Evaluation of renal function in leprosy: a study of 59 consecutive patients

Background. Renal abnormalities in leprosy have been largely described in medical literature, but there are few studies evaluating renal function in these patients. Methods. This is a cross-sectional study in 59 consecutive paucibacillary (PB) and multibacillary (MB) leprosy patients. Glomerular filtration rate (GFR) was estimated by simplified-MDRD formula. Microalbuminuria was determined by 24 h urine collection. Urinary acidification capacity was measured after water deprivation and acid-loading with CaCl2. Urinary concentration capacity was evaluated after desmopressin acetate administration, using the urinary to plasma osmolality (U/P-osm) ratio. All parameters except microalbuminuria were measured in a control group of 18 healthy volunteers. Results. Age and gender were similar between leprosy (MB or PB) and control groups. GFR <= 80 ml/min/1.73 m(2) was observed in 50% of the leprosy patients. GFR and U/P-osm in leprosy patients were significantly lower than in controls (P < 0.001). Urinary acidification defect was found in 32% of PB and in 29% of MB patients and urinary concentrating ability was abnormal in 83% of PB and 85% of MB patients. Microalbuminuria was found in 4 patients (8.5%), leukocyturia was found in 13 (22%) and haematuria was present in 16 patients (27%). Plasma creatinine (P-cr) > 1.2 mg/dl was observed in 17.9% of MB patients and in none of the controls (P = 0.020). A negative correlation was observed between GFR and time of treatment (r = -0.339; P = 0.002). Age and time of treatment were independent risk factors for GFR <= 80 ml/min/1.73 m(2) in multivariate analysis. Conclusions. Asymptomatic GFR changes and renal tubular dysfunction, including urine concentration defect and impaired acidifying mechanisms, can be caused by leprosy on specific treatment and without any reaction episodes.

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

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.

Association of HDL cholesterol and triglycerides with mortality in patients with heart failure

It has been demonstrated that there is an association between serum lipoproteins and survival rate in patients with ischemic cardiomyopathy, as well as in patients with non-ischemic causes of heart failure. We tested the hypothesis of an association between serum lipoprotein levels and prognosis in a cohort of outpatients with heart failure, including Chagas' heart disease. The lipid profile of 833 outpatients with heart failure in functional classes III and IV of the New York Heart Association, with a mean age of 46.9 ± 10.6 years, 655 (78.6%) men and 178 (21.4%) women, was studied from April 1991 to June 2003. The survival rate was estimated by the Kaplan-Meyer's method and the Cox proportional hazards models. Etiology of heart failure was ischemic cardiomyopathy in 171 (21%) patients, Chagas' heart disease in 144 (17%), hypertensive cardiomyopathy in 136 (16%), and other etiologies in 83 (10%). In 299 (36%) patients, heart failure was ascribed to idiopathic dilated cardiomyopathy. Variables significantly associated with mortality were age (hazard ratio, HR = 1.02; 95%CI = 1.01-1.03; P = 0.0074), male gender (HR = 1.77; 95%CI = 1.2-2.62; P = 0.004), idiopathic dilated cardiomyopathy (HR = 1.81; 95%CI = 1.16-2.82; P = 0.0085), serum triglycerides (HR = 0.97; 95%CI = 0.96-0.98; P < 0.0001), and HDL cholesterol (HR = 0.99; 95%CI = 0.99-1.0; P = 0.0280). Therefore, higher serum HDL cholesterol and higher serum triglycerides were associated with lower mortality in this cohort of outpatients with heart failure.

Loxosceles gaucho Venom-Induced Acute Kidney Injury - In Vivo and In Vitro Studies

Background: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings: In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

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.

Populations III.1 and III.2 gamma-ray bursts: constraints on the event rate for future radio and X-ray surveys

Aims. We calculate the theoretical event rate of gamma-ray bursts (GRBs) from the collapse of massive first-generation (Population III; Pop III) stars. The Pop III GRBs could be super-energetic with the isotropic energy up to E(iso) greater than or similar to 10(55-57) erg, providing a unique probe of the high-redshift Universe. Methods. We consider both the so-called Pop III.1 stars (primordial) and Pop III.2 stars (primordial but affected by radiation from other stars). We employ a semi-analytical approach that considers inhomogeneous hydrogen reionization and chemical evolution of the intergalactic medium. Results. We show that Pop III.2 GRBs occur more than 100 times more frequently than Pop III.1 GRBs, and thus should be suitable targets for future GRB missions. Interestingly, our optimistic model predicts an event rate that is already constrained by the current radio transient searches. We expect similar to 10-10(4) radio afterglows above similar to 0.3 mJy on the sky with similar to 1 year variability and mostly without GRBs (orphans), which are detectable by ALMA, EVLA, LOFAR, and SKA, while we expect to observe maximum of N < 20 GRBs per year integrated over at z > 6 for Pop III.2 and N < 0.08 per year integrated over at z > 10 for Pop III.1 with EXIST, and N < 0.2 for Pop III.2 GRBs per year integrated over at z > 6 with Swift.

