Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, K-cs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus; SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Genetic polymorphisms related to meat traits in purebred and crossbred Nelore cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of Laser Fluorescence in the Monitoring of the Initial Stage of the De-/Remineralization Process: An in vitro and in situ Study

This study aimed to evaluate laser fluorescence (LF) for monitoring the initial stage of subsurface de- and remineralization (<150 mu m depth). Ninety-six sound blocks of bovine enamel, selected according to surface hardness (SH) and LF were used in two experimental studies, in vitro and in situ. In vitro, blocks were exposed to a demineralizing solution, then remineralized by pH cycling for 6 days. In situ, 10 volunteers wore acrylic palatal appliances, each containing 4 dental enamel blocks that were demineralized for 14 days by exposure to 20% sucrose solution. Following this treatment, blocks were submitted to remineralization for 1 week with fluoride dentifrice (1,100 mu g F/g). In both experiments, SH and LH were measured after demineralization and after remineralization. Further, enamel blocks were selected after the demineralization/remineralization steps for measurement of cross-sectional hardness and integrated loss of subsurface hardness (Delta KHN). SH and Delta KHN showed significant differences among the phases in each study. LF values for sound, demineralized and remineralized enamel were: 5.2 +/- 1.1, 8.1 +/- 1.2 and 5.6 +/- 0.8, respectively, in the in vitro study, and 5.3 +/- 0.3, 16.5 +/- 4.7 and 6.5 +/- 2.5, respectively, in the in situ study, values for demineralized enamel being significantly higher than for sound and remineralized enamel in both studies. However, LF was correlated with Delta KHN only in situ. LF was capable of monitoring de- and remineralization in early lesions in situ, when bacteria are presumably present in the caries lesion body, but is not correlated with mineral changes in bacteria-free systems. Copyright (C) 2009 S. Karger AG, Basel

Macromolecular properties of cepacian in water and in dimethylsulfoxide

Cepacian is the exopolysaccharide produced by the majority of the so far investigated clinical strains of the Burkholderia cepacia complex. This is a group of nine closely related bacterial species that might cause serious lung infections in cystic fibrosis patients, in some cases leading to death. In this paper the aggregation ability and the conformational properties of cepacian chain were investigated to understand its role in biofilm formation. Viscosity and atomic force microscopy studies in water and in mixed (dimethylsulfoxide/water) solvent indicated the formation of double stranded molecular structures in aqueous solutions. Inter-residue short distances along cepacian chain were investigated by NOE NMR, which showed that two side chains of cepacian were not conformation ally free due to strong interactions with the polymer backbone. These interactions were attributed to hydrogen bonding and contributed to structure rigidity. (c) 2007 Elsevier Ltd. All rights reserved.

Evaluation of metals in water and sediments of micro-basins in the city of Americana, São Paulo state, Brazil

Water pollution found in major rivers in Brazil has its origin from urban sewage discharges and industrial effluent, carried out by small streams and rivers crossing cities. Therefore, studies related to hydrographic micro-basins offer the opportunity to establish environmental management strategies for restoring water resources, based on diagnosis of the water quality. Despite this understanding, few studies in urban and rural areas have been performed in a systematic manner in Brazilian micro-basins. The main goal of this research was to diagnose the water resources in micro-basins in the region of the district of Americana, São Paulo state, Brazil, through the quantification of metals in water and sediment. The methodology was based on the investigation of metals (Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn), in four micro-basins, determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The most significant result showed high concentration levels of chromium (969 μg L-1), downstream of the discharge of sewage from the city of Nova Odessa. This concentration in the river was above the allowed limit of Brazilian regulation agency (50 μg L-1 for Cr). Also high levels of Cr were found in the sediment (98.9 μg g-1) collected at the same monitored site. These results are important indicators of environmental performance and anthropogenic activities to help the government establish environmental management strategies aimed at the reduction of water pollution. © 2013 WIT Press.

In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus

Oropouche, Caraparu, Guama, Guaroa and Tacaiuma viruses (Orthobunyavirus genus) cause human febrile illnesses and/or encephalitis. To achieve a therapeutical agent to prevent and/or treat these diseases we evaluated the antiviral action of Interferon-alpha (IFN-alpha) on these orthobunyaviruses. In vitro results showed that all the studied orthobunyaviruses are susceptible to antiviral action of IFN-alpha, but this susceptibility is limited and dependent on both concentration of drug and treatment period. In vivo results demonstrated that IFN-alpha present antiviral action on Oropouche and Guaroa viruses when used as a prophylactic treatment. Moreover, a treatment initiated 3 It after infection prevented the death of Guaroa virus infected-mice. Additionally, mortality of mice was related to the migration and replication of viruses in their brains. Our results suggest that IFN-alpha could be potentially useful in the prevention of diseases caused by Oropouche virus and in the prevention and/or treatment of diseases caused by Guaroa virus. (C) 2007 Elsevier B.V. All rights reserved.

