High Serum Vaspin Concentrations in Patients with Ulcerative Colitis

Background: Adipocytokines are associated with energy homeostasis and mediate various immune responses and inflammatory processes. Vaspin is a novel adipocytokine that is thought to exhibit anti-inflammatory effects. Aim: We aimed to evaluate serum vaspin levels in inflammatory bowel disease (IBD) and determine its possible associations with the course and to clarify its intestinal localization. Methods: Serum samples were obtained from patients with Crohn\u27s disease (CD; n = 30) and ulcerative colitis (UC; n = 33) and from healthy volunteers (controls; n = 26). Enzyme-linked immunosorbent assays were performed for all patients. Vaspin immunohistochemical staining was performed for intestines affected with IBD. Results: Serum vaspin concentrations were significantly higher in patients with UC than in patients with CD and controls (422.9 ± 361.9 vs. 163.4 ± 116.2 vs. 147.5 ± 89.4 pg/mL, respectively; P < 0.01). There was no difference in the serum vaspin concentrations between the patients with CD and controls. There was also no difference in the serum vaspin concentrations between the patients with active IBD and those with inactive IBD. However, the serum vaspin concentrations of most patients with UC increased after remission induction. Vaspin was expressed in the adipocytes of the mesenteric adipose tissues but not in the epithelial or inflammatory cells of large intestines of the patients with IBD. Conclusions: Serum vaspin concentrations are elevated in patients with UC and increase further after remission induction, suggesting that vaspin may aid the auxiliary diagnosis of UC and may be useful for assessing disease activity in patients

Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4.

BACKGROUND:Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response. METHODS:This cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response. RESULTS:Our results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively). CONCLUSION:IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients

Predictors of SVR using univariate and multivariate logistic regression analysis.

<p>Predictors of SVR using univariate and multivariate logistic regression analysis.</p

Genotypes distribution for <i>IL28B (rs12979680)</i>, <i>PD-1</i>.<i>3 (rs11568821) and CTLA-4 49A/G</i> (rs231775) genes.

<p>Genotypes distribution for <i>IL28B (rs12979680)</i>, <i>PD-1</i>.<i>3 (rs11568821) and CTLA-4 49A/G</i> (rs231775) genes.</p

ROC curve provided by the model constructed to establish the predictive value for SVR.

<p>Area under the receiver-operating curve = 0.822 (95% CI = 0.76–0.88).</p

Baseline demographic, clinical and virological characteristics of HCV infected study population.

<p>Baseline demographic, clinical and virological characteristics of HCV infected study population.</p

Genetic and Epigenetic Regulation of MEFV Gene and Their Impact on Clinical Outcome in Auto-Inflammatory Familial Mediterranean Fever Patients

Epigenetic modifications play a pivotal role in autoimmune/inflammatory disorders and could establish a bridge between personalized medicine and disease epidemiological contexts. We sought to investigate the role of epigenetic modifications beside genetic alterations in the MEFV gene in familial Mediterranean fever (FMF). The study comprised 63 FMF patients diagnosed according to the Tel Hashomer criteria: 37 (58.7%) colchicine-responders, 26 (41.3%) non-responders, and 19 matched healthy controls. MEFV mutations were detected using a CE/IVD-labeled 4-230 FMF strip assay. DNA methylation of MEFV gene exon 2 was measured using bisulfite modification and related to pyrin level, phenotypic picture, MEFV mutations, disease severity, serum amyloid A (SAA), CRP, ESR, disease severity, and colchicine response. Our results showed that FMF patients exhibited significantly higher methylation percentage (p p p < 0.004). High methylation percentage of the MEFV exon 2 and low pyrin concentration were correlated with disease severity, high SAA, ESR levels, H-pylori, and renal calculi. In conclusion, this study highlights the relation between high methylation percentage, reduced pyrin level, and different biomarkers in FMF, which underscores their role in the pathogenesis of FMF and could be considered as potential therapeutic targets

Soluble Receptor for Advanced Glycation End-Product (sRAGE)/Pentosidine Ratio: A Potential Risk Factor Determinant for Type 2 Diabetic Retinopathy

This study aims to investigate potential diabetic retinopathy (DR) risk factors by evaluating the circulating levels of pentosidine, soluble receptor for advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited. Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement. DNR and DR patients showed significantly higher levels of plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients. Proliferative DR patients had significantly higher levels of plasma pentosidine, sRAGE, AOPP and sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level, long duration of diabetes and low sRAGE/pentosidine ratio were determined as the risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR