Gamma-glutamyl Transpeptidase Levels Research Articles

Test validity of periodic liver function tests in a population of Japanese male bank employees

The validity (sensitivity and specificity) of annual liver function tests, determined by assaying blood levels of aspartate aminotransferase, alanine aminotransferase and gammaglutamyl transpeptidase, was evaluated using the results of health checkups of male bank workers. The specificity of each liver function test to detect persons with fatty liver, excess alcohol users, and hepatic virus carriers, diagnosed respectively by ultrasound, detailed inquiry, and virus marker tests, was always higher than 80%, except for alanine aminotransferase in excess alcohol users (63.5%). However, the highest sensitivity to detect virus carriers was alanine aminotransferase to detect HCV antibody-positive workers, but it was only 45.5%. The highest sensitivity of the liver function tests to detect excess alcohol users in obese subjects was only 33.3%. The highest sensitivity by liver function tests to detect fatty liver was 35.7% which was inferior to that of the body mass index. These results indicate that the liver function tests mandated in the workplace periodic health checkups in Japan exhibit very low sensitivity for the detection of any of the proposed target clinical conditions.

Pharmacokinetics of roxatidine acetate in patients with chronic liver disease.

Patients with liver disease are prone to develop peptic ulceration and often receive H(2)-receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H(2)-receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H(2)-receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease. Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated. There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration-time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and gamma-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found. Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified.

Papillary adenoma of the bile duct

A 51-year-old man was hospitalized because of fever and jaundice. There was no history of biliary tract disease. Evaluation disclosed a temperature of 38°C, icteric sclera, and right upper abdominal quadrant tenderness but no palpable mass. Laboratory tests revealed a leukocytosis and elevated levels of total bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase. Transabdominal US demonstrated dilation of the extrahepatic and intrahepatic bile ducts as well as an irregular hyperechoic mass without acoustic shadow in the distal common bile duct (CBD). At ERCP a smooth, bulging major duodenal papilla was noted (A). Endoscopic retrograde cholangiography (B) demonstrated dilated intrahepatic and extrahepatic bile ducts together with an irregular filling defect (arrowheads) with a stalk (arrow) in the distal CBD. After a sphincterotomy was performed with a needle knife, a polypoid lesion with a stalk was visualized endoscopically in the distal CBD (C). Histopathologic evaluation of an endoscopic biopsy specimen (D, H&E, orig. mag. ×200) disclosed a papillary adenoma with focal dysplasia. The patient refused operation, and a plastic stent was placed in the CBD to bypass the obstructing tumor. After treatment with antibiotics and remission of jaundice, the patient was discharged. He has remained asymptomatic during a 3-month period of follow-up.

The clinical significance of common bile-duct dilatation in patients without biliary symptoms or causative lesions on ultrasonography.

Although abdominal ultrasonography (US) is a good initial screening method for detection of biliary tract disease, we sometimes encounter patients who only have findings of dilatation of the common bile duct (CBD) on US, without specific biliary symptoms or jaundice. This study aimed to evaluate the causes and clinical significance of dilatation of the CBD in patients without biliary symptoms, jaundice, or causative lesions at US. A total of 77 patients who had no biliary symptoms and whose internal CBD diameter was more than 7 mm, without definite causative lesions on US, were enrolled. Of these, 49 underwent endoscopic retrograde cholangiopancreatography (ERCP) and 28 underwent follow-up US or computed tomography (CT) instead of ERCP. We excluded patients whose bilirubin level had increased beyond the upper normal level or who had previous history of upper abdominal surgery including cholecystectomy. The ERCP findings were as follows: no lesion in 20 patients (40.8%), juxtapapillary duodenal diverticulum (JDD) in 11 (22.5%), benign stricture in ten (20.4%), distal CBD mass in two (4.1%), choledochal cyst in two (4.1%), anomalous union of the pancreaticobiliary duct (AUPBD) in two (4.1%), and choledochal cyst with AUPBD in two (4.1%). There were no differences in age or in alkaline phosphatase or gamma-glutamyl transpeptidase (GGT) levels between the patients who had causative lesions revealed at ERCP and those who did not. Among the 28 patients who did not undergo ERCP, 12 had returned to normal and eight had no change in CBD diameter on follow-up US. Among eight patients who underwent CT, there were four with normal findings, one with JDD, and three with suspected choledochal cysts. We detected a significant number of causative biliary tract lesions in asymptomatic adults with dilatation of the CBD on routine abdominal US; no laboratory or demographic parameters were useful for discrimination. Further diagnostic study will be helpful for the early diagnosis of biliary tract disease in such patients.

