Serum Γ-glutamyl Transpeptidase Activity Research Articles

Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma.

Cholangiocarcinoma has been reported in workers exposed to chlorinated organic solvents and has consequently been classified as an occupational disease (occupational cholangiocarcinoma) by the Japanese Ministry of Health, Labour and Welfare. This study aimed to identify the characteristics of nine workers newly diagnosed with occupational cholangiocarcinoma. This study was a retrospective study conducted in 13 hospitals and three universities. Clinicopathological findings of nine occupational cholangiocarcinoma patients from seven printing companies in Japan were investigated and compared with 17 cholangiocarcinoma patients clustered in a single printing company in Osaka. Patient age at diagnosis was 31-57 years. Patients were exposed to 1,2-dichloropropane and/or dichloromethane. Serum γ-glutamyl transpeptidase activity was elevated in all patients. Regional dilatation of the intrahepatic bile ducts without tumor-induced obstruction was observed in two patients. Four patients developed intrahepatic cholangiocarcinoma and five developed hilar cholangiocarcinoma. Biliary intraepithelial neoplasia and/or intraductal papillary neoplasm of the bile duct was observed in four patients with available operative or autopsy specimens. Most of these patients with occupational cholangiocarcinoma exhibited typical findings, including high serum γ-glutamyl transpeptidase activity, regional dilatation of the bile ducts, and precancerous lesions, similar to findings previously reported in 17 occupational cholangiocarcinoma patients in Osaka.

Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan

An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.

Chinese Children With Chronic Intrahepatic Cholestasis and High γ‐Glutamyl Transpeptidase

The aims of the present study was to study the significance of ABCB4 mutations in mainland Chinese children with chronic intrahepatic cholestasis and to correlate genetic findings with clinical features and response to ursodeoxycholic acid (UDCA) therapy. Thirteen patients with chronic intrahepatic cholestasis and elevated serum γ-glutamyl transpeptidase activity of unknown cause were enrolled in a single pediatric center. All of the encoding exons and flanking areas of ABCB4 were sequenced. Available liver biopsy specimens were immunostained for multidrug resistance protein 3. The clinical features, biochemical parameters, and responses to therapy were compared with patients with or without ABCB4 mutation(s). Six different ABCB4 mutations were identified in 3 patients; each patient was a compound heterozygote. Apart from c.139C>T (p.R47X), all were novel, including c.344+2_+3insT, c.1376A>G (p.D459G), c.1745G>A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308). Absent or reduced multidrug resistance protein 3 canalicular immunostaining was demonstrated in patients with ABCB4 mutations. Serum total bile acid levels were higher in patients with ABCB4 mutations than in patients without ABCB4 mutations (352.5 ± 97.0 vs 55.9 ± 50.4 μmol/L, P = 7.32E-05). There was no difference in other biochemical parameters between patients with and without ABCB4 mutations. After oral UDCA administration in 3 patients with ABCB4 mutations, pruritus disappeared, growth improved, spleen size decreased, and platelet counts increased. In the 10 patients without ABCB4 mutations, an inconsistent response to UDCA therapy was observed. In mainland Chinese children, some cases of chronic intrahepatic cholestasis with high γ-glutamyl transpeptidase could be attributed to ABCB4 mutations. UDCA administration partially improved clinical symptoms and liver function.

Phyllanthus amarus extract administration increases the life span of rats with hepatocellular carcinoma

The effect of Phyllanthus amarus extract administration after induction of hepatocellular carcinoma (HCC) by N-nitrosodiethylamine (NDEA) was studied in Wistar rats. Administration of an aqueous extract of P. amarus was found to significantly increase the survival of hepatocellular carcinoma harboring animals. All the untreated rats died of tumour burden by 33.7±1.6 weeks. Administration of P. amarus extract (150 mg/kg b.w.) after tumour development increased the survival of animals to an average of 52.2±2.3 weeks. Serum γ-glutamyl transpeptidase activity which was elevated to 182±23 U/l by NDEA administration was lowered to 112±19 U/l by the administration of P. amarus extract. Similarly elevated glutathione S-transferase activity (1534±116 nmol/min per mg protein) and glutathione (20.5±2.4 nmol/mg protein) levels in the NDEA administered group were found to be lowered to 1112±89 nmol/min per mg protein and 14.2±2.2 nmol/mg protein respectively. P. amarus administration was found to be ineffective in controlling the liver weight, elevation of tissue γ-glutamyl transpeptidase, serum alkaline phosphatase and serum glutamate pyruvate transaminase of HCC harboring animals.

65Zn uptake by liver of rats fed 3′-methyl-dimethylaminoazobenzene

The uptake of 65Zn, determined by γ-counting and also by autoradiography, significantly increased with the increasing level of metallothionein in liver 4 weeks after the start of feeding a diet containing 3′-methyl-dimethylaminoazobenzene (3′-Me-DAB), at which time the serum γ-glutamyl transpeptidase activity was not yet significantly elevated. At this time, furthermore, hepatic uptake of 67Ga-citrate did not increase and that of 99mTc-Sn-colloid decreased in 3′-Me-DAB-fed rats. These results suggest that a short-life gamma-emitting isotope such as 69mZn may be useful for the detection at the early stage of hepatic carcinogenesis.

