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PubMedDate not supplied

[The use of different liver-protective substances in the course of antitubercular chemotherapy and their effectiveness in preventing and countering the appearance of metabolic and functional liver changes Clinico-statistical studies].

An open study was run on three groups of hospitalised 40 patients with medium to serious lung TB to evaluate the effectiveness of generic liver protector drugs, UDPG, and an association of UDPG-GSH in the prevention a nd hindrance of organic and metabolic-functional liver alterations in the course of chemotherapy. It was found that UDPG--particularly in association with GSH--gave highly significant results by comparison with generic protector drugs.

Amino Acids↗
PubMedDate not supplied

Sensitivity and specificity of liver function tests in the detection of parenteral nutrition-associated cholestasis.

We carried out a study to determine which of the liver function tests was the most sensitive and/or specific in detecting parenteral nutrition associated cholestasis. The tests utilized were alkaline phosphatase, gamma-glutamyl transpeptidase, cholylglycine, sulfolithocholylglycine, and bilirubin. Fifty-nine patients with no prior evidence of liver dysfunction were studied. We found gamma-glutamyl transpeptidase to be the most sensitive (89.5%) and also the least specific (61.9% specificity). Specificity of gamma-glutamyl transpeptidase was improved when it was combined with alkaline phosphatase. We recommend the combination of these two enzymes as the most cost effective way of detecting parenteral nutrition-associated cholestasis.

Adult↗
PubMed1983

Diagnostic value of serum bile acids and routine liver function tests in hepatobiliary diseases. Sensitivity, specificity, and predictive value.

Total serum bile acids measured by enzymatic fluorometry and routine liver function tests were determined in a large population including 97 healthy subjects, 138 patients free of hepatobiliary diseases but affected by other diseases, and 344 patients with mild or severe hepatobiliary diseases. In order to define the diagnostic value and some operational characteristics of serum bile acids, sensitivity, specificity, and several predictive value tables for increasing cutoff levels of serum bile acids were calculated by means of a computer program. Serum bile acids and aspartate aminotransferase were found to be similar in sensitivity, specificity, and predictive value. Serum aspartate aminotransferase was found to be more suitable than serum bile acids in detecting mild hepatobiliary diseases, whereas serum bile acids were more sensitive than routine liver tests in the evaluation of severe hepatobiliary diseases. In view of its ability to detect severe hepatobiliary diseases, serum bile acids test may play a decisive role in clinical practice (eg, decision to perform a liver biopsy).

Adolescent↗
PubMedDate not supplied

The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function.

Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis. Caffeine and theophylline concentration were assayed by gas-chromatography and fluorescent polarization immunoassay, respectively. In normals the maximum theophylline levels were found between 3 and 8 hrs (62.5% at 8 hrs) and ranged 50-420 ng/ml, whereas these levels in cirrhotic patients were noted between 3 and 12 hrs (61.1% at 8 hrs) and ranged 40-670 ng/ml. The largest difference in mean theophylline concentration between normals and cirrhotics was found at 6 hrs (348 +/- 103.7 ng/ml vs 217.1 +/- 140.8 ng/ml; p less than 0.02) and 24 hrs (101.6 +/- 57.3 ng/ml vs 172.2 +/- 119.6 ng/ml; p = 0.075) after caffeine dosing. Theophylline formation rate (theo6) differentiated controls from cirrhotics in the initial stage of the disease (Child-Pugh A), however it failed to discriminate between initial and late cirrhosis. In contrast, the ability of liver to remove theophylline (theo24) differentiated effectively these groups of patients. Theo6 to theo24 ratio was a valuable index of liver function, although its capacity to detect early cirrhosis was unsatisfactory.

Adult↗
PubMed2002

Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver-specific gene expression.

