowel disease. Inflammatory bowel disease (IBD), comprising colitis (UC) and regional enteritis (CD), may be a chronic relapsing disorder of genetically susceptible individuals exposed to environmental precipitants.The initial management of IBD is medical therapy until treatment fails or a complication arises. Most patients with CD and up to 35% of patients with UC required intestinal resection during the course of their disease.However, improved medical therapy has resulted in decreased surgical interventions among patients with IBD.

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