Inchin-ko-to (ICKT) prevents Fas-mediated liver injury. This study evaluates the effect of ICKT on conventional markers of liver function (LF) and liver fibrosis in 18 postoperative biliary atresia (BA) patients aged 3 to 23 years with elevated glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (gammaGTP) but normal serum total bilirubin (T-Bil) levels. ICKT (0.15 g/kg per day) was administered orally for 1 year. Serum GOT, GPT, gammaGTP, total bile acids (TBA), and T-Bil as markers of LF and hyaluronic acid (HA), prolyl hydroxylase (PH), procollagen III peptide (PIIIP), and type IV collagen as markers of liver fibrosis were measured before and after treatment in each patient and compared statistically. All patients tolerated ICKT well, and there were no side effects. The percentage of subjects who improved after ICKT was 45% for serum GOT, 72% for GPT, 72% for gammaGTP, 72% for TBA, 67% for HA, 40% for PH, 50% for PIIIP, and 23% for type IV collagen. Changes in the mean values of all serum markers were statistically significant (P < 0.01). It is concluded that long-term administration of ICKT in postoperative BA patients improves liver status as assessed by markers of LF and fibrosis.

The effect of phenobarbital on the expression of calcium-binding protein regucalcin mRNA in rat liver was investigated. The change of regucalcin mRNA levels was analyzed by Northern blotting using liver regucalcin cDNA (0.9 kb of open reading frame). Phenobarbital (4, 8 and 12 mg/ 100 g body weight) was intraperitoneally administered to rats 3 times with 24 h intervals, and the animals were sacrificed by bleeding at 24 h after the last administration. The hepatic regucalcin mRNA levels were markedly reduced by phenobarbital administration. This decrease was about 50% of control level with the 12 mg/100 g dose. Moreover, the hepatic regucalcin concentration was significantly decreased by the administration of phenobarbital (12 mg/100 g), although the serum regucalcin concentration was not altered appreciably. Meanwhile, serum transaminases (GOT and GPT) activities were not increased by the administration of phenobarbital (4 and 12 mg/100 g). The present study demonstrates that the expression of hepatic regucalcin mRNA is decreased by phenobarbital administration in rats, suggesting that regucalcin does not have a role in drug metabolism related to phenobarbital.

The alteration in calcium-binding protein regucalcin in the liver and serum of rats with streptozotocin (STZ)-diabetic state or ethanol ingestion was investigated. STZ (6.0 mg/100 g body weight) was subcutaneously administered in rats, and 1 or 3 weeks later they were sacrificed by bleeding. Liver regucalcin mRNA levels were not clearly altered by the diabetic state, as evidenced by Northern blotting using regucalcin cDNA (0.9 kb of open reading frame). Based on enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG, hepatic regucalcin concentration was decreased about 50% of control levels by STZ treatment. However, serum regucalcin concentration was not significantly altered by STZ treatment. Meanwhile, when rats ingested ethanol (10 and 30%) in the drinking water for 2 weeks, liver regucalcin mRNA levels were clearly increased, although hepatic regucalcin concentration was significantly decreased. Serum regucalcin concentration was not appreciably altered. Serum transaminases (GOT and GPT) activities were significantly increased at 1 or 3 weeks after STZ administration in rats, while their activities were not altered by ethanol ingestion. The present study demonstrates that hepatic regucalcin concentration is decreased independent of mRNA expression in the STZ-diabetes and during ethanol ingestion in rats.

BACKGROUND

Gemcitabine has been recognized as a standard chemotherapy in advanced pancreas cancer(APC). We conducted a phase II study of a triple combination regimen (GPT) consisting of gemcitabine (G), cisplatin(P) and erlotinib (T) in patients with APC.

METHODS

Chemotherapy-naïve patients with locally advanced or metastatic, histologically confirmed adenocarcinoma of the pancreas were treated with erlotinib 100 mg daily, 1,000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin administered on days 1 and 8, respectively, every 3 weeks.The primary end point was objective response. Secondary end points included progression-free survival, overall survival and toxicity. The study was designed according to the optimal two-stage design.

RESULTS

Twenty-two patients were enrolled between June 2009 and August 2010. No complete response was achieved and partial response was observed in 5 patients (26%), Stable disease in 7 (37%), and progressive disease in 7 (37%). The median time to progression was 4.0 months (95% CI: 2.9–5.1 months), and the median overall survival 6.8 months (95% CI: 3.7–9.9 months). The response rate in stage I reached the target (≥3/22,p0010%) established for movement to stage II but this study was determined to close earlier than planned because of unexpected treatment-related deaths (3 patients).

