RESUMEN
AIM: To investigate the inhibitory effects on gastric acid secretion of three proton pump inhibitors, omeprazole, lansoprazole and rabeprazole, using a three-way crossover design in healthy Helicobacter pylori-negative,S-mephenytoin 4'-hydroxylase (CYP2C19) homo- and hetero-extensive metabolizers. METHODS: Eight healthy Japanese male volunteers were enrolled. After the administration of rabeprazole (10 mg/day), lansoprazole (30 mg/day) or omeprazole (20 mg/day), intragastric pH monitoring was commenced from 24 h before the first proton pump inhibitor dose, and continued for days 1-3 after proton pump inhibitor administration. The pH electrode was used for 48 h and changed just before pH monitoring on day 2. RESULTS: For the administration of 10 mg/day rabeprazole, the mean ratios of the 24-h pH > or = 3 holding time were 5.7 +/- 1.1%,13.6 +/- 2.2%, 35.3 +/- 2.7% and 62.8 +/- 3.1% for the pre-treatment day and days 1, 2 and 3, respectively. The same ratios for lansoprazole (30 mg/day) were 5.7 +/- 0.7%, 7.4 +/- 1.5%, 13.6 +/- 3.4% and 26.6 +/- 4.9%; the same ratios for 20 mg/day omeprazole were 5.9 +/- 0.9%, 6.1 +/- 1.2%, 11.4 +/- 2.8% and 16.4 +/- 4.6%. The mean ratio of the 24-h pH > or = 3 holding time of days 1-3 increased significantly compared to the pre-treatment day (P < 0.01) with the administration of rabeprazole and lansoprazole. The magnitude of inhibition of gastric acid secretion after rabeprazole administration was stronger than that after lansoprazole. A significant elevation of the mean ratio of the 24-h pH > or = 3 holding time was demonstrated on days 2 and 3 with omeprazole (P < 0.01). CONCLUSIONS: In H. pylori-negative CYP2C19 extensive metabolizers, rabeprazole (10 mg/day) shows a faster onset of rising intragastric pH and a stronger inhibition of gastric acid secretion than do lansoprazole (30 mg/day) or omeprazole (20 mg/day).
Asunto(s)
Antiulcerosos/farmacología , Hidrocarburo de Aril Hidroxilasas/genética , Ácido Gástrico/metabolismo , Oxigenasas de Función Mixta/genética , Omeprazol/análogos & derivados , Inhibidores de la Bomba de Protones , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Bencimidazoles/farmacología , Ritmo Circadiano , Estudios Cruzados , Citocromo P-450 CYP2C19 , Determinación de la Acidez Gástrica , Genotipo , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Lansoprazol , Masculino , Persona de Mediana Edad , Omeprazol/farmacología , RabeprazolAsunto(s)
Giardiasis/complicaciones , Hemorragia/etiología , Síndromes de Malabsorción/etiología , Vitamina K/metabolismo , Animales , Anticoagulantes/efectos adversos , Diagnóstico Diferencial , Femenino , Giardia lamblia , Giardiasis/diagnóstico , Giardiasis/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Warfarina/efectos adversosRESUMEN
Alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and P450IIE1 are the primary enzymes that catalyze the conversion of ethanol to acetaldehyde and then to acetate. Genetic polymorphisms have been reported in ADH2, ADH3, ALDH2, and the 5'-flanking region of P450IIEI. In this study, we used multivariate analysis to determine which genetic polymorphisms in alcohol metabolizing enzymes were independently associated with the development of alcoholic cirrhosis. Thirty-four noncirrhotic alcoholic patients, including 27 with fatty liver and 7 with nonspecific changes, and 46 patients with alcoholic liver cirrhosis were studied. Restriction fragment length polymorphisms (RFLPs) in the ADH2 and P450IIE1 genes were detected by digestion of polymerase chain reaction (PCR)-amplified DNA with MaeIII and RsaI, respectively. In the ALDH2 gene, RFLPs were detected by differences in the MboII site after PCR amplification. By multivariate analysis of four significant factors including total alcohol intake, ADH, ALDH, and P450IIE1 using the multiple logistic regression model, genotype ADH2(2)/ADH2(2) (P = .029) and genotype c1/c1 of P450IIE1 (P = .013) were found to be independently associated with alcoholic cirrhosis. The odds ratios for ADH2(2)/ADH2(2) genotype and the type A genotype of P450IIE1 (c1/c1) were 4.600 and 4.006, respectively. These results suggest that ADH2 and P450IIE1 gene polymorphisms may be independently associated with the development of alcoholic liver cirrhosis in Japan.
Asunto(s)
Alcohol Deshidrogenasa/genética , Aldehído Deshidrogenasa/genética , Sistema Enzimático del Citocromo P-450/genética , Cirrosis Hepática Alcohólica/genética , Oxidorreductasas N-Desmetilantes/genética , Polimorfismo de Longitud del Fragmento de Restricción , Adulto , Anciano , Citocromo P-450 CYP2E1 , Desoxirribonucleasas de Localización Especificada Tipo II , Genotipo , Humanos , Japón , Cirrosis Hepática Alcohólica/enzimología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Reacción en Cadena de la PolimerasaRESUMEN
The urinary levels of L-fucose were measured in 93 alcoholics; 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease (p < 0.001). The urinary L-fucose level was also significantly higher (p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 +/- 97 vs. 240 +/- 95 mumol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 +/- 29 vs. 155 +/- 60 mumol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 +/- 97 mumol/g of creatinine) than with viral cirrhosis (265 +/- 42 mumol/g of creatinine) (p < 0.001). The measurement of urinary L-fucose may be a useful marker of alcoholic liver disease.
