Heat shock increases antigenic peptide generation but decreases antigen presentation

The heat shock response is a universal and highly conserved cellular response to stress. We describe here the effect of elevated temperature on the capacity of B cells to present antigen. Heat shock markedly affects the ability of these cells to process and present tetanus toxin to class II-restricted T cell clones. Inhibition of antigen presentation is due neither to a modification of antigen capture nor to a variation of major histocompatibility complex (MHC) class II molecule synthesis and cell surface expression. Stressed and nonstressed B cells are able to present peptides loaded at the cell surface with the same efficiency. Nevertheless, heat shock leads to an increase of antigen peptide generation in subcellular compartments; an enhancement of cathepsin B activity is also observed. These data suggest that such a stress induces a failure in the intracellular peptide loading onto MHC class II molecules.     

Early signal from the hippocampus for memory encoding

The mediotemporal lobe (MTL), including the hippocampus, is involved in all stages of episodic memory including memory encoding, consolidation, and retrieval. However, the exact timing of the hippocampus' involvement immediately after stimulus encounter remains unclear. In this study, we used high‐density 156‐channel electroencephalography to study the processing of entirely new stimuli, which had to be encoded, in comparison to highly overlearned stimuli. Sixteen healthy subjects performed a continuous recognition task with meaningful pictures repeated up to four consecutive times. Waveform and topographic cluster analyses of event‐related potentials revealed that new items, in comparison to repetitions, were processed significantly differently at 220–300 ms. Source estimation localized activation for processing new stimuli in the right MTL. Our study demonstrates the occurrence of a transient signal from the MTL in response to new information already at 200–300 ms poststimulus onset, which presumably reflects encoding as an initial step toward memory consolidation.     

Pharmacological priming of adipose‐derived stem cells for paracrine VEGF production with deferoxamine

Adipose‐derived stem cells (ASCs) show great potentials in applications such as therapeutic angiogenesis, regenerative medicine and tissue engineering. Pharmacological preconditioning of stem cells to boost the release of cytoprotective factors may represent an effective way to enhance their therapeutic efficacy. In this study, the aim was to determine whether deferoxamine can enhance the release of vascular endothelial growth factor (VEGF) from in vitro expanded ASCs. It is demonstrated that deferoxamine (50–300 μm ) upregulated VEGF expression in a concentration‐ and time‐dependent fashion. At the concentrations used, deferoxamine did not show any cytotoxic effects. The stimulatory effect of deferoxamine on VEGF expression was mediated by augmentation of hypoxia inducible factor‐1 in ASCs, but independent of its antioxidant properties. Moreover, deferoxamine enhanced the paracrine effects of ASCs in promoting the regenerative functions of endothelial cells (migration and in vitro wound healing activities). This study provides evidence that deferoxamine might be a useful drug with low cell toxicity for pharmacological preconditioning of ASCs to enhance their capacity of VEGF production. Copyright © 2013 John Wiley & Sons, Ltd.     

Benefit of continuous positive airway pressure on work quality in patients with severe obstructive sleep apnea

Sleep and Breathing - The objective of this prospective study was to assess the effect of CPAP therapy on job productivity and work quality for patients with severe obstructive sleep apnea (OSA). A...     

Submucous tramadol increases the anesthetic efficacy of mepivacaine with epinephrine in inferior alveolar nerve block

The purpose of this study was to evaluate the effect of submucous tramadol as adjuvant of mepivacaine with epinephrine in inferior alveolar nerve block. A double-blind, randomized, placebo-controlled, crossover clinical trial was conducted. Twenty healthy young volunteers were randomized into two treatment sequences using a series of random numbers. Sequence 1: Group A, 2% mepivacaine with 1:100,000 epinephrine plus submucous tramadol 50mg (1mL of saline) and one week later Group B, 2% mepivacaine with 1:100,000 epinephrine plus submucous placebo (1mL of saline). Sequence 2: Group B and one week later Group A. All treatments were administered 1min after that patient informed anesthesia of lower lip. We evaluated the duration of anesthesia of lower lip, anesthetic efficacy, and local and systemic adverse events. Anesthetic efficacy was better in group receiving submucous tramadol during the first 2h compared with group receiving submucous placebo (P<0.05). Submucous tramadol increased the anesthetic efficacy of mepivacaine with epinephrine of soft tissue in inferior alveolar nerve block.     

