RESUMO
A 3-year-old female intact Miniature Australian Shepherd presented with convulsive status epilepticus after milbemycinoxime administration in the recommended dosage. In addition to continuous intravenous antiepileptic therapy the dog had to be ventilated for 36 hours due to aspiration pneumonia. After extubation control of intermittent tonic-clonic seizures required a constant-rate-infusion of propofol for another 96 hours, before it could be discontinued on day 5. The patient had fully recovered by day 10. The dog was known to be homozygous for the MDR1-gene mutation. So far milbemycinoxime was regarded a save drug in MDR1-deficient dogs. However, the present case suggests using the lowest possible dosage in MDR1-deficient dogs and pet owners should be advised of potential complications.
Assuntos
Anti-Helmínticos/efeitos adversos , Doenças do Cão/induzido quimicamente , Genes MDR , Macrolídeos/efeitos adversos , Estado Epiléptico/veterinária , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/genética , Cães , Feminino , Hipnóticos e Sedativos/administração & dosagem , Pneumonia Aspirativa/induzido quimicamente , Pneumonia Aspirativa/terapia , Pneumonia Aspirativa/veterinária , Propofol/administração & dosagem , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/genéticaRESUMO
AIM: Chronic endurance exercise triggers increased cardiac dimensions, blood volumes and haemoglobin mass (Hb mass). Cardiac output and Hb mass are considered as independent contributors to aerobic performance. Therefore, increased Hb mass could counterbalance for a relative deficiency in cardiac adaptation. The purpose of the present study is to investigate relations between Hb mass and cardiac dimensions in a group of endurance athletes with respect to aerobic capacity. METHODS: Two groups of highly trained cyclists featuring high (HHB group, N.=13) and low (LHB group, N.=13) Hb mass (measured by a CO-rebreathing method) were compared for measures of aerobic performance, cardiac wall thickness, cavity size and left ventricular mass (determined by 2-D-echocardiography). Lean body mass (LBM) was chosen as anthropometrical reference for Hb mass. RESULTS: HHB featured higher cardiac wall thickness than LHB, but no difference appeared in cardiac cavity size, left ventricular mass and the performance parameters. Normalising Hb mass for body weight instead of LBM improved correlations between Hb mass and performance parameters. CONCLUSIONS: Our data provides new evidence for a connection between cardiac wall thickness and Hb mass in endurance athletes but no further evidence for a counterbalance between Hb mass and cardiac adaptation was found. Moreover, we postulate that Hb mass loses predictive value for aerobic performance when normalised for LBM.
Assuntos
Ciclismo/fisiologia , Volume de Eritrócitos/fisiologia , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Coração/anatomia & histologia , Hemoglobinas/análise , Adaptação Fisiológica , Adulto , Volume Sanguíneo/fisiologia , Débito Cardíaco , Teste de Esforço , Feminino , Coração/fisiologia , Humanos , Masculino , Consumo de Oxigênio , Estatística como AssuntoRESUMO
The interaction of LDL and LDL subfractions from a patient homozygous for familial defective apoB-100 (FDB) has been studied. His LDL cholesterol ranged from 2.65 to 3.34 g/liter. In cultured fibroblasts, binding, internalization, and degradation of the patient's LDL was diminished, but not completely abolished. The patient's apolipoprotein E concentration was low, and the amount of apolipoprotein E associated with LDL was not elevated over normal. LDL were separated into six subfractions: LDL-1 (1.019-1.031 kg/liter), LDL-2 (1.031-1.034 kg/liter), LDL-3 (1.034-1.037 kg/liter), LDL-4 (1.037-1.040 kg/liter), LDL-5 (1.040-1.044 kg/liter), and LDL-6 (> 1.044 kg/liter). LDL-5 and LDL-6 selectively accumulated in the patient's plasma. Concentrations of LDL-1 to 3 were normal. The LDL receptor-mediated uptake of LDL-1 and LDL-2 could not be distinguished from normal LDL. LDL-3 and LDL-4 displayed reduced uptake; LDL-5 and LDL-6 were completely defective in binding. When apolipoprotein E-containing particles were removed by immunoabsorption before preparing subfractions, LDL-3 and LDL-4, but not LDL-1 and LDL-2, retained some receptor binding activity. We conclude that in FDB, LDL-1 and LDL-2 contain sufficient apolipoprotein E to warrant normal cellular uptake. In LDL-3 and LDL-4, the defective apoB-100 itself displays some receptor binding; LDL-5 and LDL-6 are inable to interact with LDL receptors and accumulate in plasma.
