Hyperbaric Oxygen Therapy Induces Kidney Protection in an Ischemia/Reperfusion Model in Rats

Ischemia/reperfusion (I/R) injury remains a major cause of graft dysfunction, which impacts short- and long-term follow-up. Hyperbaric oxygen therapy (HBO), through plasma oxygen transport, has been currently used as an alternative treatment for ischemic tissues. The aim of this study was to analyze the effects of HBO on kidney I/R injury model in rats, in reducing the harmful effect of I/R. The renal I/R model was obtained by occluding bilateral renal pedicles with nontraumatic vascular clamps for 45 minutes, followed by 48 hours of reperfusion. HBO therapy was delivered an hypebaric chamber (2.5 atmospheres absolute). Animals underwent two sessions of 60 minutes each at 6 hours and 20 hours after initiation of reperfusion. Male Wistar rats (n = 38) were randomized into four groups: sham, sham operated rats; Sham+HBO, sham operated rats exposed to HBO; I/R, animals submitted to I/R; and I/R+HBO, I/R rats exposed to HBO. Blood, urine, and kidney tissue were collected for biochemical, histologic, and immunohistochemical analyses. The histopathological evaluation of the ischemic injury used a grading scale of 0 to 4. HBO attenuated renal dysfunction after ischemia characterized by a significant decrease in blood urea nitrogen (BUN), serum creatinine, and proteinuria in the I/R+HBO group compared with I/R alone. In parallel, tubular function was improved resulting in significantly lower fractional excretions of sodium and potassium. Kidney sections from the I/R plus HBO group showed significantly lower acute kidney injury scores compared with the I/R group. HBO treatment significantly diminished proliferative activity in I/R (P < .05). There was no significant difference in macrophage infiltration or hemoxygenase-1 expression. In conclusion, HBO attenuated renal dysfunction in a kidney I/R injury model with a decrease in BUN, serum creatinine, proteinuria, and fractional excretion of sodium and potassium, associated with reduced histological damage.

Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

De Angelis K, Senador DD, Mostarda C, Irigoyen MC, Morris M. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice. Am J Physiol Regul Integr Comp Physiol 302: R950-R957, 2012. First published February 8, 2012; doi: 10.1152/ajpregu.00450.2011.-Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 +/- 2 and F60: 118 +/- 2 mmHg) and dark periods (F15: 136 +/- 4 and F60: 136 +/- 5 mmHg) compared with controls (light: 111 +/- 2 and dark: 117 +/- 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

The log-exponentiated generalized gamma regression model for censored data

For the first time, we introduce a generalized form of the exponentiated generalized gamma distribution [Cordeiro et al. The exponentiated generalized gamma distribution with application to lifetime data, J. Statist. Comput. Simul. 81 (2011), pp. 827-842.] that is the baseline for the log-exponentiated generalized gamma regression model. The new distribution can accommodate increasing, decreasing, bathtub- and unimodal-shaped hazard functions. A second advantage is that it includes classical distributions reported in the lifetime literature as special cases. We obtain explicit expressions for the moments of the baseline distribution of the new regression model. The proposed model can be applied to censored data since it includes as sub-models several widely known regression models. It therefore can be used more effectively in the analysis of survival data. We obtain maximum likelihood estimates for the model parameters by considering censored data. We show that our extended regression model is very useful by means of two applications to real data.

INFERENCES FOR THE CHANGE-POINT OF THE EXPONENTIATED WEIBULL HAZARD FUNCTION

In many applications of lifetime data analysis, it is important to perform inferences about the change-point of the hazard function. The change-point could be a maximum for unimodal hazard functions or a minimum for bathtub forms of hazard functions and is usually of great interest in medical or industrial applications. For lifetime distributions where this change-point of the hazard function can be analytically calculated, its maximum likelihood estimator is easily obtained from the invariance properties of the maximum likelihood estimators. From the asymptotical normality of the maximum likelihood estimators, confidence intervals can also be obtained. Considering the exponentiated Weibull distribution for the lifetime data, we have different forms for the hazard function: constant, increasing, unimodal, decreasing or bathtub forms. This model gives great flexibility of fit, but we do not have analytic expressions for the change-point of the hazard function. In this way, we consider the use of Markov Chain Monte Carlo methods to get posterior summaries for the change-point of the hazard function considering the exponentiated Weibull distribution.

The negative binomial-beta Weibull regression model to predict the cure of prostate cancer

In this article, for the first time, we propose the negative binomial-beta Weibull (BW) regression model for studying the recurrence of prostate cancer and to predict the cure fraction for patients with clinically localized prostate cancer treated by open radical prostatectomy. The cure model considers that a fraction of the survivors are cured of the disease. The survival function for the population of patients can be modeled by a cure parametric model using the BW distribution. We derive an explicit expansion for the moments of the recurrence time distribution for the uncured individuals. The proposed distribution can be used to model survival data when the hazard rate function is increasing, decreasing, unimodal and bathtub shaped. Another advantage is that the proposed model includes as special sub-models some of the well-known cure rate models discussed in the literature. We derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes. We analyze a real data set for localized prostate cancer patients after open radical prostatectomy.

Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes

The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

A log-linear regression model for the beta-Birnbaum-Saunders distribution with censored data

The beta-Birnbaum-Saunders (Cordeiro and Lemonte, 2011) and Birnbaum-Saunders (Birnbaum and Saunders, 1969a) distributions have been used quite effectively to model failure times for materials subject to fatigue and lifetime data. We define the log-beta-Birnbaum-Saunders distribution by the logarithm of the beta-Birnbaum-Saunders distribution. Explicit expressions for its generating function and moments are derived. We propose a new log-beta-Birnbaum-Saunders regression model that can be applied to censored data and be used more effectively in survival analysis. We obtain the maximum likelihood estimates of the model parameters for censored data and investigate influence diagnostics. The new location-scale regression model is modified for the possibility that long-term survivors may be presented in the data. Its usefulness is illustrated by means of two real data sets. (C) 2011 Elsevier B.V. All rights reserved.

Structure and anomalous solubility for hard spheres in an associating lattice gas model

In this paper we investigate the solubility of a hard-sphere gas in a solvent modeled as an associating lattice gas. The solution phase diagram for solute at 5% is compared with the phase diagram of the original solute free model. Model properties are investigated both through Monte Carlo simulations and a cluster approximation. The model solubility is computed via simulations and is shown to exhibit a minimum as a function of temperature. The line of minimum solubility (TmS) coincides with the line of maximum density (TMD) for different solvent chemical potentials, in accordance with the literature on continuous realistic models and on the "cavity" picture. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4743635]

Early postoperative pelvic-floor biofeedback improves erectile function in men undergoing radical prostatectomy: a prospective, randomized, controlled trial

Erectile dysfunction (ED) and urinary incontinence are common complications following radical prostatectomy (RP). Although pelvic-floor biofeedback training (PFBT) may improve urinary continence following RP, its effects on the recovery of potency are unknown. Fifty-two patients selected for RP were prospectively randomized for a treatment group (n=26) receiving PFBT once a week for 3 months and home exercises or a control group (n=26), in which patients received verbal instructions to contract the pelvic floor. Erectile function (EF) was evaluated with the International Index of Erectile Function-5 (IIEF-5) before surgery and 1, 3, 6 and 12 months postoperatively. Patients were considered potent when they had a total IIEF-5 score >20. Continence status was assessed and defined as the use of no pads. Groups were comparable in terms of age, body mass index, diabetes, pathological tumor stage and neurovascular bundle preservation. A significant reduction in IIEF-5 scores was observed after surgery in both groups. In the treatment group, 8 (47.1%) patients recovered potency 12 months postoperatively, as opposed to 2 (12.5%) in the control group (P=0.032). The absolute risk reduction was 34.6% (95% confidence interval (CI): 3.8-64%) and the number needed to treat was 3 (95% CI: 1.5-17.2). A strong association between recovery of potency and urinary continence was observed, with continent patients having a 5.4 higher chance of being potent (P=0.04). Early PFBT appears to have a significant impact on the recovery of EF after RP. Urinary continence status was a good indicator of EF recovery, with continent patients having a higher chance of being potent.

The role of AT1 receptor-mediated reproductive function in renovascular hypertension in male rats

There is an association between hypertension and reproductive dysfunction. Angiotensin II (Ang II) is involved in the pathogenesis of hypertension and the regulation of reproduction. The present study aimed to determine whether the angiotensinergic system mediates the effects of hypertension on ieproductive function in male rats subjected to a two-kidney, one-clip (2K1C) model. Sexual behavior parameters, gametogenesis and plasma concentrations of Ang II, testosterone, prolactin and corticosterone were evaluated in male rats 28 days after 2K1C or sham surgery and losartan (Los) treatment (a type 1 angiotensin II (All) receptor antagonist) or vehicle (V) treatment. The animals were divided into Sham + V, 2K1C + V. Sham + Los and 2K1C + Los groups. The 2KiC + V group showed a hypertensive response, inhibition of sexual behavior, spermatogenesis dysfunction, and increases in plasma Ang II and prolactin. Conversely, plasma testosterone decreased, and plasma corticosterone remained constant. Losartan treatment normalized blood pressure and prevented the changes in plasma testosterone and prolactin, sexual behavior and spermatogenesis in the 2KiC + Los group. In addition, losartan treatment caused an additional increase in circulating Ang II in both groups (She m + Los arid 2K1C + Los). Together, these results suggest that Ang II, acting through the All receptor, modulates behavioral and endocrine parameters of reproductive function during renovascular hypertension. In addition, the effects of circulating Ang II on plasma testosterone and prolactin seem to contribute to the spermatogenic and sexual dysfunctions in hypertensive rats. (C) 2012 Els.evier Inc. All rights reserved.

