ABSTRACT
The apolipoprotein B (APOB) gene contains several polymorphic sites described as risk modifiers for cardiovascular events. The objective of this study was to verify the association of the classic APOB Xba I polymorphism (rs693) with atherosclerotic risk factors in a segment of the Brazilian elderly population considering their usual dietary intake. Clinical and biochemical characteristics as well as total caloric and fat intake data were determined from 644 elderly individuals. Polymorphism analysis was performed by conventional polymerase chain reaction followed by enzyme restriction. Statistical analyses compared measures and proportions according to different APOB genotypic combinations. Statistically significant association was found between Xba I polymorphism and serum LDL, total cholesterol, and total lipid levels, with important elevations among T homozygotes compared to the other genotypes. There was homogeneity in all other parameters analyzed (including intake pattern), with a tendency for reduced levels of circulating apolipoprotein B among TT individuals. Our results pointed out that genetic variation in APOB affected the lipemic profile of elderly individuals in a context not biased by diet, generating a pattern suggestive of secretory disorder of lipoprotein particles, with possible implication in atherosclerotic risk.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Apolipoproteins B/genetics , Polymorphism, Genetic/genetics , Genetic Predisposition to Disease/genetics , Atherosclerosis/genetics , Feeding Behavior , Lipids/blood , Brazil , Energy Intake , Cardiovascular Diseases/blood , Risk Factors , Atherosclerosis/blood , Gene Frequency , GenotypeABSTRACT
Além de influenciar o crescimento corpóreo, o hormônio do crescimento, ou somatotrófico, desempenha importante papel no metabolismo, composição corporal, perfil lipídico, estado cardiovascular e longevidade. Seu controle é multi-regulado por hormônios, metabólitos e peptídeos hipotalâmicos. Dados sobre a Deficiência Isolada de GH (DIGH) obtidos a partir da descrição da mutação IVS1+1G®A no gene do receptor do hormônio liberador do GH (GHRH-R) em indivíduos da cidade de Itabaianinha, SE, são revisados. São abordadas novas perspectivas sobre o modelo de resistência ao GHRH, a importância do GHRH no controle da secreção de GH, a freqüência das mutações do gene do GHRH-R, a relevância diagnóstica do IGF-I e os achados metabólicos, cardiovasculares e de qualidade de vida nestes indivíduos.
Subject(s)
Adolescent , Adult , Child , Humans , Middle Aged , Growth Hormone/deficiency , Receptors, Neuropeptide/genetics , Receptors, Pituitary Hormone-Regulating Hormone/genetics , Brazil , Growth Hormone-Releasing Hormone/physiology , Insulin-Like Growth Factor I/physiology , MutationABSTRACT
The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) =115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10,20,30,60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18 percent, P=NS), DBP (14 vs 8 percent, P=NS) and HR (22 vs 28 percent, P=NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 + 72 vs 41 + 12 nl/ml, P<0.05; time to reach CMAX (TMAX): 34 + 18 vs 52 + 11 min, P<0.05; biological hall-life (t1/2b): 0.91 + 0.54 vs 2.41 + 1.16 h, P<0.05; area under the curve (AUCT): 245 + 134 vs 79 + 54 ng h(-1) ml(-1), P<0.05; total body clearance (CLT/F):44 + 23 vs 26 + 12 ml min(-1) kg(-1), P=NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.