Reactive oxygen species generation in peripheral blood monocytes and oxidized LDL are increased in hyperlipidemic patients.

OBJECTIVES: Experimental and in vitro evidences have established that reactive oxygen species (ROS) generated by vascular wall cells play a key role in atherogenesis. Here, we evaluated the rate of ROS generation by resting peripheral monocytes in naive hyperlipidemic subjects. DESIGN AND METHODS: Primary hypercholesterolemic, combined hyperlipidemic, and normolipidemic individuals were studied. ROS generation and the mitochondrial electrical transmembrane potential were estimated by flow cytometry. Plasma oxidized (ox) LDL levels and lipid profile were measured by ELISA and enzymatic colorimetric methods. RESULTS: Both hyperlipidemic groups presented significantly higher rates of monocyte ROS generation and elevated plasma levels of ox-LDL. Combined hyperlipidemic subjects presented increased levels of small dense LDL and insulin. Significant positive correlations between monocyte ROS generation and ox-LDL concentrations were found in pooled data. CONCLUSIONS: These data provide evidence that ROS production by circulating monocytes from hyperlipidemic subjects may contribute to the systemic oxidative stress and possibly to atherogenesis.

High-density lipoprotein subfractions in normolipidemic individuals without clinical atherosclerosis lipoprotein subfractions in an adult population.

This study evaluated the serum concentrations of lipids, lipoproteins, apolipoproteins, and high-density lipoprotein (HDL) subfractions in Brazilian adults. We analyzed the distribution of lipids in HDL2 and HDL3 in a normolipidemic population without evidence of established cardiovascular disease (CVD). A total of 93 males and 92 females, healthy and normolipidemic, volunteered to be submitted to a clinical examination, a blood collection, and to answer a questionnaire aimed at determining signs and symptoms of atherosclerotic disease. Their fasting plasma lipid, lipoproteins, apolipoproteins, and the cholesterol and triglyceride concentrations in HDL2 and HDL3, isolated by microultracentrifugation, were determined by enzymatic-colorimetric methods. The interpercentile intervals (2.5-97.5) for the population were established as being 5-18 mg/dL in men and 4-28 mg/dL in women for HDL2 cholesterol (HDL2chol) and 1-57 mg/dL in men and 2-61 mg/dL in women for HDL3 cholesterol (HDL3chol). HDL2 triglyceride levels (HDL2Tg) in men were 1-26 mg/dL and in women 2-28 mg/dL; moreover, the HDL3 triglyceride (HDL3Tg) intervals were established as 4-46 mg/dL for both sexes. The determination of reference ranges for lipids in HDL subfractions in populations without clinical atherosclerosis, is an useful tool for metabolic, diagnostic, and therapeutic approaches. We determined the intervals for HDL2chol, HDL3chol, HDL2Tg, and HDL3Tg. There were variations with sex and/or age for HDL2chol, HDL3chol, and HDL2Tg in the studied population.

High frequency of Fredrickson's phenotypes IV and IIb in Brazilians infected by human immunodeficiency virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection is very prevalent in Brazil. HIV therapy has been recently associated with coronary heart disease (CHD). Dyslipidemia is a major risk factor for CHD that is frequently described in HIV positive patients, but very few studies have been conducted in Brazilian patients evaluating their lipid profiles. METHODS: In the present work, we evaluated the frequency and severity of dyslipidemia in 257 Brazilian HIV positive patients. Two hundred and thirty-eight (93%) were submitted to antiretroviral therapy (224 treated with protease inhibitors plus nucleoside reverse transcriptase inhibitors, 14 treated only with the latter, 12 naive and 7 had no records of treatment). The average time on drug treatment with antiretroviral therapy was 20 months. None of the patients was under lipid lowering drugs. Cholesterol, triglyceride, phospholipid and free fatty acids were determined by enzymatic colorimetric methods. Lipoprotein profile was estimated by the Friedewald formula and Fredrickson's phenotyping was obtained by serum electrophoresis on agarose. Apolipoprotein B and AI and lipoprotein "a" were measured by nephelometry. RESULTS: The Fredrickson phenotypes were: type IIb (51%), IV (41%), IIa (7%). In addition one patient was type III and another type V. Thirty-three percent of all HIV+ patients presented serum cholesterol levels >or= 200 mg/dL, 61% LDL-cholesterol >or= 100 mg/dL, 65% HDL-cholesterol below 40 mg/dL, 46% triglycerides >or= 150 mg/dL and 10% have all these parameters above the limits. Eighty-six percent of patients had cholesterol/HDL-cholesterol ratio >or= 3.5, 22% increased lipoprotein "a", 79% increased free fatty acids and 9% increased phospholipids. The treatment with protease inhibitors plus nucleoside reverse transcriptase inhibitors increased the levels of cholesterol and triglycerides in these patients when compared with naïve patients. The HDL-cholesterol (p = 0.01) and apolipoprotein A1 (p = 0.02) levels were inversely correlated with the time of protease inhibitor therapy while total cholesterol levels had a trend to correlate with antiretroviral therapy (p = 0.09). CONCLUSION: The highly varied and prevalent types of dyslipidemia found in Brazilian HIV positive patients on antiretroviral therapies indicate the urgent need for their early diagnosis, the identification of the risk factors for CHD and, when needed, the prompt intervention on their lifestyle and/or with drug treatment.

