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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protective effect of pyoverdins Pa A and Pf, peptidic siderophores secreted respectively by Pseudomonas aeruginosa and fluorescens, was studied in primary cultures of human hepatocytes exposed to iron (50 or 100 microM of iron-citrate). AST, ALT and MDA releases were measured as indexes of cytotoxicity. In order to demonstrate that these chelators were able to decrease iron uptake or increase iron release from the hepatocytes, labelled cells were obtained by maintaining the cultures in the presence of 1 microM 55Fe ferric chloride plus 50 microM iron citrate. One day after iron treatment, an increase in AST, ALT and MDA release was observed with 50 or 100 microM of iron citrate; it appeared that the concentrations 50 and 100 microM of iron were highly toxic for human hepatocytes. In the presence of 50 or 100 microM of iron, the addition of 50 or 100 microM of Pa A or Pf was effective to inhibit the increase observed in the enzyme leakage and the MDA production resulting from iron exposure. In human hepatocytes cultured for 1 day in the presence of 1 microM 55Fe-50 microM iron citrate plus 50 or 100 microM Pa A or Pf, a net decrease of iron uptake by the cells was observed, as demonstrated by the low intracellular iron level. When the hepatocytes were cultured for 1 day in the presence of 1 microM 55Fe-50 microM iron citrate and then for a further day in the presence of 50 or 100 microM Pa A or Pf without additional iron, the chelators increased the extracellular iron level, indicating their iron release from the loaded cells; however, the effects of Pa A and Pf on iron release did not differ significantly. In conclusion, iron loading achieved by adding iron citrate to the culture medium is highly toxic for human hepatocytes. Pyoverdins Pa A and Pf are effective in protecting human hepatocytes against the toxic effect of iron by both decreasing the uptake of the metal and increasing its release from the loaded cells.
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PMID:Inhibition of iron toxicity in human hepatocyte cultures by pyoverdins Pa A and Pf, the peptidic siderophores of Pseudomonas aeruginosa and fluorescens. 913 75

Treatment of chronic hepatitis C with alfa interferon for 6 months achieves sustained responses in 15-25% of the patients. The initial induction with higher doses and the prolongation of treatment can improve the results. A randomized, prospective study was carried out to compare the efficacy of a short term induction schedule of interferon alfa-2b (group A) versus a long term one (group B). 106 patients with chronic hepatitis C were included: 54 received 5 megaunits tiw for 8 weeks and 52 for 16 weeks; afterwards, interferon was reduced to 3 megaunits up to 9 months. The percentage of sustained responses, transient responses and non responses were 18.5%, 24% and 57.4% in group A and 23.1%, 28.8% and 48.1% in group B (NS). The following factors were related to a poor response in the univariate analysis: an increase of serum iron levels, ferritin, Gamma-GT and bilirubin, anti-nuclear antibody positivity, presumed non-parenteral infection, an AST/ALT ratio greater than 0.75, a higher Knodell's index and a greater necrosis and fibrosis score. The multivariate analysis revealed that elevated serum iron and ferritin and anti-nuclear antibody positivity had an independent predictive value related to a non response. Our results appear to suggest that an induction with higher doses and the treatment over nine months are more efficient than the classic schedule. The prolongation of the induction period does not provide additional advantages.
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PMID:A comparison between two induction regimes for the interferon treatment of chronic hepatitis C. Response related factors. 914 98

