Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unravelling the role of interferon (IFN) in the treatment of chronic hepatitis B compliance by many factors. Several mutant forms of hepatitis B virus (HBV) have recently been discovered; the most common of these is the precore mutant, characterized by hepatitis B e antigen (HBeAg) negativity and hepatitis B e antibody (HBeAb) positivity in an individual with an active HBV infection. The aim of this study was to compare the response rate to IFN therapy in patients with wild-type HBV infection and in individuals infected with the precore mutant. A second aim was to evaluate the role of an increased serum ferritin in terms of the IFN response rate in these two different types of HBV infection. IFN therapy was administered at a dose of 5 MU subcutaneously three times weekly for 6 months to 41 individuals with a chronic wild-type hepatitis B infection and 16 individuals with a precore mutant chronic HBV infection. An IFN response was defined as normalization of the serum alanine aminotransferase (ALT) level and an HBeAb to HBeAb seroconversion (in wild-type hepatitis infection), and a normalization of the serum ALT in individuals infected with a precore mutant infection. At entry, the two groups were matched for age, gender, serum ALT, serum iron, total iron binding capacity (TIBC), serum ferritin and liver histology. Forty-six per cent of the subjects with wild-type disease responded to IFN therapy. By contrast, only four of the 16 cases (25%) of the precore mutant cases responded (p < 0.05). Ferritin levels correlated well with the type of IFN response; as the serum ferritin level increased, the response rate to IFN declined. Hapatic infection caused by a precore HBV mutant is more resistant to IFN therapy than wild-type infection. The serum ferritin level appears to influence the type of IFN response achieved. Individuals with a serum ferritin level greater than 300 ng ml-1 failed to respond to IFN in 93% of the cases studied.
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PMID:Relationship between the serum alanine aminotransferase level at the end of interferon treatment and histologic changes in wild-type and precore mutant hepatitis B virus infections. 887 72

In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
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PMID:Safety profile of the oral iron chelator deferiprone: a multicentre study. 1069 60

In 1997, the Italian Ministry of Health created a special programme for the controlled distribution of deferiprone to collect data and to evaluate its safety and effectiveness in long-term use. Five hundred and thirty-two thalassaemia patients from 86 treatment centres were enrolled in this programme. One hundred and eighty-seven patients (32%) experienced a total of 269 events that led to a temporary interruption or, in some cases, to a discontinuation of treatment. The incidence of agranulocytosis and milder neutropenias were 0.4/100 and 2.1/100 patient-years respectively. Neutropenia occurred predominantly in younger and non-splenectomized patients. Transient alanine transaminase increase, gastrointestinal discomfort and arthralgia were the other most commonly reported events. Ferritin levels showed a significant decrease in time after 3 years of therapy. This is the largest number of deferiprone-treated patients to have been reported to date. These data show that the drug was effective in reducing serum ferritin levels and the incidence of adverse events was not greater than the frequency reported in clinical trials.
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PMID:The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients. 1210 Jan 70

The identification of a safe, orally active iron chelator is critically important for the prevention of morbidity and early death in patients receiving regular red cell transfusions. Based on our findings in a 1-year multicenter, prospective study of the safety and efficacy of deferiprone in patients with thalassemia major, we have extended the treatment period to 4 years. The mean dose of the chelator was 73 mg/kg per day during 531 patient-years. The rates of agranulocytosis (absolute neutrophil count [ANC] < 500 x 10(9)/L) and milder forms of neutropenia (ANC, 500-1500 x 10(9)/L) were 0.2 and 2.8 per 100 patient-years, respectively. Neutropenia occurred significantly more commonly in patients with intact spleens. Gastrointestinal and joint symptoms decreased significantly after the first year of therapy, and led to discontinuation of deferiprone in only one patient in years 2 to 4. The mean alanine aminotransferase (ALT) value of 71 U/L after 4 years of therapy was significantly higher than the baseline value of 61 U/L. Trend analysis showed no increase in the ALT levels or the percentage of patients with ALT levels greater than twice the upper limit of the reference range. Ferritin levels did not change significantly from the values at the time of change from deferoxamine to deferiprone in either the intention-to-treat analysis or in the 84 patients who completed 4 years of therapy. Because of concerns regarding the effectiveness of the studied dose of deferiprone, 47 patients discontinued therapy, whereas 15 patients interrupted therapy because of concerns regarding low iron levels. The results of this study help to define the safety and effectiveness of long-term therapy with deferiprone.
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PMID:Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. 1276 39