CONCLUSIONS

The triple regimen of GPT is effective for APC. Treatment related mortalities factored early closure of this GPT protocol. Considering effect and toxicity, this triple regimen seems to offer few benefits to the patients compared with gemcitabine based doublets. (ClinicalTrials.gov number, NCT00922896).

The recent discovery that the potent carcinogen acrylamide (AA) is present in a variety of fried and baked foods raises health concerns, particularly for children, because AA is relatively high in child-favoured foods such as potato chips and French fries. To compare the susceptibility to AA-induced genotoxicity of young versus adult animals, we treated 3- and 11-week-old male gpt delta transgenic F344 rats with 0, 20, 40 or 80 p.p.m. AA via drinking water for 4 weeks and then examined genotoxicity in the bone marrow, liver and testis. We also analysed the level of N7-(2-carbamoyl-2-hydroxyethyl)-guanine (N7-GA-Gua), the major DNA adduct induced by AA, in the liver, testis and mammary gland. At 40 and 80 p.p.m., both age groups yield similar results in the comet assay in liver; but at 80 p.p.m., the bone marrow micronucleus frequency and the gpt-mutant frequency in testis increased significantly only in the young rats, and N7-GA-Gua adducts in the testis was significantly higher in the young rats. These results imply that young rats are more susceptible than adult rats to AA-induced testicular genotoxicity.

An epidemic of Q fever in Berlin affected at least 80 patients (45 females, 35 males; age range 1-75 years). Sheep were identified as the focus of infection: they had been brought to a veterinary clinic because of nonspecific symptoms. The peak incidence of the infection was in April and May, 1992. Most of the patients were staff or students at the veterinary clinic. This is the most northern and, at the same time largest, Q fever epidemic recorded in Germany over the last 28 years. The complement fixation reaction (CFR) was not helpful diagnostically in the acute stage of the disease as it remained negative in the first 14 days (CFR < or = 1:5). Most of the patients had sudden fever to over 40 degrees C, severe headache and dry cough. Pulmonary infiltrates were seen in the chest radiograph of 8 of the 10 patients presented in this contribution. Auscultation was largely negative. Two patients had signs of hepatic involvement (GPT as high as 71 U/l). The drug of choice was doxycycline at a dosage of 200 mg twice daily for 14 days.

Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of N-acetylcysteine (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine and the two in combination, administered 2 h post-paracetamol dose, on mortality, plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activities and hepatic reduced glutathione (GSH) levels were investigated in mice 24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked reduction in plasma GOT and GPT activities to within the normal range, while significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore concluded that cimetidine and N-acetylcysteine may have an additive hepatoprotective action in the treatment of paracetamol overdose.

In this study, PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane), a derivative of alpha-tocopherol, dose-dependently (1-10 mg/kg) ameliorated the increase in plasma aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) levels caused by chronic repeated carbon tetrachloride (CCl4) intoxication in mice. Moreover, PMC significantly improved the CCl4-induced increase of hepatic glutathione peroxidase, reductase, and superoxide dismutase activities. PMC also restored the decrement in the glutathione content of hepatic tissues in CCl4-intoxicated mice. Furthermore, it also dose-dependently inhibited the formation of lipid peroxidative products during carbon tetrachloride treatment. Histopathological changes of hepatic lesions induced by carbon tetrachloride were significantly improved by treatment with PMC in a dose-dependent manner. These results suggest that PMC exerts effective protection in chronic chemical-induced hepatic injury in vivo.

OBJECTIVE

Investigation, whether water-filtered infrared-A (wIRA) irradiation during moderate bicycle ergometer endurance exercise has effects especially on local fat reduction and on weight reduction beyond the effects of ergometer exercise alone.