Alcohol consumption and blood pressure in Japanese men

In a study of Japanese men, a nonlinear association of alcohol consumption and blood pressure was not observed. This cross-sectional study was conducted to clarify the effect of infrequent or light alcohol consumption on blood pressure in normotensive Japanese men. The subjects were 2,179 male workers ranging in age from 40 to 54 years. Drinking habits were represented by three indices: episodic alcohol consumption, frequency of drinking, and monthly alcohol consumption. Seven items were analyzed as covariates: age, body mass index, salt intake, physical activity, and levels of gamma-glutamyl transpeptidase, uric acid, and plasma glucose. The association between drinking habits and blood pressure was evaluated by using analysis of covariance. Both episodic alcohol consumption and frequency of drinking were significantly associated with blood pressure in subjects aged 45 to 54 years. In those aged 40 to 44 years, there was a significant association between frequency of drinking and diastolic blood pressure. Significant associations of monthly alcohol consumption with blood pressure in every age group also were found. In subjects aged 45 to 54 years, linear associations between episodic alcohol consumption, frequency of drinking, monthly alcohol consumption, and adjusted blood pressure were observed. In those aged 40 to 44 years, nonlinear associations of monthly alcohol consumption and frequency of drinking with adjusted blood pressure were observed, and threshold effects of 540 ml of alcohol per month and a frequency of 1 to 12 days per month were found. In conclusion, habitual alcohol consumption increases blood pressure linearly in normotensive workers aged 45 to 54 years, although light consumption does not affect blood pressure in those aged 40 to 44 years.

Effects of ursodeoxycholic acid and colestilan versus ursodeoxycholic acid alone on serum bile acids and pruritus: a randomized, open-label study

Background: Pruritus associated with primary biliary cirrhosis (PBC) is often difficult to manage and may affect the quality of life of patients. The cause of pruritus in liver disease is unknown but is thought to be related to the deposition of bile salts in the skin. Objective: We studied the effects of ursodeoxycholic acid (UDCA) alone and in combination with colestilan (CLL) on refractory pruritus and bile acid levels in patients with PBC. Methods: Eleven patients with pruritus associated with PBC were entered into this trial. Six patients received UDCA 600 mg/d (200 mg TID after meals) for 8 weeks. The remaining 5 patients received UDCA 600 mg/d (200 mg TID after meals) for 4 weeks and UDCA 600 mg/d (200 mg TID after meals) plus CLL 6.42 g/d (2.14 g TID before meals) for 4 weeks. The intensity of pruritus was graded at baseline and at 2-week intervals using a self-administered questionnaire with a scale of 1 (no itching) to 10 (severe and constant itching). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γ-GTP), immunoglobulin M (IgM), and total bilirubin levels were determined immediately before administration of the drug and at weeks 4 and/or 8. Serum bile acid levels were analyzed using high-performance liquid chromatography. Results: In the UDCA monotherapy group, AST, ALT, ALP, γ-GTP, and IgM levels were significantly reduced versus baseline ( P < 0.05) after 8 weeks of therapy. In the UDCA-CLL combination therapy group, AST, ALT, ALP, γ-GTP, and IgM levels were significantly reduced versus baseline after the initial 4 weeks of UDCA monotherapy ( P < 0.05) and were further reduced after 4 weeks of UDCA-CLL combination therapy; however, the difference between values at week 4 and week 8 was not statistically significant. In the UDCA monotherapy group, the chenodeoxycholic acid/cholic acid (CDCA/CA) ratio increased and the proportion of UDCA increased to > 50%. The pruritus score did not change significantly versus values at baseline (3.7 ± 0.3 at study entry vs 2.5 ± 0.3 at week 8). In the UDCA-CLL combination therapy group, total bile acid levels decreased markedly, but the CDCA/CA ratio decreased and the UDCA level was maintained at > 50%. A significant improvement ( P < 0.05) in pruritus score was observed after 4 weeks of UDCA-CLL combination therapy (1.2 ± 0.2) compared with baseline scores (4.0 ± 0.3) and scores after 4 weeks of UDCA monotherapy (3.8 ± 0.4). Conclusion: Clinical and biochemical data after 4 weeks' treatment with UDCA-CLL suggest that the combination may be effective in the management of pruritus associated with PBC.

Development of an experimental model of liver cirrhosis in rabbits.

