Elevated Glutamic Pyruvic Transaminase Research Articles

Intrahepatic cholestasis of pregnancy: machine-learning algorithm to predict elevated bile acid based on clinical and laboratory data.

Applying machine-learning models to clinical and laboratory features of women with intrahepatic cholestasis of pregnancy (ICP) and creating algorithm to identify these patients without bile acid measurements. This retrospective study included 336 pregnant women with a chief complaint of pruritis without rash during the second/third trimesters. Data extracted included: demographics, obstetric, clinical and laboratory features. The primary outcome was an elevated bile acid measurement ≥ 10µmol/L, regardless of liver enzyme levels. We used different machine-learning models and statistical regression to predict elevated bile acid levels. Among 336 women who complained about pruritis, 167 had bile acids ≥ 10µmol/L and 169 had normal levels. Women with elevated bile acids were older than those with normal levels (p = 0.001), higher parity (p = 0.001), and higherglutamic oxaloacetic transaminase ( GOT) (p = 0.001) and glutamic-pyruvic transaminase (GPT) levels (p = 0.001). Using machine-learning models, the XGB Classifier model was the most accurate (area under the curve (AUC), 0.9) followed by the K-neighbors model (AUC, 0.86); and then the Support Vector Classification (SVC) model (AUC, 0.82). The model with the lowest predicative ability was the logistic regression (AUC, 0.72). The maximum sensitivity of the XGB model was 86% and specificity 75%. The best predictive parameters of the XGB model were elevated GOT (Importance 0.17), elevated GPT (Importance 0.16), family history of bile disease (0.16) and previous pregnancy with ICP (0.13). Machine-learning models using clinical data may predict ICP more accurately than logistic regression does. Using detection algorithms derived from these techniques may improve identification of ICP, especially when bile acid testing is not available.

Clinical characteristics and prognosis of sepsis-associated liver injure in pediatric intensive care unit

Objective To discuss the incidence, clinical characteristics of sepsis-associated liver injure in pediatric patients and risk factors that may affect the prognosis. Methods A retrospective analysis was made on the data of patients with sepsis-associated liver injure that had been hospitalized in Shanghai Children′s Hospital from January 2011 to December 2015.The cases were divided into the survival group and the death group.Logistic regression analysis was made to screen out risk factors of patients with sepsis-associated liver injure that influence the prognosis. Results The incidence of sepsis associated liver dysfunction was 9.7%(120/1 242), the mortality rate was 35.8%(43/120). The most common focus of infection was respiratory tract infection(50.0%), followed by abdominal cavity infection(33.3%) and central nervous system infection(6.7%). The pathogenic microorganisms were mainly gram-negative bacilli(51.3%), followed by virus(26.5%) and gram-positive bacterium(17.7%). The main manifestations of the liver injure were elevated glutamic-pyruvic transaminase(117 cases, 97.5%), prolonged prothrombin time(PT)(93 cases, 77.5%), hypoproteinemia(83 cases, 69.2%) and hyperbilirubinemia(70 cases, 58.3%). The total bilirubin(TBIL), PT, activated partial thromboplastin time and total bile acid of the death group were higher than thoes of the survival group.Logistic regression analysis indicated that elevated TBIL(OR=2.937, 95%CI 1.179-7.315, P=0.021) was the independent risk factor for death.The area under receiver operating characteristic curve for TBIL(cut off was 64.5 μmol/L)was 0.736 with sensitivity 57.7% and specificity 84.8%. Conclusion The incidence rate of sepsis-associated liver injure among pediatric patient is high.Gram-negative bacilli are the main pathogenic microorganisms.This disease is manifested as the elevated glutamic-pyruvic transaminase, hypoproteinemia, prolonged PT and hyperbilirubinemia.Hyperbilirubinemia is the independent risk factor that influences the prognosis. Key words: Sepsis; Total Bilirubin; Sepsis-associated liver injure; Pediatric intensive care unit; Children,

Protective action of the phyllanthin against carbon tetrachloride-induced hepatocyte damage in Cyprinus carpio.