METHODS

Randomised controlled study with 40 obese females (BMI 30-40 (median: 34.5), body weight 76-125 (median: 94.9) kg, age 20-40 (median: 35.5) years, isocaloric nutrition), 20 in the wIRA group and 20 in the control group. In both groups each participant performed 3 times per week over 4 weeks for 45 minutes bicycle ergometer endurance exercise with a constant load according to a lactate level of 2 mmol/l (aerobic endurance load, as determined before the intervention period). In the wIRA group in addition large parts of the body (including waist, hip, and thighs) were irradiated during all ergometries of the intervention period with visible light and a predominant part of water-filtered infrared-A (wIRA), using the irradiation unit "Hydrosun 6000" with 10 wIRA radiators (Hydrosun Medizintechnik, Müllheim, Germany, radiator type 500, 4 mm water cuvette, yellow filter, water-filtered spectrum 500-1400 nm) around a speed independent bicycle ergometer. MAIN VARIABLE OF INTEREST: change of "the sum of circumferences of waist, hip, and both thighs of each patient" over the intervention period (4 weeks). Additional variables of interest: body weight, body mass index BMI, body fat percentage, fat mass, fat-free mass, water mass (analysis of body composition by tetrapolar bioimpedance analysis), assessment of an arteriosclerotic risk profile by blood investigation of variables of lipid metabolism (cholesterol, triglycerides, high density lipoproteins HDL, low density lipoproteins LDL, apolipoprotein A1, apolipoprotein B), clinical chemistry (fasting glucose, alanin-aminotransferase ALT (= glutamyl pyruvic transaminase GPT), gamma-glutamyl-transferase GGT, creatinine, albumin), endocrinology (leptin, adiponectin (= adipo Q), homocysteine, insulin). All variables were at least measured before and after the intervention period. Ergometry (ECG, blood pressure behaviour, lactate curve with power at 2, 3 and 4 mmol/l) before the intervention period. In addition: nutrition training ahead of and during the intervention period with a nutrition protocol over one week for assessment of the daily energy intake; calculation of basic metabolic rate and total energy requirement. Assessment of undesired effects. Only methods of non-parametric statistics were used, both descriptive (median, percentiles of 25 and 75 (= interquartile range), minimum, maximum) and confirmatory (two-sided Mann-Whitney U test for unpaired samples for the only one main variable of interest). Total error probability: .05 (5%). An intention to treat analysis ITT with last observed carry forward method was used preferably (presented results) and in addition an on treatment analysis OT. Only 2 (treatment group) and 4 (control group) drop-outs occurred (mostly due to lack of time).

RESULTS

The "sum of circumferences of waist, hip, and both thighs of each patient" decreased during the 4 weeks significantly more (p<.001) in the wIRA group than in the control group: medians and interquartile ranges: -8.0 cm (-10.5 cm/-4.1 cm) vs. -1.8 cm (-4.4 cm/0.0 cm). As well "body weight of each patient" decreased during the 4 weeks markedly more in the wIRA group than in the control group: medians and interquartile ranges: -1.9 kg (-4.0 kg/0.0 kg) vs. 0.0 kg (-1.5 kg/+0.4 kg); median of body weight changed from 99.3 kg to 95.6 kg (wIRA) vs. 89.9 kg to 89.6 kg (control). A similar effect showed the body mass index BMI. Blood variables of interest remained unchanged or showed some slight improvements during the treatment period, concerning most variables with no obvious differences between the two groups; insulin showed a slight trend to decrease in the wIRA group and to increase in the control group. Undesired effects of the treatment were not seen.

CONCLUSIONS

The results of the study suggest, that wIRA - during moderate bicycle ergometer endurance exercise as lipolytic stimulus - increases local lipolysis with a local fat reduction (thighs) in the otherwise bradytrophic fatty tissue. The presumably underlying mechanisms of wIRA have already been proven: wIRA acts both by thermal effects and by non-thermal effects. Thermal effects of wIRA are the generation of a therapeutic field of warmth with the increase of tissue temperature, tissue oxygen partial pressure, and tissue blood flow, and by this regional metabolism. As fatty tissue normally has a slow metabolism (bradytrophic and hypothermic tissue) with a low rate of lipolysis, wIRA can increase lipolysis in fatty tissue and the mobilized fats are burned in musculature during the ergometer exercise.

CONCLUSIONS

The results of the study indicate, that wIRA irradiation during moderate ergometer endurance exercise can be used - in combination with an appropriate nutrition - to improve body composition, especially local fat distribution, and the reduction of fat and body weight in obese persons.

