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Aqueous kava extracts do not affect liver function tests in rats.

Kava ( Piper methysticum Forst. f., Piperaceae), prepared as the traditional aqueous infusion, was tested in the rat for possible effects on liver function tests. Extracts were administered in daily dosages of 200 or 500 mg of the active kavalactones/kg for two or four weeks. Sera were assayed for four enzymes that are markers of liver toxicity and liver homogenates for malondialdehyde formation that indicates changes in lipid peroxidation. The data showed that none of the enzymes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, nor malondialdehyde were elevated, in fact in some cases they were significantly reduced, suggesting the lack of a toxic effect by kava on the liver.

Alanine Transaminase↗

Glycemic control and raised serum alanine aminotransferase activity in treated diabetes mellitus.

The prevalence of raised serum liver-associated enzyme activity in stabilised, treated diabetic outpatients without concurrent hepatobiliary disease was investigated using a retrospective computer search of biochemical data. The frequency of raised alanine aminotransferase, aspartate aminotransferase, or gamma glutamyl transferase activity found among diabetic, general medical and respiratory outpatients was compared with that found in apparently healthy controls. It was established that a raised activity of any of the three enzymes occurred with a similar frequency in each outpatient group. However, only with alanine aminotransferase did the frequency of elevation (7.1%) in the patients with previously diagnosed hepatobiliary disease exceed that of healthy controls. A raised alanine aminotransferase activity in diabetic outpatients was associated with good glycemic control (hemoglobin A1 less than 8%, p less than 0.02) and treatment with oral hypoglycaemic agents (p less than 0.001).

Alanine Transaminase↗

Cholestasis-induced fibrosis is reduced by interferon alpha-2a and is associated with elevated liver metalloprotease activity.

BACKGROUND/AIM: Several drugs have been tested for the treatment of hepatic cirrhosis induced by various etiologic agents. Although interferon (IFN)alpha-2a has mostly been used to treat viral hepatitis, its anti-fibrogenic properties remain to be established. METHODS: An experimental model of cholestasis-induced cirrhosis was used to test the effect of IFNalpha-2a. Cirrhosis was induced in rats via ligation of the common bile duct. IFNalpha-2a (100,000 IU/rat, s.c.) was administered daily throughout the experiment. Collagens and TIMP-1 mRNA transcripts were determined by semi-quantitative reverse transcriptase-polymerase chain reaction in liver tissue samples. Activity of metalloproteases (MMPs) was measured using gelatin (denatured collagen) as substrate and the specific size of the enzymes was estimated by zymograms. Histology was performed using Sirius red as a specific stain for collagenous material, and computer-assisted morphometric analyses were carried out. A polyclonal mouse anti-plasminogen activator inhibitor (PAI-1) antibody was used to evaluate the distribution during treatment with IFNalpha-2a. RESULTS/CONCLUSIONS: MMP-activity was up-regulated in bile duct ligated rats treated with IFNalpha-2a. MMP-activity in homogenates of total liver was minimal as compared with activity in non-parenchymal cells isolated from the same parental perfused liver, indicating a cryptic MMP activity which was completely abolished by EDTA and 1,10 phenanthroline. Three bands of gelatin degradation were detected by zymography, corresponding to 95, 75 and 65 kDa. IFNalpha-2a decreased PAI-1 immunoreactivity in liver tissue slices as well as biochemical activity in non-parenchymal cell extracts (3.3+/-0.08 vs 7.4+/-1.1 U/mg protein). Procollagen alpha1 (III) and alpha1 (IV) genes expression were also down-regulated 1.5 and 4-fold, respectively. Interestingly, TIMP-1 gene expression did not change. Functional hepatic tests: alanine aminotransferase, aspartate aminotransferase, bilirubins and alkaline phosphatase were significantly lower in IFNalpha-2a treated animals. Analysis of histology demonstrated that IFNalpha-2a promoted resolution of fibrosis and decreased bile duct proliferation.

Alanine Transaminase↗

Ischemia and reperfusion increases susceptibility to ventilator-induced lung injury in rats.

