Association of HCV with diabetes mellitus: an Egyptian case-control study

<p>Abstract</p> <p>Background</p> <p>The highest Hepatitis C Virus (HCV) prevalence in the world occurs in Egypt. Several studies from different parts of the world have found that 13% to 33% of patients with chronic HCV have associated diabetes, mostly type II Diabetes Mellitus (DM). In Egypt the prevalence of DM is 25.4% among HCV patients. Therefore, it is important to identify the magnitude of the problem of diabetes in order to optimize the treatment of chronic hepatitis C.</p> <p>Methods</p> <p>The objective of this case-control study was to evaluate the prevalence of DM and other extrahepatic (EH) manifestations among patients with different HCV morbidity stages including asymptomatic, chronic hepatic and cirrhotic patients. In this study, 289 HCV patients older than 18 were selected as cases. Also, 289 healthy controls were included. Laboratory investigations including Liver Function tests (LFT) and blood glucose level were done. Also serological assays including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed.</p> <p>Results</p> <p>Out of 289 HCV cases, 40 (13.84%) were diabetic. Out of 289 healthy controls, 12 (4.15%) were diabetic. It was found that the diabetic HCV group mean age was [48.1 (± 9.2)]. Males and urbanians represented 72.5% and 85% respectively. Lower level of education was manifested in 52.5% and 87.5% were married. In the nondiabetic HCV group mean age was [40.7 (± 10.4)]. Males and urbanians represented 71.5% and 655% respectively. secondary and higher level of education was attained in 55.4% and 76.7% were married. Comparing between the diabetic HCV group and the non diabetic HCV group, age, residence and alcohol drinking were the only significant factors affecting the incidence of diabetes between the two groups. There was no significant difference regarding sonar findings although cirrhosis was more prevalent among diabetic HCV cases and the fibrosis score was higher in diabetic HCV patients than among the non diabetic HCV cases.</p> <p>Conclusion</p> <p>The diabetic patients in the HCV group were older, more likely to have a history of alcohol drinking than the non diabetic HCV cases. Age and alcohol drinking are factors that could potentially contribute to the development of type 2 diabetes. Logistic regression analyses showed that age and residence in urban regions were the predictive variables that could be associated with the presence of diabetes. Alcohol consumption was not a significant predictive factor.</p

Defective proliferation and osteogenic potential with altered immunoregulatory phenotype of native bone marrow-multipotential stromal cells in atrophic fracture non-union

Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271highCD45low cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271highCD45low cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing

Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies

OBJECTIVES: The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis. METHODS: The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-γ and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used. RESULTS: Combined treatment of MSC with IL-22, IFN-γ and TNF resulted in increased MSC proliferation (P = 0.008) and migration (P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated by IL-22 alone (P < 0.05). MSC osteogenesis was enhanced following IL-22 exposure (P = 0.03, measured by calcium production). The combination of IFN-γ and TNF with or without IL-22 suppressed MSC osteogenesis (P = 0.03). CONCLUSION: This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments, with MSC osteogenesis occurring only in the absence of IFN-γ/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA

Timing of initiation of low-molecular-weight heparin administration in pregnant women with antiphospholipid syndrome: a randomized clinical trial of efficacy and safety

Mohamed Ibrahem Eid,1 Mohamed Sayed Abdelhafez,1 Waleed El-refaie,2 Ahmed A El-Zayadi,1 Khaled Samir,1 Mahmoud Mohamed Abdelrazik,1 Mahmoud Thabet,1 Alaa Wageh,1 Emad Ahmed Fyala,1 Yasser Abdeldayem,1 Ahmed Badawy1 1Department of Obstetrics and Gynecology, Mansoura University, Mansoura, Egypt; 2Department of Obstetrics and Gynecology, Port Said University, Port Said, Egypt Objective: We aimed to evaluate the effect of different timing of initiation of low-molecular- weight heparin (LMWH) administration on the pregnancy outcomes in women with antiphospholipid syndrome (APS). Materials and methods: A randomized controlled study was conducted on women with obstetrical APS. All participants were randomly divided at documentation of positive pregnancy test into two groups; early initiation group in which LMWH therapy was started once positive pregnancy test was established (in the fifth week of gestation), and later initiation group in which LMWH therapy was started after sonographic confirmation of fetal cardiac pulsation (in the seventh week of gestation). In both groups, LMWH (enoxaparin) was given at a dose of 40 mg/day subcutaneously and the therapy continued until end of pregnancy. The primary outcome measure was ongoing pregnancy rate and the secondary outcome measures were fetal loss, live birth rate, preterm labor before 34 weeks of gestation, intrauterine growth restriction (IUGR), and congenital fetal malformations. Results: Ninety-four women (48 in the early initiation group and 46 in the later initiation group) were subjected to final analysis. The ongoing pregnancy rate was significantly higher in the early initiation group than in the later initiation group (81.2% vs 60.9%; P=0.040). However, both groups were similar in the incidences of fetal loss, preterm labor before 34 weeks of gestation, and IUGR, and live birth rate. No recorded congenital fetal malformations in both groups. Conclusion: Early administration of LMWH for pregnant women with obstetrical APS reduces early pregnancy loss, but does not affect the incidence of late obstetrical complications. Keywords: APS, LMWH, fetal los

Role of the IL-23 pathway in the pathogenesis and treatment of enthesitis in psoriatic arthritis

Introduction: Enthesitis is a key feature of spondyloarthritis (SpA). Several studies have underlined the role of interleukin (IL)-23 in SpA development as a crucial cytokine in the pathogenesis of enthesitis. Area covered: This review summarizes recent evidence of the role of IL-23 in the pathogenesis of and as a target of the treatment of enthesitis. We review the definition, diagnosis and clinical impact of enthesitis and its connection with microbial infections, gut dysbiosis, and mechanical stress. We also review clinical trials and real-life studies of drugs targeting the p19 or p40 subunits of IL-23. Expert opinion: Novel therapies targeting the p19 or p40 subunit of IL-23 appear to be promising treatment options for patients with enthesitis. Although we are currently unable to identify the best therapeutic window to target IL-23 in SpA disease evolution, the promising ability of this therapy to control the gut-entheseal axis is increasing our knowledge of SpA pathogenesis

The advent of IL-17A blockade in ankylosing spondylitis: secukinumab, ixekizumab and beyond.

Introduction: Secukinumab, an interleukin-17A (IL-17A) antagonist, is the first non-TNF alpha inhibitor agent licensed for ankylosing spondylitis (AS), which opens up a new era of alternative cytokine targets beyond TNF. Areas covered: This review explores the pathophysiology and scientific evidence behind the use of this new mode of action and discusses the basis for its efficacy and clinical utility in the management of AS. In particular, how the emergent data points towards the efficacy of secukinumab and ixekizumab, a second emergent IL-17A blocker, in AS has helped focus research into the IL-23/17 axis in entheseal driven disease in man and how IL-17A inhibition may be linked to the presence of innate and adaptive immune cell populations capable of IL-17A elaboration in these target tissues. Expert commentary: Collectively these emergent data point towards an efficacious role of IL-17A inhibition strategies targeting AS pathogenesis in a fundamental way whilst carrying a good safety profile