Suspensions of isolated rat hepatocytes incubated in the presence of the diabetogenic agent alloxan exhibit time- and concentration-dependent damage. At concentrations of 3.5 mM and above, alloxan caused an increase in lactate dehydrogenase (LDH), glutamate-pyruvate transaminase (GPT) and intracellular potassium (K+) leakage, all of which are indices of plasma membrane damage, and decreased the intracellular reduced glutathione content (GSH) of the cells. Preincubation (10 min) in D-glucose (50 or 100 mM, but not 10 mM) partially protected the hepatocytes from LDH, GPT and K+ leakage and the decrease in GSH produced by alloxan (7 mM) during a 60-min incubation period. Other sugars (D-galactose, 2-deoxy-D-glucose, D-fructose, D-mannoheptulose and D-mannitol) were also found to protect hepatocytes against damage caused by alloxan. D-Fructose was found to be the most potent protective sugar. These results indicate that alloxan is not selectively toxic to the pancreatic beta-cell and that sugars can protect against alloxan-induced cytotoxicity in hepatocytes.

p-Aminophenol (PAP) is a widely used industrial chemical and a metabolite of analgesics, such as acetaminophen (APAP). It was found recently that PAP, a known nephrotoxicant, could cause acute hepatotoxicity in mice but not in rats. The mechanism of hepatotoxicity is not known. The aim of this study was to investigate the role of N-acetylation of PAP to APAP in PAP-induced toxicity. Male C57BL/6 mice injected intraperitoneally (i.p.) with various doses of PAP were sacrificed at 12 hours for measurement of serum glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) levels and determination of the extent of hepatic nonprotein sulfhydryl (NPSH) and glutathione (GSH) depletion. Plasma levels of APAP and its metabolites were measured by HPLC after PAP administration. p-Aminophenol depleted NPSH in a dose- and time-dependent manner. Depletion of NPSH in mouse liver occurred at PAP doses above 400 mg/kg. Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, potentiated the PAP-induced hepatotoxicity. Ascorbate, a reducing agent, did not affect PAP-induced hepatotoxicity and NPSH depletion. After PAP treatment, APAP and its sulfate and glucuronide conjugates as well as GSH conjugates (APAP-cysteine and APAP-mercapturate) were detected in the plasma. The results suggest the roles of GSH and N-acetylation of PAP to APAP in PAP-induced hepatotoxicity.

Ten male rhesus monkeys, each weighing 3.5 kg, were divided into four groups of 3, 3, 2, and 2, and were fed daily with 100 g pelleted food containing 300, 30, 3, and 0 ppm cadmium, respectively. Urine samples were collected every 2 weeks and blood samples every 4 weeks. One monkey each of the 300 and 30 ppm groups was autopsied for pathological examination and tissue cadmium determination at the week 24 of the experiment; the remaining 8 animals were killed after 55 weeks. The lowest exposed group (3 ppm) did not show any specific biological response to cadmium over a period of 55 weeks. In the 30 ppm group, no significant changes were observed for up to 24 weeks, although cadmium concentration in the renal cortex and urine at 24 weeks were 300 mug/g wet weight and 18 mug/l., respectively. Plasma urea nitrogen and urine protein (quantitative determination) increased after 30 and 36 weeks. At 55 weeks of the experiment, qualitative tests were negative for low molecular weight proteinuria and glycosuria, and the results remained normal for renal and liver function tests and blood analysis, although cadmium concentrations in the renal cortex of two monkeys were 460 and 730 mug/g wet weight and those in the liver were 110 and 160 mug/g wet weight, respectively. In the highest exposure group (300 ppm), urine cadmium increased to 250 mug/l. by 11 weeks, and urine retinol-binding protein, plasma GOT, GPT, and LDH increased after 12 weeks. Proteinuria (quantitative determination), glycosuria, aminoaciduria (panaminoaciduria), and erythrocytopenia were observed after 16 weeks, when urine cadmium was 500-900 mug/l. Hypohemoglobinopathy and proteinuria (qualitative determination) were observed after 20 and 24 weeks, while cadmium concentrations in the renal cortex and the liver were 760 and 430 mug/g wet weight at 24 weeks, respectively. Slightly depressed tubular reabsorption of phosphate, increased urine beta(2)-microglobulin, increased plasma urea nitrogen, and increased plasma alpha(2)-globulin fraction (electrophoresis) were observed between 28 and 30 weeks of the experiment. Creatinine clearance and plasma cholinesterase decreased after 47 and 54 weeks, respectively. Cadmium concentrations in the renal cortex and the liver of two monkeys at 55 weeks were 350 and 580 mug/g wet weight and 410 and 630 mug/g wet weight, respectively. Pathological examinations revealed denaturation, destruction, and regeneration of the epithelial cells in renal proximal tubules, but no pathological changes in osseous tissues. Critical cadmium concentration in the renal cortex was estimated to be 380 mug/g wet weight for low molecular weight proteinuria and 470 mug/g wet weight for proteinuria, glycosuria, and aminoaciduria. Critical concentration in the liver was also estimated to be 210 mug/g wet weight. The apparent biological half-time of cadmium in monkeys at autopsied stage was calculated to be 0.66, 6.4, 5.2, and 22.4 years for the 300, 30, 3, and 0 ppm groups, respectively.