1. The aim of the present study was to develop an experimental model of liver cirrhosis in rabbits using CCl4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) by intragastric administration of CCl4 once weekly starting 14 days after the addition of phenobarbital to the drinking water (50 mg/day). Controls received phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl4 treatment. The initial dose of CCl4 was 20 microg and subsequent doses were calculated to maintain AST and ALT levels between 400 and 800 IU/L for the duration of treatment (16 weeks). Indocyanine green (ICG) clearance was performed before and at the end of CCl4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantitative score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals did not gain weight compared with controls (P < 0.05). A significant reduction of ICG clearance was observed in CCl4-treated rabbits compared with controls (P < 0.05). The AST, ALT, bilirubin and gamma-GGT levels were elevated in CCl4-treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochemical changes during the evolution of chronic liver disease.

Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors.

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.

Prevelance of abnormal serum aminotransferase values in overweight and obese adolescents

(1) To determine the prevalence of abnormal liver enzymes in overweight and obese adolescents and (2) to determine the relationship of alcohol ingestion and serum antioxidants to the presence of abnormal liver enzymes in overweight and obese adolescents. Serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels were measured in 2450 children between the ages of 12 and 18 years, enrolled in the National Health and Examination Survey, cycle III (NHANES III). Obesity was defined as a body mass index >95th percentile for age and sex. Overweight was defined as a body mass index >85th percentile for age and sex. Nutritional intake was assessed by 24-hour dietary recall and food frequency questionnaires. Serum antioxidants were measured by high-pressure liquid chromatography. Sixty percent of adolescents with elevated ALT levels were either overweight or obese. Overall, 6% of overweight adolescents had elevated ALT levels (odds ratio: 3.4 [95% CI: 3.5-12.8]). Ten percent of obese adolescents had elevated ALT levels (odds ratio: 6.7 [95% CI: 3.5-12.8]). In addition, approximately 1% of obese adolescents demonstrated ALT levels over twice normal. Approximately 50% of of obsese adolescents who reported modest alcohol ingestion (4 times per month or more) had elevated ALT levels (odds ratio: 10.8, 95% CI: 1.5-77). Other factors associated with elevated ALT levels in overweight and obese adolescents include increased age, elevated glycolated hemoglobin, elevated triglycerides, and decreased levels of serum antioxidants-vitamin E, beta-carotene, and vitamin C. Overweight and obesity are the most common findings in adolescents with elevated ALT levels. Even modest alcohol consumption may significantly increase the likelihood of obese adolescents developing obesity-related liver disease.

Alveolar type II cell abnormalities and peroxide formation in lungs of rats given IL-1 intratracheally.

Acute lung injury (ALI) is characterized by increased lung levels of proinflammatory cytokines, inflammation, oxidative stress, edema, and impaired gas exchange. Notably, ALI patients also exhibit pulmonary surfactant abnormalities, including increased levels of phospholipids in their lung lavages. In the present study, to assess early alterations of the lung surfactant system in ALI, we induced inflammation and acute lung injury in rats by administering interleukin-1alpha (IL-1) intratracheally. Five h after IL-1 instillation, we examined lung tissue ultrastructure by electron microscopy using both routine staining methods and cerium chloride staining to localize hydrogen peroxide (H2O2) histologically. We also measured lung lavage phospholipid levels, lung tissue gamma-glutamyl transpeptidase (GGT) activities (a marker of oxidative stress), and arterial blood oxygen tensions. We observed that lungs of rats given IL-1 intratracheally had increased neutrophil accumulation, increased H2O2 production, and increased alveolar type II (ATII) pneumocyte ultrastructural abnormalities compared to rats given saline intratracheally. Intratracheal instillation of IL-1 also increased phospholipid levels in the bronchoalveolar lavage (BAL), possibly as a consequence of the abnormal discharge of lamellar bodies into the alveolar lumen. In addition, IL-1-insuffated rats had increased lung GGT levels and impaired blood oxygenation compared to saline-insufflated rats. Treatment with mepacrine decreased lung neutrophil accumulation, ultrastructural lung abnormalities, lung lavage phospholipid levels, lung tissue GGT levels, and blood oxygenation impairment in rats given IL-1 intratracheally, suggesting a possible relationship between these events. Our results indicate that IL-1-induced acute lung injury in rats is marked by neutrophil-dependent oxidative stress, ATII cell defects, abnormal discharge of lamellar body phospholipids, and impaired blood oxygenation.

