Enantioselectivity in the Pharmacokinetic Interaction Between Fluvastatin and Lercanidipine in Healthy Volunteers

Hypertension and dyslipidemia are independent risk factors for cardiovascular mortality and are frequently present in the same patient. Fluvastatin (FV), used to reduce cholesterol levels, and lercanidipine (LER), used to control blood pressured are marketed as racemic mixtures. Therapeutic activities are 30-fold higher for (+)-3R,5S-FV and 100- to 200-fold higher for S-LER compared with their respective antipodes. The present study describes the enantioselective pharmacokinetic interaction between LER and FV in healthy volunteers. A crossover randomized study was conducted in 3 phases on 8 volunteers treated with a single oral racemic dose of LER (20 mg) or FV (40 mg) or LER plus FV. Serial blood samples were collected from 0 to 24 hours. Plasma concentrations of the LER and FV enantiomers were determined by liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were evaluated using the WinNonlin software. The Wilcoxon and Mann-Whitney tests (P < .05) were used to analyze enantiomer ratios and the pharmacokinetic drug interaction. Data are expressed as medians. In monotherapy, the kinetic disposition of both FV and LER was enantioselective. AUC values were significantly higher for (-)-3S,5R-FV than for (+)-3R,5S-FV (358.20 vs 279.68 ng.h/mL) and for S-LER compared with R-LER (13.90 vs 11.88 ng.h/mL). The pharmacokinetic parameters of FV were not enantioselective when combined with LER (AUC: (-)-3S,5R-FV: 325.21; (+)-3R,5S-FV: 316.44 ng.h/mL). There was a significant reduction in S-LER (8.06 vs 13.90 ng.h/mL) and R-LER (6.76 vs 11.88 ng.h/mL) AUC values when FV was coadministered. In conclusion, the interaction between FV-LER might be clinically relevant because AUC values of (+)-3R,5S-FV were increased when LER was coadministered, and AUC values of the 2 LER enantiomers were reduced when FV was coadministered.

Fractional quantum Hall effect in second subband of a 2DES

In the present paper we report on the experimental electron sheet density vs. magnetic field diagram for the magnetoresistance R(xx) of a two-dimensional electron system (2DES) with two occupied subbands. For magnetic fields above 9T, we found fractional quantum Hall levels centered around the filing factor v = 3/2 in both the two occupied electric subbands. We focused specially on the fractional levels of the second subband, whose experimental values of the magnetic field B of their minima do not obey a periodicity law in 1/|B-B(c)|, where B(c) is the critical field at the filling factor v = 3/2, and we explain this fact entirely in the framework of the composite fermions theory. We use a simple theoretical model to give a possible explanation for the fact. Copyright (c) EPLA, 2011

Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice

Aromatherapy uses essential oils (EOs) for several medical purposes, including relaxation. The association between the use of aromas and a decrease in anxiety could be a valuable instrument in managing anxiety in an ever increasing anxiogenic daily life style. Linalool is a monoterpene commonly found as the major volatile component of EOs in several aromatic plant species. Adding to previously reported sedative effects of inhaled linalool, the aim of this study was to investigate the effects of inhaled linalool on anxiety, aggressiveness and social interaction in mice. Additionally, we investigated the effects of inhaled linalool on the acquisition phase of a step-down memory task in mice. Inhaled linalool showed anxiolytic properties in the light/dark test, increased social interaction and decreased aggressive behavior; impaired memory was only seen the higher dose of linalool. These results strengthen the suggestion that inhaling linalool rich essential oils can be useful as a mean to attain relaxation and counteract anxiety. (C) 2009 Elsevier GmbH. All rights reserved.

