RESUMO
CYP2C8 is an important member of the cytochrome P450 family of enzymes; it affects the activity of various drugs used in routine clinical practice, including amiodarone, chloroquine, amodiaquine, and repaglinide, as well as endogenous compounds, such as arachidonic acid and retonic acid. It is also the main enzyme involved in the metabolism of the widely used anticancer drug Paclitaxel, which has a very narrow therapeutic index. There is evidence that single nucleotide polymorphisms in the CYP2C8 gene influence the adverse reactions and/or the efficacy of drugs metabolized by this enzyme. We examined the allele and genotype frequencies of widely studied functional polymorphisms of the CYP2C8 gene in a North Indian population. We assayed the genomic DNA of at least 251 healthy unrelated North Indians for CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 genetic polymorphisms by RFLP technique. These results were compared to information on other populations. The allelic frequencies of CYP2C8*2, CYP2C8*3, and CYP2C8*4 were found to be 3, 4, and 4% respectively. The two CYP2C8*3 polymorphisms (G416A and A1196G) were found to be completely linked to each other. Allele frequencies of CYP2C8 genetic variants in northern Indians were found to have a distinct pattern that differs from that of southern Indian and other global populations. This is the first report from North India on CYP2C8 polymorphisms. Ethnic differences with respect to polymorphisms are the molecular basis of interethnic variability in pharmacokinetics. Our study may help in rational use of drugs that are substrates for CYP2C8 in this population.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Polimorfismo de Nucleotídeo Único , População/genética , Citocromo P-450 CYP2C8 , Frequência do Gene , Humanos , Índia , Polimorfismo de Fragmento de RestriçãoRESUMO
Sixty-nine patients undergoing liver transplantation were evaluated to elucidate the relationship between hypotension and physiological changes seen on reperfusion of the grafted liver. Measured variables included hemodynamic profiles, core temperature, serum potassium, ionized calcium levels, arterial blood-gas tensions, and acid-base state. Measurements were taken 60 minutes after skin incision (baseline), 5 minutes before reperfusion, and 30 seconds and 5 minutes after reperfusion. On the basis of changes in mean arterial pressure (MAP) patients were divided in two groups. Group 1 (n = 49) maintained MAP greater than 70% and group 2 (n = 20) had MAP less than 70% of the baseline value for at least 1 minute within 5 minutes after reperfusion. On reperfusion, changes common to both groups were 27% increase in cardiac filling pressures, 23% base deficit, and 30% serum potassium level and a decrease of 16% in cardiac output and 9% in temperature. Compared with group 1, group 2 had greater decrease in systemic vascular resistance (SVR) (1097 +/- 868 and 741 +/- 399 dyn.s-1. cm-5, respectively, P < .05) and higher potassium level (4.5 +/- 0.8 and 5.3 +/- 0.8 mmol/L, P < .05). Collectively in both groups, there was no correlation between MAP and physiological variables; however, there was a poor correlation with SVR (r = .32, P < .01). Reperfusion hypotension seen in group 2 patients correlated only with a decrease in systemic vascular resistance (r = .5, P < .05). Acute hyperkalemia, hypothermia, and acidosis do not appear to be major causes of reperfusion hypotension.
Assuntos
Hipotensão/fisiopatologia , Transplante de Fígado , Traumatismo por Reperfusão/fisiopatologia , Adulto , Idoso , Gasometria , Temperatura Corporal , Débito Cardíaco , Técnica de Diluição de Corante , Eletrólitos/sangue , Hemodinâmica , Humanos , Pessoa de Meia-IdadeRESUMO
We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Isoquinolinas/farmacocinética , Falência Renal Crônica/metabolismo , Hepatopatias/metabolismo , Fármacos Neuromusculares não Despolarizantes/farmacocinética , Adulto , Anestesia Geral , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Isoquinolinas/farmacologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/cirurgia , Hepatopatias/fisiopatologia , Hepatopatias/cirurgia , Taxa de Depuração Metabólica/efeitos dos fármacos , Pessoa de Meia-Idade , Junção Neuromuscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologiaAssuntos
Má Oclusão/epidemiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Má Oclusão/classificação , Nigéria , População RuralRESUMO
Se hizo un estudio en niños escolares de un área rural de Ile-Ife, Nigeria para determinar su condición ortodóncica. El 51% de los niños examinados estaban libres de problemas ortodóncicos. 45% presentó maloclusión Clase I de Angle. Cuando se comparan estos resultados con los obtenidos en otros estudios en niños nigerianos de zonas urbanas, el presente estudio sugiere que: 1) la prevalencia de problemas ortodóncicos en niños escolares nigerianos de la zona rural es menor que la de niños de la zona urbana; 2) cuando ocurren los problemas ortodóncicos, son ligeramente más severos en los niños escolares de la zona urbana que en los niños de la zona rural
Assuntos
Criança , Adolescente , Humanos , Masculino , Feminino , Má Oclusão Classe I de Angle/epidemiologia , Saúde Bucal , População RuralRESUMO
Fibrinolysis activity was studied in 31 patients of leprosy and 10 healthy controls. Fibrinolytic activity was found signoficantly decreased in patients with erythema nodosum leprosum, compared to those with uncomplicated lepromatous leprosy, who in turn showed lowered activity compared to patients with tuberculoid form of leprosy and controls. The severity of ENL correlated very well with decrease in fibrinolytic activity. Fibrinolytic activity was improved to levels obtained in uncomplicated lepromatous leprosy after the subsidence of reaction. So it would seem reasonable to suggest taht estimation of fibrinolytic activity provides a reliable criteria to quantitate the severity of erythema nodosum leprosum.