BACKGROUND

Hemorrhagic shock (HS) followed by resuscitation can result in production of several inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), leading to multiple organ dysfunction. Melatonin can attenuate organ damage with its anti-inflammation effects. The present study was designed to investigate the effects of melatonin on the physiopathology and cytokine levels after HS in rats.

METHODS

HS was induced in rats by withdrawing 40% of the total blood volume (6 mL/100 gm body weight) from a femoral artery catheter, immediately followed by intravenous injection of 10mg/kg melatonin. Mean arterial pressure and heart rate were monitored continuously for 48 h after the start of blood withdrawal. Biochemical parameters, including levels of hemoglobulin, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and lactate, were determined 30 min before and 0, 1, 3, 6, 12, 24, and 48 h after induction of HS while an equal volume of normal saline was replaced as fluid resuscitation. Cytokine levels including TNF-α and IL-6 in the serum were measured at 1, 24, and 48 h after HS. The kidney, liver, lung, and small intestine were removed for pathology assessment at 48 h after HS.

RESULTS

HS significantly increased the heart rate, blood GOT, GPT, BUN, Cre, LDH, CPK, lactate, TNF-α, and IL-6 levels, and decreased hemoglobulin and mean arterial pressure in rats. Treatment with melatonin preserved the mean arterial pressure, decreased tachycardia, and markers of organ injury, and suppressed the release of TNF-α and IL-6, with no change in hemoglobulin after HS in rats.

CONCLUSIONS

Treatment with melatonin suppresses the release of serum TNF-α and IL-6, and decreases the levels of markers of organ injury associated with HS, thus ameliorating HS-induced organ damage in rats.

The toxic potential of sodium orthovanadate towards isolated perfused rat livers was investigated at a dose of 2 mmol/l. In livers from fasted rats, vanadate led to a release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH] and mitochondrial (glutamate dehydrogenase (GLDH] enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an augmented formation and release of thiobarbituric acid-reactive material by the liver. Furthermore, a marked inhibition of oxygen consumption was observed. Vanadate-induced vasoconstriction resulted in a progressive decrease in perfusate flow rate. Control experiments with similarly reduced flow rates led to a comparable reduction in oxygen consumption. GPT and LDH release and hepatic glutathione depletion were also evident, though to a lesser extent than in the presence of vanadate, but no increase in GLDH release, in tissue calcium content or TBA-reactive material in the liver or the perfusate were observed. Thus, indirect toxic effects due to a reduced flow rate contribute only partly to vanadate hepatotoxicity and do not affect mitochondrial integrity. Omission of calcium from the perfusate did not prevent hepatotoxic responses to vanadate, although less calcium was present in the treated livers than in the control organs, indicating that calcium influx is not involved in vanadate-induced hepatotoxicity in the intact organ, in contrast to isolated hepatocytes. Feeding the animals, resulting in an activation of anaerobic energy conservation reactions, strongly attenuated vanadate hepatotoxicity indicating that the energetic status of the liver is the main target of vanadate. Superoxide dismutase did not affect the hepatotoxic responses of livers from fasted rats towards vanadate, while allopurinol and deferrioxamine inhibited lipid peroxidation and hepatotoxicity due to vanadate. The strong correlation between induction of lipid peroxidation and hepatotoxicity and the inhibition of both processes in parallel by antioxidants are suggestive of a causative role for lipid peroxidation in vanadate-induced hepatotoxicity.

