Donepezil Prevents Inhibition of Cerebral Energetic Metabolism Without Altering Behavioral Parameters in Animal Model of Obesity

Neurochemical Research - Obesity is characterized by chronic inflammation of low grade. The cholinergic anti-inflammatory pathway favors the reduction of the inflammatory response. In this work the...     

Human probiotic bacteria attenuate Pseudomonas aeruginosa biofilm and virulence by quorum-sensing inhibition

Abstract

This work investigated chloroform extracts from culture supernatants of two human probiotic bacteria, Lactobacillus casei CRL 431 and Lactobacillus acidophilus CRL 730 for the production of virulence factors and quorum sensing (QS) interference against three Pseudomonas aeruginosa strains. Both extracts inhibited biofilm biomass (up to 50%), biofilm metabolic activity (up to 39%), the production of the enzyme elastase (up to 63%) and pyocyanin (up to 77%), and decreased QS, without presenting any antibacterial acgivity. In addition, the chloroform extracts of both strains disrupted preformed biofilms of the three strains of P. aeruginosa analyzed (up to 40%). GC-MS analysis revealed that the major compounds detected in the bioactive extracts were four diketopiperazines. This study suggests that the metabolites of L. casei and L. acidophilus could be a promising alternative to combat the pathogenicity of P. aeruginosa.     

Highways are a threat for giant armadillos that underpasses can mitigate

We report 24 records of giant armadillo roadkill on Brazilian highways in the Cerrado, Pantanal and Amazon biomes illustrating that highways are a threat to this species. However, we also documented the species using underpasses, demonstrating that these structures could help to reduce the risk of roadkill for giant armadillos.     

Muscle regeneration in adiponectin knockout mice showed early activation of anti-inflammatory response with perturbations in myogenesis

Activation, proliferation, and differentiation of satellite cells can be influenced by extracellular factors, such as adiponectin. This adipokine has been proposed as a regulator of in vitro myogenesis, but its action on in vivo regeneration is not still elucidated. We used C57BL/6 (wild-type [WT]) and adiponectin knockout (AdKO) mice injured with barium chloride at periods of 3, 7, and 14 days after injury. The AdKO presented a higher number of centralized nuclei after 7 days, and a reduction in myogenic genes was observed after 3 days. Moreover, these mice presented an increase in anti-inflammatory cytokines after 3 and 7 days, and an increase in the M2 gene marker and proinflammatory cytokines after 7 days. The WT demonstrated an increase in adiponectin messenger RNA after 7 days. These results demonstrate that adiponectin is important in tissue remodeling during regeneration and that its deficiency does not compromise the maturation of muscle fibers, due to an increase in anti-inflammatory response; however, there is a possible impairment in proinflammatory response and an increase in centralized myonuclei.     

The Efficacy and Safety of Sertaconazole Cream (2 %) in Diaper Dermatitis Candidiasis

Aim

Diaper dermatitis (DD) is an inflammatory irritating condition that is common in infants. Most cases are associated with the yeast colonization of Candida or diaper dermatitis candidiasis (DDC), and therefore, the signs and symptoms improve with antimycotic treatment. Sertaconazole is a broad-spectrum third-generation imidazole derivative that is effective and safe for the treatment for superficial mycoses, such as tineas, candidiasis, and pityriasis versicolor. Our goal was to assess the efficacy and safety of sertaconazole cream (2 %) in DDC.

Materials and methods

Twenty-seven patients with clinical and mycological diagnosis of DDC were enrolled and treated with 2 daily applications for 14 days and were followed-up for 2 further weeks.

Results

Three etiologic agents were isolated: Candida albicans in 88.8 %, Candida parapsilosis in 7.3 %, and Candida glabrata in 3.2 %. There was an average symptom reduction from 7.1 to 3.2 in the middle of treatment and to 1.2 and 0.4 units at the end of treatment and follow-up, respectively. The treatment evaluation at the end of the follow-up period showed a total clinical and mycological cure in 88.8 %, improvement in 3.7 %, and failure in 7.4 %. There was side effect (3.7 %) of skin irritation, but the drug was not discontinued.

Conclusions

Based on its safety and effectiveness, sertaconazole cream may be considered a new alternative for DDC treatment.     

