Methacrylate‐endcapped caprolactone and FM19G11 provide a proper niche for spinal cord‐derived neural cells

Spinal cord injury (SCI) is a cause of paralysis. Although some strategies have been proposed to palliate the severity of this condition, so far no effective therapies have been found to reverse it. Recently, we have shown that acute transplantation of ependymal stem/progenitor cells (epSPCs), which are spinal cord‐derived neural precursors, rescue lost neurological function after SCI in rodents. However, in a chronic scenario with axon repulsive reactive scar, cell transplantation alone is not sufficient to bridge a spinal cord lesion, therefore a combinatorial approach is necessary to fill cavities in the damaged tissue with biomaterial that supports stem cells and ensures that better neural integration and survival occur. Caprolactone 2‐(methacryloyloxy) ethyl ester (CLMA) is a monomer [obtained as a result of ε‐caprolactone and 2‐hydroxyethyl methacrylate (HEMA) ring opening/esterification reaction], which can be processed to obtain a porous non‐toxic 3D scaffold that shows good biocompatibility with epSPC cultures. epSPCs adhere to the scaffolds and maintain the ability to expand the culture through the biomaterial. However, a significant reduction of cell viability of epSPCs after 6 days in vitro was detected. FM19G11, which has been shown to enhance self‐renewal properties, rescues cell viability at 6 days. Moreover, addition of FM19G11 enhances the survival rates of mature neurons from the dorsal root ganglia when cultured with epSPCs on 3D CLMA scaffolds. Overall, CLMA porous scaffolds constitute a good niche to support neural cells for cell transplantation approaches that, in combination with FM19G11, offer a new framework for further trials in spinal cord regeneration. Copyright © 2013 John Wiley & Sons, Ltd.     

Sex Differences in the Hypertensive Population With Chronic Ischemic Heart Disease

Cardiopatía Isquémica Crónica e Hipertensión Arterial en la Práctica Clínica en España (CINHTIA) was a survey designed to assess the clinical management of hypertensive outpatients with chronic ischemic heart disease. Sex differences were examined. Blood pressures (BP) was considered controlled at levels of <140/90 or <130/80 mm Hg in diabetics (European Society of Hypertension/European Society of Cardiology 2003); low‐density lipoprotein cholesterol (LDL‐C) was considered controlled at levels <100 mg/dL (National Cholesterol Education Program Adult Treatment Panel III). In total, 2024 patients were included in the study. Women were older, with a higher body mass index and an increased prevalence of atrial fibrillation. Dyslipidemia, smoking, sedentary lifestyle, and peripheral arterial disease were more frequent in men. In contrast, diabetes, left ventricular hypertrophy, and heart failure were more common in women. BP and LDL‐C control rates, although poor in both groups, were better in men (44.9% vs 30.5%, P<.001 and 33.0% vs 25.0%, P<.001, respectively). Stress testing and coronary angiography were more frequently performed in men.     

Glutathione S-transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury

Individual vulnerability to drug-induced liver injury (DILI) might result from deficiencies in the detoxification process, which determines the level of exposure to the reactive metabolite. We evaluated whether a genetically determined reduction in the ability to detoxify electrophilic compounds, such as that expected among individuals with glutathione S-transferase (GST) null genotypes, might play a role in determining the risk for DILI and its clinical expression. Genomic DNA from 154 patients (74 men, 80 women; mean age, 53 years) with a diagnosis of DILI as assessed with the Council for International Organizations of Medical Science scale and 250 sex- and age-matched healthy controls were analyzed. A multiplex polymerase chain reaction-based method was used to detect GSTM1 and GSTT1 gene deletions. Carriers of double GSTT1-M1 null genotypes had a 2.70-fold increased risk of developing DILI compared with noncarriers (odds ratio 2.70, 95% confidence interval 1.45-5.03; P = 0.003). The odds ratio for DILI patients receiving antibacterials, and NSAIDs were 3.52 (P = 0.002), and 5.61 (P = 0.001), respectively. Patients with amoxicillin-clavulanate hepatotoxicity (n = 32) had a 2.81-fold increased risk (P = 0.037). Patients classified by the combined GSTT1 and GSTM1 null genotypes did not differ with regard to the type of injury, clinical presentation, or outcome, except for the predominance of women in the combined null genotype (P < 0.001). CONCLUSION: The double-null genotype for GSTT1 and GSTM1 might play a role in determining the susceptibility to develop DILI, as a general mechanism that occurs regardless of the type of drug involved, and predominantly in women.     

Haemopoietic stimulators and inhibitors in aplastic anaemia serum

Normal serum and serum from four patients with severe aplastic anaemia was fractionated by Sephadex G-150 gel filtration. Fractions were tested for direct haemopoietic activity on colony forming cells in methylcellulose cultures, and for their indirect influence on haemopoiesis via CSA- and BPA-producing cells. All aplastic anaemia sera contained abnormal inhibitors and stimulators. An inhibitor acting on both haemopoietic and factor producing cells, eluting with the IgM fraction was found in all, variable inhibitors of lower molecular weight in single patients. Stimulatory activity of 10 000-50 000 MW acting on factor producing cells, but not on colony forming cells directly, was found in all, a variable stimulator eluting with the very high MW fraction in single patients. In two patients who achieved complete autologous bone marrow remission after treatment with high dose immunosuppression, Sephadex fractions of serum before treatment and remission serum were simultaneously tested on autologous bone marrow in remission. Inhibitors were detected before treatment and disappeared in remission, stimulators were not detectable before treatment but became strong in remission. It is concluded that the effect of aplastic anaemia serum on haemopoiesis in culture is determined by the balance of inhibitors and stimulators on both haemopoietic and CSA/BPA producing cells.     

Hepatitis B virus prevalence and transmission risk factors in inflammatory bowel disease patients at Clementino Fraga Filho university hospital

AIM： To evaluate the prevalence of hepatitis B virus （HBV） infection in inflammatory bowel disease （IBD） patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission, METHODS： This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview, All these patients had already IBD diagnosis, The patient was interviewed and a questionnaire was filled out, RESULTS： In the group of 176 patients whom we examined, we found that 17% （30） were anti-HBc positive, Out of 30 patients with positive anti-HBc, 2,3% （4） had positive HBsAg and negative HBV-DNA, In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc （P = 0,085）, It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value, However, IBD patients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions （P = 0.015）. CONCLUSION= There was a high incidence of positive anti-HBc （17%） and positive HBsAg （2.3%） in IBD patient when compared with the overall population （7.9%）.