José Antônio Dias Garcia

S-Nitroso-N-Acetylcysteine (SNAC) Prevents Myocardial Alterations in Hypercholesterolemic LDL Receptor Knockout Mice by Antiinflammatory Action

We investigated the ability of S-nitroso-N-acetylcyseine (SNAC) to prevent structural and functional myocardial alterations in hypercholesterolemic mice. C57BL6 wild-type (WT) and LDL-R−/− male mice (S) were fed a standard diet for 15 days. LDL-R−/− mice (S) showed an 11% increase in blood pressure, 62% decrease in left atrial contractility, and lower CD40L and eNOS expression relative to WT. LDL-R−/− mice fed an atherogenic diet for 15 days (Chol) showed significant increased left ventricular mass compared to S, which was characterized by: (1) 1.25-fold increase in the LV weight/body weight ratio and cardiomyocyte diameter; (2) enhanced expression of the NOS isoforms, CD40L, and collagen amount; and (3) no alteration in the atrial contractile performance. Administration of SNAC to Chol mice (Chol + SNAC) (0.51 μmol/kg/day for 15 day, IP) prevented increased left ventricular mass, collagen deposit, NOS isoforms, and CD40L overexpression, but it had no effect on the increased blood pressure or atrial basal hypocontractility. Deletion of the LDL receptor gene in mice resulted in hypertension and a marked left atrial contractile deficit, which may be related to eNOS underexpression. Our data show that SNAC treatment has an antiinflammatory action that might contribute to prevention of structural and functional myocardial alterations in atherosclerotic mice independently of changes in blood pressure.

Efeito anti-inflamatório da lipoproteína de alta densidade no sistema cardiovascular de camundongos hiperlipidêmicos

Resumo Fundamento Camundongos knouckout para o gene do receptor de lipoproteina de baixa densidade (LDLr−/−) sao hiperlipidemicos espontâneos e resistentes ao desenvolvimento de lesoes neointimais. Objetivos O presente estudo teve como objetivo determinar o fator que previne o processo inflamatorio, as lesoes neointimais cardiovasculares e a resistencia insulinica nos camundongos LDLr−/−. Material e metodos Utilizaram-se tres grupos experimentais de camundongos machos com tres meses de idade: Grupo WT, camundongos selvagens; Grupo S, camundongos LDLr−/− que receberam racao padrao; Grupo HL, camundongos LDLr−/− que receberam racao hiperlipidica. Apos 15 dias, o sangue foi coletado para analise plasmatica dos lipideos, glicose e insulina. O indice de Homa foi calculado para determinar a resistencia a insulina. O coracao e aorta foram removidos e processados histologicamente. Cortes histologicos do coracao foram processados imunoistoquimicamente com anticorpo anti-CD40L para avaliar a presenca de processo inflamatorio. Cortes histologicos das arterias foram corados com hematoxilina/eosina e picrosirius red para avaliar alteracoes morfologicas e morfometricas. Resultados Os camundongos S foram resistentes ao processo inflamatorio, caracterizado por baixa imunorreatividade para o CD40L, com niveis plasmaticos de HDL elevados, e nao desenvolveram resistencia insulinica, mesmo com hiperlipidemia moderada em relacao aos WT. Os camundongos HL apresentaram uma hiperlipidemia grave, aumento na imunorreatividade cardiaca para o CD40L, pronunciadas alteracoes morfologicas na parede da aorta e resistencia insulinica, associadas a um decrescimo nos niveis plasmaticos do HDL em relacao aos S. Esta hiperlipidemia grave dos camundongos HL pode ser considerada o fator metabolico indutor do maior estresse oxidativo no sistema cardiovascular, aumentando a peroxidacao lipidica da molecula de HDL e consequentemente sua remocao hepatica, com consequente diminuicao dos niveis plasmaticos do HDL. Conclusao O nivel plasmatico elevado de HDL e o fator protetor contra o desenvolvimento de processos inflamatorios cardiovasculares e resistencia insulinica nos camundongos LDLr−/−, impedindo o desenvolvimento das lesoes neointimais.