The present study was to investigate the protective effect and possible mechanism of phyllanthin against carbon tetrachloride (CCl4)-induced hepatocyte damage in carp. Phyllanthin (5, 10, and 15 μg/ml) was added to carp primary hepatocytes before (pre-treatment) and after (post-treatment) incubation of the hepatocytes in medium containing CCl4 at 8 mM; supernatant and cell were collected for the analyses of cell viability, biochemical parameters, and gene expression. The results showed that phyllanthin at the concentration of 15 μg/ml significantly suppressed the elevation of glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), lactate dehydrogenase (LDH), and malondialdehyde (MDA), and the reduction of cell viability, superoxide dismutase (SOD) activity, cytochrome P450 1a (CYP1A), and cytochrome P450 3a (CYP3A) messenger RNA (mRNA) levels expect LDH in the post-treatment. The levels of GPT, GOT, and CYP1A mRNA were also effectively restored in the pretreatment with phyllanthin (10 μg/ml). Overall, our results suggested that phyllanthin may be used as a hepatoprotective agent to prevent liver diseases in fish.

Non-alcoholic fatty liver in children and adolescents with excess weight and obesity

Basis and objectiveHepatic steatosis, also known as non-alcoholic fatty liver (NAFL), is the most frequent liver disease in obese children. Due to an increase in infantile obesity, it is experiencing a significant increment in incidence. Our objectives are: estimate the prevalence of NAFL in children with excess weight and obesity using the glutamate pyruvate transaminase (GPT) value as a biochemical test and an abdominal ultrasound, and correlate the presence of hepatic steatosis with various anthropometric and biochemical parameters. Patients and methodCross-sectional prevalence study which includes children with excess weight and obesity between the ages of 5 and 15 years, between the years 2004 and 2012. The independent variables included were: age, sex, weight, size, body mass index (BMI), waist circumference (WC), waist size index (WSI), insulinemia, Homeostasis model assessment-insulin resistance (HOMA-R), total cholesterol, triglycerides (TG), high density lipoproteins (HDL), low density lipoproteins (LDL), glutamic-oxaloacetic transaminase (GOT), GPT and gamma-glutamyl transpeptidase (GGT). ResultsOne hundred and twenty-six patients, with an average age of 11.94 (3.12) years were recruited. A percentage of 19.66 of the patients presented elevated GPT pathology. Of the 126 abdominal ultrasounds performed, 38 patients presented hepatic steatosis (30.15%). The levels of insulinemia, HOMA-R and LDL were significantly higher in patients with altered GPT, compared to those with normal GPT values (P=.015, P=.008 and P=.002, respectively). The patients with an objective HGNA in ultrasound, also showed greater levels of insulinemia, WC, WSI, total cholesterol, TG, LDL, GLT, GPT and GGT than the patients with normal ultrasounds, thereby achieving statistical significance in insulinemia, HOMA-R, LDL and GPT values. ConclusionsNAFL is a relatively frequent disorder in obese children and adolescents. In our study, 2 of 10 children – using GPT – and 3 of every 10 – using abdominal ultrasound – present the same. The biochemical marker which best defines it is an elevation in GPT. A modification in lifestyle which includes weight loss as a principal means of avoiding complications in adult life, is essential and necessary.