Vortices in the extended Skyrme-Faddeev model

We construct analytical and numerical vortex solutions for an extended Skyrme-Faddeev model in a (3 + 1) dimensional Minkowski space-time. The extension is obtained by adding to the Lagrangian a quartic term, which is the square of the kinetic term, and a potential which breaks the SO(3) symmetry down to SO(2). The construction makes use of an ansatz, invariant under the joint action of the internal SO(2) and three commuting U(1) subgroups of the Poincare group, and which reduces the equations of motion to an ordinary differential equation for a profile function depending on the distance to the x(3) axis. The vortices have finite energy per unit length, and have waves propagating along them with the speed of light. The analytical vortices are obtained for a special choice of potentials, and the numerical ones are constructed using the successive over relaxation method for more general potentials. The spectrum of solutions is analyzed in detail, especially its dependence upon special combinations of coupling constants.

Intelligence systems methodology: a systemic approach to the organizational intelligence function

Organizational intelligence can be seen as a function of the viable structure of an organization. With the integration of the Viable System Model and Soft Systems Methodology (systemic approaches of organizational management) focused on the role of the intelligence function, it is possible to elaborate a model of action with a structured methodology to prospect, select, treat and distribute information to the entire organization that improves the efficacy and efficiency of all processes. This combination of methodologies is called Intelligence Systems Methodology (ISM) whose assumptions and dynamics are delimited in this paper. The ISM is composed of two simultaneous activities: the Active Environmental Mapping and the Stimulated Action Cycle. The elaboration of the formal ISM description opens opportunities for applications of the methodology on real situations, offering a new path for this specific issue of systems thinking: the intelligence systems. Knowledge Management Research & Practice (2012) 10, 141-152. doi:10.1057/kmrp.2011.44

Evolution of form and function: morphophysiological relationships and locomotor performance in tropidurine lizards

Locomotor capacity is often considered an excellent measure of whole animal performance because it requires the integrated functioning of many morphological, physiological (and biochemical) traits. However, because studies tend to focus on either structural or functional suits of traits, we know little on whether and how morphological and physiological traits coevolve to produce adequate locomotor capacities. Hence, we investigate the evolutionary relationships between morphological and physiological parameters related to exercise physiology, using tropidurine lizards as a model. We employ a phylogenetic principal component analysis (PCA) to identify variable clusters (factors) related to morphology, energetic metabolism and muscle metabolism, and then analyze the relationships between these clusters and measures of locomotor performance, using two models (star and hierarchical phylogenies). Our data indicate that sprint performance is enhanced by simultaneous evolutionary tendencies affecting relative limb and tail size and physiological traits. Specifically, the high absolute sprint speeds exhibited by tropidurines from the sand dunes are explained by longer limbs, feet and tails and an increased proportion of glycolytic fibers in the leg muscle, contrasting with their lower capacity for overall oxidative metabolism [principal component (PC1)]. However, when sprint speeds are corrected for body size, performance correlates with a cluster (PC3) composed by moderate loads for activity metabolic rate and body size. The simultaneous measurement of morphological and physiological parameters is a powerful tool for exploring patterns of coadaptation and proposing morphophysiological associations that are not directly predictable from theory. This approach may trigger novel directions for investigating the evolution of form and function, particularly in the context of organismal performance.

Probabilistic crack growth analyses using a boundary element model: Applications in linear elastic fracture and fatigue problems

This paper addresses the numerical solution of random crack propagation problems using the coupling boundary element method (BEM) and reliability algorithms. Crack propagation phenomenon is efficiently modelled using BEM, due to its mesh reduction features. The BEM model is based on the dual BEM formulation, in which singular and hyper-singular integral equations are adopted to construct the system of algebraic equations. Two reliability algorithms are coupled with BEM model. The first is the well known response surface method, in which local, adaptive polynomial approximations of the mechanical response are constructed in search of the design point. Different experiment designs and adaptive schemes are considered. The alternative approach direct coupling, in which the limit state function remains implicit and its gradients are calculated directly from the numerical mechanical response, is also considered. The performance of both coupling methods is compared in application to some crack propagation problems. The investigation shows that direct coupling scheme converged for all problems studied, irrespective of the problem nonlinearity. The computational cost of direct coupling has shown to be a fraction of the cost of response surface solutions, regardless of experiment design or adaptive scheme considered. (C) 2012 Elsevier Ltd. All rights reserved.

Interacting model for the cosmological dark sector

We discuss a new interacting model for the cosmological dark sector in which the attenuated dilution of cold dark matter scales as a(-3)f(a), where f(a) is an arbitrary function of the cosmic scale factor a. From thermodynamic arguments, we show that f(a) is proportional to the entropy source of the particle creation process. In order to investigate the cosmological consequences of this kind of interacting models, we expand f(a) in a power series, and viable cosmological solutions are obtained. Finally, we use current observational data to place constraints on the interacting function f(a).