Cultural Consonance, a 5HT2A Receptor Polymorphism, and Depressive Symptoms: A Longitudinal Study of Gene x Culture Interaction in Urban Brazil

In this study in urban Brazil we examine, as a predictor of depressive symptoms, the interaction between a single nucleotide polymorphism in the 2A receptor in the serotonin system (-1438G/A) and cultural consonance in family life, a measure of the degree to which an individual perceives her family as corresponding to a widely shared cultural model of the prototypical family. A community sample of 144 adults was followed over a 2-year-period. Cultural consonance in family life was assessed by linking individuals` perceptions of their own families with a shared cultural model of the family derived from cultural consensus analysis. The -1438G/A polymorphism in the 2A serotonin receptor was genotyped using a standard protocol for DNA extracted from leukocytes. Covariates included age, sex, socioeconomic status, and stressful life events. Cultural consonance in family life was prospectively associated with depressive symptoms. In addition, the interaction between genotype and cultural consonance in family life was significant. For individuals with the A/A variant of the -1438G/A polymorphism of the 2A receptor gene, the effect of cultural consonance in family life on depressive symptoms over a 2-year-period was larger (beta = -0.533, P < 0.01) than those effects for individuals with either the G/A (beta = -0.280, P < 0.10) or G/G (beta = -0.272, P < 0.05) variants. These results are consistent with a process in which genotype moderates the effects of culturally meaningful social experience on depressive symptoms. Am. J. Hum. Biol. 21:91-97, 2009. (C) 2008 Wiley-Liss, Inc.

The role of predator overlap in the robustness and extinction of a four species predator-prey network

Predators and preys often form species networks with asymmetric patterns of interaction. We study the dynamics of a four species network consisting of two weakly connected predator-prey pairs. We focus our analysis on the effects of the cross interaction between the predator of the first pair and the prey of the second pair. This is an example where the predator overlap, which is the proportion of predators that a given prey shares with other preys, is not uniform across the network due to asymmetries in patterns of interaction. We explore the behavior of the system under different interaction strengths and study the dynamics of survival and extinction. In particular, we consider situations in which the four species have initial populations lower than their long-term equilibrium, simulating catastrophic situations in which their abundances are reduced due to human action or environmental change. We show that, under these reduced initial conditions, and depending on the strength of the cross interaction, the populations tend to oscillate before re-equilibrating, disturbing the community equilibrium and sometimes reaching values that are only a small fraction of the equilibrium population, potentially leading to their extinction. We predict that, contrary to one`s intuition, the most likely scenario is the extinction of the less predated preys. (C) 2010 Elsevier B.V. All rights reserved.

Epidemiologia do Padrão Face Longa em escolares do Ensino Fundamental do município de Bauru - SP

OBJETIVO: o objetivo deste trabalho foi classificar e determinar a prevalência dos indivíduos portadores de comprometimento vertical nas relações faciais, conforme a severidade da discrepância e, especialmente, dos portadores de Padrão Face Longa. MÉTODOS: a amostra constou de 5.020 sujeitos de nacionalidade brasileira, de ambos os sexos, com idades entre 10 anos e 16 anos e 11 meses, matriculados no Ensino Fundamental do município de Bauru-SP. O exame da morfologia facial constou da observação direta da face, em normas frontal e lateral, sempre com os lábios em repouso, buscando identificar aqueles indivíduos que apresentassem comprometimento vertical nas relações faciais. Esses, uma vez identificados, foram classificados, considerando-se a severidade, em três subtipos: moderado, médio e grave. Para fins de determinação da prevalência dos portadores de Padrão Face Longa, apenas os classificados como dos subtipos médio e grave foram considerados. RESULTADOS: observou-se uma prevalência de 34,94% de comprometimento vertical nas relações faciais e 14,06% de Padrão Face Longa. CONCLUSÃO: os resultados obtidos no presente estudo permitiram concluir que a prevalência do comprometimento vertical nas relações faciais e do Padrão Face Longa foi maior do que a presumida com base na literatura.