Anti-inflammatory effect of high-density lipoprotein on the cardiovascular system of hyperlipidemic mice

Abstract Introduction LDLr-/- mice are spontaneously hyperlipidemic and resistant to the development of neointimal lesions. Objectives This study aimed to determine the factor that prevents the inflammatory process and neointimal lesions and insulin resistance in LDLr-/- mice. Methods Three groups of 3-month-old male mice were used: wild-type mice (WT group); LDLr-/- mice fed a standard diet (S group); and LDLr-/- mice fed a high-fat diet (HF group). After 15 days, blood was collected for analysis of plasma lipids, glucose and insulin. The HOMA index was calculated to determine insulin resistance. The heart and aorta were removed for histological study. Histological sections of the heart were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process. Histological sections of the aorta were stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. Results The S mice were resistant to the inflammatory process, as shown by low immunoreactivity to CD40L, with high plasma HDL levels, and did not develop insulin resistance, even with moderate hyperlipidemia compared to WT. The HF mice showed severe hyperlipidemia, increased cardiac immunoreactivity to CD40L, pronounced morphological changes in the aortic wall and insulin resistance, associated with a decrease in plasma HDL levels, compared to S. This severe hyperlipidemia in the HF mice can be considered the major metabolic factor inducing oxidative stress in the cardiovascular system, increasing the lipid peroxidation of HDL and hence its removal by the liver, with consequent lowering of plasma HDL levels. Conclusion High HDL plasma levels are a protective factor against the development of cardiovascular inflammation and insulin resistance in LDLr-/- mice, preventing the development of neointimal lesions.

Effects of phenobarbital on bone repair and biomechanics in rats

OBJETIVO: Evaluar los efectos morfologicos del tratamiento con fenobarbital, sobre la neoformacion osea y sobre la biomecanica osea del hueso de ratas Wistar. METODOS: Fueron utilizadas diez ratas divididas en dos grupos: control (CT) y fenobarbital (FE). El grupo FE recibio dosis diarias de fenobarbital 0,035 ml/kg via intramuscular, por 60 dias. El grupo CT recibio la misma dosis y via de administracion de solucion fisiologica 0,9%. Despues de 30 dias, se realizo una falla osea en el hueso parietal e implanto la hidroxiapatita porosa (HAP) en cavidades en las tibias. Despues de las cirugias, se mantuvo los respectivos protocolos hasta completar 60 dias y de ser eutanasiados, siendo recolectados los huesos. RESULTADOS: El volumen de hueso formado alrededor HAP en la falla parietal y los hallazgos biomecanicos fueron menores en los animales del grupo FE en relacion al CT. CONCLUSION: El uso prolongado del fenobarbital interfiere en la reparacion osea despues de lesiones, disminuye la oseointegracion de implantes de HAP y vuelve a los huesos menos resistentes.

Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet

INTRODUCTION AND OBJECTIVE Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. METHODS Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed. RESULTS A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group. CONCLUSION In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system.

RISCOS PARA HIPERTENSÃO ARTERIAL EM UM GRUPO DE ESTUDANTES SULMINEIROS

INTRODUCAO – A hipertensao arterial nao e mais uma doenca exclusiva de adultos e idosos, pelo contrario, torna-se cada vez mais comum criancas com niveis pressoricos elevados, representado um risco potencial para as complicacoes associadas a doenca. OBJETIVOS - Investigar a prevalencia de fatores de risco para hipertensao arterial entre escolares do ensino fundamental de uma escola privada. MATERIAL E METODOS - Estudo de corte transversal, descritivo analitico de abordagem quantitativa realizado com 26 escolares do ensino fundamental, com idade entre 9 e 10 anos. A investigacao sobre os fatores de risco associados a elevacao da pressao arterial nos escolares dividiu-se em duas partes, na quais, aplicou-se um questionario semiestruturado junto aos pais e posteriormente foi realizado um exame fisico nos escolares. RESULTADOS - 15 (57,7%) eram do sexo feminino e 11 (42,3%) do sexo masculino. De acordo com o relato dos pais apenas 14 (53,84%) tinham a pressao arterial aferida com frequencia, por outro lado, apenas 10 (38,46%) confirmaram ter presenciado o pediatra aferir a pressao arterial da crianca durante as consultas medicas, 19 (73%) nunca passaram por uma avaliacao nutricional, 14 (53,8%) assinalaram mais de tres doencas no historico familiar. 16 (61,5%) criancas nunca foram avaliadas para deteccao de alteracoes nos valores glicemicos ou niveis de colesterol e 10 (38,5%) ja foram submetidos a exames, entre estes um (10%) apresentou valores glicemicos elevados, 11 (42,30%) dos escolares estavam com sobrepeso. CONCLUSAO - Os fatores de risco associados a elevacao da pressao arterial estavam presentes em boa parte dos individuos investigados. O desafio no controle dos niveis pressoricos e observado em todas as faixas etarias, entretanto, e fundamental que os estudos sirvam de subsidios para as intervencoes em saude baseada em evidencias junto as criancas.

