Association of microRNAs genes polymorphisms with rheumatoid arthritis in Egyptian female patients

ObjectiveTo investigate whether miRNA-499 (rs3746444) and miRNA-146a (rs2910164) genes polymorphisms are independent factors for rheumatoid arthritis (RA) in Egyptians, and whether they influence disease severity and activity.MethodsTwo hundred and seventeen RA patients and 245 healthy controls were enrolled in this study. Polymorphisms of miRNA-146a and miRNA-499 genes were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).ResultsThe miRNA-499 CT genotype was an independent factor of RA. The miRNA-499 CT, CC genotypes and C allele frequencies were significantly increased in erosive RA group. Moreover, the heterozygote CT had more severe and more active form of the disease compared with homozygote CC or TT. However, we did not find any significant association of miRNA-146a polymorphism with RA risk, severity, and activity.ConclusionThe miRNA-499 polymorphism is an independent factor of RA, and influences disease severity and activity.     

Coupling of Proton Binding in Extracellular Domain to Channel Gating in Acid-Sensing Ion Channel

Protonation of several amino acid residues in the extracellular domain (ECD) of acid-sensing ion channel (ASIC) causes conformational changes that lead to opening of the channel. It is not clear how conformational changes in ECD are coupled to channel gating. Here, we show that the loop connecting β9 and α4 at the base of the thumb region of ECD interacts with post-TM1 to stabilize the channel in the closed state. Flexibility of these two regions is important for optimum gating of the channel. In ASIC1a, when Y71 (post-TM1) and W287 (β9–α4 loop) were mutated to cysteine, they formed disulfide bond in the closed state. Breaking of the disulfide bond by reducing agent dithiothreitol (DTT) or tris(2-carboxyethyl)phosphine (TCEP) potentiated the current significantly. Engineered cysteine G288C reacted with sulfhydryl-specific methanethiosulfonate ethyltrimethylammonium (MTSET) in the open state but not in closed/steady desensitized state, suggesting gating-associated conformational movement of this loop. We also identified a salt bridge between highly conserved R64 at TM1 and D432 at TM2 that is important for optimum gating. Based on our results and other published work, we propose that proton binding in ECD is followed by the displacement of the β9–α4 loop of the thumb, leading to the rotation of TM1. Conformational movement propagates to TM2 and the channel gate opens by the concomitant movement of TM2 and breaking of the salt bridge between R64 and D432.     

Amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-β1, the proinflammatory cytokines,Nrf2/HO-1 pathway and apoptosis

Cyclosporine is an immunosuppressive agent that is used to prevent organ rejection after organ transplantation. Due to the widespread use of this type of surgery, the effect of cyclosporine on reproduction and fertility should have a specific interest. Our aim was to assess the effect of carvedilol and/or alpha-lipoic acid on cyclosporine-induced testicular toxicity in rats. Sixty male Wistar rats were divided into six equal groups: Control; cyclosporine; cyclosporine + carvedilol; cyclosporine + alpha-lipoic acid; cyclosporine + carboxymethyl cellulose; and cyclosporine + carvedilol +alpha-lipoic acid. Food intake, testis weight, testicular functions, serum testosterone, luteinizing hormone and follicle-stimulating hormone were measured. Also, testicular tissue 3 β-hydroxysteroid dehydrogenase, 17 β- hydroxysteroid dehydrogenase, paroxonase-1, proinflammatory cytokines, transforming growth factor beta-1, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Heme oxygenase-1 (HO-1) content and sperm characteristics were determined. Parts of the testes were subjected to histopathological and electron microscopic examination. The carvedilol/alpha-lipoic acid combination restored the food intake, testicular weight and functions, sperm characteristics, hormonal profile and the antioxidant defences compared to the use of each of these drugs alone. Also, this combination significantly ameliorated inflammation (P < .05) and induced significant increase in tissue Nrf2/HO-1 content (P < .05) and significant improvement of the histopathological and electron microscopic picture (P < .05) compared to the use of each of these drugs alone. So, carvedilol/alpha-lipoic acid combination might represent a novel therapeutic strategy to ameliorate testicular damage induced by cyclosporine.     

Bizarre use of log splitter: a case of decapitation

Forensic Science, Medicine and Pathology - Decapitation is well-documented as an immediately lethal injury that is encountered in medicolegal autopsies. It can be due to an accident, suicide, or...     

Pediatric patients with eosinophilic esophagitis: an 8-year follow-up

BACKGROUND: Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients. OBJECTIVE: We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history. METHODS: We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years. RESULTS: In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean +/- SD, 6.2 +/- 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean +/- SD, 0.91 +/- 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed. CONCLUSION: Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus. CLINICAL IMPLICATIONS: Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.     

Salt content of some fast foods in Casablanca,Morocco: Pilot study

Introduction

High salt intake is associated with high blood pressure. This pilot study aimed to measure the salt content of some fast foods in Casablanca, Morocco.

Anti-diabetic Effect of <Emphasis Type="Italic">Boerhavia diffusa</Emphasis> L. Root Extract via Free Radical Scavenging and Antioxidant Mechanism

Objective

The present study was proposed to assess the in vitro free radical-scavenging activity of B. diffusa methanolic extract (BDME) and its modulatory effect against streptozotocin (STZ) induced diabetes in male Wistar rats.

Methods

Experimental diabetes was induced in Wistar albino rats by administering single dose of STZ 40 mg/kg. One week later rats with blood glucose level >200 mg/dL were segregated as diabetes in three groups each containing 6 rats in number.

Results

Total phenolic content in B. diffusa methanol extract (BDME) was found to be 87 mg of gallic acid equivalents/g extract and total flavonoid content found to be 54.1 mg of quercetin equivalents/g extract. Its extract also exhibited DPPH (IC₅₀, 163.1±6.7 μg/mL), nitric oxide (295 μg/mL) and H₂O₂ (159±5.25 μg/mL) radical scavenging activity. Pre-treatment with BDME (100 and 200 mg/kg b.w.) in streptozotocin-induced diabetic rats resulted in significant improvement in blood glucose, blood plasma enzymes SGOT, SGPT and ALP, weight loss, total protein, serum insulin and liver glycogen levels. Furthermore, it restores the activity of antioxidant enzymes viz. SOD, CAT and GPx.

Conclusion

Thus, the result suggests that BDME employed significant anti-diabetic effect in Wistar rats which is associated with its free radical scavenging and antioxidant activity.

     

Une lésion pigmentée du pied

Bowen’s disease (BD) is a precancerous condition of skin and/or mucosa with a predilection towards sunexposed areas. Here we present a case of pigmented Bowen’s disease on the sun-protected site of the body mimicking malignant melanoma.