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.

Hydration and N-acetylcysteine in acute renal failure caused by iodinated contrast medium: an experiment with rats

Background: The involvement of nephrotoxic agents in acute renal failure (ARF) has increased over the last few decades. Among the drugs associated with nephrotoxic ARF are the radiologic contrast media whose nephrotoxic effects have grown, following the increasing diagnostic use of these agents. Methods: We evaluated the effect of iodinated contrast (IC) medium, administered in combination, or not, with hyperhydration or N-acetylcysteine (NAC), on creatinine clearance, production of urinary peroxides and renal histology of rats. Adult Wistar rats treated for 5 days were divided into the following groups: control (saline, 3 ml/kg/day, intraperitoneally [i.p.]), IC (sodium iothalamate meglumine, 3 ml/kg/day i.p.), IC + water (12 mL water, orally + IC, 3 ml/kg/day i.p. after 1 hour), IC + NAC (NAC, 150 mg/kg/day, orally + IC, 3 ml/kg/day i.p. after 1 hour) and IC + water + NAC. Results: IC medium reduced renal function, with maintenance of urinary flow. Hyperhydration did not reduce the nephrotoxic effect of the IC agent, which was observed in the group IC + NAC. The combination of hyperhydration and NAC had no superior protective effect compared with NAC alone. An increase in urinary peroxides was observed in the IC group, with NAC or water or the combination of both reducing this parameter. Histopathologic analysis revealed no significant alterations. Conclusions: In summary, given 5 days previously, NAC was found to be more effective than hyperhydration alone in the prevention of contrast-induced acute renal failure.

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality

Aims To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Methods and results Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO2 max). Left ventricular function was evaluated noninvasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 +/- 6%) compared with SI (34 +/- 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Conclusion Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

Angiotensin receptor blockade improves the net balance of cardiac Ca(2+) handling-related proteins in sympathetic hyperactivity-induced heart failure

Aims: The clinical benefits of angiotensin II type 1 (AT1) receptor blockers (ARB) in heart failure (HF) include cardiac anti-remodeling and improved ventricular function. However, the cellular mechanisms underlying the benefits of ARB on ventricular function need to be better clarified. In the present manuscript, we evaluated the effects of AT1 receptor blockade on the net balance of Ca(2+) handling proteins in hearts of mice lacking alpha(2A) and alpha(2C) adrenoceptors (alpha(2A)/alpha(2C)ARKO), which develop sympathetic hyperactivity (SH) induced-HF. Main methods: A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)ARKO mice in a C57BL6/J genetic background (5-7 mo of age) was randomly assigned to receive either placebo or ARB (Losartan, 10 mg/kg for 8wks). Ventricular function (VF) was assessed by echocardiography, and cardiac myocyte width and ventricular fibrosis by a computer-assisted morphometric system. Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), phospholamban (PLN), phospho-Ser(16)-PLN, phospho-Thr(17)-PLN, phosphatase 1 (PP1), Na(+)-Ca(2+) exchanger (NCX), Ca(2+)/calmodulin-dependent protein kinase 11 (CaMKII) and phospho-Thr(286)-CaMKII were analyzed by Western blot. Key findings: alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis paralleled by decreased SERCA2 and increased phospho-Thr(17)-PLN, CaMKII, phospho-Thr(286)-CaMKII and NCX levels. ARB induced anti-cardiac remodeling effect and improved VF in alpha(2A)/alpha(2C)ARKO associated with increased SERCA2 and phospho-Ser(16)-PLN levels, and SERCA2:NCX ratio. Additionally, ARB decreased phospho-Thr(17)-PLN levels as well as reestablished NCX, CaMKII and phospho-Thr(286)-CaMKII toward WT levels. Significance: Altogether, these data provide new insights on intracellular Ca(2+) regulatory mechanisms underlying improved ventricular function by ARB therapy in HF. (c) 2011 Elsevier Inc. All rights reserved.