Influence of MDR1 C1236T polymorphism on lopinavir plasma concentration and virological response in HIV-1-infected children

Background

Variability in MDR1 and PXR has been associated with differences in drug plasma levels and response to antiretroviral therapy. We investigated whether polymorphisms in MDR1 (T-129C, C1236T and C3435T) and PXR (C63396T) affect lopinavir plasma concentration and the virological or immunological response to HAART in HIV-1-infected children.

Methods

Genotypes were identified in 100 blood donors and 38 HIV-1-infected children. All children received HAART with lopinavir boosted with ritonavir (LPV/r) at the time of LPV plasma level quantification, before (C_trough) and between 1 and 2 h after (C_post-dose) the administration of the next dose of drug. CD4⁺ T-cell counts and plasma viral load were analyzed before and after the initiation of LPV/r.

Results

MDR1 1236T, MDR1 3435T and PXR 63396T alleles showed a frequency of ~ 50% while the MDR1 -129C allele only reached 5%. Children heterozygotes 1236CT showed a significantly lower LPV C_post-dose than homozygotes 1236TT (median C_post-dose = 3.04 μg/ml and 6.50 μg/ml, respectively; p = 0.016). Children heterozygotes 1236CT also had a lower decrease of viral load after 36 weeks of LPV/r exposure compared with homozygotes 1236CC (median viral load changes = − 0.50 log₁₀ copies/ml and − 2.08 log₁₀ copies/ml, respectively; p = 0.047). No effect on the immunological response was observed for polymorphisms of MDR1 or PXR.

Conclusions

Our results suggest that the MDR1 C1236T SNP significantly reduces LPV plasma concentration affecting the virological response to HAART. Heterozygotes 1236CT might have an altered level of P-gp expression/activity in enterocytes and CD4⁺ T lymphocytes that limits the absorption of LPV leading to an impaired virological suppression.     

Role of Catalase and Superoxide Dismutase Activities on Oxidative Stress in the Brain of a Phenylketonuria Animal Model and the Effect of Lipoic Acid

Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7 days, on some oxidative stress parameters. Lipoic acid prevented alterations on catalase (CAT) and superoxide dismutase (SOD), and the oxidative damage of lipids, proteins, and DNA observed in HPA rats. In addition, lipoic acid diminished reactive species generation compared to HPA group which was positively correlated to SOD/CAT ratio. We also observed that in vitro Phe inhibited CAT activity while phenyllactic and phenylacetic acids stimulated superoxide dismutase activity. These results demonstrate the efficacy of lipoic acid to prevent oxidative stress induced by HPA model in rats. The possible benefits of lipoic acid administration to PKU patients should be considered.     

A simple model of the hydrophobic effect for molecular simulation of interfacial phenomena

A coarse-grained model for simulation of interfacial phenomena in aqueous systems has been developed. The model captures the hydrophobic effect by only considering the structure and cohesiveness of water. Monte Carlo (MC) simulations of water-oil mixtures show that low concentrations of oil are solvated with little perturbation of the hydrogen bonding network structure of the water, while high concentrations of oil are excluded altogether. Analysis of the water structure in the simulations indicates that the water molecules maintain close to four coordination in the presence of solutes and the distribution of bond angles is not markedly affected by the presence of solutes. MC simulations of an alkane oligomer in water and a poly(ethylene oxide) (PEO) oligomer in water indicate that the chains are quite flexible and also do not perturb the network structure of the water phase.     

Searching Responses of a Hunting Spider to Cues Associated with Lepidopteran Eggs

Cheiracanthium inclusum (Hentz), a hunting spider, feeds on eggs of Helicoverpa zea (Boddie) and other moths. This study investigated whether C. inclusum can use chemical compounds present in H. zea scales and egg residues as kairomones to find these non-motile prey items. In a series of no- choice tests, spiders were presented with a piece of florist paper containing scales alone, scales + egg residues, or untreated controls. Next, spiders were presented with solvent extracts of either scales or eggs. Polar and non-polar solvents were used in the extractions. Contact with scales alone, scales + egg residues, and non-polar solvent extracts of both scales and eggs resulted in retention and/or induction of local searching behavior. Extracts made with polar solvents induced no apparent response, indicating that the chemostimulatory compounds are lipophilic. These results show that C. inclusum responds to kairomones left by ovipositing H. zea and use these chemical cues to detect and locate H. zea eggs.