Hyperthermia has been used to treat cancer in the liver. However, significant hepatotoxicity occurs at a therapeutic temperature of 42-43 degrees C. We have proposed that heat toxicity is the result of oxidative stress from superoxide generation with resultant lipid peroxidation. Further, iron release from liver iron stores (ferritin) appears to play a central role in hyperthermic toxicity. In this study, rat livers were perfused in situ at 37 or 42.5 degrees C with and without deferoxamine for 1 h with an asanguinous perfusate. Oxidative stress was assessed by the efflux of glutathione (GSH) into the perfusage. Prior studies by Skibba et al. (1989a, 1991) showed that perfusage equivalents of GSH were primarily present as oxidized glutathione (GSSG). Lipid peroxidation was assessed by the measurement of aldehydes appearing in the perfusate and formation of hydrocarbon gases (ethane and pentane) in the perfusion chamber head space. Liver injury was assessed by the leakage of cytosolic enzymes, AST and LDH, into the perfusate. Livers perfused at 42.5 degrees C showed significant rises (p < 0.05) in AST and LDH after 60 min of perfusion but perfusion at 42.5 degrees C with deferoxamine added, was not significantly different from perfusion at 37 degrees C. Perfusion at 42.5 degrees C caused an increase in GSH into the perfusate at a level significantly (p < 0.05) greater than at 37 degrees C. GSH levels in the liver after 60 min of perfusion decreased from 4.82 +/- 0.76 microM/gm at 37 degrees C to 1.48 +/- 0.54 microM/gm at 42.5 degrees C (p < 0.05) but only fell to 3.42 +/- 1.23 microM/gm at 42.5 degrees C with deferoxamine added. Efflux of iron into the perfusate increase significantly with time and temperature. Low molecular weight chelated iron within the liver after perfusion increased from 5.88 +/- 1.46 nM/gm at 37 degrees C to 25.8 nM/gm at 42.5 degrees C (p < 0.05). Perfusate total aldehyde levels increased from 0.085 +/- 0.056 to 0.32 +/- 0.09 microM/ml after 60 min at 37 degrees C and 0.87 +/- 0.45 to 2.01 +/- 0.90 microM/ml at 42.5 degrees C (n = 8). There was a significant decrease in total aldehyde levels at 42.5 degrees C with the addition of deferoxamine to the perfusate, 0.36 +/- 0.14 to 0.86 +/- 0.27 microM/ml, when compared to 42.5 degrees C levels (p < 0.05). Levels of ethane and pentane in the perfusion chamber head space showed no significant changes with time or temperature of perfusion. The data suggest that lipid peroxidation may play a causal role in hyperthermia induced liver toxicity and that iron plays a major role in this injury. Failure of hydrocarbon analysis to support this conclusion appears related to the use of membrane oxygenators.
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PMID:Liver hyperthermia and oxidative stress: role of iron and aldehyde production. 914 47

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
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PMID:Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests. 929 68

Augmentation of gamma-gene synthesis by using recombinant human erythropoietin (r-Hu-EPO) represents a new approach to the therapy of beta-thalassemia. A prospective study was conducted in 26 transfusion-dependent beta-thalassemia major patients. r-Hu-EPO (Eprex/Cilag, Switzerland) was given to the patients at an initial dose of 500 IU/kg s.c. 3 times a week for at least 2 months during which no transfusion was applied. A sustained hemoglobin (Hb) level greater than 8 g/dl was considered as a response to EPO treatment. In the patients whose Hb levels remained under 8 g/dl or did not increase in comparison to pretreatment levels within 4 weeks, the dose of r-Hu-EPO was increased to 1,000 IU/kg 3 times a week and applied for another 4 weeks. Only 16 cases also received oral iron supplementation. The whole blood and reticulocyte counts, the biochemical tests including BUN, creatinine, AST, ALT, alkaline phosphatase and ferritin were done and the percentages of HbF and F cells were analyzed regularly. At the end of the 2nd month, 6 cases qualified to continue with the trial. At the end of the 6th month, r-Hu-EPO therapy was ceased in 3 cases of the 6 since their Hb levels had decreased below 7 g/dl. Only 3 cases (11.5%) continued with the r-Hu-EPO therapy without transfusion for up to 12 months. In conclusion, r-Hu-EPO may be useful in some selected transfusion-dependent patients with beta-thalassemia major. Selection criteria should include a mild beta-genotype of coinheritance of alpha-thalassemia, splenectomy and pretreatment reticulocyte response of the patients as well as the patients' compliance.
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PMID:Recombinant erythropoietin trial in children with transfusion-dependent homozygous beta-thalassemia. 940 97

Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end-stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty-four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty-seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P =. 001), obesity (P =.002), diabetes mellitus (P =.009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P =.03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P =.003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P =.02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P =. 09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.
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PMID:Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. 1057 11

This study was constructed to investigate the relationship between renal anaemia and erythropoietin (EPO) concentrations in chronic renal failure (CRF) patients and to evaluate the possible role of the liver. Serum EPO levels were measured in blood samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Blood cell counts, iron indices (iron, total iron-binding capacity (TIBC) and ferritin), renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (ALT, AST, ALP and bilirubin) investigations were carried out for all the subjects enrolled in this study. CRF patients without LC had serum EPO concentration of 6.21 +/- 0.53 mU/ml (mean +/- SE), which was significantly higher than that in patients having both CRF and LC (4.32 +/- 0.52) (p < 0.01). Both groups showed significantly lower values than the controls (12.75 +/- 0.70) (p < 0.001). LC patients with intact kidneys had significantly higher EPO level (22.70 +/- 1.70) (p < 0.001). No correlation was found between EPO level and any of the hematologic or iron indices.
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PMID:Assessment of erythropoietin levels and some iron indices in chronic renal failure and liver cirrhosis patients. 1068 46