Oxygen free radicals have been implicated in exercise-induced cell and tissue injury, indicating an oxidative stress. Fatigue accompanied by a number of physiological and metabolic changes is in indication of overtraining. This study aimed to examine the influence of a continuous 24-h intermittent speed driving (1 h driving/1 h stop), on the response of hormones, antioxidative factors, lipid, and enzyme levels. Seven race car drivers of national level were examined before, during, and immediately after the trial of speed driving on a test designed to check endurance to stress. The parameters measured were: testosterone (Tes), cortisol (Cor), IgM, IgA, cholesterol, HDL, billirubin, ceruloplasmin, urea, uric acid, creatine kinase, and transaminases. Stress hormone Cor declined significantly (p < 0.05), while Tes did not change significantly. Fatigue enzyme, aspartate transaminase (GOT) increased significantly (p < 0.05), while alanine transaminase (GPT) did not change and urea declined. Muscle enzyme, creatine kinase (CK) increased to sixfold (p < 0.01). IgA, IgM and lipids did not change. The primary antioxidant ceruloplasmin increased significantly (p < 0.001), while antioxidants uric acid and glucose remained unchanged. Among the factors measured, ceruloplasmin, cortisol, urea, GOT, and CK seem to give a picture of the organism's alertness and defence capabilities in conditions of stress and fatigue.

We report a case of suspected liver dysfunction after general anesthesia with sevoflurane. A 30 day old male infant underwent inguinal herniorrhaphy under sevoflurane anesthesia (sevoflurane concentration: 1.3-1.5% with 50% oxygen and nitrous oxide). Two days after the operation, he developed frequent vomiting, anorexia and fever. GOT, GPT and LDH values were 242 Ku, 326 Ku and 901 Wu, respectively and peaked at 520 Ku, 709 Ku and 1000 Wu 12-16 days after the operation. Clinical symptoms and the laboratory data became normal within 2 months. The antibody titers of EB-virus, cytomegalo-virus and HA-virus were all within normal ranges and HBs antigen was negative. There were no blood transfusion or antibiotics administration before the onset, and no epidemic of hepatitis around him. His mother had no history of hepatitis during her pregnancy. Lymphocyte stimulation test for indication of sevoflurane allergy was also negative. From these evidences, toxic (not allergic) liver dysfunction due to exposure to sevoflurane was considered to be the most probable diagnosis.

Increased human use of fenugreek seeds (Trigonella foenum graecum) entails the generation of toxicity data in experimental animals. In this investigation, toxic effects of debitterized fenugreek (DFG) powder have been assessed following acute and subchronic regimens in mice and rats. In the acute study, DFG powder intragastrically administered to albino mice (CFT-Swiss, Mus musculus) and albino rats (CFT-Wistar, Rattus norvegicus) of both sexes failed to induce any signs of toxicity or mortality up to a maximum practical dosage of 2 and 5 g/kg body weight, respectively. Further, no significant alterations either in relative organ weights or their histology were discernible at terminal autopsy. In the 90-day subchronic study, DFG fed to weanling rats of both sexes at dietary doses of 0, 1, 5 and 10% in a pure diet had no effect either on the daily food intake or growth. Terminal autopsy revealed no alterations in relative organ weights of various vital organs, or their histoarchitecture. Haematological constants in DFG-fed rats were on par with those of controls. Further, biochemical measurements in serum and liver of DFG-fed rats revealed no appreciable changes in various parameters such as enzyme levels of GPT , GOT and ALP, as well as many serum constituents such as proteins, cholesterol, urea and creatinine at any of the dietary levels. From these results, it may be concluded that DFG does not produce any significant acute and cumulative toxicity at the doses administered, as reflected by the various parameters investigated.

The hepatoprotective and antioxidant effect of an ethanolic extract of 'Rocket' Eruca sativa L. (EER), on liver injury induced by carbon tetrachloride (CCl(4)) was investigated. Wistar albino rats were administered 250 and 500 mg/kg body weight extract orally for 10 consecutive days. Marker enzymes GOT, GPT, ALP, GGT and bilirubin were estimated in serum. Whereas, non-protein sulfhydryl (NP-SH), total protein (TP) and malondialdehyde (MDA) were estimated in liver tissue as markers for oxidative stress. Histopathological assessment was also done on liver tissue. CCl(4) induced liver poisoning in all treated animals was evident by elevated serum GOT, GPT, ALP, GGT and bilirubin levels. Induction of oxidative stress in the liver tissue by CCl(4) was evidenced by a fall in the levels of NP-SH and TP; and an increased level of MDA concentration. EER administration for 10 days prevented the CCl(4) induced hepatic injury and oxidative stress. Furthermore, the extract also reduced the pentobarbital-induced prolongation of sleeping time in mice. The ability of rocket extract to protect the liver toxicity in rats was further confirmed by histological findings in the liver tissue. In conclusion, it was observed that Eruca sativa L. extract protects the liver against CCl(4) induced hepatic injury through its potent antioxidant activity in rats.

