Antinociceptive and neurochemical effects of a single dose of IB-MECA in chronic pain rat models

This study aimed to evaluate the effect of a single administration of IB-MECA, an A3 adenosine receptor agonist, upon the nociceptive response and central biomarkers of rats submitted to chronic pain models. A total of 136 adult male Wistar rats were divided into two protocols: (1) chronic inflammatory pain (CIP) using complete Freund’s adjuvant and (2) neuropathic pain (NP) by chronic constriction injury of the sciatic nerve. Thermal and mechanical hyperalgesia was measured using von Frey (VF), Randal-Selitto (RS), and hot plate (HP) tests. Rats were treated with a single dose of IB-MECA (0.5 μmol/kg i.p.), a vehicle (dimethyl sulfoxide—DMSO), or positive control (morphine, 5 mg/kg i.p.). Interleukin 1β (IL-1β), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels were measured in the brainstem and spinal cord using enzyme-linked immunosorbent assay (ELISA). The establishment of the chronic pain (CIP or NP) model was observed 14 days after induction by a decreased nociceptive threshold in all three tests (GEE, P < 0.05). The antinociceptive effect of a single dose of IB-MECA was observed in both chronic pain models, but this was more effective in NP model. There was an increase in IL-1β levels promoted by CIP. NP model promoted increase in the brainstem BDNF levels, which was reversed by IB-MECA     

Advanced oxidation processes applied for color removal of textile effluent using a home-made peroxidase from rice bran

Bioprocess and Biosystems Engineering - Enzymes are becoming tools in industrial processes because of several advantages, including activity in mild environmental conditions, and high specificity....     

Anticlastogenic effect of β-glucan, extracted from Saccharomyces cerevisiae, on cultured cells exposed to ultraviolet radiation

β-glucan is an important polysaccharide due to its medicinal properties of stimulating the immune system and preventing chronic diseases such as cancer. The aim of the present study was to determine the anticlastogenic effect of β-glucan in cells exposed to ultraviolet radiation (UV). Chromosome aberration assay was performed in drug-metabolizing cells (HTC) and non drug-metabolizing cells (CHO-K1 and repair-deficient CHO-xrs5), using different treatment protocols. Continuous treatment (UV + β-glucan) was not effective in reducing the DNA damage only in CHO-xrs5 cells. However, the pre-treatment protocol (β-glucan before UV exposition) was effective in reducing DNA damage only in CHO-K1 cells. In post-treatment (β-glucan after UV exposition) did not show significative anticlastogenic effects, although there was a tendency toward prevention. The data suggest that β-glucan has more than one action mechanism, being capable of exerting desmutagenic as well as bio-antimutagenic action. The findings also suggest that the presence of the xenobiotic metabolizing system can reduce the chemopreventive capacity of β-glucan. Therefore, these results indicate that β-glucan from Saccharomyces cerevisiae can be used in the prevention and/or reduction of DNA damage.     

Mutation analysis of GJB2 and GJB6 genes in Southeastern Brazilians with hereditary nonsyndromic deafness

In developed countries deafness has a genetic cause in over 60% of the cases. Contrastingly, in Brazil, it is estimated that only 16% of all deafnesses are caused by genetic factors. Among hereditary hearing deficiencies, approximately half is caused by mutations in the Gap Junction Protein Beta-2 (GJB2) gene, which encodes the protein Connexin 26 (Cx26). There are four mutations in this gene that present high prevalence in specific ethnical groups, namely, 35delG, 167delT, 235delC, and W24X. The 35delG mutation is the most frequent one, occurring in homozygosity or in compound heterozygosity with mutations in the GJB2 and GJB6 genes. This study aims to determine the prevalence of GJB2-35delG, GJB2-167delT, GJB2-235delC, GJB2-W24X, del (GJB6-D13S1830), and del (GJB6-D13S1854) mutations in patients with nonsyndromic deafness in the Espirito Santo State, Brazil. A total of 77 individuals were evaluated, from which 88.3% presented normal genotypes for all analyzed mutations, 1.3% were compound heterozygotes for 35delG-GJB2/D13S1830-GJB6, 1.3% were compound heterozygotes for 35delG/D13S1854-GJB6, 3.9% were homozygotes for the 35delG mutation and 5.2% were heterozygotes for 35delG/GJB2. The frequency of mutant alleles 35delG/GJB2, del (D13S1830/GJB6), and del (D13S1854/GJB6) was 7.8, 0.65, and 0.65%, respectively. Mutations 167delT, 235delC, and W24X were not detected. Determining the prevalence of specific mutations related to inherited deafness in a population can contribute to the development of more efficient and affordable molecular diagnostic protocols, and help in the genetic counseling of patients and their families.     

