Activity

In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-γ production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs.Simvastatin (SV) is an often prescribed statin reducing the LDL-concentration in circulating blood. The aim of this study was to evaluate the pleiotropic effects of SV to primary human odontoblast-like cells. Twenty four wisdom teeth of different subjects were extracted and the pulp tissue was removed and minced under sterile conditions. After mincing, the requested cells were passaged according to established protocols. Osteoblastic marker (ALP conversion), viability and mineralization were determined at days 14, 17 and 21 after simvastatin exposition (0.01 µM, 0.1 µM, 1.0 µM, 2.0 µM). The sample size per group was 24 cultures with three replicates per culture for ALP-conversion and mineralization and 6 replicates for viability. A Kruskal-Wallis test was used for statistical analysis. After adding SV, viability was significantly (p less then 0.01) decreased in a time- and dose-dependent manner, whereas after 21 days, mineralization was significant (p less then 0.01). ALP-conversion in groups with SV concentrations of 1 and 2 µM SV was significantly (p less then 0.01) increased. Pleiotropic effects regarding mineralization in higher SV concentrations were possibly induced via alternative mineralization pathways as almost equal elevations of ALP conversion were not evident in the control and experimental groups.Mutations in the EPM2A and EPM2B genes, encoding laforin and malin proteins respectively, are responsible for Lafora disease, a fatal form of progressive myoclonus epilepsy with autosomal recessive inheritance. Neuroimaging studies of patients with Lafora disease have shown different degrees of brain atrophy, decreased glucose brain uptake and alterations on different brain metabolites mainly in the frontal cortex, basal ganglia and cerebellum. 2,3-Butanedione-2-monoxime Mice deficient for laforin and malin present many features similar to those observed in patients, including cognitive, motor, histological and epileptic hallmarks. We describe the neuroimaging features found in two mouse models of Lafora disease. We found altered volumetric values in the cerebral cortex, hippocampus, basal ganglia and cerebellum using magnetic resonance imaging (MRI). Positron emission tomography (PET) of the cerebral cortex, hippocampus and cerebellum of Epm2a-/- mice revealed abnormal glucose uptake, although no alterations in Epm2b-/- mice were observed. Magnetic resonance spectroscopy (MRS) revealed significant changes in the concentration of several brain metabolites, including N-acetylaspartate (NAA), in agreement with previously described findings in patients. These data may provide new insights into disease mechanisms that may be of value for developing new biomarkers for diagnosis, prevention and treatment of Lafora disease using animal models.This study aims to deeply understand the effect of contact stress and slip ratio on wear performances of bainitic rail steels. The results showed that the wear loss increased as the contact stress and slip ratio increased. Based on the surface damage morphology and microstructural analyses, it revealed that the rolling contact fatigue wear mechanism played a significant role under the low slip ratio, but the dominant wear mechanism transferred to the abrasive wear at the high slip ratio. Meanwhile, the bainitic steel specifically presented worse wear resistance under the abrasive wear mode. Compared with the influence of a slip ratio, the increase in contact stress led to severer plastic flows and contributed to the propagation of cracks. In addition, the contact stress and slip ratio had the opposite effect on the friction coefficient, that is, the friction coefficient of bainitic steels behaved the inverse proportion with the contact stress, but positive proportion with the slip ratio. At last, the increase in slip ratio had more significant effect on the reduction of retained austenite (RA) than the enlargement of contact stress due to the fact that the RA would probably be removed before the martensitic transformation occurred under the abrasive wear mechanism.Data concerning metabolic consequences in women with polycystic ovary syndrome (PCOS) are delivered mainly by cross-sectional studies. In this research, we re-examined 31 Caucasian PCOS women after a median period of 120.9 months to evaluate the changes in metabolic syndrome components. Clinical examination, oral glucose tolerance test with estimations of glucose and insulin, lipids, sex hormone-binding globulin (SHBG) and sex hormones assessments were performed on two occasions. Additionally, the euglycaemic hyperinsulinaemic clamp technique was used at the baseline to assess insulin sensitivity (M-clamp value). In the end, the median age of participants was 35. We observed an increase in glucose concentrations, a decrease in insulin concentrations and no changes in insulin resistance markers. Final mean glucose, mean insulin, Matsuda index and body mass index (BMI) were correlated with baseline M-clamp value and SHBG (p less then 0.01). During the follow-up, no one in the sample developed diabetes. The annualised incidence rate for conversion from normoglycaemia to prediabetes totalled 4.5%. Baseline BMI, free androgen index, fasting glucose and M-clamp value were identified as prediabetes predictors in young PCOS women (respectively, OR = 1.17, OR = 1.42, OR = 1.2, OR = 0.73, p less then 0.05). Prediabetes appeared in 76.47% of the women with a final BMI of ≥ 25 kg/m2 and in 7.14% of the normal-weight women (p = 0.0001). In conclusion, we report a high rate of adverse change in glucose metabolism in overweight and obese participants, a deterioration in β-cell function and strong correlations between metabolic parameters assessed in the third and the fourth decade in PCOS women, emphasising the role of early intervention to prevent cardiometabolic diseases.