Comparison of manganese oxide nanoparticles and manganese sulfate with regard to oxidative stress, uptake and apoptosis in alveolar epithelial cells

Due to their physicochemical characteristics, metal oxide nanoparticles (NPs) interact differently with cells compared to larger particles or soluble metals. Oxidative stress and cellular metal uptake were quantified in rat type II alveolar epithelial cells in culture exposed to three different NPs: manganese(II,III) oxide nanoparticles (Mn₃O₄-NPs), the soluble manganese sulfate (Mn-salt) at corresponding equivalent doses, titanium dioxide (TiO₂-NPs) and cerium dioxide nanoparticles (CeO₂-NPs). In the presence of reactive oxygen species an increased apoptosis rate was hypothesized. Oxidative stress was assessed by detection of fluorescently labeled reactive oxygen species and by measuring intracellular oxidized glutathione. Catalytic activity was determined by measuring catalyst-dependent oxidation of thiols (DTT-assay) in a cell free environment. Inductively coupled plasma mass spectrometry was used to quantify cellular metal uptake. Apoptosis rate was determined assessing the activity of caspase-3 and by fluorescence microscopic quantification of apoptotic nuclei. Reactive oxygen species were mainly generated in cells treated with Mn₃O₄-NPs. Only Mn₃O₄-NPs oxidized intracellular glutathione. Catalytic activity could be exclusively shown for Mn₃O₄-NPs. Cellular metal uptake was similar for all particles, whereas Mn-salt could hardly be detected within the cell. Apoptosis was induced by both, Mn₃O₄-NPs and Mn-salt. The combination of catalytic activity and capability of passing the cell membrane contributes to the toxicity of Mn₃O₄-NPs. Apoptosis of samples treated with Mn-salt is triggered by different, potentially extracellular mechanisms.     

ADORA2A Gene Variation,Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

There is converging evidence for genetic, biochemical, and neuropsychological factors to increase the risk for anxiety and anxiety disorders. The pathogenesis of anxiety disorders is assumed to be influenced by a complex interaction of these individual risk factors on several levels, affecting intermediate phenotypes of anxiety such as the startle reflex. Thus, in the present double-blind, placebo-controlled study we attempted to paradigmatically investigate a multi-level pathogenetic model of anxiety by testing the effect of 300 mg caffeine citrate as an antagonist at the adenosine A2A receptor vs placebo on the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) startle reflex in 110 healthy individuals (male=56, female=54) stratified for the adenosine A2A receptor (ADORA2A) 1976T>C polymorphism (rs5751876). In addition to the expected main effect of picture category (highest startle amplitude for unpleasant, lowest for pleasant pictures) groups across all ADORA2A 1976T>C genotype and intervention (caffeine vs placebo) groups, an interaction effect of genotype, intervention, and picture category was discerned: In ADORA2A 1976TT risk genotype carriers, highest startle magnitudes were observed after caffeine administration in response to unpleasant pictures, with this effect arising particularly from the female subgroup. Our data point to a complex, multi-level, and potentially gender-specific pathogenetic model of anxiety, with genetic and biochemical factors interactively increasing the risk of maladaptive emotional processing and thereby possibly also anxiety disorders. The present findings may eventually aid in improving primary and secondary prevention by sharpening the risk profiles of anxiety-prone individuals.     

脊柱手术并发脑脊液漏26例病因分析及防治策略

目的探讨脊柱手术并发脑脊液漏的病因及防治策略。方法对2003～2011年笔者在本院所行胸腰椎前后路手术并发脑脊液漏26例,采用直接缝合、筋膜覆盖、使用可吸收明胶海绵、严密缝合切口各层组织、头低臀高位和切口加压包扎。结果 26例均痊愈出院,无一例发生脑脊液感染,无继发深部感染、脑脊液囊肿及马尾神经疝。结论对于脊柱手术并发硬脊膜损伤者,根据损伤程度不同给予相应的修复,恰当处理可有效治疗脑脊液漏。     

Adjuvants and vector systems for allergy vaccines

Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.     

A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy

OBJECTIVE: We conducted a randomized placebo-controlled trial to examine the effects of metformin on visceral adipose tissue (VAT), appendicular fat, lipid profile and insulin sensitivity in HIV-infected persons with central adiposity and mild insulin resistance. METHODS: Forty-eight HIV-infected men and women with a self-reported increase in abdominal girth and an abnormal waist-to-hip ratio were randomly assigned in double-blind fashion to receive metformin 1500 mg or placebo daily for 24 weeks. Persons with diabetes were excluded. The following measures were obtained at baseline and 24 weeks: single-slice computed tomography (CT) scan, dual-energy X-ray absorptiometry (DEXA), lipid profile and oral glucose tolerance test. RESULTS: The median fasting insulin concentration of all participants was 12.3 microU/mL. The percentage change in VAT was not significantly different between the metformin and placebo groups in univariate analysis and linear regression analysis adjusting for age, height, baseline VAT and insulin area under the curve (10.1% vs 3.2%; P=0.58). Metformin was associated with a significant decrease in appendicular fat mass compared with placebo (-686.0 vs 161.0 g; P=0.03). There was no significant change in lipid profile or insulin sensitivity between the two groups at 24 weeks. CONCLUSION: Metformin should be used with caution in the treatment of HIV lipodystrophy, and, if used, should be reserved for persons with adequate peripheral fat and marked insulin resistance.