Accumulation of endogenous LITAF in aggresomes

LITAF is a 161 amino acid cellular protein which includes a proline rich N-terminus and a conserved C-terminal domain known as the simple-like domain. Mutations in LITAF have been identified in Charcot-Marie tooth disease, a disease characterized by protein aggregates. Cells transfected with cellular LITAF reveal that LITAF is localized to late endosomes/lysosomes. Here we investigated the intracellular localization of endogenous LITAF. We demonstrated that endogenous LITAF accumulates at a discrete cytoplasmic site in BGMK cells that we identify as the aggresome. To determine the domain within LITAF that is responsible for the localization of LITAF to aggresomes, we created a construct that contained the C-terminal simple-like domain of LITAF and found that this construct also localizes to aggresomes. These data suggest the simple-like domain is responsible for targeting endogenous LITAF to the aggresome.     

Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting.

In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months'' hormone treatment followed by three months'' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.     

Exploring N-Acylhydrazone Derivatives Against Clinical Resistant Bacterial Strains

Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N–H–FUR–NO₂, N–Br–FUR–NO₂, N–F–FUR–NO₂, N–Cl–FUR–NO₂) showed promising MIC and MBC values (MIC = MBC = 1–16 μg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.     

Elucidating the mechanism of poricidal anther dehiscence in Miconia species (Melastomataceae)

Melastomataceae have porate anthers. However, unlike Solanaceae and many monocots, in which the poricidal dehiscence depends on the presence of a mechanical layer (often the endothecium), most members of Melastomataceae have no evident specialized layer related to the poricidal opening. The goal of this study was to characterize the tissues that form the apical pore of the anther in 10 Miconia species, which may help to understand the nearly unknown mechanism of anther dehiscence in this genus, considered to be one of the largest and most diverse New World genera. Before anthesis, the apical pores of all of the species are closed by a uniseriate epidermis, the cells of which lack a cuticle. In contrast, the epidermis of the remainder of the anther is covered by a thick, ornamented cuticle. Among Myrtales, the Melastomataceae form a clade with Alzateaceae, Crypteroniaceae and Penaeaceae, almost all of which have anthers with endothecium lacking wall thickenings. In these families, the endothecium may or may not be present in the mature anther, with degenerating cells in the latter case. Anther dehiscence does not depend on the endothecium as the mechanical layer, and this process is still not well understood. However, in the Miconia species studied here, the cuticle may prevent tissue dehydration, and the pore opening seems to be due to the passive process of dehydration taking place only in the pore region due to the absence of the cuticle.     

Drinking Patterns and Alcohol Use Disorders in S?o Paulo,Brazil: The Role of Neighborhood Social Deprivation and Socioeconomic Status

Background

Research conducted in high-income countries has investigated influences of socioeconomic inequalities on drinking outcomes such as alcohol use disorders (AUD), however, associations between area-level neighborhood social deprivation (NSD) and individual socioeconomic status with these outcomes have not been explored in Brazil. Thus, we investigated the role of these factors on drink-related outcomes in a Brazilian population, attending to male-female variations.

Methods

A multi-stage area probability sample of adult household residents in the São Paulo Metropolitan Area was assessed using the WHO Composite International Diagnostic Interview (WMH-CIDI) (n = 5,037). Estimation focused on prevalence and correlates of past-year alcohol disturbances [heavy drinking of lower frequency (HDLF), heavy drinking of higher frequency (HDHF), abuse, dependence, and DMS-5 AUD] among regular users (RU); odds ratio (OR) were obtained.

Results

Higher NSD, measured as an area-level variable with individual level variables held constant, showed an excess odds for most alcohol disturbances analyzed. Prevalence estimates for HDLF and HDHF among RU were 9% and 20%, respectively, with excess odds in higher NSD areas; schooling (inverse association) and low income were associated with male HDLF. The only individual-level association with female HDLF involved employment status. Prevalence estimates for abuse, dependence, and DSM-5 AUD among RU were 8%, 4%, and 8%, respectively, with excess odds of: dependence in higher NSD areas for males; abuse and AUD for females. Among RU, AUD was associated with unemployment, and low education with dependence and AUD.

Conclusions

Regular alcohol users with alcohol-related disturbances are more likely to be found where area-level neighborhood characteristics reflect social disadvantage. Although we cannot draw inferences about causal influence, the associations are strong enough to warrant future longitudinal alcohol studies to explore causal mechanisms related to the heterogeneous patterns of association and male-female variations observed herein. Hopefully, these findings may help guide future directions for public health.