What can light scattering spectroscopy do for membrane-active peptide studies

Highly charged peptides are important components of the immune system and belong to an important family of antibiotics. Although their therapeutic activity is known, most of the molecular level mechanisms are controversial. A wide variety of different approaches are usually applied to understand their mechanisms, but light scattering techniques are frequently overlooked. Yet, light scattering is a noninvasive technique that allows insights both on the peptide mechanism of action as well as on the development of new antibiotics. Dynamic light scattering (DLS) and static light scattering (SLS) are used to measure the aggregation process of lipid vesicles upon addition of peptides and molecular properties (shape, molecular weight). The high charge of these peptides allows electrostatic attraction toward charged lipid vesicles, which is studied by zeta potential (zeta-potential) measurements. Copyright (c) 2008 European Peptide Society and John Wiley & Sons, Ltd.

Evidence-based guidelines for interpreting change scores for the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30

Aim: To use published literature and experts' opinion to investigate the clinical meaning and magnitude of changes in the Quality of Life (QOL) of groups of patients measured with the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Methods: An innovative method combining systematic review of published studies, expert opinions and meta-analysis was used to estimate large, medium, and small mean changes over time for QLQ-C30 scores. Results: Nine hundred and eleven papers were identified, leading to 118 relevant papers. One thousand two hundred and thirty two mean changes in QOL over time were combined in the meta-analysis, with timescales ranging from four days to five years. Guidelines were produced for trivial, small, and medium size classes, for each subscale and for improving and declining scores separately. Estimates for improvements were smaller than respective estimates for declines. Conclusions: These guidelines can be used to aid sample size calculations and interpretation of mean changes over time from groups of patients. Observed mean changes in the QLQ-C30 scores are generally small in most clinical situations, possibly due to response shift. Careful consideration is needed when planning studies where QOL changes over time are of primary interest; the timing of follow up, sample attrition, direction of QOL changes, and subscales of primary interest are key considerations. (C) 2012 Elsevier Ltd. All rights reserved.

Hepatitis B virus genotypes from European origin explains the high endemicity found in some areas from southern Brazil

Southern Brazil is considered an area of low Hepatitis B endemicity, but some areas of higher endemicity have been described in the Southwest of Parana and Santa Catarina states. The aim of this study was to evaluate viral genotypes circulating throughout Parana state. PCR amplification and partial sequencing of the S gene was carried out in 228 samples from HBsAg positive candidate blood donors. Samples have been collected in seven different counties (Cascavel, Curitiba, Foz do Iguacu, Francisco Beltrao, Matinga Londrina and Paranagua). The most common HBV genotype in Parana state was D (82.9%; 189/228), followed by A (14.1%; 32/228). Genotypes F (1.3%; 3/228), C (1.3%; 3/228) and H (0.4%; 1/228) were also found. Distribution of genotypes was different in the studied counties, but genotype D was the most frequent in all of them. In Francisco Beltrao, all studied samples belonged to genotype D. The high prevalence of HBV genotype Din South of Brazil is explained by the intense migration of settlers from Europeans countries. Subgenotypes A1 and A2 were identified circulating in all cities where HBV/A was found. As observed in other areas of Brazil, HBV/A1 is more frequent than the HBV/A2 in Parana state and its presence was significantly larger in black and mulatto individuals. Genotype C was found only in individuals with Asian ancestry from Londrina and Maringa. Most HBV/F sequences identified in this study were classified as subgenotype F2a that was previously described in Brazil. The sole case of subgenotype F4 was from Foz do Iguacu city, near to Northern Argentina, where F4 is highly prevalent. The single genotype H sample was from Curitiba. This is the first case of this genotype described in Brazil. Further studies should be carried out to determine if more genotype H samples can be found in other populations from Brazil. (C) 2012 Elsevier B.V. All rights reserved.

Synthesis, anti-inflammatory activity and molecular docking studies of 2,5-diarylfuran amino acid derivatives

A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS-stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed. (C) 2011 Elsevier Masson SAS. All rights reserved.