Hígado graso no alcohólico en pacientes con sobrepeso y obesidad infantojuvenil

Basis and objectiveHepatic steatosis, also known as non-alcoholic fatty liver (NAFL), is the most frequent liver disease in obese children. Due to an increase in infantile obesity, it is experiencing a significant increment in incidence. Our objetives are: Estimate the prevalence of NAFL in children with excess weight and obesity using the glutamate pyruvate transaminase (GPT) value as a biochemical test and an abdominal ultrasound, and correlate the presence of hepatic steatosis with various anthropometric and biochemical parameters. Patients and methodCross-sectional prevalence study which includes children with excess weight and obesity between the ages of 5 and 15 years, between the years 2004-2012. The independent variables included were: age, sex, weight, size, body mass index (BMI), waist circumference (WC), waist size index (WSI), insulinemia, Homeostasis model assessment-insulin resistance (HOMA-R), total cholesterol, triglycerides (TG), high density lipoproteins (HDL), low density lipoproteins (LDL), glutamic-oxaloacetic transaminase (GOT), GPT and gamma-glutamyl transpeptidase (GGT). ResultsOne hundred and twenty-six patients, with an average age of 11.94 (3.12) years were recruited. A percentage of 19.66 of the patients presented elevated GPT pathology. Of the 126 abdominal ultrasounds performed, 38 patients presented hepatic steatosis (30.15%). The levels of insulinemia, HOMA-R and LDL were significantly higher in patients with altered GPT, compared to those with normal GPT values (P=.015, P=.008 and P=.002, respectively). The patients with an objective HGNA in ultrasound, also showed greater levels of insulinemia, WC, WSI, total cholesterol, TG, LDL, GLT, GPT and GGT than the patients with normal ultrasounds, thereby achieving statistical significance in insulinemia, HOMA-R, LDL and GPT values. ConclusionsNAFL is a relatively frequent disorder in obese children and adolescents. In our study, 2 of 10 children –using GPT– and 3 of every 10 –using abdominal ultrasound– present the same. The biochemical marker which best defines it is an elevation in GPT. A modification in lifestyle which includes weight loss as a principal means of avoiding complications in adult life, is essential and necessary.

907 Diagnosing Infectious Mononucleosis in Primary Care - Case Studies from a Pediatric Outpatient Clinic

BackgroundAlthough a common viral disease Infectious Mononucleosis may represent a diagnostic challenge for the primary care physician.ObjectivesTo describe the clinical and biological features of Infectious Mononucleosis by analizing cases diagnosed,...

Low Prevalence of Chronic Hypertransaminasemia in a Cohort of HIV-Infected Patients with No Coinfections

Liver disease is very common in patients with HIV infection. The association between chronic infection with hepatotropic viruses and being a target for other diseases, such as opportunistic infections and tumors, nonalcoholic fatty liver disease (NAFLD), and toxicity to drugs, including antiretroviral therapy (ART), results in liver disease being a leading cause of morbidity and mortality in these persons. The aim of this study was to determine the prevalence of chronic hypertransaminasemia (CHT) in a cohort of patients with HIV infection but no coinfection and to examine the factors associated with CHT. We undertook a cross-sectional, case-control study of all HIV-infected patients who regularly attended the infectious diseases office of our center from March to August 2009. A case was defined as any patient with glutamate pyruvate transaminase (GPT) values above normal (78 IU/L) at least 2 consecutive revisions (3 months or more between the 2 measurements). Patients were excluded if they had a positive serology to a hepatotropic virus or opportunistic events during the previous month. A control was defined as a patient attending the office paired for age (+5 years) and sex with a case and who had a normal GPT value, using the same exclusion criteria as for the cases. Hepatotoxicity of ART was defined as CHT due to ART, and to make this diagnosis, other causes of elevated GPT values were ruled out in all cases and NAFLD by the presence of steatosis in an abdominal ultrasound in patients consuming <50 g/d of alcohol. The statistical analysis was done with SPSS 17.0 (SPSS, Chicago, Illinois). During the study period, 861 patients attended the office, of whom 454 (52.7%) had a negative serology for hepatotropic virus. Of these, 31 met the inclusion criteria, giving a prevalence of CHT of 6.8%. Most were men, the mean age was 45.7 years, and the predominant mode of transmission of the HIV infection was sexual. In all cases except 1, the elevation of the GPT was mild (<3 times the normal values). The only parameter that differed between cases and controls was a greater body mass index in the cases. Table 1 shows the characteristics of the cases and controls. There were no differences in the use of ART. At least 1 other drug was being taken by 61.2% of the 31 cases and 48.3% of the controls. Lipidlowering drugs were being taken by more of the cases than the controls (15 versus 7, P < .05). An abdominal ultrasound was performed in 11 patients, 9 of whom showed signs of hepatic steatosis. No case had signs of portal hypertension. Liver stiffness could be assessed by elastometry (FibroScan) in 20. The mean stiffness was 5.9 Kps, with a range of 3.3 to 8.8 kPa. No patient had a liver biopsy. The most usual clinical diagnosis attributable to the CHT was ART toxicity, followed by NAFLD. Three patients were convalescing from hepatitis A virus (HAV) infection and 1 from secondary syphilis. Three patients required withdrawal of ART because of the CHT (Table 1). The prevalence of CHT in our series was much lower than the previously reported 11% to 15% values. The prevalence of CHT in a large Swiss cohort was 13.2%, and it was associated with alcohol consumption, NAFLD, and the use of ART. The same study found the incidence to be 3.9 cases per 100 person-years. These differences are probably due to the methods used, the study population, and the differences at the time of the study. Of note, although, is the scarce clinical importance, with just 1 case of moderate CHT and few patients having to cease ART. On the other hand, although only just over one third of our patients had an ultrasound study, NAFLD can currently be considered one of the main causes of CHT in HIV-infected patients with no coinfection. Hepatic steatosis is very usual in the general population, with very large

