N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity

Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m², mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m², mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95% CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.

Leptin levels in different forms of Chagas' disease

Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG), and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group) consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group) consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group) and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001) in the CHF group (1.4 ± 0.8 ng/mL) when compared to the IF group (5.3 ± 5.3 ng/mL), ECG group (9.7 ± 10.7 ng/mL), and control group (8.1 ± 7.8 ng/mL). NT-proBNP levels were significantly higher (P < 0.001) in the CHF group (831.8 ± 800.1 pg/mL) when compared to the IF group (53.2 ± 33.3 pg/mL), ECG group (83.3 ± 57.4 pg/mL), and control group (32 ± 22.7 pg/mL). Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

Manifestaciones renales en pacientes con síndrome de Alagille: Reporte de casos y revisión de la literatura.

El síndrome de Alagille es una condición autosómica dominante que se define clínicamente por alteraciones de cinco sistemas principales: escasez de ductos biliares con colestasis crónica, compromiso cardíaco (estenosis pulmonar), óseo (vétebras en mariposa), oftálmico (embriotoxon posterior) y de la cara (fascies dismórficas leves pero reconocibles). La afectación renal es común en estos pacientes; sin embargo, no hace parte de los criterios que definen el síndrome. Reportamos los casos de 3 pacientes con síndrome de Alagille y compromiso renal y realizamos una revisión de la literatura para establecer la importancia de incluir la evaluación de este sistema en el diagnóstico del síndrome. Concluimos que el compromiso renal es frecuente, y por lo tanto sugerimos que en todos los casos se evalúe la posibilidad de compromiso renal tanto a nivel estructural como funcional glomerular y tubular.

Prevalencia de enfermedad de Fabry en pacientes en lista de trasplante y posttrasplante renal en fundación cardioinfantil Bogotá

Introducción: La Enfermedad de Fabry (EF), es una enfermedad multisistémica de almacenamiento lisosomal ligada al cromosoma X que afecta principalmente a hombres, pero también puede causar significativa morbilidad en las mujeres heterocigotas (1–5). La deficiencia de la enzyma α-galactosidaseA (α-Gal A,) provoca acumulación de glicosfingolipidos que afectan diferentes tipos celulares entre ellos el endotelio vascular en vasos de pequeño calibre, células epiteliales y Músculo liso en el sistema cardiovascular (cardiomiocitos), sistema nervioso y células epiteliales tubulares del riñón (6,7). Complicaciones como la falla renal es la causa de muerte más frecuente en la EF (7,8). La incidencia se ha calculado en 1 de cada 117.000 nacidos vivos. (9). Objetivos: Determinar la prevalencia de la Enfermedad de Fabry en pacientes con Insuficiencia renal terminal que se encuentren en lista de trasplante y Post-trasplante Renal en Fundación Cardioinfantil Bogotá. Materiales y Métodos: Se realizó un estudio observacional en donde se evaluó la prevalencia de la EF en todos los sujetos mayores de 18 años que se encuentren en lista de trasplante y post-trasplante renal. Resultados: La prevalencia de Enfermedad de Fabry en 98 pacientes con enfermedad renal crónica fue de 7.1% para la muestra general y 12.9% para la muestra con etiología idiopática Conclusiones: La Enfermedad de Fabry es una importante casusa de Enfermedad Renal Crónica Terminal principalmente en el grupo de etiología idiopática. Palabras Clave: Enfermedad de Fabry (FA)

Chagas disease-related mortality trends, state of Sao Paulo, Brazil, 1985 to 2006: a study using multiple causes of death

