Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in improved cardiac function and survival in a genetic model of heart failure

beta-blockers, as class, improve cardiac function and survival in heart failure (HF). However, the molecular mechanisms underlying these beneficial effects remain elusive. In the present study, metoprolol and carvedilol were used in doses that display comparable heart rate reduction to assess their beneficial effects in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild-type mice (WT) were used as controls. HF mice displayed baseline tachycardia, systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT. All these responses were significantly improved by both treatments. Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i) transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also increased [Ca(2+)] transient decay dynamics. We then examined the influence of carvedilol in cardiac oxidative stress as an alternative target to explain its beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac reduced/oxidized glutathione ratio compared with WT, which was significantly improved only by carvedilol treatment. Taken together, we provide direct evidence that the beneficial effects of metoprolol were mainly associated with improved cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins while carvedilol preferentially improved cardiac redox state. (C) 2008 Elsevier Inc. All rights reserved.

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

Meconium (MEC) is a potent inactivator of pulmonary surfactant. The authors studied the effects of polyethylene glycol addition to the exogenous surfactant over the lung mechanics and volumes. Human meconium was administrated to newborn rabbits. Animals were ventilated for 20 minutes and dynamic compliance, ventilatory pressure, and tidal volume were recorded. Animals were randomized into 3 study groups: MEC group (without surfactant therapy); S100 group (100 mg/kg surfactant); and PEG group (100 mg/kg porcine surfactant plus 5% PEG). After ventilation, a pulmonary pressure-volume curve was built. Histological analysis was carried out to calculate the mean alveolar size (Lm) and the distortion index (DI). Both groups treated with surfactant showed higher values of dynamic pulmonary compliance and lower ventilatory pressure, compared with the MEC group (P .05). S100 group had a larger maximum lung volume, V30, compared with the MEC group (P .05). Lm and DI values were smaller in the groups treated with surfactant than in the MEC group (P .05). No differences were observed between the S100 and PEG groups. Animals treated with surfactant showed significant improvement in pulmonary function as compared to nontreated animals. PEG added to exogenous surfactant did not improve lung mechanics or volumes.

Richards growth model and viability indicators for populations subject to interventions

In this work we study the problem of modeling identification of a population employing a discrete dynamic model based on the Richards growth model. The population is subjected to interventions due to consumption, such as hunting or farming animals. The model identification allows us to estimate the probability or the average time for a population number to reach a certain level. The parameter inference for these models are obtained with the use of the likelihood profile technique as developed in this paper. The identification method here developed can be applied to evaluate the productivity of animal husbandry or to evaluate the risk of extinction of autochthon populations. It is applied to data of the Brazilian beef cattle herd population, and the the population number to reach a certain goal level is investigated.

Dependence of the crossover exponent with the diffusion rate in the generalized contact process model

We study how the crossover exponent, phi, between the directed percolation (DP) and compact directed percolation (CDP) behaves as a function of the diffusion rate in a model that generalizes the contact process. Our conclusions are based in results pointed by perturbative series expansions and numerical simulations, and are consistent with a value phi = 2 for finite diffusion rates and phi = 1 in the limit of infinite diffusion rate.

A Classificação Internacional de Funcionalidade, Incapacidade e Saúde e a AIDS: uma proposta de core set

O advento da terapia anti-retroviral de alta potência (HAART) alterou a história natural da aids, diminuindo sua mortalidade e a incidência de doenças oportunistas e aumentando a esperança de vida das pessoas vivendo com aids.Como uma doença crônica, outras questões passam a ser relevantes, entre elas a adesão ao tratamento, seus efeitos adversos e a qualidade de vida das pessoas nessa condição. A CIF constitui um instrumento adequado para identificar as características da funcionalidade, do ambiente e condições pessoais que interferem na qualidade de vida. Instrumentos para a sua aplicação, core sets, têm sido desenvolvidos para várias condições de saúde. Com o objetivo de propor um core set para aids, foram desenvolvidas duas etapas preliminares do modelo proposto para a construção desses instrumentos. A primeira etapa, de revisão sistemática buscou no MEDLINE artigos com descritores HAART e qualidade de vida, publicados em inglês, de 2000 a 2004. Foram selecionados 31 estudos que resultou em 87 conceitos dos quais 66 puderam ser identificados como categorias da CIF. Estas formaram as perguntas da entrevista aplicada em 42 voluntários, pacientes de um centro de referência para DST e Aids de São Paulo. Entre as condições mais freqüentemente associadas ao tratamento, estão às mudanças na imagem corporal, conseqüência da lipodistrofia, apontada em 84 por cento dos estudos e em 93 por cento das entrevistas. Alterações das funções digestivas, das relações íntimas, e das funções sexuais foram condições importantes identificadas no estudo. As duas etapas definiram 40 categorias da CIF como proposta preliminar de um core set para pacientes com aids

