Adaptations in autonomic function during exercise training in heart failure

Although neurohumoral excitation is the hallmark of heart failure (HF), the mechanisms underlying this alteration are not entirely known. Abnormalities in several systems contribute to neurohumoral excitation in HF, including arterial and cardiopulmonary baroreceptors, central and peripheral chemoreceptors, cardiac chemoreceptors, and central nervous system abnormalities. Exercise intolerance is characteristic of chronic HF, and growing evidence strongly suggests that exercise limitation in patients with chronic HF is not due to elevated filling pressures or inadequate cardiac output during exercise, but instead due to skeletal myopathy. Several lines of evidence suggest that sympathetic excitation contributes to the skeletal myopathy of HF, since sympathetic activity mediates vasoconstriction at rest and during exercise likely restrains muscle blood flow, arteriolar dilatation, and capillary recruitment, leading to underperfused areas of working muscle, and areas of muscle ischemia, release of reactive oxygen species (ROS), and inflammation. Although controversial, either unmyelinated, metabolite-sensitive afferent fibers, and/or myelinated, mechanosensitive afferent fibers in skeletal muscle underlie the exaggerated sympathetic activity in HF. Exercise training has emerged as a unique non-pharmacological strategy for the treatment of HF. Regular exercise improves functional capacity and quality of life, and perhaps prognosis in chronic HF patients. Recent studies have provided convincing evidence that these benefits in chronic HF patients are mediated by significant reduction in central sympathetic outflow as a consequence of improvement in arterial and chemoreflex controls, and correction of central nervous system abnormalities, and increase in peripheral blood flow with reduction in cytokines and increase in mass muscle.

Baroreflex deficit blunts exercise training-induced cardiovascular and autonomic adaptations in hypertensive rats

P>1. Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex-mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long-term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50-70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re-established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.

Effect of the duration of daily aerobic physical training on cardiac autonomic adaptations

The present study has investigated in conscious rats the influence of the duration of physical training sessions on cardiac autonomic adaptations by using different approaches; 1) double blockade with methylatropine and propranolol; 2) the baroreflex sensitivity evaluated by alternating bolus injections of phenylephrine and sodium nitroprusside; and 3) the autonomic modulation of HRV in the frequency domain by means of spectral analysis. The animals were divided into four groups: one sedentary group and three training groups submitted to physical exercise (swimming) for 15, 30, and 60 min a day during 10 weeks. All training groups showed similar reduction in intrinsic heart rate (IHR) after double blockade with methylatropine and propranolol. However, only 30-min and 60-min physical training presented an increase in the vagal autonomic component for determination of basal heart rate (HR) in relation to group sedentary. Spectral analysis of HR showed that the 30-min and 60-min physical training presented the reduction in low-frequency oscillations (LF = 0.20-0.75 Hz) and the increase in high-frequency oscillations (HF = 0.75-2.5 Hz) in normalized units. These both groups only showed an increased baroreflex sensitivity to tachycardiac responses in relation to group sedentary, however when compared, the physical training of 30-min exhibited a greater gain. In conclusion, cardiac autonomic adaptations, characterised by the increased predominance of the vagal autonomic component, were not proportional to the duration of daily physical training sessions. In fact, 30-minute training sessions provided similar cardiac autonomic adaptations, or even more enhanced ones, as in the case of baroreflex sensitivity compared to 60-minute training sessions. (C) 2010 Elsevier B.V. All rights reserved.

Comparison of the effects of aerobic and resistance training on cardiac autonomic adaptations in ovariectomized rats

We have compared the effects of two types of physical training on the cardiac autonomic control in ovariectomized and sham-operated rats according to different approaches: double autonomic blockade (DAB) with methylatropine and propranolol; baroreflex sensibility (BRS) and spectral analysis of heart rate variability (HRV). Wistar female rats (+/- 250 g) were divided into two groups: sham-operated and ovariectomized. Each group was subdivided into three subgroups: sedentary rats, rats submitted to aerobic trained and rats submitted to resistance training. Ovariectomy did not change arterial pressure, basal heart rate (HR), DAB and BRS responses, but interfered with HRV by reducing the low-frequency oscillations (LF = 0.20-0.75 Hz) in relation to sedentary sham-operated rats. The DAB showed that both types of training promoted an increase in the predominance of vagal tonus in sham-operated rats, but HR variations due to methylatropine were decreased in the resistance trained rats compared to sedentary rats. Evaluation of BRS showed that resistance training for sham-operated and ovariectomized rats reduced the tachycardic responses in relation to aerobic training. Evaluation of HRV in trained rats showed that aerobic training reduced LF oscillations in sham-operated rats, whereas resistance training had a contrary effect. In the ovariectomized rats, aerobic training increased high frequency oscillations (HF = 0.75-2.5 Hz), whereas resistance training produced no effect. In sham-operated rats, both types of training increased the vagal autonomic tonus, but resistance training reduced HF oscillations and BRS as well. In turn, both types of training had similar results in ovariectomized rats, except for HRV, as aerobic training promoted an increase in HF oscillations. (C) 2011 Elsevier B.V. All rights reserved.

