Factor VII as a marker of hepatocellular synthetic function in liver disease.
(9/4731)
Factor VII levels have been measured in 100 patients with liver disease following parenteral vitamin K1 therapy. There was good agreement between specific factor VII measurements and the one-stage prothrombin time apart from six patients with compensated cirrhosis in whom the prothrombin time was prolonged despite the presence of normal factor VII levels. A mean activity of 58% was found in patients with cirrhosis. Cirrhotic patients with features of hepatic decompensation had a significantly lower mean level of activity (40%) than the "contrast" patients with surgical obstruction of the major bile ducts (93%). Patients with chronic active liver disease had moderate depression of factor VII levels and those with non-cirrhotic liver damage had mean activities similar to the contrast group. Factor VII levels could not be correlated with BSP retention but there was a correlation with serum albumin concentration. It is concluded that the prothrombin time using Quick test with a standardized thromboplastin showing good sensitivity to factor VII, eg, the Manchester reagent (BCT), provides a reliable index of coagulability in chronic liver disease, and specific factor VII assays are not indicated. (+info)
An interpretation of the serum alkaline phosphatase isoenzyme patterns in patients with obstructive liver disease.
(10/4731)
Earlier studies have identified two main isoenzymes of alkaline phosphatase in the sera of patients with obstructive liver disease. This paper reports on a study of these isoenzymes in specific types of liver disease where the pathology in relation to bile duct obstruction is known. The results have been used to support the theory that in biliary obstruction the increase in serum alkaline phosphatase is in part due to regurgitation of the biliary isoenzymes. (+info)
Regulation of fatty acid homeostasis in cells: novel role of leptin.
(11/4731)
It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes, thus protecting them from lipotoxicity. The fact that TG content in nonadipocytes normally remains within a narrow range, while that of adipocytes varies enormously with food intake, is consistent with a system of TG homeostasis in normal nonadipocytes. The facts that when leptin receptors are dysfunctional, TG content in nonadipocytes such as islets can increase 100-fold, and that constitutively expressed ectopic hyperleptinemia depletes TG, suggest that leptin controls the homeostatic system for intracellular TG. The fact that the function and viability of nonadipocytes is compromised when their TG content rises above or falls below the normal range suggests that normal homeostasis of their intracellular TG is critical for optimal function and to prevent lipoapoptosis. Thus far, lipotoxic diabetes of fa/fa Zucker diabetic fatty rats is the only proven lipodegenerative disease, but the possibility of lipotoxic disease of skeletal and/or cardiac muscle may require investigation, as does the possible influence of the intracellular TG content on autoimmune and neoplastic processes. (+info)
Quantitative study of the variability of hepatic iron concentrations.
(12/4731)
BACKGROUND: The hepatic iron concentration (HIC) is widely used in clinical practice and in research; however, data on the variability of HIC among biopsy sites are limited. One aim of the present study was to determine the variability of HIC within both healthy and cirrhotic livers. METHODS: Using colorimetric methods, we determined HIC in multiple large (microtome) and small (biopsy-sized) paraffin-embedded samples in 11 resected livers with end-stage cirrhosis. HIC was also measured in multiple fresh samples taken within 5 mm of each other ("local" samples) and taken at sites 3-5 cm apart ("remote" samples) from six livers with end-stage cirrhosis and two healthy autopsy livers. RESULTS: The within-organ SD of HIC was 13-1553 microg/g (CV, 3.6-55%) for microtome samples and 60-2851 microg/g (CV, 15-73%) for biopsy-sized samples. High variability of HIC was associated with mild to moderate iron overload, because the HIC SD increased with increasing mean HIC (P <0.002). Livers with mean HIC >1000 microg/g exhibited significant biological variability in HIC between sites separated by 3-5 cm (remote sites; P <0.05). The SD was larger for biopsy-sized samples than for microtome samples (P = 0.02). CONCLUSION: Ideally, multiple hepatic sites would be sampled to obtain a representative mean HIC. (+info)
Liver disease in pregnancy.
(13/4731)
Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy. (+info)
Effect of central corticotropin-releasing factor on carbon tetrachloride-induced acute liver injury in rats.
(14/4731)
Central neuropeptides play important roles in many instances of physiological and pathophysiological regulation mediated through the autonomic nervous system. In regard to the hepatobiliary system, several neuropeptides act in the brain to regulate bile secretion, hepatic blood flow, and hepatic proliferation. Stressors and sympathetic nerve activation are reported to exacerbate experimental liver injury. Some stressors are known to stimulate corticotropin-releasing factor (CRF) synthesis in the central nervous system and induce activation of sympathetic nerves in animal models. The effect of intracisternal CRF on carbon tetrachloride (CCl4)-induced acute liver injury was examined in rats. Intracisternal injection of CRF dose dependently enhanced elevation of the serum alanine aminotransferase (ALT) level induced by CCl4. Elevations of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels by CCl4 were also enhanced by intracisternal CRF injection. Intracisternal injection of CRF also aggravated CCl4-induced hepatic histological changes. Intracisternal CRF injection alone did not modify the serum ALT level. Intravenous administration of CRF did not influence CCl4-induced acute liver injury. The aggravating effect of central CRF on CCl4-induced acute liver injury was abolished by denervation of hepatic plexus with phenol and by denervation of noradrenergic fibers with 6-hydroxydopamine treatment but not by hepatic branch vagotomy or atropine treatment. These results suggest that CRF acts in the brain to exacerbate acute liver injury through the sympathetic-noradrenergic pathways. (+info)
Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy.
(15/4731)
AIMS: To evaluate the reliability of the omeprazole hydroxylation index as a marker for polymorphic CYP2C19 activity in a Japanese population of healthy young subjects (n = 78) and patients with peptic ulcer (n = 72). METHODS: Healthy subjects were administered a single dose of omeprazole (20 mg), whereas patients received 20 mg daily for at least 1 week. The ratio of the serum concentration of omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant alleles associated with the poor metaboliser phenotype of (S)-mephenytoin, CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in the initial codon were analysed. RESULTS: In the healthy volunteer study there was complete concordance between genotype and phenotype. However, eight of the patients who had the EM genotype had a high value for their hydroxylation index, and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were detected in the eight mismatched patients. They were all genotypic heterozygous EMs, elderly (> or = 65 years) and/or had hepatic disease. Therefore, impaired CYP2C19 activity combined with partial saturation of omeprazole metabolism during multiple dosing may have contributed to the discrepancy between CYP2C19 genotyping and phenotyping. CONCLUSION: Although omeprazole has been used instead of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be reliable enough for clinical application in Japanese patients. (+info)
Production of specific monoclonal antibodies to Aspergillus species and their use in immunohistochemical identification of aspergillosis.
(16/4731)
Two anti-Aspergillus murine monoclonal antibodies (MAbs), designated 164G and 611F, have been produced; both specifically recognize cytoplasmic antigens of A. fumigatus, A. flavus, and A. niger by enzyme-linked immunosorbent assay. The MAbs can identify Aspergillus spp. both in frozen sections by immunofluorescence and in paraffin-embedded clinical specimens by immunofluorescence and immunoperoxidase staining. (+info)