System Identification and Prediction of Dengue Fever Incidence in Rio de Janeiro

Identification, prediction, and control of a system are engineering subjects, regardless of the nature of the system. Here, the temporal evolution of the number of individuals with dengue fever weekly recorded in the city of Rio de Janeiro, Brazil, during 2007, is used to identify SIS (susceptible-infective-susceptible) and SIR (susceptible-infective-removed) models formulated in terms of cellular automaton (CA). In the identification process, a genetic algorithm (GA) is utilized to find the probabilities of the state transition S -> I able of reproducing in the CA lattice the historical series of 2007. These probabilities depend on the number of infective neighbors. Time-varying and non-time-varying probabilities, three different sizes of lattices, and two kinds of coupling topology among the cells are taken into consideration. Then, these epidemiological models built by combining CA and GA are employed for predicting the cases of sick persons in 2008. Such models can be useful for forecasting and controlling the spreading of this infectious disease.

Comparison of the effects of carbon dioxide and helium pneumoperitoneum on renal function

Background and Purpose: Carbon dioxide pneumoperitoneum is associated with significant hypercarbia and acidosis. The aim of this study is to evaluate the effects of carbon dioxide and helium pneumoperitoneum on renal function. Materials and Methods: Thirty adult dogs were put randomly into one of three groups ( n = 10 animals each): group A - pneumoperitoneum not performed; group B - CO2 pneumoperitoneum; and group C - helium pneumoperitoneum. The groups were analyzed with consideration given to body weight, hematologic values, hemodynamic parameters ( heart rate, mean arterial pressure, central venous pressure, cardiac output, stroke volume, systemic vascular resistance, pulmonary vascular resistance, left cardiac work index, cardiac index, mean pulmonary artery pressure, and pulmonary capillary wedge pressure), and renal function ( plasma renin activity, urinary output, creatinine clearance, and sodium excretory fraction). Results: An accentuated decrease in urinary output was observed during pneumoperitoneum in groups B and C compared to the control group. In groups B and C, creatinine clearance declined significantly during pneumoperitoneum in comparison to group A, but after deflation a faster recovery of glomerular filtration was noticed for group C, and a significant increase in sodium excretory fraction was seen for group B. On the other hand, in comparison to the control group, group B had a significant increase in plasma renin activity, with late recovery of glomerular function. Conclusion: Helium ameliorates renal alterations when used for pneumoperitoneum, and it might be used for patients with compromised renal function who have to undergo laparoscopic surgery.

Factor (NF) kappa B polymorphism is associated with heart function in patients with heart failure

Background: Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression. NFkB, an important transcription factor involved in many cell survival pathways, has been implicated in the remodeling process, but its role in the heart is still controversial. Recently, a promoter polymorphism associated with a lesser activation of the NFKB1 gene was also associated with Dilated Cardiomyopathy. The purpose of this study was to evaluate the association of this polymorphism with clinical and functional characteristics of heart failure patients of different etiologies. Methods: A total of 493 patients with HF and 916 individuals from a cohort of individuals from the general population were investigated. The NFKB1-94 insertion/deletion ATTG polymorphism was genotyped by High Resolution Melt discrimination. Allele and genotype frequencies were compared between groups. In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotype groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the polymorphism were compared regarding disease onset and mortality incidence in HF patients. Results: We did not find differences in genotype and allelic frequencies between cases and controls. Interestingly, we found an association between the ATTG(1)/ATTG(1) genotype with right ventricle diameter (P = 0.001), left ventricle diastolic diameter (P = 0.04), and ejection fraction (EF) (P = 0.016), being the genotype ATTG(1)/ATTG(1) more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG(1)/ATTG(1) carriers. Conclusion: There is no genotype or allelic association between the studied polymorphism and the occurrence of HF in the tested population. However, our data suggest that a diminished activation of NFKB1, previously associated with the ATTG(1)/ATTG(1) genotype, may act modulating on the onset of disease and, once the individual has HF, the genotype may modulate disease severity by increasing cardiac remodeling and function deterioration.