Numerous studies have established the pivotal role of liver-enriched transcription factors in organ development and cellular function, and there is conclusive evidence for transcription factors to act in concert in liver-specific gene expression. During organ development and in progenitor cells the timely expression of certain transcription factors is necessary for cellular differentiation, and there is overwhelming evidence for hierarchical and cooperative principles in a networked environment of transcription factors. The search for molecular switches that control stem cell imprinting and liver-specific functions has lead to the discovery of many interactions between such different molecules as transcription factors, coactivators, corepressors, enzymes, DNA, and RNA. Many of these interactions either repress or activate liver-specific gene expression. It thus can be demonstrated that specific mutational changes in liver-enriched transcription factors lead to altered intermolecular interactions with the consequence of human disease. This review provides an overview of our current knowledge about liver-enriched transcription factors and their role in liver function and development. We review the basic principles of gene transcription, the role of liver-enriched transcription factors in liver gene regulation, and the classification of transcription factors by their DNA-binding domains.

Animals↗
PubMed1998

Correlation of endothelium-dependent and -independent vasodilatation with liver function tests during prolonged perfusion of the rat liver.

Twelve male Wistar rats were anaesthetized with pentobarbitone (3 mg 100g(-1) i.p.), the livers were excised and perfused in vitro through the hepatic artery and portal vein at constant flow rates of 0.32+/-0.01 (mean+/-S.E.) and 0.98+/-0.03 ml min(-1) g liver(-1), respectively. The tone of the preparation was raised by methoxamine (7.5 x 10(-6) M). Responses to mid-range doses of acetylcholine (-11 log mol) and sodium nitroprusside (-9 log mol) produced submaximal degrees of vasodilatation (-log mol ED50 = 12.18+/-0.08) and (-log mol ED50 = 9.95+/-0.23), respectively, which did not subside until 5.5 h of perfusion. These did not coincide with the increase in activities of lactic acid dehydrogenase (LDH) and aspartate serine transaminase (AST) activity at 2.5 h, which were indicative of hepatocellular mitochondrial and cytoplasmic damage, respectively. Vascular responses suggested that there was little deterioration in endothelial or smooth muscle function in the hepatic artery up to 5 h perfusion. This model can be reliably used to investigate endothelium-dependent and -independent vasodilators in vascular pharmacological studies of the rat liver although some minimal increases may occur in AST and LDH activity before hemodynamic changes appear at 5.5 h.

Acetylcholine↗
PubMed1998

Continuous calcium channel blocker infusion in experimentally induced acute pancreatitis: effects on pancreas and liver function.

In this study we examined the effects of continuous calcium channel blocker (CCB) infusion on pancreatic duct-ligated acute pancreatitis (AP) in rabbits. Thirty rabbits were used for this study. Animals in group 1 (n = 10), which served as a control group, underwent dummy operations and received 0.5 microliter/h normal saline via the internal jugular vein. Animals in group 2 (n = 10) with artificially-induced pancreatitis received the same dosage of saline in the same manner. Animals in group 3 (n = 10) with artificially-induced pancreatitis received 180 micrograms/kg/h CCB (Verapamil) via the jugular vein starting from just before pancreatic duct ligation. AP histology score, plasma amylase levels and liver function tests were measured after 48 h. Verapamil infusion did not prevent the rise in plasma amylase levels, nor did it prevent pancreatic inflammation and damage. Serum levels of serum glutamate pyruvate transaminase, serum glutamate oxalacetate transaminase and alkaline phosphatase were significantly elevated in group 2 and significant reductions were seen in the Verapamil treated animals (group 3). The findings in this study imply that a continuous 180 micrograms/kg/h dose Verapamil infusion does not ameliorate the pathogenesis of pancreatitis induced by ligation of pancreatic duct but do not rule out a dose-dependent protective effect. Meanwhile, the lowering of liver function test scores should be considered the beneficial effect of CCBs, and this should be investigated in further studies.

Acute Disease↗
PubMed2002

Quantitative testing of liver function compared to prognostic scores in patients with primary biliary cirrhosis.