前立腺癌患者に対するフルタミド投与前後の肝機能の検討

The incidence of flutamide-induced liver toxicity was studied in 30 consecutive patients with prostate cancer who were treated with total androgen blockage (TAB) therapy (luteinizing hormone releasing hormone [LHRH] analogue and flutamide) in our hospital during the last 3 years and in 20 consecutive patients with prostate cancer who were treated by partial androgen blockage (PAB) therapy (LHRH analogue alone). Liver function test, including measurement of serum levels of aspartate aminotransferase (AST) alanine aminotransferase (ALT), total cholesterol, total bilirubin, gamma-glutamyl transpeptidase (gamma-GTP), and cholinesterase were performed at regular interval. The incidence of liver toxicity in patients receiving TAB (10 cases of 25 patients) was significantly higher than in patients receiving PAB (2 of 18 patients). Two patients in whom severe liver toxicity developed after receiving TAB were hospitalized. However, after flutamide was discontinued all patients with liver damage recovered with normalization of AST and ALT levels. Levels of total cholesterol and gamma-GTP did not differ significantly in either patient group. In two patients receiving TAB total bilirubin levels showed slight, transient elevations after maximum elevations of AST and ALT. In 80% of patients receiving TAB serum levels of cholinesterase were significantly higher than those in patients receiving PAB. These data suggest that the risk of flutamide-induced liver toxicity is significant in patients receiving TAB. However, this damage can be normalized after flutamide has been discontinued. Serum levels of cholinesterase also increase significantly in patients receiving TAB. This previously unreported phenomenon suggests an unknown effect of flutamide on liver function in patients with prostate cancer.

Oxidative stress during selenium deficiency in seedlings of Trigonella foenum-graecum and mitigation by mimosine Part II. Glutathione metabolism.

Adaptive alterations in glutathione (GSH) metabolism were studied during oxidative stress induced by selenium (Se) deficiency in germinating seedlings of Trigonella foenum-graecum grown for 72 h and the response to supplementation individually of Se or mimosine was explored. Growth enhancement with improved mitochondrial efficiency was elicited by supplementation of Se at 0.5-0.75 ppm or mimosine at 0.1-0.2 mM. Total thiol and protein levels of mitochondrial and soluble fractions, in general, did not vary significantly with supplementation of either Se or mimosine except that the mitochondrial protein levels in mimosine groups (0.1-0.2 mM) decreased by 20-30%. Mitochondrial glutathione peroxidase (GSH-Px) increased by twofold in activity toward H2O2, cumene hydroperoxide (CHP), and t-butyl hydroperoxide (tBHP) in Se groups, and by 50-60% increase toward H2O2 and CHP but by a twofold enhancement in enzyme activity with tBHP in mimosine groups. Soluble GSH-Px activity increased by 30-40% only in mimosine groups and remained unaltered in Se groups. Glutathione S-transferase activity (GST) in the soluble fraction of both Se and mimosine groups increased dramatically by fivefold to sixfold. Distinct differences were noted in the response of the stressed seedlings toward exposure to Se or mimosine and included a decline in glutathione reductase (GR) activity by 50-60% in both mitochondria and soluble fractions of Se groups and an increase in GR activity of the mitochondria by twofold and of the soluble enzyme activity by 30% in the mimosine groups. Mimosine exposure resulted in a dose-dependent decrease in the gamma-glutamyl transpeptidase levels, but, in contrast, a significant enhancement by 50% was noted in the Se group at 0.75 ppm. The results including the differential response of GR activity to Se or mimosine supplementation are reflective of an effective reductive environment in Se groups and increased turnover of GSH in the presence of mimosine.

Ursodeoxycholic acid treatment in children with Byler disease

There have been a few reports of patients with Byler disease and the best medical treatment is not known. The aim of the present study is to show the effect of ursodeoxycholic acid (UDCA) on clinical, laboratory and histologic findings in children with Byler disease. Nine children aged between 1.5 and 9 years with Byler disease were administered UDCA orally at doses of 15-20 mg/kg per day. They were followed for at least 12 months. Clinical, laboratory and histologic outcomes were evaluated after 12 months of treatment. Seven children presented in the first 6 months of life with itching and/or jaundice. Gamma-glutamyl transpeptidase and cholesterol levels were normal in all patients, despite severe cholestasis. With UDCA therapy, pruritus disappeared/diminished in four (44.4%) patients. The mean serum concentrations of alanine aminotransferase, aspartate aminotransferase (AST), total and conjugated bilirubin decreased, although it was significant only for AST (P = 0.01). Before treatment, all biopsy materials showed cellular/canalicular cholestasis and fibrosis. After UDCA therapy cholestasis was ameliorated. Two patients died during follow up. The results suggest that administration of UDCA leads to clinical and biochemical improvement in children with Byler disease. The UDCA ameliorates symptoms partially, improves the life quality of patients and may be given for as long as the disease continues.