Macroscopic assessment of exposure to ethanol and alcoholic detoxification on gastric lesions in rats

Aims: To investigate the effects of chronic ethanol consumption and alcohol detox on macroscopic gastric lesions in rats. Methods: This is an experimental study in which 18 adult male rats (Rattus norvegicus) of the Wistar strain, with 40 days of life were divided into three randomized groups with six animals each: Control Group (CT), Detoxicated Group (DE) and Alcohol Group (AC). The AC animals have been subjected to an experimental model termed as chronic alcoholics, in which, after a period of adaptation, they received ethanol as the only liquid food available until completion of 13 weeks of the experiment. The DE was subjected to the same protocol as the AC, however, after six weeks of alcohol consumption, the animals were subjected to the alcohol detoxification process. At the end of the experiment, the stomach of the three groups of animals were collected in order to investigate the presence of gastric lesions. Results: The animals in the CG showed no lesions. The animals in DE exhibited a larger number of lesions in comparison to the AC (44±3.7 and 21±0.3 respectively). Macroscopic examination of the animals stomachs indicates that the animals in the DE were those with the highest injury rate in the gastric mucosa. Conclusions: Ethanol consumed chronically or after alcohol detoxification triggered gastric lesions in AC and DE, but sharply in the group submitted to detoxification, which can characterize a possible synergism between ethanol consumption and alcohol detox post-stress in the pathogenesis of gastric ulcer.AIMS: To investigate the effects of chronic ethanol consumption and alcohol detox on macroscopic gastric lesions in rats. METHODS: This is an experimental study in which 18 adult male rats (Rattus norvegicus) of the Wistar strain, with 40 days of life were divided into three randomized groups with six animals each: Control Group (CT), Detoxicated Group (DE) and Alcohol Group (AC). The AC animals have been subjected to an experimental model termed as chronic alcoholics, in which, after a period of adaptation, they received ethanol as the only liquid food available until completion of 13 weeks of the experiment. The DE was subjected to the same protocol as the AC, however, after six weeks of alcohol consumption, the animals were subjected to the alcohol detoxification process. At the end of the experiment, the stomach of the three groups of animals were collected in order to investigate the presence of gastric lesions. RESULTS: The animals in the CG showed no lesions. The animals in DE exhibited a larger number of lesions in comparison to the AC (44±3.7 and 21±0.3 respectively). Macroscopic examination of the animal’s stomachs indicates that the animals in the DE were those with the highest injury rate in the gastric mucosa. CONCLUSIONS: Ethanol consumed chronically or after alcohol detoxification triggered gastric lesions in AC and DE, but sharply in the group submitted to detoxification, which can characterize a possible synergism between ethanol consumption and alcohol detox post-stress in the pathogenesis of gastric ulcer.

Efeitos do fenobarbital sobre o reparo e a biomecânica de ossos em ratos Wi star

OBJETIVO: Evaluar los efectos morfologicos del tratamiento con fenobarbital, sobre la neoformacion osea y sobre la biomecanica osea del hueso de ratas Wistar. METODOS: Fueron utilizadas diez ratas divididas en dos grupos: control (CT) y fenobarbital (FE). El grupo FE recibio dosis diarias de fenobarbital 0,035 ml/kg via intramuscular, por 60 dias. El grupo CT recibio la misma dosis y via de administracion de solucion fisiologica 0,9%. Despues de 30 dias, se realizo una falla osea en el hueso parietal e implanto la hidroxiapatita porosa (HAP) en cavidades en las tibias. Despues de las cirugias, se mantuvo los respectivos protocolos hasta completar 60 dias y de ser eutanasiados, siendo recolectados los huesos. RESULTADOS: El volumen de hueso formado alrededor HAP en la falla parietal y los hallazgos biomecanicos fueron menores en los animales del grupo FE en relacion al CT. CONCLUSION: El uso prolongado del fenobarbital interfiere en la reparacion osea despues de lesiones, disminuye la oseointegracion de implantes de HAP y vuelve a los huesos menos resistentes.