AIM: Primary biliary cirrhosis (PBC) is a slowly progressive liver disease which can lead to cirrhosis. We investigated if quantitative tests of liver function (QTLF) and serum levels of a surrogate marker of hepatic fibrogenesis (PIIINP) provide information in addition to established prognostic scores. METHODS: In 34 PBC patients PIIINP, PBC-relevant parameters, histological staging and QTLF at entry and at 2 years were determined and compared with the Christensen (CPS I, CPS II) and Mayo prognosis score. QTLF included aminopyrine breath test, galactose elimination capacity, sorbitol and indocyanine green clearance. RESULTS: Bilirubin, serum IgM and PIIINP were elevated at both time points, whereas albumin and prothrombin time remained normal. Clinical findings (ascites, cirrhosis, central cholestasis) and histological staging worsened after 2 years, as did the CPS II. However, QTLF, PIIINP, CPS I and the Mayo score revealed no significant changes. CONCLUSIONS: Only CPS II changed after 2 years, whereas CPS I and the Mayo score remained unaltered. QTLF and PIIINP did not provide any further information on progression of PBC, suggesting that QTLF cannot predict prognosis of PBC patients in a two-year interval and that CPS II is superior to CPS I and the Mayo score in short-term studies for PBC.

Aminopyrine↗
PubMed1980

Effects of methyl methacrylate on liver function in patients undergoing total hip or total knee replacement.

In an unselcted group of patients undergoing total hip or total knee replacement, it was shown that liver changes occur postoperatively in those in whom polymethyl methacrylate was used. The changes are transient and return to normal by two weeks after operation. These liver changes are seen more frequently in patients also receiving halothane. Elevations in the serum alkaline phosphatase level are secondary to increases in the isoenzyme levels from liver and not bone. A routine SMA study should be supplemented by routine preoperative tests specific for liver function, such as the enzyme gamma glutamyl transpeptidase or others. Patients with abnormal liver test results before total joint replacement with cement probably should not be given halothane as an anesthetic.

Alkaline Phosphatase↗
PubMed1989

Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis. Effects on splanchnic and systemic hemodynamics and liver function.

The results of a study to characterize the effects of the oral administration of isosorbide-5-mononitrate (Is-5-Mn), the active metabolite of isosorbide dinitrate, on portal hypertension in 23 patients with cirrhosis are reported. Patients received 20 mg of Is-5-Mn (n = 10), 40 mg (n = 9), or a placebo (n = 4). No significant changes were observed after the administration of the placebo. However, both doses of Is-5-Mn significantly reduced portal pressure, as evaluated by measurements of the hepatic venous pressure gradient. The fall in portal pressure averaged 10% after the 20-mg dose and 18% after 40 mg and was maintained for the 2 h of observation. Reduction of portal pressure was due to a decrease in the wedged hepatic vein pressure, with no changes in the free hepatic venous pressure. After the 20-mg dose, the decrease in portal pressure was associated with an increase in hepatic blood flow (16%), suggesting a fall in hepatic vascular resistance. However, after the 40-mg dose, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure (-19%) appeared to contribute to the greater reduction in portal pressure, as suggested by a significant decrease in azygos blood flow (-15%). These beneficial effects on portal pressure were not associated with adverse effects on liver function, as evaluated by measurements of the hepatic clearance of indocyanine green and the hepatic intrinsic clearance. Neither dose of Is-5-Mn caused significant changes in these quantitative parameters of liver function. These findings suggest that Is-5-Mn could be a potentially useful and safe agent in the treatment of portal hypertension.

Adult↗
PubMed1997

Sublethal effects of hexavalent chromium on the body growth rate and liver function enzymes of phenobarbitone-pretreated and promethazine-pretreated rabbits.

