Gamma-glutamyl Transferase Concentrations Research Articles

Sclerosing cholangitis in cystic fibrosis.

Four of 102 patients with cystic fibrosis with symptoms or signs suggesting sclerosing cholangitis had typical findings at endoscopic retrograde cholangiography (ERC), indicating this syndrome. All patients had pulmonary symptoms, pancreatic insufficiency, and pathologic sweat test results. Three females (aged 15-20 years), two of whom had unspecific colitis, presented with abdominal pain, and a 25-year-old male patient was asymptomatic. Two of the patients had persistently and one patient only intermittently pathologic serum concentrations of transaminases and gamma-glutamyltransferase. The fourth patient, who only had a transient increase of standard liver function tests, showed no progress in any variable (including liver biopsy and ERC) for 3 years, indicating a benign course. Disturbances of the liver and biliary system are well-known complications in cystic fibrosis. Our observations indicate that sclerosing cholangitis is another expression of biliary tract involvement in this disease.

Two dry-reagent systems evaluated for determinations of enzyme activities.

We evaluated the Kodak Ektachem DT60/DTSC and the Boehringer Mannheim Reflotron for measuring activity concentrations of six enzymes. The Ektachem CVs for low concentrations of aspartate aminotransferase and alanine aminotransferase were high. As compared with the Ektachem and a routine "wet-chemistry" system, values for aspartate aminotransferase and alanine aminotransferase were lower as measured by the Reflotron, because no pyridoxal 5'-phosphate is included in the Reflotron slides. Activity concentrations of gamma-glutamyltransferase and creatine kinase measured with the Ektachem and with the routine procedure did not agree well, possibly because the Ektachem gave too-high results for the enzyme activities. Assays of several commercial test sera indicated that test results by the dry-chemistry and routine procedures are not interconvertible. This contrasts with our previous experience, in which between-test agreement for several analytes was acceptable.

Relationship between hepatotoxicity and induction of replicative DNA synthesis following single or multiple doses of carbon tetrachloride.

The in vivo-in vitro DNA repair and DNA replication assay in mouse hepatocytes has promise as a short-term test for detecting potential mouse liver carcinogens. In addition, this assay may provide information on the mode of action of known hepatic carcinogens. The induction of DNA repair is clearly a response to hepatic DNA damage. However, it is unclear whether induction of replicative DNA synthesis (S phase) represents regenerative hyperplasia in response to hepatotoxicity or is a result of direct mitogenic stimulation of the hepatocytes by the test compound. The objective of the present study was to examine the relationship between hepatotoxicity, which was assessed by measuring serum concentrations of glutamic-oxalacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (AP), and gammaglutamyl transferase (GGT), and induction of S phase following either single or multiple doses of the model mouse hepatocarcinogen carbon tetrachloride (CCl4). Under the experimental conditions in this study, CCl4 elevated SGPT and SGOT but did not affect serum concentrations of AP or GGT. CCl4 did not induce DNA repair. An increase in the percentage of hepatocytes in S phase followed the appearance of elevated SGOT and SGPT in all single-dose studies. The results from the multiple-dose studies showed a similar relationship except that with 20 mg/kg X d the concentrations of SGOT and SGPT decayed to control values after 14 d of dosing whereas the percentage of hepatocytes in S phase remained markedly elevated (greater than 10 X control). The daily dose of CCl4 that gave a no-observed-effect level for induction of S phase was lower with multiple administrations than it was following a single exposure. A single administration of CCl4 at 25 mg/kg did not increase S phase, SGOT, or SGPT, but if 20 mg/kg X d was given for 7 d the number of hepatocytes in S phase and the concentrations of SGOT and SGPT increased more than 10-fold. These data support the hypothesis that induction of replicative DNA synthesis in the mouse liver following CCl4 administration is related to hepatotoxicity. In single-dose studies elevation in S phase was always associated with elevation of SGOT and SGPT. However, in the multidose studies, SGOT and SGPT declined after 14 d of administering 20 mg/kg X d while S phase remained elevated.(ABSTRACT TRUNCATED AT 400 WORDS)

Colostral transfer of gamma glutamyl transferase in lambs

Serum gamma glutamyl transferase (GGT) levels in blood samples taken from normal lambs which had suckled colostrum were found to be up to 140 times normal adult levels. These high serum levels declined rapidly reaching a stable level approximately 60% higher than normal adult values by 24 days of age. Newborn lambs which had not yet consumed colostrum had GGT levels which would be considered normal in adult sheep. The GGT concentration in ewes' colostrum was up to 470 times normal serum levels. There was a significant positive correlation between serum GGT and gamma globulin levels in blood samples taken from lambs within 24 hours of birth. Lambs' serum alkaline phosphatase (AP) and serum glutamate oxaloacetate transaminase (SGOT) levels also rose concurrently with the absorption of colostral gamma globulin, with the day 1 AP values being significantly correlated with the serum gamma globulin levels. Serum AP levels declined gradually but were still well above normal adult levels at 45 days of age while SGOT levels returned to normal adult levels by two to three days after birth. It is concluded therefore that, as previously shown in calves, lambs acquire high levels of serum GGT activity from their mothers' colostrum in proportion to the amount of gamma globulin absorbed and also show a concurrent rise in serum AP activity. However the rise in SGOT levels at this time has not been observed in calves.