Asunto(s)
Fucosa/orina , Hepatopatías Alcohólicas/diagnóstico , Adulto , Anciano , Biomarcadores/orina , Biopsia , Humanos , Hígado/patología , Cirrosis Hepática Alcohólica/diagnóstico , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Alcohólica/orina , Hepatopatías Alcohólicas/patología , Hepatopatías Alcohólicas/orina , Pruebas de Función Hepática , Masculino , Persona de Mediana EdadRESUMEN
Serum levels of carbohydrate-deficient transferrin (CDT) were assayed in 87 patients with alcoholic liver disease, 25 alcoholics without liver disease, 25 cases with viral liver disease and 37 healthy subjects, by two different methods (Pharmacia CDT RIA kit and Axis % CDT kit). The serum level of Pharmacia-CDT was significantly higher in the patients with alcoholic liver disease (38.9 +/- 2.8 U/l) compared to the normal subjects (18.9 +/- 0.2 U/l), alcoholics without liver disease (21.7 +/- 1.5 U/l) and non-alcoholic liver disease (viral liver disease) (23.4 +/- 1.6 U/l) (P < 0.001). The serum level of Axis-CDT was also significantly higher in the patients with alcoholic liver disease (4.22 +/- 0.48%) compared to the normal subjects (0.84 +/- 0.14%), alcoholics without liver disease (1.14 +/- 0.23%) and non-alcoholic liver disease (1.84 +/- 0.29%) (P < 0.001). A significant correlation was found between serum levels of CDT determined by the two kits (r = 0.718, P < 0.001). The serum level of Axis-CDT was significantly higher in patients with alcoholic hepatitis compared to the normal subjects (P < 0.005), while the serum level of Pharmacia-CDT was not increased in the patients with alcoholic hepatitis. These results indicate that determination of serum CDT levels is a useful marker of alcoholic liver disease, not a marker for alcohol consumption. Axis-CDT is more useful than Pharmacia-CDT for assaying the serum level of CDT in patients with alcoholic liver disease.
Asunto(s)
Hepatopatías Alcohólicas/diagnóstico , Transferrina/análogos & derivados , Adulto , Anciano , Biomarcadores/sangre , Cromatografía por Intercambio Iónico , Femenino , Hepatitis Crónica/sangre , Hepatitis Crónica/diagnóstico , Hepatitis Viral Humana/sangre , Hepatitis Viral Humana/diagnóstico , Humanos , Cirrosis Hepática Alcohólica/sangre , Cirrosis Hepática Alcohólica/diagnóstico , Hepatopatías Alcohólicas/sangre , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Juego de Reactivos para Diagnóstico , Transferrina/análisisRESUMEN
Sixty-three patients with alcoholic cirrhosis were retrospectively studied for the prevalence of antibodies to core (P22) and nonstructural (C100) region of hepatitis C virus (HCV). The prevalence rate of anti-P22 antibodies in patients with alcoholic cirrhosis was higher than that of anti-C100 antibodies (63.5% vs. 54.9%). The positivity rate of anti-C100 and/or anti-P22 antibodies was 73.0% (46/63) in alcoholic cirrhosis. We performed a multivariate analysis on the effects of age, sex, cumulative alcohol intake, anti-HCV antibodies, indocyanine green excretion test, and serum albumin on the development of hepatocellular carcinoma HCC in patients with cirrhosis, using Cox's proportional-hazards model, which revealed that anti-HCV positivity was the only independent prognostic variable for HCC in patients with alcoholic cirrhosis. The probability of HCC was significantly higher in the anti-HCV-positive patients than in the negative patients with alcoholic cirrhosis (p < 0.05). The 3-, 5- and 10-yr cumulative occurrence rate of HCC was, respectively, 13.3%, 41.3%, and 80.7% for anti-HCV-positive patients with alcoholic cirrhosis, compared with 0%, 8.3%, and 18.5% for anti-HCV-negative patients. In nonalcoholic patients with type C cirrhosis, the 3-, 5-, and 10-yr cumulative occurrence rate of HCC was 7.3%, 23.1%, and 56.5%, respectively. The follow-up studies indicate that hepatocarcinogenesis is hastened significantly in patients with alcoholic cirrhosis if they are positive for anti-HCV antibody, and that heavy alcohol consumption also is a risk factor for the development of HCC in patients with type C cirrhosis.
Asunto(s)
Antígenos Virales , Carcinoma Hepatocelular/epidemiología , Hepatitis C/complicaciones , Cirrosis Hepática Alcohólica/complicaciones , Neoplasias Hepáticas/epidemiología , Proteínas no Estructurales Virales , Adulto , Anciano , Carcinoma Hepatocelular/etiología , Femenino , Estudios de Seguimiento , Hepacivirus/inmunología , Anticuerpos Antihepatitis/análisis , Hepatitis C/diagnóstico , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C , Antígenos de la Hepatitis C , Humanos , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Pruebas Serológicas , Proteínas del Núcleo Viral/inmunología , Proteínas Virales/inmunologíaAsunto(s)
Hepatopatías Alcohólicas/epidemiología , Adulto , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
The relationship between serum concentration of inorganic fluoride (F(-)) and cytochrome P-450 content after sevoflurane anesthesia was investigated in ethanol treated rats. Twenty male Wistar rats were randomly divided into 2 isocaloric diet groups of 10 rats each: one group receiving a standard diet and the other an ethanol diet. After 28 days on the diets the animals were administered 2.5% sevoflurane for 2 hr with 30% oxygen and 70% nitrous oxide. Cytochrome P-450 and cytochrome b(5) were induced by the ethanol diet. In the ethanol diet group serum concentration of F(-) was significantly higher than that of the standard diet group after sevoflurane anesthesia. These results suggest that cytochrome P-450 and b(5), which were induced by ethanol, enhanced sevoflurane defluorination.
RESUMEN
Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.