Bathymetric distribution of the shrimp Rimapenaeus constrictus (Stimpson, 1874) (Decapoda, Penaeidae) in two locations off the southeastern Brazilian coast

The distribution of benthic organisms is directly or indirectly associated with the physical and chemical properties of the water and sediment. This study analysed the spatial and temporal distribution of Rimapenaeus constrictus in unconsolidated sublittoral sediments of two areas off the northern coast of the state of Sao Paulo, Brazil. We also analysed the association of environmental factors with the occurrence of this species. Shrimp were collected monthly from July 2001 to June 2003, with a fishing boat equipped with two double-rig nets, in the regions of Ubatuba (UBA) and Caraguatatuba (CA). The collections were made during the day, along five transects with mean depths of 5, 10, 15, 20, 25, 30, and 35 m. We obtained a total of 5478 individuals, 3403 (UBA = 2025 and CA = 1378) during the first year, and 2075 (UBA = 875 and CA = 1200) during the second year. Significant differences in abundance were observed in relation to depth, season of the year, and also in the interaction between region and depth. Higher abundances occurred in fall and winter, independently of the sampling year. The largest numbers of shrimp were caught on the 20-m transect in UBA and the 25-m transect in CA. It is concluded that the distribution pattern of this species is closely related to environmental factors, and the temperature of the bottom water and the sediment texture were the most significant variables affecting the distribution.

Only subtle protein conformational adaptations are required for ligand binding to thyroid hormone receptors: Simulations using a novel multipoint steered molecular dynamics approach

Thyroid hormone receptors (TR) are hormone-dependent transcription regulators that play a major role in human health, development, and metabolic functions. The thyroid hormone resistance syndrome, diabetes, obesity, and some types of cancer are just a few examples of important diseases that are related to TR malfunctioning, particularly impaired hormone binding. Ligand binding to and dissociation from the receptor ultimately control gene transcription and, thus, detailed knowledge of binding and release mechanisms are fundamental for the comprehension of the receptor`s biological function and development of pharmaceuticals. In this work, we present the first computational study of ligand entry into the ligand binding domain (LBD) of a nuclear receptor. We report molecular dynamics simulations of ligand binding to TRs using a generalization of the steered molecular dynamics technique designed to perform single-molecule pulling simulations along arbitrarily nonlinear driving pathways. We show that only gentle protein movements and conformational adaptations are required for ligand entry into the LBDs and that the magnitude of the forces applied to assist ligand binding are of the order of the forces involved in ligand dissociation. Our simulations suggest an alternative view for the mechanisms ligand binding and dissociation of ligands from nuclear receptors in which ligands can simply diffuse through the protein surface to reach proper positioning within the binding pocket. The proposed picture indicates that the large-amplitude protein motions suggested by the apo- and holo-RXR alpha crystallographic structures are not required, reconciling conformational changes of LBDs required for ligand entry with other nuclear receptors apo-structures that resemble the ligand-bound LBDs.

Bleaching of melanin in the epidermis of South American fur seal and its application on enzyme immunohistochemistry

The South American fur seal (Arctocephalus australis) is an amphibious marine mammal distributed along the Atlantic and Pacific coasts of South America. The species is well adjusted to different habitats due to the morphology of its fin-like members and due to some adaptations in their integumentary system. Immunohistochemical studies are very important to evaluate the mechanisms of skin adaptation due the differential expression of the antigens present in the tissue depending of the region of the body surface. However, its strongly pigmented (melanin) epidermis prevents the visualization of the immuno-histochemical chromogens markers. In this study a melanin bleaching method was developed aimed to allow the visualization of the chromogens without interfering in the antigen-antibody affinity for immunohistochemistry. The analysis of PCNA (proliferating cell nuclear antigen) index in the epidermis of A. australis by immunohistochemistry with diaminobenzidine (DAB) as chromogen was used to test the method. The bleaching of the melanin allowed to obtain the cell proliferation index in epidermis and to avoid false positive results without affecting the immunohistochemical results.

Pode a atividade física materna modular a programação fetal induzida pela nutrição?