Hepatotoxic effects of chromium have been studied on the liver function enzymes of male New Zealand white rabbits, Oryctolagus cuniculus, with and without pretreatment with phenobarbitone (PB) and promethazine (PM). The total body weight was decreased under all experimental conditions. After PB administration (5 mg/kg body wt/day for 5 days), the serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and isocitrate dehydrogenase (ICDH) activities decreased 21%, 65%, 25%, and 37%, respectively, whereas the alkaline phosphatase (AP) activity increased 70%. After PM treatment (5 mg/kg body wt/day for 5 days) the serum GPT was inhibited 73%, whereas LDH activity was increased 37%. The hepatic GPT and AP activities decreased after PB (52% and 31%, respectively), and PM (48% and 44%, respectively) treatments, whereas the activities of LDH and ICDH increased (after PB: 817% and 109%, respectively, and after PM: 136% and 44%, respectively). Potassium dichromate, administered at a dose of 8 mg/kg body wt/day for 5 days, decreased serum GOT (44%), GPT (61%), LDH (63%), and AP (44%) activities. The hepatic GOT, GPT and AP activities were likewise decreased (86%, 51%, and 46%, respectively), whereas hepatic LDH and ICDH activities increased 667% and 193%, respectively. When administered to PB-pretreated animals, the serum GOT and AP activities were decreased (50% and 68%), whereas ICDH was increased (29%). The hepatic GOT, LDH, and ICDH activities increased 79%, 221%, and 130%, respectively. In the PM-pretreated animals, the chromium treatment inhibited the activities of serum GOT (48%), GPT (44%), and LDH (43%). The hepatic GPT, LDH, and ICDH activities increased 90%, 133%, and 52%, respectively.

Alanine Transaminase↗
PubMed2001

Diethylnitrosamine causes pituitary damage, disturbs hormone levels, and reduces sexual dimorphism of certain liver functions in the rat.

The acute toxicity of diethylnitrosamine (DEN) to the liver has been well documented in the literature, but whether DEN also affects the endocrine parameters has been addressed in only a few studies. We thus investigated the effects of DEN on pituitary, serum hormone levels, and certain sex-differentiated liver enzymes in this study. Adult male Wister rats were intraperitoneally injected with DEN at a single dose of 200 mg/kg and were sacrificed at 1, 3, 7, and 35 days after injection; DEN-treated females were included as controls at days 7 and 35. Electron microscopic observation showed that during the first week after injection, all types of granular cells of the anterior pituitary in male animals exhibited cellular damage, including disrupted organelles and cellular structure, as well as pyknotic or lytic nuclei. Many undamaged secretory cells exhibited dilated endoplasmic reticula, hypertrophic Golgi complexes, and peripheral location of secretory granules, which usually are morphologic features of increased cellular activities. In male rats, the serum level of total testosterone decreased and the corticosterone increased 1 day after DEN treatment. The serum level of growth hormone (GH) decreased and the prolactin level increased on day 3. The hepatic expression of the male-specific cytochrome P450 2C11 (CYP2C11) decreased to 1-5% of the normal levels during the first week and was still 50% lower than the normal level on day 35, whereas the female-specific CYP2C12 expression increased only slightly. Activities of the male predominant 16alpha, 16beta, and 6beta hydroxylation of androstenedione by microsome decreased in an in vitro assay, whereas the non-sex-differentiated 7alpha hydroxylation and the female-predominant 5alpha reduction of androstenedione were unaffected. In female rats, decreased serum GH level was observed on day 7. The CYP2C12 expression in females was decreased to about 1% and 80% of the normal levels on day 7 and day 35, respectively, but the CYP2C11 expression was unchanged. These data suggest that in male rats, DEN treatment may cause pituitary damage, disturb serum hormone levels, and induce long-lasting reduction of sexual dimorphism in certain liver functions.

Alkylating Agents↗
PubMed1996

Influence of biochemical parameters of liver function on vancomycin pharmacokinetics.