Electrochemical Evidence of Strong Electronic Interaction of PtRu on Carbon Nanotubes with High Density of Defects

We show that carbon nanotubes (CNTs) with high density of defects can present a strong electronic interaction with nanoparticles of Pt-Ru with average particle size of 3.5 +/- 0.8 nm. Depending on the Pt-Ru loading on the CNTs, CO and methanol oxidation reactions suggest there is a charge transfer between Pt-Ru that in turn provokes a decrease in the electronic interaction taking place between Ru and Pt in the PtRu alloy. The CO stripping potentials were observed at about 0.65 and 0.5 V for Pt-Ru/CNT electrodes with Pt-Ru loadings of 10 and 20, and 30 wt %, respectively. (C) 2008 The Electrochemical Society. [DOI: 10.1149/1.2990222] All rights reserved.

Some questions about the Metropolitan Areas in Buenos Aires, Sao Paulo and Santiago regions

Among the numerous problems that are common to the Latin-American metropolises, such as the deep socio-spatial segregation, the impressive territorial fragmentation and the real estate valorisation that overvalues some territories, whilst it depreciates others, we have chosen to focus on the management of the metropolitan regions. That question clearly indicates that due to the great current changes of the economical restructuring - a process that strengthened the capitalist logic of social development - the traditional form of thinking urban planning has found its limits. Consequently, this issue of metropolitan management shows the need to look for new ways of metropolitan administration that can answer to the The main metropolitan regions of South America: Buenos Aires, Sao Paulo and Santiago form our references to characterize the recent changes from a territorial point of view on the one hand; and relative to the new determinations of the metropolis on the other hand. This leads us to discuss the challenges that metropolitan management face in a scenario of governability fragmentation.

Biologically Plausible Connectionist Prediction of Natural Language Thematic Relations

In Natural Language Processing (NLP) symbolic systems, several linguistic phenomena, for instance, the thematic role relationships between sentence constituents, such as AGENT, PATIENT, and LOCATION, can be accounted for by the employment of a rule-based grammar. Another approach to NLP concerns the use of the connectionist model, which has the benefits of learning, generalization and fault tolerance, among others. A third option merges the two previous approaches into a hybrid one: a symbolic thematic theory is used to supply the connectionist network with initial knowledge. Inspired on neuroscience, it is proposed a symbolic-connectionist hybrid system called BIO theta PRED (BIOlogically plausible thematic (theta) symbolic-connectionist PREDictor), designed to reveal the thematic grid assigned to a sentence. Its connectionist architecture comprises, as input, a featural representation of the words (based on the verb/noun WordNet classification and on the classical semantic microfeature representation), and, as output, the thematic grid assigned to the sentence. BIO theta PRED is designed to ""predict"" thematic (semantic) roles assigned to words in a sentence context, employing biologically inspired training algorithm and architecture, and adopting a psycholinguistic view of thematic theory.

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18 x 10(20) protons on target in which neutrinos of energies between similar to 500 MeV and 120 GeV are produced predominantly as nu(mu), the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the nu(mu) flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C. L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles theta(24) and theta(34) are constrained to be less than 11 degrees and 56 degrees at 90% C. L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime tau(3)/m(3) > 2.1 x 10(-12) s/eV at 90% C.L.