Exposure of rat cortical neurons to the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 in vitro causes a rise in the intracellular Ca2+ level and a subsequent translocation of protein kinase C (PKC) from the cytosol to the membrane. Such a translocation persists for at least 2 h, but only in cultures with media not depleted of endogenous glutamate. Enzymatic degradation of glutamate in the medium by the enzyme glutamate-pyruvate transaminase (GPT) abolishes the long-lasting effect of gp120 on the association state of PKC; under this incubation condition the translocation period is < 1 h. Memantine and the ganglioside GM1 prevent N-methyl D-aspartate receptor-mediated long-term translocation of PKC and gp120-mediated neurotoxicity (in the absence of GPT); they have no effect on short-term translocation of PKC. We suggest that gp120-caused neuronal death involves an indirect sensitization step of the NMDA receptors, which ultimately induces neuronal death.

OBJECTIVE

The aim of this study was to evaluate the usefulness of glutamate pyruvate transaminase (GPT) levels in the diagnosis of metabolic syndrome (MS) in obese Japanese children.

METHODS

We examined 193 obese boys (mean age: 12.1 yrs; mean percent overweight [POW]: 53.9%) and 37 obese girls (mean age: 11.4 yrs; mean POW: 57.2%). Anthropometric measurements, blood pressure and levels of liver transaminases, serum lipids and lipoproteins, fasting blood glucose (FBG), serum insulin and adiponectin were measured. The subjects were divided into either an MS or a non-MS group according to the MS definition criteria for Japanese children.

RESULTS

The level of GPT was significantly higher in the MS group in both genders. Correlation analysis revealed positive correlations between GPT and waist circumference, blood pressure, maximum preperitoneal fat thickness, serum insulin and homeostasis model assessment-insulin resistance (HOMA-R), but no correlation between GPT and FBG. ANOVA showed a significant difference in GPT levels between MS and non-MS subgroups, whereas there was no difference in FBG between the two groups. Receiver operating characteristic curves demonstrated that GPT was clearly superior to FBG as a diagnostic marker of MS.

CONCLUSIONS

We conclude that an elevation in GPT in obese children most likely reflects insulin resistance and that GPT is superior to FBG as a marker of MS.

Treatment of male Sprague-Dawley rats with buthionine sulfoximine (BSO), prior to administration of carbon-14(14C)-labelled 2-methylfuran (2MF) caused a marked decrease in the covalent binding of 14C-labelled 2MF metabolites to both DNA and protein, although there was no apparent change in the distribution of the labelled parent 2MF. BSO pretreatment also protected against hepatotoxicity of 2MF, as indicated by lower serum glutamic pyruvic transaminase (GPT) levels. Pretreatment with BSO offered protection only if administered 1.5 hr before 2MF dosage. Administration of 2MF, 4 and 6 hr after BSO resulted in manifestation of the hepatotoxicity of 2MF. Prior treatment with diethylmaleate (DEM), increased covalent binding of [14C]2MF to liver proteins and also elevated serum GPT levels. Thus, depletion of tissue glutathione (GSH) by two different chemicals acting by different mechanisms produced opposite effects on the covalent binding and toxicity of 2MF. Pretreatment with L-2-oxothiazolidine-4-carboxylate (OTZ), a promoter of GSH biosynthesis, increased the hepatic covalent binding of [14C]2MF and potentiated hepatotoxicity. However, administration of OTZ and BSO prior to an i.p. dose of 100 mg/kg of 2MF, decreased the hepatic covalent binding of [14C]2MF and decreased the hepatoxicity. The marked instability of the GSH conjugate of the reactive metabolite of 2MF may account for the potentiation of hepatotoxicity of 2MF by OTZ. A single s.c. dose of BSO, caused a transient increase in plasma cystine levels concurrent with the depletion of liver GSH. Administration of 2MF, 1.5 hr after BSO, significantly decreased plasma cystine levels as compared to control animals that received vehicle alone. Pretreatment with BSO also resulted in increased excretion of urinary metabolites in 2MF treated animals as compared to animals receiving 2MF alone. Thus, BSO probably protects against hepatoxicity of 2MF by indirectly causing more detoxification of the reactive metabolite of 2MF, as it does not alter the distribution of unmetabolized 2MF and does not have any apparent effect on the microsomal mixed-function oxidase which mediates the activation of 2MF. The enhanced detoxification of 2MF in BSO treated animals appears independent of the depleted GSH levels; it may result from increased availability of a better alternative nucleophile (i.e. cysteine), capable of conjugating with acetyl acrolein. Acetyl acrolein (AA) appears to be the principal reactive metabolite of 2MF which binds covalently to tissues. Previous in vitro studies have shown that cysteine is a better trapping agent of AA than GSH or N-acetyl-cysteine.