OBJECTIVES: Hemorrhagic shock followed by resuscitation (HSR) commonly triggers an inflammatory response that leads to acute respiratory distress syndrome. HYPOTHESIS: HSR exacerbates mechanical stress-induced lung injury by rendering the lung more susceptible to ventilator-induced lung injury. METHODS: Rats were subjected to HSR, and were randomized into an HSR + high tidal volume and zero positive end-expiratory pressure (PEEP) or a HSR + low tidal volume with 5 cm H(2)O PEEP. A sham-operated rat + high tidal volume and zero PEEP served as a control. RESULTS: HSR increased susceptibility to ventilator-induced lung injury as evidenced by an increase in lung elastance and the wet/dry ratio and a reduction in Pa(O(2)) as compared with the other groups. The lung injury observed in the HSR + high tidal volume group was associated with a higher level of interleukin 6 in the lung and blood, increased epithelial cell apoptosis in the kidney and small intestine villi, and a tendency toward high levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatinine in plasma. CONCLUSIONS: HSR priming renders the lung and kidney more susceptible to mechanical ventilation-induced organ injury.

Alanine Transaminase↗

Effect of bioactive tannoid principles of Emblica officinalis on iron-induced hepatic toxicity in rats.

The tannoid principles of the fruits of the plant Emblica officinalis Gaertn comprising of emblicanin A. emblicanin B, punigluconin and pedunculagin, have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin A (37%) and B (33%) enriched fraction of fresh juice of Emblica fruits (EOT), administered prophylactically (10, 20 and 50 mg/kg, p.o.) for 10 consecutive day, was found to inhibit acute iron overload (30 mg/kg, i.p.) hepatic lipid peroxidation and the increase of serum levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, used as markers of the induced hepatic dysfunction. A similar effect was produced by silymarin (20 mg/kg, p.o.), an antioxidant hepatoprotective agent. The results support the use of Emblica fruits for hepatoprotection in Ayurveda.

Alanine Transaminase↗

Correlates of body mass index in hazardous materials firefighters.

We analyzed results from the medical examinations of 340 hazardous materials (HAZMAT) firefighters and observed the relationships between selected parameters and body mass index (BMI). Heights and weights were available for 98% of the subjects (333 of 340). The mean BMI was 28.9 +/- 4.1 kg/m2. Eighty-seven percent (290 of 333) of subjects were overweight (BMI > or = 25) and 34% (113 of 333) were obese (BMI > or = 30). Two percent (7 of 333) were morbidly obese (BMI > or = 39). For comparison purposes, we divided subjects into low (BMI < 27), medium (BMI 27 to < 30), and high (BMI > or = 30) BMI groups. The results demonstrated adverse associations between increasing BMI and resting blood pressures, forced vital capacity, alanine aminotransferase, aspartate aminotransferase, serum cholesterol, and overall morbidity scores. The high prevalence of overweight and obesity and the associated adverse health effects support the development and implementation of fitness-promotion programs for firefighters.

Adult↗

The effect of a single intense effort on the activity of aminotransferases and concentration of free amino acids in the plasma of rats.

Untrained rats were subjected to a single intense physical effort. In the plasma the activity of alanine aminotransferase, aspartate aminotransferase, and the concentrations of amino acids: glycine, cystine, alanine and leucine with isoleucine were measured. The results were compared with the data obtained in a control group. Despite lack of statistically significant differences in the activity of aminotransferases and concentration of amino acids between these groups a correlation was found between the activity of AIAT and alanine concentration in the animals after exercise. The concentration of alpha-amino nitrogen was decreased statistically significantly in the group of animals subjected to intensive exercise.

Alanine↗

Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study.

OBJECTIVE: In experimental animals, recent results suggest that the addition of inulin-type fructans such as oligofructose (OFS) in the diet decreases triacylglycerol accumulation in the liver tissue. Therefore, we have investigated the effect of daily ingestion of OFS in seven patients with nonalcoholic steatohepatitis (NASH), confirmed by liver biopsies. DESIGN: They received 16 g/day OFS or maltodextrine (placebo) for 8 weeks in a randomized double-blind crossover design. Energy intake, body composition, liver steatosis and blood parameters were analysed after 4 and 8 weeks of dietary supplementation. RESULTS: Compared to placebo, OFS decreased significantly serum aminotransferases, aspartate aminotransferase after 8 weeks, and insulin level after 4 weeks, but this could not be related to significant effect on plasma lipids. CONCLUSION: This pilot study supports the putative interest of OFS in the management of liver diseases associated with abnormal lipid accumulation in humans.