It has been proposed that iron overload may adversely affect liver disease outcome. The recent identification of 2 mutations in the HFE gene related to hereditary haemochromatosis (Cys282Tyr and His63Asp) provided an opportunity to test whether they are associated with hepatic iron accumulation and the activity and severity of liver disease in hepatitis C virus (HCV) infection. We investigated the prevalence of HFE mutations in 135 male patients with chronic HCV hepatitis, and correlated genotype distribution with different parameters of iron status and the activity and severity of liver disease. Of these 135 patients, 6 (4.4%) carried Cys282Tyr and 32 (23.7%) carried His63Asp, frequencies which were similar to those observed in healthy controls. Serum iron levels and transferrin saturation (but not ferritin levels or liver iron content) were significantly higher in carriers than in non-carriers of HFE mutations. No difference was observed in serum ALT, AST and GGT levels between carriers and non-carriers. Finally, scores for necroinflammatory activity and fibrosis in the liver were significantly higher in HFE carriers than in non-carriers. Patients with chronic HCV infection carrying HFE mutations tend to present more evident body iron accumulation and a higher degree of necroinflammatory activity and fibrosis in the liver. HFE gene mutations might be an additional factor to be considered among those implicated in the determination of a worse prognosis of the liver disease in chronic HCV infection.
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PMID:Are haemochromatosis mutations related to the severity of liver disease in hepatitis C virus infection? 1069 80

A recent review of the results of gastroplasties done at the University of Alberta Hospital showed that there was a high incidence of late weight loss failure. Therefore a new operation, gastroplasty/distal gastric bypass, has been performed on 263 patients. This operation results In a profound (mean greatest percentage excess weight loss of 87% at approximately 2 years) and lasting weight loss (mean final percentage excess weight loss of 78%) at 4 years, range 2-7.5 years post-operatively. Only 0.9 % of patients failed to maintain at least a 40% excess weight loss. The operation achieves its effect through a moderate restriction that permits patients to eat normal table food from the time of discharge and with a mild metabsorption that is not ordinarily associated with diarrhea or notable deficiencies. Certain patients required debanding of the stoma and others developed staple-line eventration. Neither of these events after long-term follow-up resulted in weight loss failure nor in other serious side-effects. It Is concluded that moderate failure of the gastroplasty stoma and staple line does not necessarily result in weight loss failure, because the malabsorptive portion of the operation remains intact. Low hemoglobin occurred in 16% of cases and deficiency of serum iron In 34%; a much smaller number of patients had chronic or Intermittent deficiencies of these entities. Correction was easily achieved with oral replacement. Deficiencies in albumin, calcium, phosphorus and folate were rarely seen and minimal elevation of serum AST values occurred In just over 1% of patients. Chronic deficiencies or elevations were not seen in these patients. Stomal ulcer occurred in 6% of patients and bleeding associated with stomal ulcer in 1%. Half the patients with ulcer were managed with H&inf2; blockers, the other half with vagotomy. Both forms of treatment when individualized effectively prevent re-ulceration.
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PMID:The Rationale and Results of Gastroplasty/Distal Gastric Bypass. 1076 65

The toxicological literature is replete with studies attempting to explain the mechanism of action of organophosphorus (OP) insecticides to their anticholinesterase activities, but not much is known about the metabolism and detoxification of these compounds. The goal of this study was to ascertain the toxic effects of chlorpyrifos, one of the most widely used OPs, on the liver of male rats and also to evaluate the protective potential of zinc in mediating its toxic effects. It was observed that chlorpyrifos (13.5 mg/kg body weight) treatment resulted in significant inhibition (p < 0.001) of serum and hepatic acetylcholinesterase (AChE) activities after 8 wk. However, zinc-treated (227 mg/L drinking water) animals resulted in significant normalization of the inhibited AChE activities. Similarly, a significant increase in the levels of various serum and liver marker enzymes (viz. alkaline phosphatase, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) was observed following treatment with chlorpyrifos. However, coadministration of zinc to these animals restored these enzymes to within normal limits, even though some increase in the activity of serum ALT and hepatic alkaline phosphatase still persisted at the end of the study. Chlorpyrifos treatment diminished serum and hepatic zinc levels significantly (p < 0.01 to p < 0.001) compared to normal control animals. Serum iron concentrations also plummeted significantly following chlorpyrifos treatment. On the contrary, serum copper levels were significantly increased (p < 0.01) in chlorpyrifos-treated animals, but they were normalized following zinc supplementation to the rats in this group. Interestingly, chlorpyrifos treatment resulted in elevated hepatic levels of copper, iron, and selenium, but zinc treatment could only partially restore the raised elemental concentrations. These data clearly demonstrate the potential role of zinc in mediating the toxic effects of chlorpyrifos, presumably because of their antioxidant properties and also their possible interaction with other trace elements in maintaining the cellular harmony.
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PMID:Protective effects of zinc in chlorpyrifos induced hepatotoxicity: a biochemical and trace elemental study. 1105 90


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