uvby-beta photometry of solar twins The solar colors, model atmospheres, and the T(eff) and metallicity scales

Aims. Solar colors have been determined on the uvby-beta photometric system to test absolute solar fluxes, to examine colors predicted by model atmospheres as a function of stellar parameters (T(eff), log g, [Fe/H]), and to probe zero-points of T(eff) and metallicity scales. Methods. New uvby-beta photometry is presented for 73 solar-twin candidates. Most stars of our sample have also been observed spectroscopically to obtain accurate stellar parameters. Using the stars that most closely resemble the Sun, and complementing our data with photometry available in the literature, the solar colors on the uvby-beta system have been inferred. Our solar colors are compared with synthetic solar colors computed from absolute solar spectra and from the latest Kurucz (ATLAS9) and MARCS model atmospheres. The zero-points of different T(eff) and metallicity scales are verified and corrections are proposed. Results. Our solar colors are (b - y)(circle dot) = 0.4105 +/- 0.0015, m(1,circle dot) = 0.2122 +/- 0.0018, c(1,circle dot) = 0.3319 +/- 0.0054, and beta(circle dot) = 2.5915 +/- 0.0024. The (b - y)(circle dot) and m(1,circle dot) colors obtained from absolute spectrophotometry of the Sun agree within 3-sigma with the solar colors derived here when the photometric zero-points are determined from either the STIS HST observations of Vega or an ATLAS9 Vega model, but the c(1,circle dot) and beta(circle dot) synthetic colors inferred from absolute solar spectra agree with our solar colors only when the zero-points based on the ATLAS9 model are adopted. The Kurucz solar model provides a better fit to our observations than the MARCS model. For photometric values computed from the Kurucz models, (b - y)(circle dot) and m(1,circle dot) are in excellent agreement with our solar colors independently of the adopted zero-points, but for c(1,circle dot) and beta circle dot agreement is found only when adopting the ATLAS9 zero-points. The c(1,circle dot) color computed from both the Kurucz and MARCS models is the most discrepant, probably revealing problems either with the models or observations in the u band. The T(eff) calibration of Alonso and collaborators has the poorest performance (similar to 140 K off), while the relation of Casagrande and collaborators is the most accurate (within 10 K). We confirm that the Ramirez & Melendez uvby metallicity calibration, recommended by Arnadottir and collaborators to obtain [Fe/H] in F, G, and K dwarfs, needs a small (similar to 10%) zero-point correction to place the stars and the Sun on the same metallicity scale. Finally, we confirm that the c(1) index in solar analogs has a strong metallicity sensitivity.

In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction

This work aimed to evaluate cardiac morphology/function and histological changes induced by bone marrow cells (BMCs) and cultured mesenchymal stem cells (MSCs) injected at the myocardium of spontaneously hypertensive rats (SHR) submitted to surgical coronary occlusion. Female syngeneic adult SHR, submitted (MI) or not (C) to coronary occlusion, were treated 24 h later with in situ injections of normal medium (NM), or with MSCs (MSC) or BMCs (BM) from male rats. The animals were evaluated after 1 and 30 days by echocardiography, histology of heart sections and PCR for the Y chromosome. Improved ejection fraction and reduced left ventricle infarcted area were observed in MSC rats as compared to the other experimental groups. Treated groups had significantly reduced lesion tissue score, increased capillary density and normal (not-atrophied) myocytes, as compared to NM and C groups. The survival rate was higher in C, NM and MSC groups as compared to MI and BM groups. In situ injection of both MSCs and BMCs resulted in improved cardiac morphology, in a more physiological model of myocardial infarction represented by surgical coronary occlusion of spontaneously hypertensive rats. Only treatment with MSCs, however, ameliorated left ventricle dysfunction, suggesting a positive role of these cells in heart remodeling in infarcted hypertensive subjects.