Adult↗

Sustained phenotypic correction of canine hemophilia B after systemic administration of helper-dependent adenoviral vector.

We have evaluated the potential of liver-directed, helper-dependent adenoviral (HDAd) vector-mediated gene therapy in the hemophilia B dog. Two dogs were injected intravenously with HDAd (3 x 10(12) VP/kg) bearing a liver-restricted canine coagulation factor IX (FIX) expression cassette. After injection, the whole blood clotting time for both dogs declined from >60 min to </=20 min for at least 604 and 446 days, respectively. Peak FIX activities of 34.1 and 129.2% were detected at 12x14 days and then slowly declined to 2 to 5% by 120 days and stabilized at these therapeutic levels for at least 418 and 257 days. For one dog, a peak FIX level of 500 ng/ml was achieved and stabilized at >170 ng/ml for at least 256 days. For the other dog, a peak FIX level of 1258 ng/ml was achieved and stabilized at >400 ng/ml for at least 213 days. Inhibitor formation was not evident in either animal. Importantly, whereas untreated hemophilia B dogs suffer five or six spontaneous bleeds per year, the treated dogs suffered no such bleeds postinjection. Significantly, this study is the first to demonstrate long-term phenotypic correction of a genetic disorder in a large animal with HDAd. Although no evidence of chronic toxicity was observed in either animal, systemic vector administration at 3 x 10(12) VP/kg was accompanied by acute, albeit transient and variable laboratory abnormalities (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine phosphokinase, and platelet counts). The results of this study highlight both the potential benefit and the risk associated with systemic intravascular delivery of high-dose HDAd for liver-directed gene therapy.

Alanine Transaminase↗

[Comparative characterization of the hepatotoxicity of isoniazid, rifampicin and pyrazinamide].

In experiments of rats it was established that administration of isoniazid and rifampicin in equimolecular doses (50 and 250 mg/kg) for 14 days increased the activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in the serum, enhanced lipid peroxidation in hepatocytic membranes, caused significant disturbances of bile excretion. Pyrazinamide administered in an equimolecular dose (45 mg/kg) moderately suppresses bile excretion and exerts no effect on the activity of the liver enzymes in the serum and the level of lipid peroxidation.

Alanine Transaminase↗

Evaluation of the efficacy of Melothria maderaspatana in the alleviation of carbon tetrachloride-induced liver dysfunction.

An investigation was carried out to evaluate the ability of Melothria maderaspatana to protect the livers of albino rats from carbon tetrachloride-mediated alterations in liver histopathology and serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Treatment with an aqueous extract of Melothria aerial parts (either before or after CCl4 administration) markedly decreased CCl4-mediated alterations in liver histopathology as well as serum enzyme levels. Results provide supportive evidence for the folklore view that this plant is a good hepatotonic.

Alanine Transaminase↗

Efficacy of ursodeoxycholic acid in the treatment of primary sclerosing cholangitis in children.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to be beneficial in reducing disease activity in adult patients with primary sclerosing cholangitis (PSC). However, there has been little published regarding PSC in children and no studies investigating the efficacy of UDCA as a treatment for PSC. METHODS: This retrospective study included 10 children who were found to have the diagnosis of PSC during the past 15 years at the Texas Children's Hospital and Herman Hospital, both in Houston, Texas. The male:female ratio was 8:2, the median age of onset was 12 years (range, 1-17 years), and eight patients had coexistent inflammatory bowel disease (IBD; six ulcerative colitis, one Crohn's disease, one unspecified). At the time of diagnosis, five patients were asymptomatic, all of whom had IBD with elevated liver enzymes and three of whom had hepatomegaly. Nine patients were treated with UDCA. The one patient who did not receive UDCA was lost to follow-up soon after diagnosis. The mean dose of UDCA was 17 mg/kg with the doses ranging from 9 to 37 mg/kg. RESULTS: There were no side effects from the medication recorded for any of the patients. These patients showed a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase at 1, 3, 6, 15, and 20 months after treatment. CONCLUSIONS: This study demonstrates that children with PSC treated with UDCA have significant improvements in liver biochemical indices. However, the long-term effect of UDCA on clinical outcome is unknown.