Existe considerável evidência para a indução de diferentes fenótipos em reposta às variações no ambiente fetal e neonatal. O aporte inadequado de nutrientes no período crítico do desenvolvimento está associado ao risco alto de doenças metabólicas na vida adulta, este fenômeno biológico é chamado de programação. A atividade física durante a gestação resulta em adaptações fisiológicas da mãe e no aumento da disponibilidade de nutrientes e oxigênio no espaço feto-placentário. Este trabalho tem como objetivo discutir os mecanismos da indução de programação fetal pela nutrição e o provável efeito modulador da atividade física durante a gestação. Foram utilizadas as bases de dados do Medline Pubmed, Lilacs e Bireme, com publicações entre 1990 até 2008. Os termos de indexação utilizados foram: nutrition, fetal programming, gestation, physical activity, physical exercise, metabolism. Em conclusão, o aporte inadequado de nutrientes programa o aparecimento de doenças metabólicas na vida adulta, enquanto que a atividade física durante a gestação aumenta a disponibilidade de nutrientes e oxigênio, repercutindo positivamente no crescimento fetal e no peso ao nascer.

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

Determinação de hormônios estrógenos em água potável usando CLAE-DAD

An analytical procedure for determination of estriol, 17β-estradiol, estrone and 17α-ethinylestradiol in drinking water is presented. The method employs solid phase extraction (SPE) and sample dechlorination as cleanup procedures, followed by HPLC-DAD analysis. Validation was carried out using RE No. 899/2003 guidelines established by the Agência Nacional de Vigilância Sanitária (National Agency of Sanitary Surveillance, Brazil), with some adaptations. The statistically evaluated results have shown that the method is selective, precise (0,06% to 19,40% CV) and accurate (91,52% to 109,41% average recoveries). The developed method was applied to the analysis of these contaminants in drinking water from São Luís, MA.

Chorion biopsy in mongrel dogs

With the great development of the gestational studies in all of the species, we noticed the necessity of adaptations of these techniques for prenatal diagnosis in dogs. Based on this, we studied the feasibility of chorion biopsy guided by ultrasound. Our results demonstrated accuracy on the sex determination being 2 males and 12 females, as well as it would be possible to identify chromosome alteration due to the quality of samplings. Sex determination was accomplished with the identification of Y gene chromosomes in PCR technique. After the collection, fragments were prepared for light microscopy studies and revealed fetal chorion tissue, blood colloid and erythrocyte. In the whole material we found hemosiderin impregnations due to the hemolysis and to the residue of blood of the placental marginal hematomes. The submitted female dogs to this technique demonstrated normal puppy births without death.

Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

Background: Cutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of T. rubrum exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST) collection by constructing one cDNA library and nine suppression subtractive hybridization libraries. Results: The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS) categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had not been previously deposited in public databases. Conclusion: In this study, we identified novel T. rubrum genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of T. rubrum to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs.

INTERPOPULATION COMPARISON OF REPRODUCTION OF THE ATLANTIC SHRIMP HIPPOLYTE OBLIQUIMANUS (CARIDEA: HIPPOLYTIDAE)

The genus Hippolyte is represented by typically small shrimps with intriguing mechanisms of reproduction. In order to study possible variability in reproductive aspects among different populations, we conducted an exhaustive comparative study of H. obliquimanus from South (Brazil) and Central American (Costa Rica) waters. The study focuses on fecundity and reproductive output. Mean size of ovigerous females was significantly larger, and both mean reproductive output and mean fecundity were significantly higher in specimens from Costa Rica then in those collected in Brazil. Embryo volume was significantly smaller in the Costa Rican population, and in both populations embryos doubled their volume during embryogenesis. We discuss and compare our findings with the information available regarding H. obliquimanus and other hippolytid shrimp. The reproductive traits of both populations of H. obliquimanus show some important differences which may reflect adaptations to local environmental conditions, demonstrating a high plasticity of reproductive features of the species in Brazilian and Costa Rican waters.

A reliable measure of similarity based on dependency for short time series: an application to gene expression networks

Background: Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges. Results: The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions. Conclusion: Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.

Characterization of mitochondrial genotypes in the foundation herd of the Canchim beef cattle breed

The Canchim (5/8 Charolais + 3/8 Zebu) beef cattle breed was developed at Southeast-Embrapa Cattle to take advantage of hybrid vigor and to combine the higher growth rate and beef quality of Charolais with tropical adaptations of Zebu. The development of three lineages (old, new, and crossbred) has increased its genetic basis. The genotypic origin (Bos taurus or Bos indicus) of the mitochondrial DNA (mtDNA) of the Canchim breed was unknown. We characterized the mtDNA genotype of this founder herd by allele-specific polymerase chain reaction. The 173 founder Zebu females (62 Indubrasil, 3 Guzerat, and 108 Nellore) and their 6749 offspring were identified. The frequency of B. indicus mtDNA ranged from 1.15 to 2.05% among the descendants (N = 6404) of each maternal line with available DNA, and among animals that were alive (N = 689) in December 2007 among the three lineages. Though mtDNA characterization can be used to direct animal selection, the low frequency of B. indicus mtDNA impairs the evaluation of its effects on production traits in these animals. The high prevalence of B. taurus mtDNA in Canchim proves that the founder Zebu females from the Indubrasil, Guzerat and Nellore breeds were obtained from crosses of Zebu sires with local B. taurus dams.