Carbohydrate-related regulation of the ethanol-induced increase in serum γ-glutamyl transpeptidase activity in adult men

The dietary influence on ethanol-induced increase in serum gamma-glutamyl transpeptidase (gamma-GTP) activity was studied in 2165 healthy men 18-85 y of age living in Nagano Prefecture, Japan. As ethanol consumption increased, the intake of cereals, potatoes, vegetables, milk and dairy products, oils, fruit, confections, and sugar decreased, whereas the intake of meat increased. These associations suggest that ethanol consumption led to the decrease in the intake of carbohydrate and vegetable fat. Serum gamma-GTP activity was found to be positively related to ethanol consumption and negatively related to the intake of sugar, fruit, and confections. The activity was the highest in those whose percent energy intake from carbohydrates was the lowest. Stepwise-multiple-regression analysis identified the three variables ethanol, sugar, and fruit, as the factors associated with the value of gamma-GTP activity: ethanol on the one hand increased the activity, whereas sugar and fruit on the other hand decreased the activity. Moreover, a lowered sugar intake augmented the ethanol-induced increase in the enzyme activity. These results suggest that sugar intake plays a role in the ethanol-induced increase in serum gamma-GTP activity.

Relationship between Serum Butyrylcholinesterase Activity, Hypertriglyceridaemia and Insulin Sensitivity in Diabetes Mellitus

1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.

γ-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

γ-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum γ-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic γ-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There were no inhibitors or activators of liver γ-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum γ-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic γ-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.

?-Glutamyl Transpeptidase Levels in Thyroid Disease

To evaluate the association between serum γ-glutamyl transpeptidase activity (GGT) and thyroid function, we measured the GGT, alkaline phosphatase, free thyroxine index (FT 4 I), free triiodothyronine index (FT 3 I), and thyrotropin (TSH) levels in patients with hyperthyroidism and hypothyroidism and in normal subjects. Ten of 16 hyperthyroid patients had elevations of GGT activity. There was no difference in mean FT 4 I or FT 3 I between the groups with high GGT and normal GGT levels. Six months after treatment with radioactive iodine, serum GGT levels decreased, while there was no significant change in mean serum alkaline phosphatase levels. Mean serum GGT levels were decreased in patients with hypothyroidism and correlated well with serum TSH levels. Replacement therapy with levothyroxine sodium caused an elevation in mean serum GGT levels in six hypothyroid patients. Thus, serum GGT activity is frequently increased in patients with hyperthyroidism and may be decreased in patients with hypothyroidism. Euthyroidism results in restoration of normal GGT levels. ( Arch Intern Med 1982;142:79-81)

A novel fluorometric ultramicro determination of serum gamma-glutamyltranspeptidase activity.

A simple and highly sensitive rate assay of serum γ-glutamyltranspeptidase activity is described, using a novel fluorogenic substrate, 7-(γ-L-glutamyl)-4-methylcoumarinylamide. The reaction is initiated by adding 20 μl of serum, and fluorescence development in 1 min due to the 7-amino-4-methylcoumarin liberated at 37°C is followed directly on a recorder. A close correlation was found between activities measured by the fluorometric method and by a conventional method using a chromogenic substrate, γ-L-glutamyl-p-nitronanilide.

Serum γ-Glutamyl Transpeptidase Activity in Viral Hepatitis: Suppression in Pregnancy and by Birth Control Pills

gamma-Glutamyl transpeptidase (GGT) activity in serum was increased in the majority of women with viral hepatitis occurring in the first half of pregnancy. By contrast, GGT activity was abnormal less frequently and the mean value was relatively depressed, even though hepatitis was as severe, in the second half of gestation. Mean GGT activity was also lower, and abnormal values were less frequent, in nonpregnant women with viral hepatitis who were taking birth control pills (BCP). Depressed GGT is not attributable to an inhibitor in serum in women in late pregnancy or taking BCP. The data suggest that estrogen and/or progestational compounds affect liver such that less GGT is released into blood with acute hepatocellular injury. In addition, hyperbilirubinemia was found to be associated with depressed serum GGT activity, and bilirubin added to serum in vitro interfered with measured activity of the enzyme.

Serum γ-glutamyl transpeptidase and physical exercise

The immediate and delayed influence of exercise of variable type, duration and intensity on the serum γ-glutamyl transpeptidase activity (γ-GT) has been examined in athletes and untrained persons. The possible effects of exercise-induced changes in other parameters (plasma free glutamate, serum triglyceride, haemoconcentration) on the measured postexercise serum γ-GT have been discussed, partly on the basis of our own experimental data. It appears that neither exercise itself, nor any one of the above mentioned factors (excepting a slight, transient effect of haemoconcentration after brief, intensive exertion) have noticeable influence on serum γ-GT. Determinations of this enzyme for diagnostic purposes are therefore likely to be used without regard to acute and chronic exercise history in man.

Serum γ-glutamyl transpeptidase activity in alcoholism

Serum γ-glutamyl transpeptidase (GGTP) activity was elevated in three-quarters of seventy-six anicteric alcoholics or heavy drinkers, 44 of whom (58%) were ambulant out-patients without clinical evidence of liver disease. Transaminase elevation was observed in less than one third, and alkaline phosphatase elevation in less than one tenth. GGTP was the only enzyme elevated in the group classified as heavy drinkers rather than alcoholics. GGTP determination is methodologically simple ; its measurement is considered to be a sensitive and highly specific test for the detection of liver cell injury in the suspected alcoholic and to be superior to transaminase determination for this purpose.

Determination of Serum γ-Glutamyl Transpeptidase Activity and its Clinical Applications

Determination of Serum γ-Glutamyl Transpeptidase Activity and its Clinical Applications