RESUMEN
Within an open, non-randomized clinical study, the authors investigated the effect of a three-month therapy by a standard product of so-called essential phospholipids in a group of patients (31 men and 2 women, average age being 45.6 +/- 10.8 years) with toxic liver damage--steatosis and steatohepatitis which have developed after exposure to the polychlorinated phenols and cresols, or other potentially toxic chemical substances occurring in working environment and/or exposition to alcohol. The therapy included a recommended change in life routine with a decrease in alcohol consumption, or entire exclusion of alcohol abuse. Within the process of observation, the authors used non-invasive methods (clinical examinations, laboratory examinations, ultrasonographic examination). A special attention was paid to the evaluation of the biotransformation capacity the liver and the assessment of spartein-debrisoquin-dextromethorphan metabolic fenotype. The results of investigation indicated: (1) significant improvement of the subjective status of the treated patients associated with an improvement of ultrasonographic findings of liver steatosis, trend of withdrawal of biochemical activity indices and favourable development of the biotransformation capacity of the liver in a majority of the investigated patients. (2) A very good tolerance of the administered drug without adverse effects. The use of non-invasive surrogate markers in coincidence with clinical investigation of the effect of applied medicamentous therapy in patients with chronic liver diseases represents a methodic increase in current modest options of evaluation of effectively and safety of the new therapeutic procedures in clinical hepato-pharmacology. (Tab. 5, Ref. 42.)
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Hígado Graso/terapia , Enfermedades Profesionales/terapia , Fosfatidilcolinas/uso terapéutico , Templanza , Adulto , Anciano , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Hígado Graso/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamenteRESUMEN
The aim of this study was to estimate the occurrence of the phenotype of poor metabolizers of sparteine (in the frame of sparteine-debrisoquine-dextromethorphane polymorphism) in Slovakia. The authors examined a group of 216 of healthy volunteers (73 women and 143 men, average age of the group 24, 9 +/- 0.4 years), university students coming from various regions of Slovakia. The test substance-sparteine (1 x 100 mg tbl.) was administered perorally to all probands, in the evening after fasting. A 12-hour gathering of urine was subsequently performed. A sample of urine was subdued to examination. Isolation, separation, identification and assessment of the concentration of sparteine and its metabolites (2- and 5-dehydrosparteine) were performed by the method of gas chromatography. The metabolic MR ratio calculated from the ratio of the detected concentrations of sparteine and (2- and 5-dehydrosparteine) served for the assessment of the phenotype of poor (MR > 20), or rapid (MR < 20) metabolizers of sparteine in 8 authors found the poor metabolizer phenotype of 216 examined probands (i.e. in 3.75%). Its prevalence of the presented phenotype was lower than that anticipated on the basis of epidemiologic studies performed in other European countries. Study represents the first data on the phenotype of poor sparteine metabolizers in Slovakia. (Tab. 4, Fig. 1, Ref. 24.)
Asunto(s)
Polimorfismo Genético , Esparteína/metabolismo , Adulto , Femenino , Humanos , Masculino , Oxidación-Reducción , Farmacogenética , Fenotipo , Valores de ReferenciaRESUMEN
Distribution of 14C-bendamustine following intravenous (i.v.) administration to mice was examined by whole body autoradiographic (WBAR) and quantitative techniques. The WBAR study showed that 14C-bendamustine-derived radioactivity was distributed extremely unevenly at each time interval investigated. After 5 min of administration the highest density of radioactive material was found in the liver and in the kidney. At all time intervals investigated the brain remained free of the label. In a detailed quantitative distribution study it was found that 14C-bendamustine-derived radioactivity was also unevenly distributed throughout the mouse tissues. At 5 min postdosing the level of 14C was by one order higher in the liver and in the kidney in comparison to the lungs, heart, spleen, and muscle. The results of both WBAR and quantitative tissue distribution studies suggest that bendamustine was selectively taken up from the blood by liver and kidney tissues. Because of this pharmacokinetic property, dose modification should be taken into consideration when administering the drug to patients suffering from hepatobiliary and kidney disorders.
Asunto(s)
Antineoplásicos/farmacocinética , Riñón/metabolismo , Hígado/metabolismo , Compuestos de Mostaza Nitrogenada/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/sangre , Autorradiografía , Clorhidrato de Bendamustina , Radioisótopos de Carbono , Inyecciones Intravenosas , Marcaje Isotópico , Masculino , Ratones , Compuestos de Mostaza Nitrogenada/administración & dosificación , Compuestos de Mostaza Nitrogenada/sangre , Estándares de Referencia , Distribución Tisular , Recuento Corporal TotalRESUMEN
Chlorinated phenols are widely used in the manufacture of biocides and wood preservatives. 2,4-dichlorophenol administered perorally 3 times a week at a dose of 40 mg in 0.2 ml of olive oil per kg of body weight to guinea pigs increased lipid peroxidation in liver and adrenals after 2 weeks of treatment. A high intake of ascorbic acid (50 mg/animal/day) significantly decreased lipid peroxidation in the liver of 2, 4-dichlorophenol treated guinea pigs in comparison to guinea pigs with low ascorbic acid intake (2 mg/animal/day). 2,4-dichlorophenol accumulation was also decreased in the liver of animals with high ascorbic acid intake. Increased daily intake of vitamin C to persons involved in production and use of chlorophenoxy herbicides is recommended.
Asunto(s)
Ácido Ascórbico/farmacología , Clorofenoles/farmacología , Peroxidación de Lípido/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Análisis de Varianza , Animales , Cobayas , Hígado/metabolismo , Masculino , Análisis de RegresiónRESUMEN
A method is described for the isolation, derivatization, separation and determination of chlorinated phenols and cresols in urine. After acid hydrolysis, solid-phase extraction on Separcol SI C18 was used. Quantification was based on the internal standard method using 2,6-dibromophenol. Before GC determination the isolated compounds were derivatized with pentafluorobenzyl bromide. The separation of interfering substances followed on a Ekosorb column using elution with dichloromethane-toluene (15:85). The recovery of the method ranged from 72.3 +/- 9.9 to 109.9 +/- 6.3% and the limit of determination varied from 0.0005 to 0.002 micrograms ml-1. Using this method, 52 persons from occupationally and non-occupationally exposed groups were examined for the presence of chlorinated compounds in urine. The levels of chlorinated phenols and cresols were several times higher in the group of occupationally exposed workers, especially for 2,4-dichlorophenol.
Asunto(s)
Clorofenoles/orina , Cromatografía de Gases/métodos , Cresoles/orina , Industria Química , Diazometano , Fluorobencenos , Humanos , Metilación , Cloruro de Metileno , Exposición Profesional , ToluenoRESUMEN
A method is presented for the isolation, separation and determination of sparteine and its metabolites in urine. The isolation is based on rapid extraction with dichloromethane and pentane in a glass separator. For the separation and determination, capillary gas chromatography with nitrogen-phosphorus detection was used. The recovery of the method ranged from 81.6% to 94.8%, and the limit of determination varied between 0.2 and 0.5 microgram ml-1. For quantification, 17-ethylsparteine was used as the internal standard.