RESUMO
<p><b>OBJECTIVE</b>To evaluate the possible vascular effects of an environment carcinogen benzo(a)pyrene (BaP).</p><p><b>METHODS</b>The cytotoxicit of BaP and rat liver S9 (0.25 mg/mL)-activated BaP were examined by MTT assay. Thoracic aortic rings were dissected from Sprague-Dawley rats. Contraction of aortic rings was induced by 60 mmol/L KCl or 10(-6) mol/L phenylephrine (PE) in an ex-vivo perfusion system after BaP (100 μmol/L) incubation for 6 h. [Ca(2+)](i) was measured using Fluo-4/AM. For in-vivo treatment, rats were injected with BaP for 4 weeks (10 mg/kg, weekly, i.p.).</p><p><b>RESULTS</b>BaP (1-500 μm) did not significantly affect cell viability; S9-activated BaP stimulated cell proliferation. BaP did not affect the contractile function of endothelium-intact or -denuded aortic rings. BaP did not affect ATP-induced ([Ca(2+)](i)) increases in human umbilical vein endothelial cells. In BaP-treated rats, heart rate and the number of circulating inflammatory cells were not affected. Body weight decreased while blood pressure increased significantly. The maximum aortic contractile responses to PE and KCl and the maximum aortic relaxation response to acetylcholine were significantly decreased by 25.0%, 34.2%, and 10.4%, respectively.</p><p><b>CONCLUSION</b>These results suggest, in accordance with its DNA-damaging properties, that metabolic activation is a prerequisite for BaP-induced cardiovascular toxicity.</p>
Assuntos
Animais , Humanos , Masculino , Ratos , Aorta , Benzo(a)pireno , Farmacologia , Cálcio , Metabolismo , Células Endoteliais , Metabolismo , VasoconstriçãoRESUMO
<p><b>AIM</b>To investigate whether adriamycin induces DNA damage and the formation of gammaH2AX (the phosphorylated form of histone H2AX) foci in mature spermatozoa.</p><p><b>METHODS</b>Human spermatozoa were treated with adriamycin at different concentrations. gammaH2AX was analyzed by immunofluorescent staining and flow cytometry and double-strand breaks (DSB) were detected by the comet assay.</p><p><b>RESULTS</b>The neutral comet assay revealed that the treatment with adriamycin at 2 microg/mL for different times (0.5, 2, 8 and 24 h), or for 8 h at different concentrations (0.4, 2 and 10 microg/mL), induced significant DSB in spermatozoa. Immunofluorent staining and flow cytometry showed that the expression of gH2AX was increased in a dose-dependent and time-dependant manner after the treatment of adriamycin. Adriamycin also induced the concurrent appearance of DNA maintenance/repair proteins RAD50 and 53BP1 with gammaH2AX in spermatozoa. Wortmannin, an inhibitor of the phosphatidylinositol 3-kinase (PI3K) family, abolished the co-appearance of these two proteins with gammaH2AX.</p><p><b>CONCLUSION</b>Human mature spermatozoa have the same response to DSB-induced H2AX phosphorylation and subsequent recruitment of DNA maintenance/repair proteins as somatic cells.</p>
Assuntos
Humanos , Masculino , Androstadienos , Farmacologia , Antibióticos Antineoplásicos , Farmacologia , Células Cultivadas , Ensaio Cometa , Quebras de DNA de Cadeia Dupla , Dano ao DNA , Enzimas Reparadoras do DNA , Metabolismo , Proteínas de Ligação a DNA , Metabolismo , Doxorrubicina , Farmacologia , Interações Medicamentosas , Citometria de Fluxo , Histonas , Metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Metabolismo , Fosforilação , Inibidores de Proteínas Quinases , Farmacologia , Espermatozoides , Biologia Celular , Metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chromatography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharmacokinetic parameters. The mean C(max), t(max), and AUC((0-12))were (21.88+/-10.52) microg/ml, (1.20+/-0.95) h, and (52.546+/-13.215) microg.h/ml, respectively. The level of AUC((0-12)) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC((0-12)) showed statistically significant difference according to the patient's gender.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ciclosporina , Imunossupressores , Farmacocinética , Transplante de Rim , Fisiologia , Ácido Micofenólico , Farmacocinética , TacrolimoRESUMO
<p><b>OBJECTIVE</b>To study the determination of desloratadine in human serum and its pharmacokinetics in healthy volunteers.</p><p><b>METHODS</b>A single oral dose of 10 mg desloratadine was given to 18 healthy volunteers. The serum concentrations of desloratadine were determined by HPLC-MS assay. The pharmacokinetics parameters of desloratadine tablets were calculated with program 3P97.</p><p><b>RESULT</b>The main pharmacokinetics parameters of desloratadine tablets were as followsút(max)(1.611 +/-0.366)h, C(max) (4.455+/-1.990)microg x L(-1), AUC(0-t) (58.50+/-21.34)microg x L(-1) x h(-1), AUC(0-infinity) (60.59+/-22.32)microg x L(-1) x h(-1), t(1/2(ke)) (20.303+/-5.833)h, Ke (0.0372+/-0.0116)h(-1) and CL(0.1838+/-0.0563)L x h(-1).</p><p><b>CONCLUSION</b>Desloratadine tablet is absorbed quicker in the 18 healthy volunteers than the reports and its peak blood concentration reached at 1.5 h after oral administration with t(1/2) 20 h.</p>