RESUMEN
A transdermal delivery system of isosorbide dinitrate (ISDN-TDS) and an HPLC method for the measurement of ISDN were developed. The system is composed of backing, drug reservoir, control membrane, contact adhesive and protective layer. The influences of drug reservoir, solvent, control membrane, viscosity and penetration enhancer azone on the release of ISDN were investigated. The cumulative released amount of ISDN/time profile indicated that ISDN was permeated through excised skin in a zero-order kinetic in 48 h. The release of ISDN from ISDN-TDS can last 72 h at least. The mean permeation rate is 13.76 micrograms.h-1/cm2. Releasing ISDN from ISDN-TDS was more stable than that from Frandol tape-s whose release profile was found to follow a linear Q vs t1/2 relationship with a release flux of 114.39 micrograms.h-1/cm2.
Asunto(s)
Dinitrato de Isosorbide/administración & dosificación , Administración Cutánea , Animales , Sistemas de Liberación de Medicamentos , Cobayas , Técnicas In Vitro , Absorción CutáneaRESUMEN
A sensitive and rapid high-performance liquid chromatographic method has been developed for the determination of diclofenac in human serum. The average recovery of diclofenac was 98.2% to 102.5%. The relative standard deviation was 1.29% to 4.52%. The calibration curve was linear in the range from 0.2 microgram/ml to 10.0 micrograms/ml with r = 0.9999. The detection limit of the method was 10 ng/ml. The serum drug concentration-time curve exhibited a 1-compartment open model and the mean T1/2 was 2.15 h.
Asunto(s)
Diclofenaco/farmacocinética , Adulto , Cromatografía Líquida de Alta Presión/métodos , Diclofenaco/sangre , Femenino , Humanos , MasculinoRESUMEN
To investigate the expression of mutant p53 protein (mP53) and alpha-fetoprotein (AFP) during hepatocarcinogenesis, we detected immunohistochemically the specimens from 4 cases of normal human liver, 5 of cirrhosis, 5 of adenomatous hyperplasia (AH), and 16 of hepatocellular carcinoma (HCC) (by Edmondson classification. The 4 cases with normal liver showed negative mP53 and AFP. Four of the 5 cirrhosis cases were positive for mP53 and AFP. In 5 AH cases, 4 were positive for mP53 and AFP. In the 4 cases of grade I HCC, 2 were positive for mP53 and AFP. In the 6 cases of grade II HCC, 4 were positive for mP53 and AFP. In the 6 cases of grade III HCC, 1 showed mP53 positive staining but negative AFP, and 2 were negative for mP53 but positive for AFP, while 3 were negative for both mP53 and AFP. The results indicated that the mutation of p53 gene occurred in the early stage of hepatocarcinogenesis, and may be correlated with the initiation of hepatocarcinogenesis, and that mutant p53 protein probably related to the reactivation of AFP gene.
Asunto(s)
Carcinoma Hepatocelular/genética , Genes p53 , Neoplasias Hepáticas/genética , Mutación , alfa-Fetoproteínas/biosíntesis , Adulto , Anciano , Femenino , Eliminación de Gen , Expresión Génica , Humanos , Cirrosis Hepática/genética , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , alfa-Fetoproteínas/genéticaRESUMEN
OBJECTIVE: To investigate the effect of apolipoprotein E (ApoE) gene polymorphism on lipid metabolism among renal transplant recipients before and after transplantation. No prisoners or organs from prisoners were used in this study. METHODS: ApoE gene polymorphism was detected with polymerase chain reaction-restriction fragment length polymorphism; serum lipid levels were measured with biochemical methods. RESULTS: Serum lipid levels in the recipients were increased significantly at 3 months after renal transplantation, and further elevated at 6 months and 1 year. The recipients with higher total serum cholesterol (TC) and triglyceride (TG) levels only accounted for 2.9% and 7.6%, respectively, before renal transplantation; but for 28.6% and 46.7%, respectively, at 3 months (P < .01); 40.0% and 59.0% at 6 months; and 42.9% and 62.9% at 12 months. ApoE gene polymorphism showed no statistical difference in ApoE allele or ApoE genotype between the control and the study groups. The effect of ApoE genotype on serum lipid levels was different between controls and recipients either before or after renal transplantation. The levels of serum TC, TG, low-density lipoprotein cholesterol, ApoB, ApoE were: (ε)2/2+(ε)2/3; (ε)3/3; (ε)3/4+(ε)4/4 from low to high in controls and recipients before transplantation, but the levels of TG and ApoE reversed among recipients after renal transplantation. CONCLUSION: Renal transplant recipients are liable to develop hyperlipidemia, particularly hypertriglyceridemia among recipients with ApoE genotypes (ε)2/2 or (ε)2/3.
Asunto(s)
Apolipoproteínas E/genética , Trasplante de Riñón/fisiología , Lípidos/sangre , Polimorfismo Genético , Adulto , Apolipoproteína A-I/genética , Apolipoproteínas B/genética , Colesterol/sangre , Cartilla de ADN , Femenino , Genotipo , Humanos , Hiperlipidemias/epidemiología , Hiperlipidemias/genética , Lipoproteína(a)/genética , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Valores de Referencia , Triglicéridos/sangreRESUMEN
AIM: To study the effects of simvastatin (Sim) on pharmacokinetics of ciclosporin (Cic). METHODS: Seven healthy young volunteers took Cic 100 mg alone or in combination with Sim 10 mg in a randomized crossover study. The Cic concentrations in blood were determined by specific fluorescence polarization immunoassay. Data were analyzed with 3P87 program. RESULTS: The blood concentration-time curve was fitted to open 2-compartment model, and the pharmacokinetic parameters of Cic alone and Cic + Sim were: Cmax (646 +/- 94) and (698 +/- 340) micrograms.L-1; Tmax (1.12 +/- 0.13) and (1.13 +/- 0.21) h; AUC (2.3 +/- 0.4) and (2.6 +/- 1.2) mg.h.L-1; T1/2 beta (12 +/- 6) and (23 +/- 8) h (P < 0.05). CONCLUSION: Sim delays the metabolism rate of Cic when they are given simutaneously.