Ursodeoxycholic acid treatment in children with Byler disease

Abstract Background: There have been a few reports of patients with Byler disease and the best medical treatment is not known. The aim of the present study is to show the effect of ursodeoxycholic acid (UDCA) on clinical, laboratory and histologic findings in children with Byler disease. Methods: Nine children aged between 1.5 and 9 years with Byler disease were administered UDCA orally at doses of 15–20 mg/kg per day. They were followed for at least 12 months. Clinical, laboratory and histologic outcomes were evaluated after 12 months of treatment. Results: Seven children presented in the first 6 months of life with itching and/or jaundice. Gamma-glutamyl transpeptidase and cholesterol levels were normal in all patients, despite severe cholestasis. With UDCA therapy, pruritus disappeared/diminished in four (44.4%) patients. The mean serum concentrations of alanine aminotransferase, aspartate aminotransferase (AST), total and conjugated bilirubin decreased, although it was significant only for AST (P=0.01). Before treatment, all biopsy materials showed cellular/canalicular cholestasis and fibrosis. After UDCA therapy cholestasis was ameliorated. Two patients died during follow up. Conclusions: The results suggest that administration of UDCA leads to clinical and biochemical improvement in children with Byler disease. The UDCA ameliorates symptoms partially, improves the life quality of patients and may be given for as long as the disease continues.

Gamma-glutamyl transpeptidase is up-regulated on memory T lymphocytes.

The ectoenzyme gamma-glutamyl transpeptidase (GGT) hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH levels and modifies the activity of GSH-containing adducts. Previous data suggested that this enzyme was present on mitogen-activated T lymphocytes. However, the level of GGT protein expression on human mononuclear cell subsets has not been determined. A novel mAb to human GGT, 3A8, was developed. 3A8 was used to show that the expression of GGT is, in fact, highest on resting T cells that express markers of the memory phenotype, specifically CD45RO and decreased expression of CD45RB. The peripheral blood of patients with rheumatoid arthritis was found to have expanded numbers of T cells expressing levels of GGT up to 10-fold higher than controls. In addition, the CD4(+) T cell subset with the capacity to migrate across a human endothelial cell monolayer expresses high GGT levels. GGT expression was up-regulated on peripheral blood T cells following activation in vitro by either superantigen, phorbol ester, or IL-15, a stimulatory cytokine synthesized in rheumatoid synovium. Resting peripheral blood T cells that express GGT have higher levels of intracellular thiols than those that do not. These observations suggest that GGT may play an important role in the regulation of lymphocytes that are at a particular developmental stage.

Serum leucine aminopeptidase as an activity indicator in systemic lupus erythematosus: a study of 46 consecutive cases.

To determine whether elevations in serum leucine aminopeptidase (LAP) levels reflected the underlying evolution of active disease in systemic lupus erythematosus (SLE). We studied serum LAP levels, other laboratory indicators, and SLE Disease Activity Index (SLEDAI) scores, in 46 consecutive patients with SLE admitted to Tokyo Metropolitan Komagome Hospital. LAP levels in 46 patients with rheumatoid arthritis were also measured. Thirty-three SLE patients had elevated LAP levels. LAP levels correlated positively with levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase, and negatively with the total serum haemolytic complement and leucocyte, neutrophil and lymphocyte counts, but showed no correlation with alkaline phosphatase, gamma-globulin, beta2-microglobulin or C-reactive protein levels, or platelet count. The SLEDAI score correlated positively with LAP levels. The LAP level in patients with rheumatoid arthritis was near normal. The serum LAP level may be a potential activity indicator for SLE.