Objectives. To study mortality trends related to Chagas disease taking into account all mentions of this cause listed on any line or part of the death certificate. Methods. Mortality data for 1985-2006 were obtained from the multiple cause-of-death database maintained by the Sao Paulo State Data Analysis System (SEADE). Chagas disease was classified as the underlying cause-of-death or as an associated cause-of-death (non-underlying). The total number of times Chagas disease was mentioned on the death certificates was also considered. Results. During this 22-year period, there were 40 002 deaths related to Chagas disease: 34 917 (87.29%) classified as the underlying cause-of-death and 5 085 (12.71%) as an associated cause-of-death. The results show a 56.07% decline in the death rate due to Chagas disease as the underlying cause and a stabilized rate as associated cause. The number of deaths was 44.5% higher among men. The fact that 83.5% of the deaths occurred after 45 years of age reflects a cohort effect. The main causes associated with Chagas disease as the underlying cause-of-death were direct complications due to cardiac involvement, such as conduction disorders, arrhythmias and heart failure. Ischemic heart disease, cerebrovascular disorders and neoplasms were the main underlying causes when Chagas was an associated cause-of-death. Conclusions. For the total mentions to Chagas disease, a 51.34% decline in the death rate was observed, whereas the decline in the number of deaths was only 5.91%, being lower among women and showing a shift of deaths to older age brackets. Using the multiple cause-of-death method contributed to the understanding of the natural history of Chagas disease.

Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas` heart disease

Chronic chagasic cardiac patients are exposed to oxidative stress that apparently contributes to disease progression. Benznidazole (BZN) is the main drug used for the treatment of chagasic patients and its action involves the generation of reactive species. 41 patients with Chagas` heart disease were selected and biomarkers of oxidative stress were measured before and after 2 months of BZN treatment (5 mg/kg/day) and the subsequent antioxidant supplementation with vitamin E (800 UI/day) and C (500 mg/day) during 6 months. Patients were classified according to the modified Los Andes clinical hemodynamic classification in groups IA, IB, II and III, and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the contents of reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), protein carbonyl (PC), vitamin E and C and nitric oxide (NO), myeloperoxidase (MPO) and adenosine deaminase (ADA) activities were measured in their blood. Excepting in group III, after BZN treatment SOD, CAT, GPx and GST activities as well as PC levels were enhanced while vitamin E levels were decreased in these groups. After antioxidant supplementation the activities of SOD, GPx and GR were decreased whereas PC, TBARS, NO, and GSH levels were decreased. In conclusion, BZN treatment promoted an oxidative insult in such patients while the antioxidant supplementation was able to attenuate this effect by increasing vitamin E levels, decreasing PC and TBARS levels, inhibiting SOD, GPx and GR activities as well as inflammatory markers, mainly in stages with less cardiac involvement. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Avaliação histopatológica e imuno-histoquímica do miocárdio de cães com leishmaniose visceral: Fernando Azadinho Rosa. -

Pós-graduação em Ciência Animal - FMVA

Avaliação dos marcadores de injúria miocárdica induzida pela exposição ao metilmercúrio em modelos experimentais de primatas do novo mundo (Cebus Apella)