In vitro and in vivo hepatoprotective and antioxidant effects of Astragalus polysaccharides against carbon tetrachloride-induced hepatocyte damage in common carp (Cyprinus carpio)

The present study is aiming at evaluating the hepatoprotective and antioxidant effects of Astragalus polysaccharide (APS) on the carbon tetrachloride (CCl(4))-induced hepatocyte and liver injury in common carp in vitro and in vivo. In vitro, APS (200, 400 and 800μg/ml) was added to the carp primary hepatocytes before (pre-treatment), after (post-treatment) and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4) at 8mM in the culture medium. APS at concentrations of 200, 400 and 800μg/ml significantly improved cell viability and inhibited the elevation of glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), lactate dehydrogenase (LDH) and malondialdehyde (MDA) and significantly increased the reduced level of superoxide dismutase (SOD). In vivo administration of APS at the doses of 1.5 and 3g/kg in the diet for 60days prior to CCl(4) intoxication significantly reduced the elevated activities of GPT, GOT and LDH and increased the reduced levels of total protein and albumin in the serum; meanwhile, the reduced levels of SOD, glutathione and total antioxidant capacity (T-AOC) were markedly increased and the MDA formation was significantly inhibited in liver tissue. Overall results proved the hepatoprotective action of APS, which is likely related to its antioxidant activity. The results support the use of APS as a hepatoprotective and antioxidant agent in fish.

Hepatoprotection of Gentiana scabra Extract and Polyphenols in Liver of Carbon Tetrachloride-Intoxicated Mice

In traditional Chinese medicine, the rhizomes of Gentiana scabra are used to treat hepatitis, stomatitis, and inflammatory diseases. This study aimed to examine the protective effects of G. scabra aqueous extract (GS) and polyphenols in liver of CCl4-intoxicated mice. Antioxidant activities of GS were also evaluated. Results showed that GS exhibited anti-lipid peroxidation, 2,2-diphenyl-1-picrylhydrazyl, and superoxide radical scavenging activities with IC50 values of 45.84, 183.38, and 56.25 μ/mL, respectively. High-performance liquid chromatography analysis revealed that the major polyphenolic constituents of GS were kaempferol, ellagic acid, and quercetin. Daily oral administration of 500 mg/kg GS (GS500) and 1000 mg/kg GS (GS1000) significantly prevented the elevation of glutamic pyruvic transaminase and thiobarbituric acid reactive substances levels, while enhancing the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and serum total antioxidant activity in mice with hepatoxicity. At 1000 mg/kg, GS was as effective as 100 mg/kg silymarin in reducing oxidative stress and preventing liver injury. Histopathological studies further confirmed the hepatoprotective activity of GS. Taken together, these results show that the antioxidant activities and polyphenolic compounds (kaempferol, ellagic acid, and quercetin) of GS may have contributed to its hepatoprotective activity in CCl4-intoxicated mice, and its mechanism of action could be mediated through the reduction of oxidative stress in liver tissue.

Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in children and adolescents with intellectual disabilities

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3–21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value ( R 2 = 0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value ( R 2 = 0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

Diagnosis and treatment of congenital cytomegalovirus infection in neonates

Obiective To summarize the main clinical features, diagnosis and treatment of congenital cytomegalovirus (CMV) infected neonates. Methods Serum CMV antibodies were tested by enzyme-linked immunosorbent assay, and urine CMV-DNA was detected by fluorescent real-time quantitative polymerase chain reaction. From Jan. 2007 to Dec. 2008,145 neonates were diagnosed as congenital CMV infection. Effects and side effects were observed in 56 of 101 symptomatic patients treated with ganciclovir. Results The main clinical manifestations and abnormal laboratory items in symptomatic infection included pathologic jaundice, hepatosplenomegaly, interstitial pneumonitis, petechiae, poor suck, thrombocytopenia, elevated glutamic-pyruvic transaminase. There were 87 patients(60.0%) had positive urine CMV-DNA, 43(29.7%) had positive CMV-IgM, 21(14.5%) had 4 times increase of CMV-IgG titers within 2 weeks after birth, 13 patients showed positive CMV-DNA in urine or CMV-IgM in serum and their serum CMV IgG levels were more than doubled compared to their mothers. There was significant improvement in clinical and laboratory findings after ganciclovir treatment with minimal side effects including lightly decreasing of granulocyte and platelet, but without damage of liver and kidney function. Conclnsions Neonatal congenital CMV infection might lead to multiple organs damage and had various clinical features. Urine CMV-DNA test might have higher positive rate in infected neonates. The other evidence for the diagnosis is positive CMV-IgM and 4 times increasing of CMV-IgG titers. Over two times of the CMV-IgG level in the neonates than in the mothers is one of the laboratory findings also. Ganciclovir is effective in the treatment of symptomatic CMV infection. Key words: Cytomegalovirus infections; Infant, newborn; Ganciclovir

Analysis of the efficacy and safety of gefitinib in the treatment of recurrent advanced non-small cell lung cancer in an expanded access program (EAP)

The aim of this study is to evaluate the efficacy and safety of Gefitinib in the treatment of Chinese patients with recurrent advanced non-small-cell lung cancer (NSCLC). 120 patients were enrolled in this trial from September 2002 to March 2005, and 103 patients were evaluable. All patients were histologically or/and cytologically confirmed to have a locally advanced or metastatic NSCLC, and failed to previous standard treatments. The patients received orally 250 mg of Gefitinib once daily until the disease progression or intolerance to toxicity. First evaluation of response was undertaken one month after drug initiation, then every 2 or 3 months till disease progression. Each patient was followed up every 6 months untill death or end of follow-up. Among the 103 evaluable patients, the objective response rate was 18.4% (19/103), and the disease control rate was 51.5% (53/103). The median time to progression (mTTP) was 3 months (range: 0.2 approximately 40), the median survival time (MST) was 9.8 months (range: 0.5 approximately 51), the 1-, 2-, 3-year survival rates were 44.7%, 26.4% and 13.2%, respectively. The TTP of 41 patients was longer than 6 months with a MST of 25.5 months. The results of COX model analysis suggested that the patients with adenocarcinoma, rash and favourable performance status (PS) had longer TTP. The patients with favourable PS and well controlled disease had longer survival time. Adverse events included skin rash, dry skin, diarrhea and elevation of serum glutamate pyruvate transaminase (SGPT), and were usually mild. Gefitinib is effective in treatment of patient with recurrent advanced NSCLC. The patients with controlled disease may achieve a long survival, and the adverse reactions are mild and tolerable.

Preventive and curative role of a 43kD protein from the leaves of the herb L on thioacetamide-induced hepatotoxicity in vivo

An approximately 43kD protein has been isolated and purified from the herb Cajanus indicus L and believed to be the most active principle for its hepatoprotective action. In this study, experiments have been performed to evaluate the effectiveness of that protein for the preventive and curative action against thioacetamide-induced toxicity in vivo using a murine model. Mice were treated with the protein intraperitoneally at a dose of 2mg/kg body weight for 2 and 6 days before and separately 1-5 days after thioacetamide administration to evaluate its preventive and curative role, respectively. Thioacetamide was administered once at a dose of 150mg/kg body weight and after 48h of its application, the animals were sacrificed. Levels of various markers related to physiological and pathological conditions of the liver, e.g., glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), etc. were determined in the murine sera under different experimental conditions. In addition, antioxidant enzymes glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) as well as thiobarbituric acid reactive substances (TBARS), were measured from the liver homogenates. The antioxidant property of the protein was compared with the potent antioxidant, vitamin E (used as a positive control). The active principle effectively reduced the elevated GPT and ALP levels in serum and lipid peroxidation in the liver tissue. The reduced levels of SOD, CAT and GST by thioacetamide were again brought back to almost normal levels upon pre- and post-treatment with the protein. Histopathological changes in the liver of TAA control and protein-treated groups also prove that the protein possesses hepatoprotective activity. The protein acts dose-dependently and maximum hepatoprotectivity was obtained when administered at a dose of 2mg/kg body weight. Data suggest that the active principle plays an important preventive and curative role against thioacetamide-induced hepatotoxicity.