Cold Nuclear Matter Effects on J/psi Yields as a Function of Rapidity and Nuclear Geometry in d plus A Collisions at root S(NN)=200 GeV

We present measurements of J/psi yields in d + Au collisions at root S(NN) = 200 GeV recorded by the PHENIX experiment and compare them with yields in p + p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/psi rapidity (-2.2 < y < 2.4) with high statistical precision and are compared with two theoretical models: one with nuclear shadowing combined with final state breakup and one with coherent gluon saturation effects. In order to remove model dependent systematic uncertainties we also compare the data to a simple geometric model. The forward rapidity data are inconsistent with nuclear modifications that are linear or exponential in the density weighted longitudinal thickness, such as those from the final state breakup of the bound state.

Time correlation function in systems with two coexisting biological species

We study a stochastic lattice model describing the dynamics of coexistence of two interacting biological species. The model comprehends the local processes of birth, death, and diffusion of individuals of each species and is grounded on interaction of the predator-prey type. The species coexistence can be of two types: With self-sustained coupled time oscillations of population densities and without oscillations. We perform numerical simulations of the model on a square lattice and analyze the temporal behavior of each species by computing the time correlation functions as well as the spectral densities. This analysis provides an appropriate characterization of the different types of coexistence. It is also used to examine linked population cycles in nature and in experiment.

Simple analytic model for astrophysical S factors

We propose a physically transparent analytic model of astrophysical S factors as a function of a center-of-mass energy E of colliding nuclei (below and above the Coulomb barrier) for nonresonant fusion reactions. For any given reaction, the S(E) model contains four parameters [two of which approximate the barrier potential, U(r)]. They are easily interpolated along many reactions involving isotopes of the same elements; they give accurate practical expressions for S(E) with only several input parameters for many reactions. The model reproduces the suppression of S(E) at low energies (of astrophysical importance) due to the shape of the low-r wing of U(r). The model can be used to reconstruct U(r) from computed or measured S(E). For illustration, we parametrize our recent calculations of S(E) (using the Sao Paulo potential and the barrier penetration formalism) for 946 reactions involving stable and unstable isotopes of C, O, Ne, and Mg (with nine parameters for all reactions involving many isotopes of the same elements, e. g., C+O). In addition, we analyze astrophysically important (12)C+(12)C reaction, compare theoretical models with experimental data, and discuss the problem of interpolating reliably known S(E) values to low energies (E less than or similar to 2-3 MeV).

Quantum system under the actions of two counteracting baths: A model for the attenuation-amplification interplay

We analyze the dynamical behavior of a quantum system under the actions of two counteracting baths: the inevitable energy draining reservoir and, in opposition, exciting the system, an engineered Glauber's amplifier. We follow the system dynamics towards equilibrium to map its distinctive behavior arising from the interplay of attenuation and amplification. Such a mapping, with the corresponding parameter regimes, is achieved by calculating the evolution of both the excitation and the Glauber-Sudarshan P function. Techniques to compute the decoherence and the fidelity of quantum states under the action of both counteracting baths, based on the Wigner function rather than the density matrix, are also presented. They enable us to analyze the similarity of the evolved state vector of the system with respect to the original one, for all regimes of parameters. Applications of this attenuation-amplification interplay are discussed.

Exact nonequilibrium work generating function for a small classical system

We obtain the exact nonequilibrium work generating function (NEWGF) for a small system consisting of a massive Brownian particle connected to internal and external springs. The external work is provided to the system for a finite-time interval. The Jarzynski equality, obtained in this case directly from the NEWGF, is shown to be valid for the present model, in an exact way regardless of the rate of external work.