Increasing trends of sleep complaints in the city of Sao Paulo, Brazil

Objective: The aim of this study was to compare the prevalence of sleep habits and complaints and to estimate the secular trends through three population-based surveys carried out in 1987, 1995, and 2007 in the general adult population of the city of Sao Paulo, Brazil. Methods: Surveys were performed using the same three-stage cluster-sampling technique in three consecutive decades to obtain representative samples of the inhabitants of Sao Paulo with respect to gender, age (20-80 years), and socio-economic status. Sample sizes were 1000 volunteers in 1987 and 1995 surveys and 1101 in a 2007 survey. In each survey, the UNIFESP Sleep Questionnaire was administered face-to-face in each household selected. Results: For 1987, 1995, and 2007, respectively, difficulty initiating sleep (weighted frequency %; 95% CI) [(13.9; 11.9-16.2), (19.15; 16.8-21.6), and (25.0; 22.5-27.8)], difficulty maintaining sleep [(15.8; 13.7-18.2), (27.6; 24.9-30.4), and (36.5; 33.5-39.5)], and early morning awakening [(10.6; 8.8-12.7), (14.2; 12.2-16.5), and (26.7; 24-29.6)] increased in the general population over time, mostly in women. Habitual snoring was the most commonly reported complaint across decades and was more prevalent in men. There was no statistically significant difference in snoring complaints between 1987 (21.5; 19.1-24.2) and 1995 (19.0; 16.7-21.6), but a significant increase was noted in 2007 (41.7; 38.6-44.8). Nightmares, bruxism, leg cramps, and somnambulism complaints were significantly higher in 2007 compared to 1987 and 1995. All were more frequent in women. Conclusions: This is the first study comparing sleep complaints in probabilistic population-based samples from the same metropolitan area, using the same methodology across three consecutive decades. Clear trends of increasing sleep complaints were observed, which increased faster between 1995 and 2007 than from 1987 to 1995. These secular trends should be considered a relevant public health issue and support the need for development of health care and educational strategies to supply the population`s increased need for information on sleep disorders and their consequences. (C) 2010 Elsevier B.V. All rights reserved.

Elderly online: Effects of a digital inclusion program in cognitive performance

There is little empirical data about the impact of digital inclusion on cognition among older adults. This paper aimed at investigating the effects of a digital inclusion program in the cognitive performance of older individuals who participated in a computer learning workshop named ""Idosos On-Line`` (Elderly Online). Forty-two aged individuals participated in the research study: 22 completed the computer training workshop and 20 constituted the control group. All subjects answered a sociodemographic questionnaire and completed the Addenbrooke`s cognitive examination, revised (ACE-R), which examines five cognitive domains: orientation and attention, memory, verbal fluency, language, and visuo-spatial skills. It was noted that the experimental group`s cognitive performance significantly improved after the program, particularly in the language and memory domains, when compared to the control group. These findings suggest that the acquisition of new knowledge and the use of a new tool, that makes it possible to access the Internet, may bring gains to cognition. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

In vitro safety assessment of papain on human skin: A qualitative Light and Transmission Electron Microscopy (TEM) study

Papain is a thiol proteolytic enzyme widely used in dermatology that found applications in wound treatment. Recently, papain was also used as absorption enhancer which can modify the peptide/ protein material in the bilayer domain. We investigated papain safety using human skin that was exposed to papain in vitro at different times: 4, 24 and 48 hours. The samples were examined using Light and Transmission Electron Microscopy (TEM) to study of the mechanisms involved in enhancer-skin interaction. After 24 hours, changes occurred in corneosomes. However, samples of 48 hours did not show major changes in agreement with the control. These findings indicated that papain could be used safely onto the skin.

Patterns of brain asymmetry in the perception of positive and negative facial expressions

The divided visual field technique was used to investigate the pattern of brain asymmetry in the perception of positive/approach and negative/withdrawal facial expressions. A total of 80 undergraduate students (65 female, 15 male) were distributed in five experimental groups in order to investigate separately the perception of expressions of happiness, surprise, fear, sadness, and the neutral face. In each trial a target and a distractor expression were presented simultaneously in a computer screen for 150 ms and participants had to determine the side (left or right) on which the target expression was presented. Results indicated that expressions of happiness and fear were identified faster when presented in the left visual field, suggesting an advantage of the right hemisphere in the perception of these expressions. Fewer judgement errors and faster reaction times were also observed for the matching condition in which emotional faces were presented in the left visual field and neutral faces in the right visual field. Other results indicated that positive expressions (happiness and surprise) were perceived faster and more accurately than negative ones (sadness and fear). Main results tend to support the right hemisphere hypothesis, which predicts a better performance of the right hemisphere to perceive emotions, as opposed to the approach-withdrawal hypothesis.

Genetic Susceptibility Loci in Rheumatoid Arthritis Establish Transcriptional Regulatory Networks with Other Genes

Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non-HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA-DRB1 in RA pathogenesis.