Biochemical effects of some pesticides on lipid peroxidation and free-radical scavengers

Oxidative stress was studied in blood samples obtained from lindane, malathion and propoxur poisoning cases admitted to the Guru Teg Bahadur Hospital, Delhi and evaluated for lipid peroxidation, oxygen free radical (OFR) scavenging enzymes, and glutathione (GSH) and related enzymes. Acetylcholine esterase (AChE), gamma glutamyl transpeptidase (GGT) and GSH level were also assayed in lymphocytes. The level of thiobarbituric acid reacting substances and activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and GGT were increased and GSH level was decreased in pesticide poisoning. Apparently lindane (at the concentration examined) was more potent than malathion and propoxur in producing alteration in lipid peroxidation, GSH related parameters and OFR scavenging enzymes. However, AChE activity and GSH level in lymphocytes of malathion poisoning cases were reduced and GGT activity was enhanced in comparison to control subjects. The present results suggest that OFR scavenging enzymes were induced while combating oxidative stress in a differential manner in organochlorine, organophosphate and carbamate poisoning. Increased lipid peroxidation, coupled with altered levels of GSH and OFR scavenging enzymes in the blood are discussed in the light of oxidative stress.

Clinicopathological study of chronic hepatitis induced by alcohol with or without hepatitis G virus.

The concept of chronic hepatitis induced by alcohol (AL-CH) has not been widely accepted, because AL-CH may be due to non-A-E hepatitis virus in heavy drinkers. Recently, hepatitis G virus (HGV) was identified as a positive-strand RNA virus related to members of the Flaviviridae family. In this study, we determined serum HGV in patients with AL-CH and analyzed the clinicopathological changes after abstinence to evaluate whether AL-CH is caused by alcohol or not. Serum samples were obtained from 16 patients with AL-CH who had neither hepatitis B nor C virus. The diagnosis was confirmed histologically. In eight patients, liver biopsy was performed twice, within 3 days and 4 to 8 weeks after abstinence. The NS3 region of the HGV genome was detected using an reverse transcriptase-polymerase chain reaction method. Serum levels of AST, ALT and gamma-glutamyltranspeptidase were measured once a week sequentially after admission. Serum HGV-RNA was detected in only one patient with AL-CH (6.3%). In all patients, including one patient with HGV, serum levels of AST, ALT and gamma-glutamyltranspeptidase clearly decreased to normal levels after abstinence. Inflammatory activity in the periportal area of patients with actively drinking decreased or disappeared after abstinence for 4 to 8 weeks. These results suggest that HGV may not play an important role for development of AL-CH, and that AL-CH may be caused by alcohol itself, although a more larger number of patients with AL-CH are needed to obtain definitive conclusions.

Biochemical profiles of hydatid cyst fluids of Echinococcus granulosus of human and animal origin in Libya

A comparative study on the biochemical parameters in hydatid cyst fluids of sheep, goats, camels, cattle and human cystic forms of Echinococcus granulosus has been made in Libya. Quantitative variations in the levels of sodium, potassium, calcium, cholesterol, glucose, urea, creatinine and gamma glutamyl transpeptidase (γGT) were found in the cystic fluids of different host origins although these differences were statistically insignificant compared with the hydatid fluids of sheep. However, the concentration of triglycerides and proteins were significantly elevated in the cyst fluids of sheep compared with the other fluids studied. Similarities in the biochemical composition of different hydatid cyst fluids suggest the existence of sheep strains of E. granulosus in human and other domestic animal intermediate hosts in Libya.

Altered expression of gamma-glutamyl transpeptidase in human tumors

Elevated levels of gamma-glutamyl transpeptidase (GGT) activity and intracellular glutathione in tumor cells have been correlated with resistance to several classes of chemotherapeutic drugs. In this study, the first comprehensive analysis of GGT expression in human malignant neoplasms, 451 tumors were immunostained with an antibody directed against a c-terminus peptide of the human GGT protein. Analysis of the immunostaining revealed that GGT was expressed in 22 of 44 lung carcinomas and 16 of 22 ovarian surface epithelial carcinomas, although normal pulmonary and ovarian epithelium are GGT-negative. The tumor samples were obtained from patients before the start of therapy; therefore, GGT was not induced by radiation or chemotherapy. There was no GGT expression in mesotheliomas, Hodgkin's disease, non-Hodgkin's lymphomas, melanomas, basal cell carcinomas, and most soft tissue sarcomas, all of which are derived from GGT-negative cells. Carcinomas arising from some GGT-positive epithelium retained their GGT-positive phenotype. These included renal cell carcinomas, hepatocellular and cholangiocarcinomas, and carcinomas of the prostate and thyroid whereas both pancreatic adenocarcinomas and infiltrating carcinomas of the breast showed a wide range of GGT expression. Further studies are underway to determine whether expression of GGT plays a role in the inherent resistance of some tumors to alkylating agents and other classes of chemotherapeutic drugs.