Application of tetra-isopalmitoyl ascorbic acid in cosmetic formulations: Stability studies and in vivo efficacy

Liposoluble vitamin C derivatives, such as tetra-isopalmitoyl ascorbic acid (IPAA), are often used in dermocosmetic products due to their higher stability than vitamin C free form as well as its proposed effects in skin; however, there are no studies analyzing IPAA stability or its in vivo effects when present in dermocosmetic formulations. Thus, this study aimed to evaluate chemical stability and pre-clinical and clinical efficacy of dermocosmetic formulations containing IPAA in skin hydration and microrelief. Chemical stability of the formulations added with 1% IPAA was evaluated by heat stress during 35 days by HPLC. For pre-clinical evaluation, experimental formulations were topically applied on hairless skin mice during 5 days and animal skins were analyzed by non-invasive biophysic techniques (water content of stratum corneum, TEWL, viscoelasticity, and microrelief) and by histopathological studies. For clinical efficacy tests, the formulations were topically applied to the forearm and face of human volunteers, and 3 h and 15 days after applications, the skins were evaluated by the same non-invasive techniques mentioned before. Results showed that formulations containing IPAA had medium stability and had pronounced moisturizing effects on stratum corneum and on viable epidermis. These formulations also improved skin microrelief especially in relation to skin smoothness and roughness. (C) 2012 Elsevier B.V. All rights reserved.

Synthesis, biological evaluation and molecular docking studies of 3-(triazolyl)coumarin derivatives: Effect on inducible nitric oxide synthase

A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-alpha secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that it pi center dot center dot center dot pi interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored. (C) 2012 Elsevier Masson SAS. All rights reserved.

A graph-theoretical approach in brain functional networks. Possible implications in EEG studies

Abstract Background Recently, it was realized that the functional connectivity networks estimated from actual brain-imaging technologies (MEG, fMRI and EEG) can be analyzed by means of the graph theory, that is a mathematical representation of a network, which is essentially reduced to nodes and connections between them. Methods We used high-resolution EEG technology to enhance the poor spatial information of the EEG activity on the scalp and it gives a measure of the electrical activity on the cortical surface. Afterwards, we used the Directed Transfer Function (DTF) that is a multivariate spectral measure for the estimation of the directional influences between any given pair of channels in a multivariate dataset. Finally, a graph theoretical approach was used to model the brain networks as graphs. These methods were used to analyze the structure of cortical connectivity during the attempt to move a paralyzed limb in a group (N=5) of spinal cord injured patients and during the movement execution in a group (N=5) of healthy subjects. Results Analysis performed on the cortical networks estimated from the group of normal and SCI patients revealed that both groups present few nodes with a high out-degree value (i.e. outgoing links). This property is valid in the networks estimated for all the frequency bands investigated. In particular, cingulate motor areas (CMAs) ROIs act as ‘‘hubs’’ for the outflow of information in both groups, SCI and healthy. Results also suggest that spinal cord injuries affect the functional architecture of the cortical network sub-serving the volition of motor acts mainly in its local feature property. In particular, a higher local efficiency El can be observed in the SCI patients for three frequency bands, theta (3-6 Hz), alpha (7-12 Hz) and beta (13-29 Hz). By taking into account all the possible pathways between different ROI couples, we were able to separate clearly the network properties of the SCI group from the CTRL group. In particular, we report a sort of compensatory mechanism in the SCI patients for the Theta (3-6 Hz) frequency band, indicating a higher level of “activation” Ω within the cortical network during the motor task. The activation index is directly related to diffusion, a type of dynamics that underlies several biological systems including possible spreading of neuronal activation across several cortical regions. Conclusions The present study aims at demonstrating the possible applications of graph theoretical approaches in the analyses of brain functional connectivity from EEG signals. In particular, the methodological aspects of the i) cortical activity from scalp EEG signals, ii) functional connectivity estimations iii) graph theoretical indexes are emphasized in the present paper to show their impact in a real application.