Development of radioimmunoassay for gamma-glutamyl transferase using pancreatic enzyme.

A radioimmunoassay (RIA) for the determination of gamma-glutamyl transferase (GGT) was developed using human pancreatic enzyme as antigen. The assay allows the determination of GGT in concentrations as low as 80 ng/ml, and it is reproducible and specific. A good parallel relation was demonstrated between the standard curve and dilution curves for serum, urine, bile, and partially purified kidney GGT. In normal individuals, the mean serum concentration of GGT determined by RIA was found to be 3.43 micrograms/ml (SD +/- 1.20). Enzyme activity calculated from the GGT concentration measured by the radioimmunoassay using a regression equation was approximately twice as great as that determined by conventional enzyme assay.

Correlations of serum lipids and lipoproteins with gamma-glutamyltransferase and attitude to alcohol consumption.

The correlation of three markers of alcohol consumption: serum concentration of gamma-glutamyltransferase (GT), high density lipoprotein cholesterol (HDL-cholesterol), apolipoprotein AI (Apo AI), and the results of a questionnaire (Mm-MAST) designed to measure the attitude towards alcohol consumption were determined in a population of healthy men aged 48 years. Apo AI (r = 0.27) and GT (r = 0.31) were correlated (P less than 0.001) to the questionnaire score to a similar degree while the correlation between HDL-cholesterol and the questionnaire score was (r = 0.18), somewhat less good but statistically significant (P less than 0.01). There was no correlation between GT and HDL-cholesterol or Apo AI.

Hepatic function assessed (in rats) during chemotherapy with some anti-cancer drugs.

Using rats, we studied how best to assess hepatic damage after administering therapeutic doses of each of five anti-cancer drugs or of the hepatotoxin, carbon tetrachloride. As indexes, we compared measurement of the concentration of administered antipyrine in plasma with measurement in serum of alpha-fetoprotein or of the activities of five enzymes that reportedly best reflect hepatic damage. The biological half-life of antipyrine in the plasma was increased more than threefold on pretreating the rats with any of the five cytotoxic drugs or with carbon tetrachloride. In contrast, the concentrations of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyltransferase, or glutamate dehydrogenase were not consistently increased. Of the enzymes tested in serum, aspartate aminotransferase and ornithine carbamoyltransferase best indicated hepatic impairment resulting from the treatment with anti-cancer drugs. Our results imply that determination of the pharmacokinetics of marker drugs such as antipyrine better indicates hepatic dysfunction induced by cytotoxic agents than does measurement of the enzymes liberated into serum as a result of damage to liver mitochondria.

Increased D-glucaric acid excretion by jaundiced patients.

The urinary excretion of D-glucaric acid, a catabolite of glucuronic acid, is considered to be a reliable index of the state of hepatic microsomal enzyme activity. Because enzyme activity may be altered in liver disease, we examined the effect of liver disease on the excretion of this metabolite and its correlation with liver function tests. We studied 89 patients with nonhemolytic jaundice, 39 with viral hepatitis, 33 with obstructive jaundice, six with cirrhosis, and 11 patients with jaundice of mixed etiology. Glucaric acid excretion was significantly increased in all these patients as compared to controls, most pronounced in the obstructive jaundice group. No correlation was found between glucaric acid excretion and concentrations of bilirubin, albumin, globulin, aspartate aminotransferase, alkaline phosphatase, cholesterol, or gamma-glutamyltransferase in serum, even though the concentrations of these analytes did vary with the type of liver disease. We suggest that this increase in glucaric acid excretion is an indication of normal or even increased glucuronidation (UDP-glucuronosyltransferase activity), which occurs in liver disease.

Serum gamma-glutamyltransferase as a measure of sporidesmin-induced liver damage in sheep.

Abstract The relationship between serum concentrations of the enzyme gamma-glutamyltransferase (GGT) after experimental sporidesmin intoxication, and the severity of the liver damage seen on post-mortem examination of the liver, has been examined. Serum GGT activity in blood collected 2 to 3 weeks after ad-ministering the toxin is positively correlated to a subjective liver damage score and to losses in bodyweight associated with the intoxication. Determination of GGT activities provides a sensitive method for detecting and measuring liver damage in experimental sporidesmin poisoning. In the field, GGT determinations should prove useful in diagnosing liver damage associated with subclinical and clinical facial eczema giving additional information about the severity of the lesion.