Este estudo teve como objetivo analisar os efeitos dos mecanismos de injúria celular que produzem lesão no coração do macaco Cebus apella expostos durante 120 dias consecutivos com doses diárias de 1,5 mg de metilHg, através de alterações detectadas no marcador bioquímico de lesão miocárdica CK-MB, nos achados histopatológicos assim como pela técnica de imuno-marcação de células apoptóticas. Para tanto foram relacionados os perfis séricos da CK-MB, CK total, AST, ALT, uréia, creatinina e bilirrubina total com os achados histopatológicos e imunohistoquímicos no processo de acometimento do músculo cardíaco durante a exposição ao metilHg, comparando com o grupo controle. O método utilizado para dosagem e análise das substâncias bioquímicas séricas e para a dosagem de mercúrio no sangue foi o cinético ultravioleta e espectrometria de absorção atômica, respectivamente; para análise histopatológica utilizou-se a técnica de Hematoxilina Eosina e para detecção dos perfis apoptóticos o método APOPTAG. Foram obtidas consideráveis informações que permitem correlacionar as alterações bioquímicas, histopatológicas e os perfis apoptóticos ao mecanismo do acometimento cardíaco nos três animais expostos ao metilHg comparando-os com o grupo controle. Verificou-se que de todas as substâncias bioquímicas analisadas, houve apenas acentuado aumento sérico da enzima CK-MB, enquanto que na histopatologia observou-se lesão celular reversível por acúmulo de água nos três órgãos analisados (coração, fígado e rim). Destaca-se também a observação de uma nítida marcação células apoptóticas no tecido cardíaco, hepático e renal dos animais expostos, evidenciando-se maior número de células positivas nas células dos túbulos renais, ressaltando que não se observou infiltrado inflamatório em torno destes elementos descritos em nenhum dos tecidos analisados e ausência das referidas lesões nos tecidos dos três animais controle. Concluiu-se que a enzima CK-MB, a degeneração hidrópica e o mecanismo de apoptose podem ser indicadores de lesão miocárdica na exposição aguda ao metilHg, cuja etiopatogenia pode estar relacionada a descompensação mitocondrial pelo comprometimento maciço na bomba de Na+ / K+ e Ca++. Fazendo-se necessário um maior aporte de estudos experimentais que venham esclarecer com precisão a etiopatogenia, o mecanismo de agressão e injúria celular em indivíduos expostos a doses tóxicas de metilHg.

O comportameno clínico-cardiológico, eletrocardiográfico e radiológico do tórax de pacientes com leptospirose internados no Hospital Universitário João de Barros Barreto, no período de 2002-2003, Belém-Pará

A leptospirose apresenta alta prevalência em nossa região. É uma doença infecciosa, multissistêmica, que acomete vários órgãos e o envolvimento cardíaco é freqüente, constituindo atualmente uma das principais causas de morte dos portadores desta afecção. O objetivo do trabalho foi avaliar o comportamento clínico-epidemiológico, eletrocardiográfico e radiológico do tórax de pacientes com diagnóstico clínico-epidemiológico, eletrocardiográfico e radiológico do tórax de pacientes em diagnóstico clínico-epidemiológico de leptospirose na fase aguda e em ambiente hospitalar. Para este propósito, foi realizado um estudo transversal com 41 pacientes, seis do sexo feminino e 35 do sexo masculino, com idades entre 15 e 78 anos, internados no Hospital Universitário João de Barros Barreto, no período de fevereiro de 2002 a junho de 2003. Os participantes do estudo submeteram-se à anamnese e exame clínico, com ênfase ao aparelho cardiovascular, realizaram de um a três eletrocardiogramas, uma radiografia do tórax e exames laboratoriais de rotina. Analisando-se os achados clínicos, 37 (90,2 %) apresentaram sinais e sintomas compatíveis com envolvimento miocárdico. As anormalidades eletrocardiográficas ocorreram em 20 casos, correspondendo a 48,7 % do total. O nível médio de potássio foi de 3,8 meq/l. A maioria das alterações foram reversíveis e, a principal, correspondeu ao supradesnivelamento de segmento ST, sem diferença estatística significante (p>0,05) entre elas. Nos 37 enfermos que apresentaram sintomas e sinais sugestivos de comprometimento cardíaco, não houve diferença estatística significativa (p> 0,05) entre os eletrocardiogramas normais e os alterados. Em apenas oito indivíduos houve anormalidades radiológicas (19,5 %), sendo que o aumento discreto do ventrículo esquerdo com infiltrado intersticial nas bases pulmonares foi o principal achado, com diferença estatística significante (p<0,05) entre outros tipos de infiltrados pulmonares. Portanto, neste estudo, os principais achados clínicos foram: hepatomegalia e dispnéia; eletrocardiográficos: supradesnível de segmento ST e taquicardia sinusal com reversão na maioria dos caos e radiológicos: aumento ventricular esquerdo discreto com infiltrado pulmonar nas bases.