Power Doppler Ultrasound Findings before and after Focused Extracorporeal Shock Wave Therapy for Achilles Tendinopathy: A Pilot Study on Pain Reduction and Neovascularization Effect

Extracorporeal shock wave therapy (ESWT) has been found to have a positive effect in the treatment of pain in Achilles tendinopathy, although the exact mechanism is not yet completely understood. Among the mechanisms suggested to underlie ESWT effects are direct stimulation of healing, neovascularization and direct suppressive effects on nociceptors and hyperstimulation, which would block the gate-control system. The neovascularization observed in flogistic tissue is associated with stimulated nerve fibers around tendons and induces a painful condition. The objectives of the present study were to evaluate the effect of ESWT on pain and function in patients with non-insertional Achilles tendinopathy (NIAT) and to assess the neovascularization phenomenon using power Doppler ultrasound (PDU). Twelve patients with NIAT underwent five sessions of focused ESWT over 5 wk. Outcome measures were the visual analogue scale, the Victorian Institute of Sport Assessment–Achilles questionnaire and active dorsiflexion and plantar flexion ankle articular range of motion. Moreover, the patients’ clinical impressions of treatment results after ESWT were investigated using the Roles and Maudsley score. Patients were assessed at baseline and 1 and 3 mo after treatment. They had a significant reduction in pain with improvement of arthrokinematic motion and functionality and a positive clinical impression of treatment outcome (50% of patients considered their clinical picture as good/excellent after 3 mo). However, the pulse Doppler ultrasound exam did not reveal neovascularization in 91.7% of the patients 1 and 2 mo after focused ESWT, and in some patients there was a reduction in blood vessels related to flogistic processes. The present observational study confirmed the efficacy of ESWT in pain reduction in NIAT, with a higher degree of patient satisfaction, although doubt persists over the neovascularization effect on the Achilles tendons treated.     

In vivo kinetics of the genotoxic and cytotoxic activities of cladribine and clofarabine

The aim of the present in vivo study was to determine the kinetics of the genotoxic and cytotoxic activities of cladribine and clofarabine in mouse normoblasts using flow cytometry. Mice in groups of five were treated with cladribine or clofarabine. Blood samples were obtained from the mouse tails before treatment and every 8 hr posttreatment for 72 hr. These samples were cytometrically scored for micronucleated reticulocytes (RETs), and the percentage of RETs was determined. The results showed that clofarabine and cladribine have early cytotoxic effects that are related to the genotoxic effects reported in previous studies; the drugs have both complex long-lasting genotoxic and cytotoxic kinetic activity, with similar profiles that suggest a relationship between the genotoxic and cytotoxic parameters. The initial genotoxkinetics timing of clofarabine is equivalent to those of difluorodeoxycytidine, likely because both agents inhibit DNA polymerase. Clofarabine shows a higher genotoxic and cytotoxic efficiency than cladribine, in agreement with previous results.     

Dissemination of bla(IMP-1)-carrying integron In86 among Klebsiella pneumoniae isolates harboring a new trimethoprim resistance gene dfr23

The genetic context of the bla_IMP-1 gene was evaluated in 9 Klebsiella pneumoniae isolates recovered from 2 hospitals in São Paulo, Brazil. All isolates harbored a copy of In86 carrying bla_IMP-1, aac(6′)-31, and aadA1. Eight strains from the same hospital also carried another class 1 integron harboring a new trimethoprim resistance gene (dfr23) that was chromosomally embedded. In86 was likely to be in a 30-kb nontransferable plasmid and was flanked upstream by a sequence identical to one identified in an IMP-1–producing Pseudomonas putida isolate. The bla_IMP-1-carrying integron In86 was recently reported from nonfermentative bacilli isolated in São Paulo. These isolates appear to be the source of this integron now acquired by K. pneumoniae strains from different hospitals in the same city. Metallo-β-lactamase production is still rare among Enterobacteriaceae isolates in Brazil, but the acquisition of genetic structures carrying these mobile resistance determinants is worrisome and could lead to an increase in the prevalence of these phenotypes of resistance.