Antioxidant and hepatoprotective activities of low molecular weight sulfated polysaccharide from Laminaria japonica

A low molecular weight sulfated polysaccharide (LMWF) was prepared from Laminaria japonica by mild acid hydrolysis. The antioxidant activity of LMWF in vitro was studied using three kinds of oxygen free radical systems. LMWF had effective scavenging abilities on superoxide radical, hydroxyl radical and hypochlorous acid directly in vitro. The hepatoprotective effect of LMWF was studied using two acute liver injury mice models induced by carbon tetrachloride (CCl4) and D-galactosamine (D-GalN). Addition of LMWF significantly lowered the content of serum malonaldehyde and markedly increased the activities of superoxide dismutase and glutathione peroxidase, compared with the model groups in both kinds of liver injury mice. Moreover, administration of LMWF significantly inhibited the elevation of glutamate pyruvate transaminase induced by CCl4 and D-GalN in mice. The results suggest that the antioxidant activity of LMWF plays an important role in its hepatoprotective effect in the liver injury mice induced by CCl4 and D-GalN.

Hepatoprotective and antioxidative properties of Salacia reticulata: preventive effects of phenolic constituents on CCl4-induced liver injury in mice.

The hepatoprotective effects of the hot water (SRHW) and methanolic (SRM) extracts from the roots and stems of Salacia reticulata were examined using an oxidative stress-induced liver injury model. Both SRHW and SRM extracts (400 mg/kg, p.o.) significantly suppressed the increase in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in carbon tetrachloride (CCl4)-treated mice. These extracts also inhibited CCl4-induced thiobarbituric acid-reactive substance (TBA-RS) formation, which indicates increased lipid peroxidation in the liver. A good correlation (r=0.945, p<0.01) was observed between the amount of phenolic compounds in the extracts and their inhibitions of TBA-RS formation. The IC50 values of the extracts on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging were less than 10 microg/ml and the antioxidative activities of six phenolic compounds from the roots of S. reticulata were examined. Mangiferin, (-)-4'-O-methylepigallocatechin, and (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin, which a principal phenolic compounds, showed potent scavenging activity on DPPH radicals and their concentrations required for 50% reduction of 40 microM DPPH radicals were 5.9, 10, and 3.2 microM, respectively. On the other hand, against the CCl4-induced serum GOT and GPT elevations and TBA-RS formation in mice, mangiferin and (-)-4'-O-methylepigallocatechin showed potent activity at a dose of 100 mg/kg, but (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin did not. These results suggest that the antioxidative activity of the principal phenolic compounds is involved in the hepatoprotective activity of S. reticulata.

The natural history of liver glycogenosis due to phosphorylase kinase deficiency: A longitudinal study of 41 patients

We report a longitudinal study of 41 patients with liver glycogenosis due to phosphorylase kinase deficiency. In their youth, patients displayed hepatomegaly (92%), growth retardation (68%), delayed motor development (52%), hypercholesterolaemia (76%), hypertriglyceridaemia (70%), elevation of glutamate pyruvate transaminase (56%) and fasting hyperketosis (44%). With age, these clinical and biochemical abnormalities gradually disappeared and most adult patients were asymptomatic.