Adolescent↗

Haematological and biochemical studies on experimental Theileria annulata infection in crossbred calves.

Administration of ground-up tick tissue stabilate (0.75 tick equivalent) by the subcutaneous route to crossbred calves aged 1 week to 1 month led to the development of acute theileriosis. Haematological studies revealed significant progressive decreases in haemoglobin concentration, packed cell volume and red blood cell count, whereas the total leukocyte count showed an initial non-significant leukocytosis followed by a significant leukopenia. Analysis of serum revealed significant increases in levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase and gamma-glutamyltransferase, and in the concentrations of uric acid, blood urea nitrogen and bilirubin. The concentrations of total protein, albumin, glucose, cholesterol and calcium showed non-significant decreases, while phosphorus decreased significantly during the terminal stages of the disease.

Alanine Transaminase↗

Nonparametric probability density estimation: improvements to the histogram for laboratory data.

The histogram has long been used in the clinical laboratory for the depiction and manipulation of frequency data. We present recent results of refinements to the usual histogram procedures along with modern alternative methods of estimating frequency distributions, including the kernel and discrete maximum penalized likelihood estimation (DMPLE) approaches. We compared these nonparametric methods on 15 different types of simulated distributions, and on several sets (greater than 1000 subjects/set) of real data, including alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels. Each frequency curve estimation technique was evaluated by measuring the integrated mean square error between each technique's prediction and the true underlying distribution, using Monte Carlo techniques on sample sets with size 49 and 119. The kernel method was the clear method of choice, both in performance (best in 22/36 cases) and in practical usage.

Alanine Transaminase↗

Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.

Adult↗

Isoprinosine in classical acute viral hepatitis.

A prospective double-blind controlled study was performed on the effects of isoprinosine in 81 patients with clinical and histological features of classical acute viral hepatitis. Appetite was assessed daily. Serum alanine aminotransferase, aspartic aminotransferase, and bilirubin levels were assessed weekly. Changes in biochemical parameters, number of deaths, number of patients showing rise of aminotransferase levels despite treatment, and duration required for appetite to return to normal in each group were compared. Observation was continued for 4 weeks. Contrary to preliminary reports, no therapeutic benefit was demonstrated in any of these parameters. We concluded that isoprinosine was ineffective in the acute phase of classical acute viral hepatitis.

Alanine Transaminase↗

Protective effect of ternatin, a flavonoid isolated from Egletes viscosa less., in experimental liver injury.

The effect of ternatin, a tetramethoxyflavone from Egletes viscosa Less., on liver injury induced by carbon tetrachloride (CCl4) was investigated in rats. Twenty-four hours following CCl4 insult (2.5 ml/kg s.c.), changes in the serum enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase, as well as liver cell histology were used as indices of hepatic dysfunction. The results show that ternatin (30 mg/kg i.p. daily for 5 consecutive days) causes marked inhibition of CCl4-induced serum enzymes and morbid histologic changes. The observation suggests that ternatin possesses antihepatotoxic activity.

Alanine Transaminase↗

Arginase, a new marker of mammary carcinoma.

Activities of arginase, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were determined in sera obtained in a group of healthy women, women with verified carcinoma of the breast, benign mastopathy, a group of patients with carcinoma of various organs and a group of patients with acute viral hepatitis. Preoperative values of serum arginase activity in patients with breast carcinoma were up to 4-fold those found in healthy women. Sensitivity of the test was 86%. After the surgery, the activity decreased abruptly during the first week and normalised within 15-30 days. In benign diseases of the breast, the activity of arginase was normal. Serum arginase activity is raised in both benign and malignant liver diseases, however, the quotients alanine aminotransferase/arginase, aspartate aminotransferase/arginase and alkaline phosphatase/arginase differ significantly. Thus, use of alanine aminotransferase/arginase quotient implies a high degree of confidence in differentiating between increased arginase activity in mammary carcinoma (alanine aminotransferase/arginase = 0.572 +/- 0.278) and high arginase activity in hepatitis (alanine aminotransferase/arginase = 12.226 +/- 1.822).

Adult↗