Non invasive methods for genetic analysis applied to ecological and behavioral studies in Latino-America

Documenting the presence and abundance of the neotropical mammals is the first step for understanding their population ecology, behavior and genetic dynamics in designing conservation plans. The combination of field research with molecular genetics techniques are new tools that provide valuable biological information avoiding the disturbance in the ecosystems, trying to minimize the human impact in the process to gather biological information. The objective of this paper is to review the available non invasive sampling techniques that have been used in Neotropical mammal studies to apply to determine the presence and abundance, population structure, sex ratio, taxonomic diagnostic using mitochondrial markers, and assessing genetic variability using nuclear markers. There are a wide range of non invasive sampling techniques used to determine the species identification that inhabit an area such as searching for tracks, feces, and carcasses. Other useful equipment is the camera traps that can generate an image bank that can be valuable to assess species presence and abundance by morphology. With recent advances in molecular biology, it is now possible to use the trace amounts of DNA in feces and amplify it to analyze the species diversity in an area, and the genetic variability at intraspecific level. This is particularly helpful in cases of sympatric and cryptic species in which morphology failed to diagnose the taxonomic status of several species of brocket deer of the genus Mazama.

Clinical, cytogenetic and toxicological studies in rural workers exposed to pesticides in Botucatu, São Paulo, Brazil

Pesticidas podem causar mutações gênicas e aberrações cromossômicas em indivíduos expostos. Investigamos 24 trabalhadores expostos a pesticidas, nos quais foram executados exames clínicos e testes citogenéticos e toxicológicos. Dez indivíduos não expostos foram usados como controles. Dosagem toxicológica de cobre, zinco e manganês (metais encontrados em alguns pesticidas), dosagem de enzimas hepáticas (GOT, GPT, AP) e atividade de acetilcolinesterase foram executadas em 16 trabalhadores e oito controles. Nos trabalhadores expostos, os sintomas clínicos mais pertinentes foram digestão pobre, com sensação de plenitude após alimentação, olhos irritados, enxaqueca e fasciculações. O grupo exposto mostrou dosagem de manganês e atividade de acetilcolinesterase significativamente mais baixas, e nível significativamente mais alto de fosfatase alcalina. Estudos citogenéticos mostraram freqüências de aberrações cromossômicas significativamente mais altas no grupo exposto quando comparado ao grupo de controle. Embora usassem vestuário protetor contra névoa de pesticidas, o qual incluía calças de borracha, botas, luvas, máscara e chapéu, os resultados clínicos revelaram que os trabalhadores foram contaminados. Concluímos que estudos citogenéticos, toxicológicos, juntamente com exames clínicos, são importantes no controle da saúde do trabalhador, mesmo em condições de proteção.

Cytogenetics studies in Brazilian species of Pseudophyllinae (Orthoptera: Tettigoniidae): 2n(♂)=35 and fn=35 the probable basic and ancestral karyotype of the family tettigoniidae

The karyotypes of five species of Brazilian Pseudophyllinae belonging to four tribes were here studied. The data available in the literature altogether with those obtained with species in here studied allowed us to infer that 2n(♂)=35 is the highest chromosome number found in the family Tettigoniidae and that it is present in species belonging to Pseudophyllinae, Zaprochilinae and in one species of Tettigoniinae. In spite of that all five species exhibit secondary karyotypes arisen surely by a mechanism of chromosomal rearrangement of centric fusion, tandem fusion and centric inversion types from those with 2n(♂)=35 and FN=35, they share some common traits. The X chromosome is submetacentric (FN=36), heteropicnotic during the first prophase, the largest of the set but its size is rather variable among the species and the sex chromosomal mechanism is of the XO( ♂ ), XX( ♀ ) type. The chromosomal rearrangements involved in the karyotype evolution of the Pseudophyllinae and its relationship with those of the family Tettigoniidae are discussed and we propose that the basic and the ancestral karyotype of the Tettigoniidae is formed by 2n(♂)=35, FN=35 and not by 2n(♂)=31, FN= 31, as usually accepted.

In vitro and in vivo studies on CCR10 regulation by Annexin A1

The mode of action of annexin A1 (ANXA1) is poorly understood. By using rapid subtraction hybridization we studied the effects of human recombinant ANXA1 and the N-terminal ANXA1 peptide on gene expression in a human larynx cell line. Three genes showed strong downregulation after treatment with ANXA1. In contrast, expression of CCR10, a seven transmembrane G-protein coupled receptor for chemokine CCL27 involved in mucosal immunity, was increased. Moreover the reduction in CCR10 expression induced by ANXA1 gene deletion was rescued by intravenous treatment with low doses of ANXA1. These findings provide new evidence that ANXA1 modulates gene expression. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Labaditin, a cyclic peptide with rich biotechnological potential: preliminary toxicological studies and structural changes in water and lipid membrane environment

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Loading of praziquantel in the crystal lattice of solid lipid nanoparticles Studies by DSC and SAXS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)