Exercise training associated with diet improves heart rate recovery and cardiac autonomic nervous system activity in obese children

The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Delta HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Delta HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Delta HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 +/- 0.2 years; body mass index (BMI) >95(th) percentile) were divided into 2 groups: D (n = 15; BMI = 31 +/- 1 kg/m(2)) and DET (n = 18; 29 +/- 1 kg/m(2)). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Delta HRR1 was defined as the difference between heart rate at peak and at 1-min post-exercise. CANSA was assessed using power spectral analysis of heart rate variability at rest. The sympathovagal balance (low frequency and high frequency ratio, LF/HF) was measured. After interventions, all obese children showed reduced body weight (P < 0.05). The D group did not improve in terms of peak VO(2), Delta HRR1 or LF/HF ratio (P > 0.05). In contrast, the DET group showed increased peak VO(2) (P = 0.01) and improved Delta HRR1 (Delta HRR1 = 37.3 +/- 2.6; P = 0.01) and LF/HF ratio (P = 0.001). The DET group demonstrated significant relationships among Delta HRR1, peak VO(2) and CANSA (P < 0.05). In conclusion, DET, in contrast to D, promoted improved Delta HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.

Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure

Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

Cardiac anti-remodelling effect of aerobic training is associated with a reduction in the calcineurin/NFAT signalling pathway in heart failure mice

Cardiomyocyte hypertrophy occurs in response to a variety of physiological and pathological stimuli. While pathological hypertrophy in heart failure is usually coupled with depressed contractile function, physiological hypertrophy associates with increased contractility. In the present study, we explored whether 8 weeks of moderate intensity exercise training would lead to a cardiac anti-remodelling effect in an experimental model of heart failure associated with a deactivation of a pathological (calcineurin/NFAT, CaMKII/HDAC) or activation of a physiological (Akt-mTOR) hypertrophy signalling pathway. The cardiac dysfunction, exercise intolerance, left ventricle dilatation, increased heart weight and cardiomyocyte hypertrophy from mice lacking alpha(2A) and alpha(2C) adrenoceptors (alpha(2A)/alpha(2C)ARKO mice) were associated with sympathetic hyperactivity induced heart failure. The relative contribution of Ca(2+)-calmodulin high-affinity (calcineurin/NFAT) and low-affinity (CaMKII/HDAC) targets to pathological hypertrophy of alpha(2A)/alpha(2C)ARKO mice was verified. While nuclear calcineurin B, NFATc3 and GATA-4 translocation were significantly increased in alpha(2A)/alpha(2C)ARKO mice, no changes were observed in CaMKII/HDAC activation. As expected, cyclosporine treatment decreased nuclear translocation of calcineurin/NFAT in alpha(2A)/alpha(2C)ARKO mice, which was associated with improved ventricular function and a pronounced anti-remodelling effect. The Akt/mTOR signalling pathway was not activated in alpha(2A)/alpha(2C)ARKO mice. Exercise training improved cardiac function and exercise capacity in alpha(2A)/alpha(2C)ARKO mice and decreased heart weight and cardiomyocyte width paralleled by diminished nuclear NFATc3 and GATA-4 translocation as well as GATA-4 expression levels. When combined, these findings support the notion that deactivation of calcineurin/NFAT pathway-induced pathological hypertrophy is a preferential mechanism by which exercise training leads to the cardiac anti-remodelling effect in heart failure.

Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice

The role of exercise training (ET) on cardiac renin-angiotensin system (RAS) was investigated in 3-5 month-old mice lacking alpha(2A-) and alpha(2C-)adrenoceptors (alpha(2A)/alpha(2C)ARKO) that present heart failure (HF) and wild type control (WT). ET consisted of 8-week running sessions of 60 min, 5 days/week. In addition, exercise tolerance, cardiac structural and function analysis were made. At 3 months, fractional shortening and exercise tolerance were similar between groups. At 5 months, alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction and fibrosis associated with increased cardiac angiotensin (Ang) II levels (2.9-fold) and increased local angiotensin-converting enzyme activity (ACE 18%). ET decreased alpha(2A)/alpha(2C)ARKO cardiac Ang II levels and ACE activity to age-matched untrained WT mice levels while increased ACE2 expression and prevented exercise intolerance and ventricular dysfunction with little impact on cardiac remodeling. Altogether, these data provide evidence that reduced cardiac RAS explains, at least in part, the beneficial effects of ET on cardiac function in a genetic model of HF.