BACKGROUND

[D-Ala(2), D-Leu(5)] enkephalin (DADLE) is a synthetic delta class of opioid and is reported to induce hibernation as well as hibernation induction trigger (HIT) in the serum of hibernating mammals. DADLE and HIT have been demonstrated to protect the heart, lung, and jejunum against ischemia-reperfusion (I-R) injury. In the present study, we examined the effect of DADLE on I-R injury of the liver in rats.

METHODS

After administration of DADLE (DADLE group) or normal saline as a vehicle (Control group), partial hepatic ischemia was induced by occluding the vessels supplying 92% of the liver for 45 min, followed by declamping the vessels and resection of the non-ischemic lobe. After 120 min of reperfusion, serum glutamic-pyruvic transaminase (GPT), hyaluronic acid (HA) levels, and concentrations of malondialdehyde (MDA) of the liver tissue were measured. Additionally, bile output from the ischemic lobes was measured after reperfusion.

RESULTS

GPT levels were significantly lower in the DADLE group as compared to those of the Control group (P < 0.05), but the serum levels of HA were not different between the two groups. The concentrations of MDA of the liver tissue were significantly lower in the DADLE group than in the Control group (P < 0.01). The bile output after reperfusion was not significantly different between the two groups.

CONCLUSIONS

DADLE protects against I-R injury in hepatocytes, but not in the sinusoidal endothelial cells of the liver in rats. An anti-oxidative effect is suggested to be responsible for this effect.

A randomized double blind study was performed to evaluate the tolerance and the acceptance of mefloquine alone (Lariam) compared to a combined drug regimen consisting of mefloquine, sulfadoxine and pyrimethamine (MSP; Fansimef) in the prophylaxis of malaria. 175 Europeans travelling to different malaria endemic areas received either mefloquine alone (250 mg/week) or its combination with sulfadoxine (500 mg/week) plus pyrimethamine (25 mg/week). One person taking mefloquine and two taking MSP discontinued the drug intake because of moderate clinical side effects. Mild and moderate adverse clinical reactions predominantly concerning the gastro-intestinal tract and the autonomous nervous system were reported with a significantly higher occurrence in the MSP group. With both prophylactic regimens, reversibly elevated liver enzyme activities (glutamate oxalate transaminase and glutamate pyruvate transaminase [GPT]) were observed after prophylaxis. The increase of GPT serum activity correlated significantly with relatively high GPT levels before prophylaxis in both groups. This finding suggests a limited use of both regimens in cases of liver dysfunction. One case of mefloquine-resistant Plasmodium falciparum malaria was observed from West Africa; this patient was cured by a standard regimen of chloroquine.

OBJECTIVE

To determine the effects of exercise training on physical condition in 25 college rugby players during a summer training camp, and to compare these variables by the different players' positions.

METHODS

Changes in body composition parameters and blood biochemistry were examined before and after a summer training camp.

RESULTS

Body weight and percentage body fat did not change significantly during the camp. There were significant decreases in levels of serum total cholesterol, triglycerides, phosphate, uric acid, and immunoglobulin G and M. In contrast, there were significant increases in levels of serum potassium, markers of renal, hepatic, and muscular damage (BUN, GOT, GPT, LDH, CK), and complement C4. Comparison of the changes in biochemical parameters between rugby players playing in different positions showed a significant increase in serum albumin level in the forwards, and significant decreases in serum triglyceride and sodium levels in the backs. The magnitude of change in serum LDH during the camp was significantly greater (p<0.05) for the forwards than for the backs.

CONCLUSIONS

These data suggest that, in rugby players attending a 20 day camp, exercise training resulted in muscular damage, loss of electrolytes due to sweating, and changes in immune function. Backs exhibited a higher rate of fat metabolism and loss of electrolytes than forwards, possibly because they did more running during the camp. In contrast, forwards experienced more physical contact, performed more physically strenuous exercise, and exhibited higher levels of muscular damage and tissue protein degradation.