Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h-1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower

Cardiac pacing in hypertrophic cardiomyopathy: a cohort with 24 years of follow-up

FUNDAMENTO: O benefício da estimulação cardíaca em pacientes portadores de cardiomiopatia hipertrófica (CMH) tem sido questionado, sendo escassas as pesquisas sobre este assunto no Brasil. OBJETIVO: Descrever a indicação, a resposta clínica, as complicações e a sobrevida relacionadas ao implante de marcapasso em pacientes portadores de CMH. MÉTODOS: Foram estudados, retrospectivamente, 39 pacientes portadores de cardiomiopatia hipertrófica (41% do sexo masculino) submetidos a implante de marcapasso, no período de maio de 1980 a novembro de 2003. RESULTADOS: Houve 27 portadores da forma obstrutiva e 12 portadores da forma não-obstrutiva com média de idade de 46,4 anos (14-77 anos) seguidos por 6,4 ± 4,1 anos. As principais indicações para implante foram: bloqueio atrioventricular espontâneo ou induzido (54%), refratariedade à terapêutica associada a gradiente elevado (33%), suporte para terapia medicamentosa por bradicardia (8%) e prevenção de fibrilação atrial (5%). Houve melhora na classe funcional de 2,41±0,87 para 1,97±0,92 (p = 0,008), bem como redução do número de sintomas referidos, sem ter havido diferença na utilização da terapia medicamentosa. Não houve óbitos relacionados ao procedimento que, apesar de demonstrar-se seguro, não foi isento de complicações (6 pacientes - 15,4%). Ocorreram três óbitos durante o seguimento, todos em pacientes mulheres, portadoras de fibrilação atrial e com evidências de deterioração funcional. Observou-se uma forte associação de piora clínica com surgimento de fibrilação atrial ou flutter. CONCLUSÃO: A estimulação cardíaca artificial em pacientes com CMH foi bem-sucedida, com evidências de alívio sintomático em pacientes portadores da forma obstrutiva. Não se observou melhora funcional para a forma não-obstrutiva.BACKGROUND: The benefits of heart stimulation in hypertrophic cardiomyopathy (HCM) patients have been questioned. Research work available in Brazil on those benefits is scarce. OBJECTIVE: To describe the indication, clinical response, complications and survival time related to pacemaker implant in HCM patients. METHODS: Thirty-nine hypertrophic cardiomyopathy patients were studied (41% males) and submitted to pacemaker implant from May, 1980 through November, 2003. RESULTS: Twenty-seven patients presented obstructive hypertrophic cardiomyopathy, and 12, non-obstructive. Mean age was 46.4 years of age (range 14 - 77), with follow-up of 6.4 ± 4.1 years. Major indications for implant were: spontaneous or induced atrioventricular block (54%), refractoriness to therapeutic conduct associated to high gradient (33%), support for drug therapy to treat bradychardia (8%), and atrial fibrillation prevention (5%). Functional class was shown to improve from 2.41±0.87 to 1.97±0.92 (p = 0.008), and symptoms referred were reduced. No change was made in drug therapy administration. No procedure-related deaths were reported. Although shown to be safe, the procedure was not free from complications (6 patients - 15.4%). Three deaths occurred in the follow-up period - the three of them were atrial fibrillation female patients, with evidence of functional deterioration. A close association was observed between clinical condition worsening and the onset of atrial fibrillation or flutter. CONCLUSION: Cardiac pacing in HCM patients was successful, with evidence of symptoms relief in obstructive HCM patients. No functional improvement was observed in non-obstructive patients

Serum NT pro-BNP: relation to systolic and diastolic function in cardiomyopathies and pericardiopathies

FUNDAMENTO: O NT pro-BNP é marcador de disfunção sistólica e diastólica. OBJETIVO: Determinar os níveis de NT pro-BNP em pacientes com cardiopatia chagásica, hipertrófica, restritiva e afecções pericárdicas, e sua relação com medidas ecocardiográficas de disfunção sistólica e diastólica. MÉTODOS: Cento e quarenta e cinco pacientes foram divididos nos respectivos grupos: 1) cardiopatia chagásica (CCh) - 14 pacientes; 2) miocardiopatia hipertrófica (CMH) - 71 pacientes; 3) endomiocardiofibrose (EMF) - 26 pacientes; 4) derrame pericárdico (DP) - 18 pacientes; 5) e pericardite constritiva (PC) - 16 pacientes. Foi constituído um grupo-controle de 40 indivíduos sem doença cardíaca. O grau de acometimento miocárdico e o derrame pericárdico foram avaliados pelo ecocardiograma bidimensional e a restrição pelo Doppler pulsátil do fluxo mitral. O diagnóstico de PC foi confirmado por meio da ressonância magnética. Os níveis de NT pro-BNP foram medidos por imunoensaio com detecção por eletroquimioluminescência. RESULTADOS: O NT pro-BNP esteve aumentado (p < 0,001) na CCh (mediana 513,8 pg/ml), CMH (mediana 848 pg/ml), EMF (mediana 633 pg/ml), PC (mediana 568 pg/ml), DP (mediana 124 pg/ml), quando comparados ao grupo-controle (mediana 28 pg/ml). Não foram observadas diferenças estatisticamente significativas entre PC e EMF (p = 0,14). No grupo hipertrófico, o NT pro-BNP correlacionou-se com tamanho de átrio esquerdo (r = 0,40; p < 0,001) e relação E/Ea (p < 0,01). No grupo restritivo, houve uma tendência de correlação com pico de velocidade de onda E (r = 0,439; p = 0,06). CONCLUSÃO: O NT pro-BNP encontra-se aumentado nas diversas miocardiopatias e afecções pericárdicas, e apresenta relação com o grau de disfunção sistólica e diastólica.BACKGROUND: NT pro-BNP is a marker of systolic and diastolic dysfunction. OBJECTIVE: To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction. METHODS: A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD) - 14 patients; 2) hypertrophic cardiomyopathy (HCM) - 71 patients; 3) endomyocardial fibrosis (EMF) - 26 patients; 4) pericardial effusion (PE) - 18 patients; and 5) constrictive pericarditis (CP) - 16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay. RESULTS: NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06). CONCLUSION: NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction

Air Pollution’s Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy

BackgroundChagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis.MethodsWe studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-γ, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis.ResultsChagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups.ConclusionsA possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy

Archaea Symbiont of T. cruzi Infection May Explain Heart Failure in Chagas Disease

Background: Archaeal genes present in Trypanosoma cruzi may represent symbionts that would explain development of heart failure in 30% of Chagas disease patients. Extracellular vesicles in peripheral blood, called exosomes (&lt; 0.1 μm) or microvesicles (&gt;0.1 μm), present in larger numbers in heart failure, were analyzed to determine whether they are derived from archaea in heart failure Chagas disease.Methods: Exosomes and microvesicles in serum supernatant from 3 groups were analyzed: heart failure Chagas disease (N = 26), asymptomatic indeterminate form (N = 21) and healthy non-chagasic control (N = 16). Samples were quantified with transmission electron microscopy, flow cytometer immunolabeled with anti-archaemetzincin-1 antibody (AMZ 1, archaea collagenase) and probe anti-archaeal DNA and zymography to determine AMZ1 (Archaeal metalloproteinase) activity.Results: Indeterminate form patients had higher median numbers of exosomes/case vs. heart failure patients (58.5 vs. 25.5, P &lt; 0.001), higher exosome content of AMZ1 antigens (2.0 vs. 0.0; P &lt; 0.001), and lower archaeal DNA content (0.2 vs. 1.5, P = 0.02). A positive correlation between exosomes and AMZ1 content was seen in indeterminate form (r = 0.5, P &lt; 0.001), but not in heart failure patients (r = 0.002, P = 0.98). Higher free archaeal DNA (63.0 vs. 11.1, P &lt; 0.001) in correlation with exosome numbers (r = 0.66, P = 0.01) was seen in heart failure but not in indeterminate form (r = 0.29, P = 0.10). Flow cytometer showed higher numbers of AMZ1 microvesicles in indeterminate form (64 vs. 36, P = 0.02) and higher archaeal DNA microvesicles in heart failure (8.1 vs. 0.9, P &lt; 0.001). Zymography showed strong% collagenase activity in HF group, mild activity in IF compared to non-chagasic healthy group (121 ± 14, 106 ± 13 and 100; P &lt; 0.001).Conclusions: Numerous exosomes, possibly removing and degrading abnormal AMZ1 collagenase, are associated with indeterminate form. Archaeal microvesicles and their exosomes, possibly associated with release of archaeal AMZ1 in heart failure, are future candidates of heart failure biomarkers if confirmed in larger series, and the therapeutic focus in the treatment of Chagas disease

Borexino : geo-neutrino measurement at Gran Sasso, Italy

Geo-neutrinos, electron anti-neutrinos produced in beta-decays of naturally occurring radioactive isotopes in the Earth, are a unique direct probe of our planet's interior. After a brief introduction of the geo-neutrinos' properties and of the main aims of their study, we discuss the features of a detector which has recently provided breakthrough achievements in the field, Borexino, a massive, calorimetric liquid scintillator detector installed at the underground Gran Sasso Laboratory. With its unprecedented radiopurity levels achieved in the core of the detection medium, it is the only experiment in operation able to study in real time solar neutrino interactions in the challenging sub-MeV energy region. Its superior technical properties allowed Borexino also to provide a clean detection of terrestrial neutrinos. Therefore, the description of the characteristics of the detected geo-neutrino signal and of the corresponding geological implications are the main core of the discussion contained in this work

Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

Abstract\ud \ud Background\ud Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage.\ud \ud \ud Methods\ud Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects.\ud \ud \ud Results\ud The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%.\ud \ud \ud Conclusions\ud Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.FAPES