The influence of biochemical parameters of hepatic function on vancomycin pharmacokinetics was retrospectively evaluated in 76 adult patients (age 18 to 81 years), from biochemistry data gathered during routine therapeutic drug monitoring. All subjects had normal serum creatinine levels. Vancomycin concentrations were determined by fluorescence polarization immunoassay in 101 paired serum samples. All data for vancomycin concentration versus time were fitted to a one-compartment model using the bayesian approach. Bilirubin, transaminases (n = 101), gamma-glutamyl transferase (n = 97), alkaline phosphatase (n = 95), albumin (n = 92) and lactate dehydrogenase (n = 42) were determined. No strong correlation was seen between any of the pharmacokinetic and biochemistry parameters studied. In patients with hyperbilirubinaemia, the mean Vss and t1/2 were increased (Vss: 0.75 +/- 0.31 versus 0.92 +/- 0.42 1.kg-1, p = 0.020; t1/2 5.93 +/- 3.30 versus 7.48 +/- 4.44 hr, p = 0.049). When liver function was evaluated according to hepatic profile (normal, mildly altered and severely altered), no significant differences were observed in vancomycin pharmacokinetics among the groups. In conclusion, vancomycin pharmacokinetics are only weakly influenced by the biochemistry parameters of liver function.

Adolescent↗
PubMedDate not supplied

[The use of the antipyrine test in assessing liver function in patients with insulin-dependent diabetes mellitus].

The antipyrine test in the authors' modification was used for investigation of liver function in patients with insulin dependent diabetes mellitus. The drug was administered per os a dose of 15 mg per 1 kg of body mass. Its concentration was determined in saliva spectrophotometrically and calculated a period of its half-life [correction of semielimination] (T1/2). In half of 19 patients T1/2 of antipyrine was inhibited 3.2 times, in 4 patients it was decreased 2.1-fold, and in 6 patients it was unchanged. Indices of routine biochemical liver tests were within normal. In patients with inhibited excretion of antipyrine there were signs of disturbed lipid and carbohydrate metabolism. The antipyrine test can be recommended as an auxiliary method for evaluation of the gravity of liver parenchymal lesion in patients with diabetes mellitus.

Adolescent↗
PubMedDate not supplied

Aminopyrine breath test: development of a 13C-breath test for quantitative assessment of liver function in humans.

BACKGROUND/AIM: 14C-aminopyrine breath test (ABT) has been shown to be well correlated to the severity of liver diseases, but its use is limited in countries where radioactive isotopes are severely controlled. The goal of this study was to develop a 13C-ABT based on a highly sensitive method to measure 13CO2 in breath samples. MATERIALS AND METHODS: The relevant parameters were studied in 26 controls and 27 patients: the 13CO2 enrichment of expired breath between t-10 and t+60 minutes was determined as the most simple and clinically useful parameter. The 13C-ABT was then prospectively compared to clinico-biological data and the galactose elimination capacity (GEC) in 82 patients. RESULTS: The 13C-ABT was well correlated to: i) the Child-Pugh classification; ii) GEC results; iii) the hepatic volume. The presence of ascites or alcoholic consumption did not alter significantly the results of the test. 13C-ABT appeared more sensitive than GEC to evaluate minor liver dysfunctions. CONCLUSIONS: The 13C-ABT is a simple and sensitive test to measure liver function. The use of the stable isotope 13C ensures the harmlessness of the test and the possibility to repeat it in a given patient.

Adult↗
PubMed1994

Expression of liver functions in immortalised rat hepatocyte cell lines.

The differentiated hepatic function of two rat liver cell lines, P9 and SV40RH1, immortalised by transfection with SV40 DNA has been investigated in terms of the glutathione synthesis, and the activities of gamma-glutamyltransferase, glutathione-S-transferase and UDP-glucuronosyltransferase. SV40RH1 is a highly differentiated cell line at early passage, but the expression of some aspects of its differentiated phenotype is unstable and some functions are lost by passage 12-13. P9 is a less-well differentiated cell line, with relatively stable expression of functions between passages 4 and 13. In terms of differentiated function both cell lines represent a marked improvement over primary cultures of rat hepatocytes which de-differentiate rapidly within 24-48 h in culture. This retention of liver function in proliferating cell lines offers the opportunity to use such cells in in vitro toxicological studies.

Animals↗