Proteinase-activated receptor-2: physiological and pathophysiological roles

Protease-activated receptor 2 (PAR2) is the second member of a new subfamily of G-protein coupled receptors: the protease-activated receptors (PARs). At present, four different PARs have been cloned and all of them share the same basic mechanism of activation. A serine protease cleaves the extended, extracellular N-terminus of the receptor at a specific site within the protein chain to expose an N-terminal tethered ligand domain, which binds to and activates the cleaved receptor. In this manner, trypsin and mast cell beta-tryptase activate PAR2. PARs are single use receptors because proteolytic activation is irreversible and the cleaved receptors are degraded in lysosomes. Thus, PARs play important roles in emergency situations, such as trauma and inflammation. Emerging evidence indicates that PAR2 is involved in the cardiovascular, pulmonary and gastrointestinal systems, where it controls inflammation and nociception. Work with selective agonists and knockout animals suggests a contribution of PAR2 to certain inflammatory diseases. Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases.     

Characterization of fifteen microsatellite markers for the kelp Laminaria ochroleuca and cross species amplification within the genus

The brown algal genus Laminaria (Phaeophyceae, Laminariales) is ecologically and economically important. Laminaria ochroleuca is the genus member with the southernmost distribution in the Northern hemisphere, from Southern Great Britain to Morocco. Here we describe the characterization of 15 microsatellite loci that can be used to study genetic diversity at different spatial scales and its dynamics in declining southern populations. These loci identified a number of alleles ranging from 3 to 26 (mean = 9). Expected heterozygosities range from 0.0824 to 0.9401. We also tested cross-amplification of these microsatellite markers in two other species within the genus, L. hyperborea and L. digitata. A total of eight and ten alleles cross-amplified in L. hyperborea and L. digitata, respectively. These 15 variable microsatellite loci are an important molecular tool to conduct population genetics studies in L. ochroleuca and other species within the genus.     

Combined remote ischemic perconditioning and local postconditioning on liver ischemia–reperfusion injury

Background

Remote ischemic perconditioning (rPER) is the newest technique described to mitigate ischemia and reperfusion (IR) injury. Local postconditioning (POS) is also an effective technique for this purpose. It is uncertain if adding local POS to rPER provides superior liver protection, so we tested this hypothesis.

Materials and methods

Twenty five Wistar rats were assigned into five groups: sham, IR, POS, rPER, and rPER + POS. Animals were subjected to liver ischemia for 60 min. POS consisted of four cycles of 5-min liver perfusion followed by 5-min liver ischemia (40 min total) after the major ischemic period. rPER consisted of four cycles of 5-min hindlimb ischemia followed by 5 min hindlimb perfusion contemporaneously to major liver ischemic period, during its last 40 min. After 2 h, median and left lobes were harvested for malondialdehyde and Trolox equivalent antioxidant capacity (TEAC) measurement, and blood for the measurement of serum transaminases.

Results

All tissue conditioning techniques were able to reduce transaminases serum levels, having no differences among them. All tissue conditioning techniques were able to reduce hepatic tissue MDA level; however, only rPER + POS had higher values than SHAM. All tissue conditioning techniques also enhanced TEAC; however, only POS had lower TEAC than SHAM.

Conclusions

rPER appears as the most promising technique to avoid IR injury. This technique reduced oxidative stress of cell membranes and lowered transaminases serum level. There was no additive protection when POS and rPER were held together.     

Physical exercise and vascular endothelial growth factor (VEGF) in elderly: A systematic review

The aim of this study was to conduct a systematic review of studies that verified the effects of physical exercise on vascular endothelial growth factor (VEGF) in elderly.     

Seniors Road Safety Enhancement through Perceptual-Motor Competences Training Program Impact upon the Performance on the Useful Field of Vision (UFOV)

The purpose of this study was to verify the efficacy of a Perceptual-Motor Competences Training Program upon the performance on UFOV of an experimental active group of elderly drivers. Program tasks were conceived to force subjects to divide their attention for central and peripheral stimuli, using a visual strategy of gazing at an anchor-point and, from there, detect important clues on peripheral visual field. For this purpose, almost all tasks were performed on groups of two, being one responsible for testing the other and switching functions from time to time (for instance, dropping one of two juggling handkerchiefs hold apart, one in each tester hand, with the partner having to detect which was dropped and react as quick as possible, catching it before it felt to the floor). We found a significant improvement in the capacity of dividing attention for central and peripheral stimuli under a visual environment full of distractors (selective attention UFOV test) following the Program, as well as a significant reduction on the category of risk (component based upon the three UFOV subtests results), which evidence very clearly the benefits of this training program on the elderly experimental group and its potential to reduce their risk of being involved in car accidents, on their fault, due to perceptual reasons.     

Multidrug-Resistant Nontuberculous Mycobacteria Isolated from Cystic Fibrosis Patients

Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of pulmonary infections in cystic fibrosis (CF) patients, with an estimated prevalence ranging from 5 to 20%. This work investigated the presence of NTM in sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal clinical supervision at a regional reference center in Rio de Janeiro, Brazil. From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of 129 children were obtained. Molecular identification of NTM was performed by using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene, and susceptibility tests were performed that followed Clinical and Laboratory Standards Institute recommendations. For evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE) and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) was performed. The species identified were Mycobacterium abscessus subsp. bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium fortuitum (n = 3), Mycobacterium marseillense (n = 2), and Mycobacterium timonense (n = 1). Most of the isolates presented resistance to five or more of the antimicrobials tested. Typing profiles were mainly patient specific. The PFGE profiles indicated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in two patients. Given the observed multidrug resistance patterns and the possibility of transmission between patients, we suggest the implementation of continuous and routine investigation of NTM infection or colonization in CF patients, including countries with a high burden of tuberculosis disease.     

DC-SIGN polymorphisms are associated to type 1 diabetes mellitus

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend on the type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, we analysed the SNPs rs4804803 (−336 A>G) and rs735239 (−871 A>G), both at DC-SIGN promoter region, in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset of the disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as the alleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associated with protection of T1DM development. We did not find association between these variations with the age of onset of the disease and the presence of other autoimmune disorders. Our results suggest that SNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilian population.