Parâmetros ecocardiográficos e variabilidade da frequência cardíaca em fêmeas caninas com sepse de ocorrência natural devido à piometra e suas correlações com valores séricos de TNF-alfa, IL-1 beta, IL-6, IL-10 e proteína C reativa

Pós-graduação em Medicina Veterinária - FCAV

L'Amiloidosi transtiretino correlata ereditaria: profilo clinico, fisiopatologico e storia naturale

Background. Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectrum of ATTR in a non-endemic, Caucasian area and evaluated prevalence, genetic background and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA) Methods and Results. In this Italian multicenter study, 186 patients with ATTR were characterized at presentation. Thirty patients with SSA and 30 age-gender matched HCM patients were used for comparison. Phenotype was classified as: exclusively cardiac (n= 31, 17%), exclusively neurologic (n= 46, 25%), mixed cardiac/neurologic (n=109, 58%). Among the 8 different mutations responsible for an exclusively cardiac phenotype, Ile68Leu was the most frequent (23/31). Five patients with an exclusively cardiac phenotype developed mild abnormalities at neurological examination but no symptoms during a 36 [14−50] month follow-up. Exclusively cardiac phenotype was characterized by male gender, age > 65 years, heart failure symptoms, concentric left ventricular (LV) “hypertrophy” and moderately depressed LV ejection fraction. This profile was similar to SSA but relatively distinct from HCM. Compared to patients with a mixed phenotype, patients with a exclusively cardiac phenotype showed a more pronounced cardiac involvement on both echocardiogram and ECG. Conclusion. A clinically relevant subset of Caucasian ATTR patients present with an exclusively cardiac phenotype, mimicking HCM or SSA. Echocardiographic and ECG findings are useful to differentiate ATTR from HCM but not from SSA. The role of liver transplantation in these patients is questionable.

Role of gender in transthyretin-related amyloidosis: an international perspective based on the Transthyretin Amyloid Outcomes Survey (THAOS)

Background. Transthyretin amyloidosis (ATTR) is an underdiagnosed disease caused by destabilization of transthyretin (TTR) due to pathogenic mutations (ATTRm) or aging (ATTRwt). We explored the role of gender in determining clinical picture using the largest available database on ATTR, the ongoing Transthyretin Amyloid Outcomes Survey (THAOS) international registry. Methods. Data through 1st April 2019 were explored. Symptomatic ATTRm (n=3737), asymptomatic ATTRm (n=644) and ATTRwt (n=874) patients were studied. Results. Male prevalence was 61% in the entire registry, 53% in ATTRm and 95% in ATTRwt. In the overall cohort, cardiac phenotype was more frequent in males (30.7% vs 10.5%, p<0.001). Among ATTRm, 72.3% of patients with amyloidotic cardiomyopathy (ATTR-CM) were males (p<0.001) but echocardiographic features showed no substantial gender differences. Sensory abnormalities (70.1% vs 64.1%, p<0.001), autonomic abnormalities (60% vs 48.5%, p<0.001) and walking disabilities were more frequent among ATTRm males. Carpal tunnel syndrome was more frequent in ATTRm males (18.6% vs 15.5%, p=0.014). In ATTRwt cohort, females had a more pronounced (but anyhow mild) walking disability. Male-to-female ratio varied within genotype, from 0.61 in Val30Met to 11.11 in ATTRwt; furthermore, males’ imbalance was more evident among symptomatic patients rather than in asymptomatic ones. Male gender, age at presentation and specific genotype were independently associated with the presence of ATTR-CM. Conclusions. In ATTR, cardiac involvement is more frequent in men, supporting the hypothesis that some biologic characteristics may “protect” from myocardial amyloid infiltration in women. Further investigations are needed to identify possible underlying protective mechanism and orient the research for innovative, gender-tailored therapeutic approaches.

Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells

Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum- and glucocorticoid-regulated kinase type 1

Persistent beta-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg-1 day-1) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg-1 day-1). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor beta, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor a, interleukin 1 beta, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.