Assuntos
Apolipoproteínas B/genética , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Receptores de LDL/metabolismo , Adolescente , Adulto , Apolipoproteína B-100 , Sequência de Bases , Criança , Colesterol/sangue , Primers do DNA , Feminino , Fibroblastos/metabolismo , Triagem de Portadores Genéticos , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/metabolismo , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Pravastatina/uso terapêutico , Pele/metabolismo , Triglicerídeos/sangueRESUMO
The structure of low-density lipoprotein (LDL) particles from three different density ranges (LDL-1: d = 1.006-1.031 g/ml; LDL-3: d = 1.034-1.037 g/ml; LDL-6: d = 1.044-1.063 g/ml) was determined by X-ray small-angle scattering. By using a theoretical particle model, which accounted for the polydispersity of the samples, we were able to obtain fits of the scattering intensity that were inside the noise interval of the measured intensity. The assumption of deviations from radial symmetry is not supported by our data. This implies a spread-out conformation of the apolipoprotein B (apoB) molecule, which appears to be localized in the outer surface shell. A globular structure is not consistent with our data. Furthermore, different models exist concerning the structure of the cholesterol ester core below the phase transition temperature. The electron density data suggest an arrangement in which the steroid moieties are localized at average radii of 3.2 and 6.4 nm. Model calculations show that packing problems can only be avoided if approximately half of the acyl chains of each shell are pointing towards the center of the particle, the other half towards the surface. This arrangement of the acyl chains has never been proposed before. The LDL particles of different density classes differ mainly with respect to the size of the core but also with respect to the width of the surface shells. Model calculations show that the size of different LDL particles can be accurately predicted from the compositional data.
Assuntos
Lipoproteínas LDL/ultraestrutura , Apolipoproteínas B/análise , Análise de Fourier , Humanos , Lipídeos/análise , Lipoproteínas LDL/análise , Substâncias Macromoleculares , Masculino , Estrutura Molecular , Peso Molecular , Conformação Proteica , Espalhamento de Radiação , Temperatura , Raios XRESUMO
BACKGROUND: Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid-lowering agents, it remains controversial whether these agents also lower dense LDL (dLDL), a predominance of which is considered to contribute to the atherogenicity of the metabolic syndrome. METHODS AND RESULTS: In a multicenter, double-blind, randomized, placebo-controlled study, we determined the effect of the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal women with combined hyperlipidemia and increased dLDL were treated with either fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks' treatment, significant reductions (P<0.001) in total cholesterol (-19%), IDL cholesterol (-35%), LDL cholesterol (-23%), apolipoprotein B (-21%), and apolipoprotein B in dLDL (-42%) were apparent among fluvastatin recipients. No significant changes in triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL was correlated with baseline values. There was no consistent relationship, however, between the effect of fluvastatin on triglycerides and the decrease in dLDL. CONCLUSIONS: Fluvastatin lowers total and LDL cholesterol and the concentration of dLDL. This profile may contribute to an antiatherogenic effect for fluvastatin that is greater than expected on the basis of changes in lipids and apolipoproteins.
Assuntos
Anticolesterolemiantes/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Indóis/administração & dosagem , Lipoproteínas LDL/sangue , Apolipoproteínas B/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Fluvastatina , Humanos , Hiperlipidemias/sangue , Lipoproteínas/sangue , Fenótipo , Pós-Menopausa , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
Pregnancy is accompanied by changes in the maternal lipoprotein metabolism that may serve to satisfy the nutritional demands of the fetus. In this study lipoprotein metabolism was investigated in 23 women during normal pregnancy in the first, second, and third trimesters and in 15 healthy nonpregnant women with regular menstrual cycles. Lipid and apolipoprotein concentrations were measured in total plasma, very low density, intermediate density, low density (LDL), and high density lipoproteins, and in each of six LDL subfractions. During early pregnancy, triglycerides, and dense LDL were higher than in the nonpregnant state. With advancing gestation, triglycerides increased and the distribution of apolipoprotein B-100-containing lipoproteins became increasingly dominated by the accumulation of very low density and intermediate density lipoproteins and buoyant, triglyceride-rich LDL. This is the first study that investigates LDL subfractions in pregnancy using a method that strictly separates LDL subfractions by virtue of density. The accumulation of buoyant, triglyceride-rich lipoproteins may be related to the down-regulation of maternal lipase activities by placental hormones. As a consequence, the metabolic changes of late pregnancy may result in an increased flux of lipoprotein-derived lipids to the placenta, which, with advancing gestation, increasingly expresses receptors with a high affinity for triglyceride-rich lipoproteins.