Phase I study of the antifolate N10-propargyl-5,8-dideazafolic acid, CB 3717

The thymidylate synthase (TS) inhibitor CB 3717 was administered intravenously to 24 adult patients as a single bolus repeated every 3–4 weeks. The doses were escalated from 50 to 400 mg/m 2 . At the highest level, hydration and urinary alkalinization were routinely performed. A > 20% decrease of the creatinine clearance value occurred in 35% of the cycles performed at 400 mg/m 2 , a dose which could be recommended for phase II studies. Hepatic toxicity, represented by an increase of the glutamic pyruvic transaminase (GPT) plasma levels, occurred in 70% of the patients after the first cycle. GPT peak levels were neither related to the dose nor to the peak drug plasma concentrations or AUC values in the dose range from 225 to 400 mg/m 2 . Malaise, reported after 46% of the cycles, was the most disturbing side-effect and its occurrence was statistically correlated with the degree of elevation of GPT. A suggestion of antitumor activity was reported for dosages of 300 and 400 mg/m 2 in three patients with ovarian cancer refractory to cisplatin. Further clinical evaluations of TS inhibitors rely on the development of more water soluble and less hepato- and nephrotoxic agents.

Prevention of Acetaminophen and Cocaine Hepatotoxicity in Mice by Cimetidine Treatment

Hepatotoxicity occurs in animals after administration of large doses of acetaminophen and cocaine and is thought to result from production of reactive metabolites of these parent drugs by cytochrome P450. Because cimetidine binds to cytochrome P450 and inhibits hepatic drug metabolism in both humans and animals, we determined the effects of cimetidine coadministration on acetaminophen and cocaine hepatotoxicity in mice. Marked elevations of serum glutamic pyruvic transaminase and severe pericentral hepatocellular necrosis occurred in animals receiving intraperitoneal doses of 350 mg/kg acetaminophen or 35 mg/kg cocaine, while minimal serum glutamic pyruvic transaminase elevations and liver necrosis were seen in animals who also received 100 mg/kg cimetidine 1 h before and 1 h after administration of either acetaminophen or cocaine. Consistent with the hypothesis that these in vivo protective effects resulted from interaction with cytochrome P450, cimetidine inhibited in vitro hepatic microsomal metabolism of cocaine. However, despite its protective effect against acetaminophen-induced hepatic injury, concomitant administration of cimetidine did not significantly affect plasma pharmacokinetics of acetaminophen, prevent depletion of hepatic glutathione after acetaminophen administration, or alter in vivo covalent binding of [3H]acetaminophen to hepatic proteins. These studies suggest that current theories regarding production of acetaminophen-induced liver damage require reexamination. The possibility that cimetidine treatment might be useful in preventing hepatic damage due to acetaminophen and other hepatotoxins in humans is intriguing and also warrants consideration.

Effects of geniposide isolated from Gardenia jasminoides on metabolic alterations in high sugar diet-fed rats.

The effects of geniposide isolated from Gardeniae Fructus ("San-shi-shi"in Japanese) on metabolic alterations in high sugar diet-fed rats were investigated. It was found that the oral administration of the high sugar diet caused hyperlipemia, liver injury with elevation of glutamic pyruvic transaminase (GPT) in the serum, and the accumulation of lipid peroxide in the liver. Geniposide reduced the serum triglyceride, lipid peroxide, phospholipid, glucose, insulin and GPT in the high sugar diet-fed rats. It was found that the administration of geniposide reduced the sucrase activity in the small intestine and the deposition of lipid peroxide in the liver.

Hepatic Transaminase Activity in Alcoholic Liver Disease

Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activity were measured in precutaneous needle biopsy specimens of human liver tissue and compared with transaminase values in serum obtained on the day of biopsy. Hepatic GPT activity was significantly decreased in liver tissue of patients with alcoholic hepatitis and cirrhosis compared with the activity in individuals with normal livers (P less than 0.05) and individuals with primary biliary cirrhosis (P less than 0.05). The decreased hepatic GPT activity was not related to the presence of cirrhosis in biopsy specimens and was not increased by the addition of saturating amounts of pyridoxal phosphate to the assay mixture. Hepatic GOT was also slightly but significantly lowered in individuals with alcoholic liver disease (P less than 0.05). The GOT/GPT ratio in serum and liver tissue was increased only in individuals with alcoholic liver disease, but the increase did not reach statistical significance. The increased GOT/GPT ratio is due primarily to the low activity of GPT in liver and serum. The less than expected elevation of GPT in serum of patients with alcoholic hepatic reflects the diminished hepatic GPT activity and lesser amounts of this enzyme available to leak into serum from damaged hepatocytes.