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1.
Lab Anim ; 42(4): 495-504, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18840618

RESUMEN

The purpose of this study was to investigate the galactose single point (GSP) method, a residual liver function test recently recommended by the US Food and Drug Administration, which can be a useful tool for rat liver function measurement. Rats were treated either with carbon tetrachloride (CCl(4)) alone (1 mL/kg, intraperitoneally [i.p.]) for one day or with isoniazid (INH) alone (150 mg/kg, i.p.) or (in order to ameliorate the effects of INH) with a combination of INH and bis-p-nitrophenyl phosphate (BNPP) (25 mg/kg, i.p.) for 21 days. Hepatotoxicity was assayed by plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and scores of histological activity index-necroinflammation (HAI-NI) of the respective liver specimens. The GSP method in rats was defined by the galactose blood level after 60 min. Significant differences in GSP values were observed between controls and the CCl(4)-treated rats. After 21 days of treatment, no significant changes in AST and ALT values were observed among the control, INH and INH-BNPP groups. There were significant differences in average GSP values for controls (P < 0.001) and INH-BNPP (P < 0.001) compared with INH alone. Highly significant correlations (P < 0.001) were obtained between GSP and scores of HAI-NI for all the groups. GSP was concluded to be a more sensitive biomarker of INH-induced hepatotoxicity than AST or ALT in the rats. The GSP method has been proved to be a simple and useful tool for the quantitative determination of liver function in rats, which can possibly be extended to other animals.


Asunto(s)
Galactosa/sangre , Pruebas de Función Hepática/veterinaria , Hígado/metabolismo , Alanina Transaminasa/sangre , Animales , Animales de Laboratorio , Aspartato Aminotransferasas/sangre , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Histocitoquímica/veterinaria , Isoniazida , Hepatopatías/sangre , Pruebas de Función Hepática/métodos , Masculino , Ratas , Ratas Sprague-Dawley
2.
Anaesthesia ; 58(10): 951-6, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12969036

RESUMEN

The aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular-bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51-73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (CIsev) during the first hour of anaesthesia. During constant volume-controlled ventilation, we measured CIsev and end-tidal sevoflurane (CEsev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both CIsev-CEsev and Asev-PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near-constant uptake into the body.


Asunto(s)
Anestésicos por Inhalación/farmacocinética , Encéfalo/metabolismo , Éteres Metílicos/farmacocinética , Anciano , Anestesia General , Anestésicos por Inhalación/sangre , Cromatografía de Gases , Puente de Arteria Coronaria , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Éteres Metílicos/sangre , Persona de Mediana Edad , Sevoflurano , Distribución Tisular
3.
Br J Anaesth ; 92(5): 712-5, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15003978

RESUMEN

BACKGROUND: A long-acting analgesic may be particularly desirable in patients suffering from long-lasting pain. The aim of the study was to evaluate the antinociceptive effect of a novel nalbuphine preparation and to determine its duration of action. METHODS: The antinociceptive effects of i.m. nalbuphine HCl in saline and nalbuphine base in sesame oil were evaluated in rats. The in vitro drug-releasing profiles of nalbuphine HCl and base in different preparations were also evaluated. RESULTS: We found that i.m. nalbuphine HCl 25, 50 and 100 micromol kg(-1) produced dose-related antinociceptive effects with a duration of action of 1.5, 2 and 3 h, respectively. i.m. nalbuphine base 100, 200 and 400 micromol kg(-1) also produced dose-related antinociceptive effects but with longer durations of action: 27, 49 and 55 h, respectively. In vitro studies demonstrated that nalbuphine base in sesame oil had the slowest drug-releasing profile of the different preparations. CONCLUSIONS: i.m. injection of an oil formulation of nalbuphine base produced a long-lasting antinociceptive effect.


Asunto(s)
Analgésicos Opioides/farmacología , Nalbufina/farmacología , Analgésicos Opioides/administración & dosificación , Animales , Química Farmacéutica , Relación Dosis-Respuesta a Droga , Excipientes , Inyecciones Intramusculares , Masculino , Nalbufina/administración & dosificación , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Aceite de Sésamo , Cloruro de Sodio
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