Assuntos
Glicoproteínas , Lipoproteínas LDL/sangue , Gravidez/sangue , Adulto , Arteriosclerose/sangue , Proteínas de Transporte/sangue , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol , Estradiol/sangue , Feminino , Humanos , Tamanho da Partícula , Fenótipo , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , UltracentrifugaçãoRESUMO
In order to interpret the known lipoprotein changes in probucol-treated patients, serum concentrations of apolipoproteins (A-I, A-II, B, C-II, C-III, E) were measured before, during and after probucol administration (2 X 500 mg p.d.), in 16 healthy males (30.3 +/- 5.6 years old). Cholesterol concentrations were determined in LDL and VLDL fractions as well as in HDL subfractions which were isolated by preparative ultracentrifugation. In addition, apolipoprotein A-I and A-II concentrations were measured in the HDL subfractions. Compared with the baseline values, significant apolipoprotein changes were found in the serum apolipoprotein A-I (151 +/- 18 to 115 +/- 31 mg/dl; P less than 0.001) and C-II levels during administration. The HDL subfraction analysis showed that the decrease of HDL-cholesterol and apolipoprotein A-I (59.9 +/- 23.5 to 34.4 +/- 16.4 mg/dl, P less than 0.001, and 65.7 +/- 49.0 to 37.5 +/- 23.5 mg/dl, P less than 0.05, respectively) was predominantly related to the HDL2b subfraction (d = 1.063-1.100 g/ml).
Assuntos
Apolipoproteínas/sangue , Colesterol/sangue , Lipoproteínas/sangue , Fenóis/farmacologia , Probucol/farmacologia , Adulto , Humanos , Masculino , Valores de ReferênciaRESUMO
Elevated serum ferritin concentrations between 200 and 500 microg/l have been found to be a strong risk factor for acute myocardial infarction in Finnish men, but the reason for this association is still uncertain. In the Finnish population ferritin concentrations correlated with factors of insulin resistance syndrome. As these factors have been found to be associated with an LDL subfraction phenotype of increased concentrations of small, dense LDL particles, we hypothesized an association between ferritin and an atherogenic LDL subfraction profile, a finding which could be an explanation for the observed relationship between ferritin and atherosclerosis. Therefore we determined serum ferritin levels, metabolic cardiovascular risk factors, and the LDL subfraction phenotype in 93 healthy men without signs for infection or coronary heart disease. We found that men with moderately elevated ferritin levels (200-500 microg/l; n = 31) had a significantly worse coronary risk profile than men with lower levels ( < 200 microg/l; n = 62). Elevated ferritin concentrations were associated with significantly higher values for serum triglycerides, VLDL cholesterol, VLDL apolipoprotein B (P < 0.01), IDL cholesterol, fasting glucose (P < 0.05) and uric acid (P < 0.01), and lower levels for HDL2b and HDL2a cholesterol and apolipoprotein A-I (P < 0.05), and lipoprotein(a) (P < 0.01). Elevated ferritin levels were, however, not associated with an unfavourable LDL subfraction profile of increased concentrations of small, dense LDL particles.
Assuntos
Doenças Cardiovasculares , Ferritinas/sangue , Adulto , Apolipoproteína A-I/sangue , HDL-Colesterol/sangue , Humanos , Lipoproteínas/sangue , Masculino , Concentração Osmolar , Valores de Referência , Fatores de RiscoRESUMO
In order to investigate the changes in HDL subfractions induced by a single period of extended physical exercise, 9 endurance-trained adults were examined before and 6 min, 1 and 6 h after a 30 km cross-country race. In contrast to less evident changes in the concentrations of total HDL, apolipoprotein A-I and A-II, there were significant changes in HDL subfractions. Resting levels of protein and cholesterol content of the HDL subfractions 1-3 increased (subfraction 1, density gradient 1.093: 1.68 +/- 0.58 to 3.24 +/- 0.86 mmol/1 cholesterol, P less than 0.001), while the concentrations in HDL subfractions 11-12 decreased proportionately (subfraction 12, density gradient 1.142: 3.68 +/- 0.81 to 2.19 +/- 0.22 mmol/1 cholesterol, P less than 0.001). The results suggest that physical exercise induces an increased formation of HDL particles of lower density from HDL particles of higher density. It was concluded that this formation is related to the catabolism of triglyceride-rich lipoproteins in the post-exercise period.