Avaliaçäo crítica da interferência da bilirrubina na dosagem de creatinina sérica pela reaçäo de Jaffé / Critical evaluation of bilirubin interference in the Jaffé reaction for serum creatinine determination

Estudamos a deteminaçäo da creatinina em "pools" de soro (normal e alterado) acrescidos de quantidades conhecidas de bilirrubina e também em soros ictéricos de pacientes, através da reaçäo de Jaffé, utilizando os métodos de ponto-final e cinético. Verificamos a interferência negativa da bilirrubina na dosagem cinética de creatinina, que näo foi observada na reaçäo de ponto-final. A reaçäo cinética, entretanto, pode ser utilizada em soros ictéricos desde que haja uma inversäo da ordem de adiçäo dos reagentes, com pré-incubaçäo das amostras com NaOH 0,5 N

Dosagem de creatinina: fatores de erro na reação de Jaffé / Creatinine dosage: error factors in the Jaffé Reaction

Estudamos o mecanismo da reação de Jaffé para a determinação da creatinina humana, utilizando os métodos cinético e ponto-final. Foi analisada a magnitude de interferência nas constantes físicas (tempo e temperatura de incubação) e no equilíbrio da reação, obtendo-se valores subestimados a 25'C nos 2 métodos estudados. Os resultados a 30'C são coerentes com os valores de referência descritos na literatura. A hiperglicemia interfere mais significativamente na reação de ponto-final, elevando os resultados de creatinina a partir de 290 mg%. O método cinético mostrou-se bastante eficaz na dosagem da creatinina sérica discriminando valores sem interferência de substâncias redutoras e com reprodutibilidade compatível às melhores técnicas laboratoriais (AU).

Efeito da hidroclorotiazida e metildopa sobre o metabolismo lipídico em hipertensos essenciais

Os beneficios do tratamento da hipertensäo leve estäo sujeitos a controvérsias, tendo surgido questöes sobre efeitos colaterais dos anti-hipertensivos influenciando desfavoravelmente estes resultados, principalmente em relaçäo a distúrbios do metabolismo lipídico. Foram analisados comparativamente os efeitos a médio prazo (16 semanas) da hidroclorotiazida (HCTZ) e metildopa (MD) sobre lípides e lipoproteínas plasmáticas em 22 hipertensos essenciais leves ou moderados com hipercolesterolemia e/ou hipertrigliceridemia após quatro semanas de placebo. Verificou-se queda transitória de triglicérides e beta-lipoproteínas no período de tratamento com MD e alfa-lipoproteínas com HCTZ. Näo se alteraram colesterol e triglicérides com HCTZ. Conclui-se que a HCTZ e MD näo induziram modificaçäo no metabolismo lipídico durante o período estudado

Tratamiento da hiperlipidemia primária com ácido 5-metil-pirazina-2-carbocilico (acipimox) / Treatment of primary hyperlipidemia with 5-methylpyrazinecarboxylic acid (acipimox)

Após período controle de 2 meses, 14 pacientes hiperlipidêmicos foram tratados com acipimox (geralmente 750 mg/dia) durante aproximadamente 12 meses. Ocorreu reduçäo média de colesterolemia de 17%, sem que diminuisse significantemente a trigliceridemia, exceto nos casos de hipertrigliceridemia acima de 600 mg/100 ml. Por outro lado a colesterolemia descreveu 23% nos casos de hiperlipidemia combinada (hipercolesterolemia com hipertrigliceridemia), mas apenas 13% nos casos de hipercolesterolemia isolada. Houve diminuiçäo porcentual das beta-lipoproteínas de 49,3% para 43,5% com simultâneo aumento desejável das alfa-LP de 18,5% para 25,9%, mas as pré-beta-LP ficaram estáveis. O incremento de uricemia foi de 13,7%, porém a glicemia, os testes orais de tolerância à glicose, a funçäo hepática e a renal näo se alteraram. Efeitos colaterais foram despresíveis e a tolerância foi consideravelmente melhor do que aquela atribuída ao ácido nicotínico