Assuntos
Lipoproteínas HDL/análise , Esforço Físico , Colesterol/análise , HDL-Colesterol , Humanos , Masculino , Triglicerídeos/metabolismoRESUMO
Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31+/-9 years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13-2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG < 1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles (d < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids.
Assuntos
HDL-Colesterol/sangue , Lipoproteínas LDL/sangue , Triglicerídeos/sangue , Adulto , Apolipoproteínas B/sangue , Índice de Massa Corporal , Centrifugação com Gradiente de Concentração , Colesterol/sangue , VLDL-Colesterol/sangue , Humanos , Lipoproteínas/sangue , Lipoproteínas LDL/química , Masculino , UltracentrifugaçãoRESUMO
The relation between LDL subfractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subfractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tertile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tertile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9% of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.
Assuntos
Lipoproteínas LDL/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Análise de Variância , Antropometria , Apolipoproteínas B/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Fibrinolíticos/sangue , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Análise de Regressão , Fumar/sangue , Ativador de Plasminogênio Tecidual/sangue , Triglicerídeos/sangueRESUMO
There is evidence that a low-density lipoprotein (LDL) subfraction profile of increased concentrations of small, dense LDL particles is less common among trained than among sedentary normocholesterolemic men, but it is still uncertain whether there is a similar association in hypercholesterolemia also. Therefore, we determined the lipid and apolipoprotein concentration and composition of six LDL subfractions (density gradient ultracentrifugation) in 20 physically fit, regularly exercising (>three times per week) hypercholesterolemic men and 20 sedentary hypercholesterolemic controls. Trained (maximal oxygen consumption [VO2max], 57.3 +/- 7.4 mL/kg/min) and sedentary (VO2max, 37.5 +/- 8.8 mL/kg/min) individuals (aged 35 +/- 11 years; body mass index [BMI], 23.9 +/- 2.7 kg/m2) were matched for LDL apolipoprotein (apo) B levels (108 +/- 23 and 112 +/- 36 mg/dL, respectively). Trained subjects had significantly lower serum triglyceride (P < .05) and very-low-density lipoprotein (VLDL) cholesterol levels (P < .05) and higher high-density lipoprotein 2 (HDL2) cholesterol levels (P < .01) than sedentary controls. LDL particle distribution showed that trained individuals had significantly less small, dense LDL (d = 1.040 to 1.063 g/mL) and more large LDL (d = 1.019 to 1.037 g/mL) subfraction particles than sedentary controls, despite equal total LDL particle number. Analysis of LDL composition showed that LDL particles of hypercholesterolemic trained men had a higher free cholesterol content than LDL of untrained hypercholesterolemic men. Small, dense LDL in hypercholesterolemic trained men were richer in phospholipids than those in sedentary controls. These data demonstrate the significant influence of aerobic fitness on lipoprotein subfraction concentration and composition, thereby emphasizing the role of exercise in the treatment and risk reduction of hypercholesterolemia.
Assuntos
Exercício Físico/fisiologia , Hipercolesterolemia/metabolismo , Lipoproteínas LDL/metabolismo , Aptidão Física/fisiologia , Centrifugação com Gradiente de Concentração , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Humanos , Lipoproteínas LDL/química , Masculino , Triglicerídeos/sangue , Ultracentrifugação/métodosRESUMO
Obesity, insulin resistance (IR) with hyperinsulinemia, and a dyslipoproteinemia characterized by reduced high-density lipoprotein 2 (HDL2) cholesterol and elevated levels of small, dense low-density lipoprotein (LDL) particles are risk factors for coronary artery disease (CAD). The impact of obesity independent of hyperinsulinemia on the concentration and composition of small, dense LDL subfractions is uncertain. The aim of this study was to investigate the relationship between obesity indices, namely body mass index (BMI), skinfold measurements (SF), and waist to hip ratio (WHR), and LDL-subfraction particle concentration and composition in 200 healthy men without evidence of IR. A precise analysis of the concentration of lipids and apolipoproteins and the composition of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and two HDL- and six LDL-subfraction particles was obtained using the technique of density-gradient ultracentrifugation. Dividing the individuals according to BMI showed that those with a BMI greater than 27 kg/m2 had significantly lower HDL2 cholesterol and apolipoprotein (apo) A-I and higher VLDL and IDL cholesterol and apo B concentrations than those with a BMI less than 25 kg/m2. Regarding LDL particles, we found that men with a BMI above 25 kg/m2 had significantly more small, dense LDL particles (d 1.044 to 1.063 g/mL) and correspondingly fewer medium, dense LDL particles (d 1.031 to 1.037 g/mL) than leaner men; those with a BMI above 27 kg/m2 had the highest concentration of circulating small, dense LDL particles. These findings were not influenced by fasting insulin concentrations, IR, or WHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Insulina/sangue , Lipoproteínas LDL/sangue , Obesidade/sangue , Adulto , Apolipoproteínas B/sangue , Apoproteínas/sangue , Constituição Corporal , Índice de Massa Corporal , Colesterol/sangue , Humanos , Resistência à Insulina/fisiologia , Lipoproteínas LDL/fisiologia , Lipoproteínas VLDL/sangue , Masculino , Obesidade/fisiopatologia , Fenótipo , Dobras Cutâneas , Triglicerídeos/sangue , Ultracentrifugação/métodosRESUMO
Insulin resistance is associated with dyslipoproteinemia characterized by increased serum triglycerides, reduced high-density lipoprotein 2 (HDL2) cholesterol, and increased small, dense low-density lipoprotein (LDL) subfraction particles. Physical activity and weight reduction are known to improve insulin resistance and dyslipoproteinemia, but their influence on LDL subfractions in diabetic patients is unknown. Therefore, we investigated the effect of a 4-week intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/d: 50% carbohydrate, 25% protein, and 25% fat; polyunsaturated/saturated fat ratio, 1.0) on glycemic control and HDL and LDL subfractions in 34 obese patients with non-insulin-dependent diabetes (age, 49 +/- 9 years; body mass index [BMI], 33.1 +/- 5.1 kg/m2). Reductions in body weight (P < .001) and improvements in fasting blood glucose, insulin, fructosamine (P < .001), and free fatty acids (P < .01) by intervention were associated with reductions in serum cholesterol and apolipoprotein B (apo B) concentrations in very-low-density lipoprotein (VLDL) (P < .01), intermediate-density lipoprotein (IDL), and small, dense (>1.040 g/mL) LDL particles (P < .001). These data underlie the positive influence of weight reduction induced by exercise and diet on insulin resistance and lipoprotein metabolism in obese diabetic patients, particularly showing improvements of the LDL subfraction profile with a decrease of small, dense LDL particles. This is of particular importance, as these particles have been shown to be associated with coronary artery disease.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus/sangue , Diabetes Mellitus/dietoterapia , Terapia por Exercício , Lipoproteínas LDL/sangue , Obesidade , Adulto , Apolipoproteínas/sangue , Peso Corporal/fisiologia , Carboidratos/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 2/terapia , Humanos , Resistência à Insulina/fisiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
One of the first steps in lipid autoxidation leads to the generation of lipid peroxides (LPO). The time course of LPO generation during Cu++ catalyzed oxidation of LDL before and after treatment with probucol was determined in this study. Before analysis the samples had been stored for about 3 years at -20 degrees C. The results show that in LDL samples without probucol the total antioxidative potential had been depleted during the long-term storage. In contrast, LDL containing probucol showed almost no signs of lipid autoxidation. In addition, the ratio of vitamin E to cholesterol was significantly higher in serum samples containing probucol. We conclude that, in vivo, probucol is incorporated into LDL particles in concentrations high enough to inhibit even early steps of lipid autoxidation.
Assuntos
Antioxidantes/farmacologia , Peróxidos Lipídicos/antagonistas & inibidores , Lipoproteínas LDL/administração & dosagem , Probucol/administração & dosagem , Probucol/farmacologia , Colesterol/sangue , Humanos , Hipercolesterolemia/tratamento farmacológico , Masculino , Vitamina E/sangueRESUMO
The distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and within HDL subfractions (HDL2b, HDL2a, HDL3) was examined in 26 sedentary and 19 endurance trained normolipemic male individuals. The concentrations of lipids and apolipoproteins in serum and HDL subfractions and the concentrations of LpA-I and LpA-I:A-II were determined. Significant differences (Mann-Whitney-U-test) were found in serum concentrations of apoB (P < 0.05), apoA-II (P < 0.01) and LpA-I:A-II (P < 0.001). In HDL3 apoA-II concentration was significantly lower in the trained group (P < 0.05) but in HDL2 subclasses the concentrations of apoA-I and apoA-II did not differ between the groups. Despite similar concentrations of the two apolipoproteins, there were difference in the distribution of lipoprotein species within HDL2 subfractions. The concentrations of LpA-I did not differ, but the concentrations of LpA-I:A-II particles were higher in the trained group. Untrained and trained had similar concentrations of apoA-II (in HDL2b) but obviously more apoA-II containing particles and this leads to the assumption that within HDL2 of endurance trained individuals LpA-I:A-II particles have a lower apoA-II content compared with particles of untrained individuals. The data emphasize, that normolipemic individuals of different maximum oxygen uptake have a different distribution and composition of lipoprotein species (LpA-I, LpA-I:A-II).
Assuntos
Apolipoproteína A-II/análise , Apolipoproteína A-I/análise , Exercício Físico/fisiologia , Lipoproteínas HDL/sangue , Resistência Física/fisiologia , Adulto , Humanos , Lipoproteínas HDL2 , Lipoproteínas HDL3 , MasculinoRESUMO
Working muscle plays a central role in the control of lipid metabolism. Increased physical activity induces a number of positive changes in the metabolism of lipoproteins: serum triglycerides are lowered by the increased lipolytic activity and the production of native high density lipoprotein (HDL) particles is increased. The increased lecithin: cholesterol acyltransferase activity leads to an increased production of HDL2, which in addition is catabolised more slowly due to a decreased activity of hepatic lipase. The 3 effects explain the increased HDL levels of endurance trained individuals. These effects have been demonstrated in cross-sectional as well as longitudinal studies by different groups, and can be induced by training, independent of changes in bodyweight. The influence of endurance activity on the quality and quantity of low density lipoprotein (LDL) particles is a further reason for the antiatherogenic potential of increased physical activity. It has been shown by several groups that small dense LDL particles represent a particular risk factor for atherosclerosis. Recent studies presented strong evidence that LDL level and composition can be influenced favorably by physical activity. In addition to the direct influence of physical activity on lipids and lipoproteins, physical exercise may improve the disturbances of haemorheological factors, particularly those associated with hypertriglyceridaemia. In conclusion, there is increased evidence that physical activity is able to favourably influence all 3 components of the atherogenic lipoprotein phenotype: the HDL concentration increases, the concentration of small dense LDL decreases, and serum triglycerides are reduced.
Assuntos
Exercício Físico/fisiologia , Lipoproteínas/metabolismo , Músculos/fisiologia , Esportes/fisiologia , Apolipoproteínas/metabolismo , Humanos , Lipoproteínas HDL/metabolismoRESUMO
OBJECTIVE: While 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors effectively decrease LDL cholesterol, it remains controversial whether these agents also lower dense LDL, which are considered particularly atherogenic. METHODS: We examined the effects of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin on lipids, lipoproteins, and apolipoproteins in 69 patients with elevated fasting glucose, impaired glucose tolerance, or type 2 diabetes, combined hyperlipoproteinemia and increased concentrations of dense LDL (apo B in LDL-5 plus LDL-6 > 25 mg/dl). The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n = 34) and placebo (n = 35). RESULTS: Cerivastatin significantly reduced cholesterol (- 20 %, p < 0.001), IDL cholesterol - 37 %, p < 0.001), LDL cholesterol (- 26 %, p < 0.001), apolipoprotein B (- 25 %, p < 0.001), triglycerides (- 12 %, p < 0.05), and raised HDL cholesterol (+ 7.5 %, p < 0.05) and apolipoprotein AI (+ 7.2 %, p < 0.05). Cerivastatin signficantly lowered apolipoprotein B in all LDL subfractions (- 21 to - 28 %, p < 0.05). Absolute changes were greatest in dense LDL and the change in dense LDL made the largest contribution to the change of total LDL. The change of dense LDL was highly correlated with baseline values. There was no consistent relationship between the effect of cerivastatin on triglycerides and the decrease of dense LDL. CONCLUSIONS: The HMG CoA reductase inhibitor cerivastatin lowers total and LDL cholesterol and the concentration of dense LDL in patients with elevated fasting glucose, impaired glucose tolerance or type 2 diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Intolerância à Glucose/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperglicemia/sangue , Lipoproteínas LDL/sangue , Piridinas/uso terapêutico , Adulto , Idoso , Índice de Massa Corporal , Método Duplo-Cego , Humanos , Lipoproteínas/sangue , Lipoproteínas LDL/efeitos dos fármacos , Pessoa de Meia-Idade , PlacebosRESUMO
INTRODUCTION: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome and type 2 diabetes and may be one of the factors responsible for the increased risk for coronary artery disease in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied in a sequential design. METHODS: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation. RESULTS: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 % and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028); LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential than assessed by the reduction of total LDL-cholesterol and triglycerides alone.