Ferritin is an indispensable parameter in the diagnosis of latent iron deficiency anemia or siderosis. In this study, we evaluated the utility of a reagent for ferritin measurement in a latex agglutination (LA) test, using general chemistry analyzers. The intraassay coefficient of variation (CV) was 0.8-3.4% and the interassay CV was 0.0-0.7%. Linearity was observed up to 1100 ng/mL. The effective sensitivity value was 4.0 ng/mL. In addition, good results were obtained with the prozone test, the effects of interferences, correlation with the enzyme immunoassay (EIA) method, and functional assay sensitivity. A significant positive correlation with C-reactive protein (r=0.586, P<0.001) was found. When compared with liver-related biochemical parameters (asparate aminotransferase (AST) and alanine aminotransferase (ALT)) in patients with impaired liver function, ferritin varied in parallel with the liver-related parameters. This assay system was able to measure ferritin accurately over a wide range, and thus could be used to diagnose cancer, siderosis, and iron deficiency anemia. The LA assay system can be employed for measurement with general chemistry analyzers, with rapid and convenient execution. In addition, the LA test allows the simultaneous measurement of other markers of iron deficiency anemia, so clinicians can rapidly obtain examination results.
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PMID:Latex agglutination test for ferritin measurement. 1461 45

A study was conducted to determine the relationship between ferritin and glycosylated isoforms of ferritin and insulin resistance in 69 HIV-infected men receiving HAART. Ferritin levels were significantly correlated with aspartate aminotransferase, alanine aminotransferase, bilirubin and with insulin resistance. The ferritin isoelectric focusing patterns of five insulin-resistant HIV-infected patients under HAART showed large amounts of hyperglycosylated isoforms, which was not found in 56 control subjects and 46 untreated HIV-1-infected patients.
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PMID:Hyperglycosylated ferritin in sera of HIV-1-infected patients treated with highly active antiretroviral therapy. 1643 82

We quantified and studied the impact of post transfusional iron overload alone in post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 mg/L. Liver iron content (LIC) was 117 mmoles/gdw. Correlation RBCs and ferritin was (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal ferritin group in terms of RBCs transfused (p<10(-3)), ALT (p<0.009). But occurrence of liver dysfunction was not significant. Magnitude of iron overload correlates closely to the number of RBCs and is quantified by MRI. Impact on liver dysfunction is moderate in absence of co-morbidity.
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PMID:Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). 1755 Aug 61

Emerging scientific evidence suggests that increases in body iron represent a risk factor for the development of metabolic syndrome and diabetes. The aim of our study was to determine the body iron stores in patients with metabolic syndrome, and to evaluate the potential relationship of iron overload with specific features of the metabolic syndrome, such as fatty liver. A total of 490 individuals were enrolled. The diagnosis of metabolic syndrome was based on National Cholesterol Education Program-Adult Treatment Panel III (ATPIII) criteria. The metabolic syndrome group was consisted of 185 patients having three or more criteria, whereas individuals with less than three criteria constituted the control group. Metabolic syndrome patients displayed higher ferritin concentration as compared to control individuals. Ferritin levels were positively correlated with insulin concentration, as well as with Homeostasis Model Assessment (HOMA) index values. Multiple regression analysis revealed that ferritin was the most important independent determinant of insulin resistance indices. Patients with metabolic syndrome also exhibited increased concentrations of alanine aminotransferase and gamma-glutamyltranspeptidase compared to controls. Multiple regression analysis revealed that ferritin concentration was the most important determinant of gamma-glutamyltranspeptidase levels. Patients with the metabolic syndrome exhibit an increase in body iron stores as well as elevated concentrations of liver enzymes compared to the individuals who do not fulfill the criteria for the diagnosis of this syndrome. Our data support a direct role of increased body iron in the pathogenesis of insulin resistance, whereas iron overload may also contribute to the development of specific features of the metabolic syndrome, such as fatty liver.
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PMID:Increased serum ferritin concentrations and liver enzyme activities in patients with metabolic syndrome. 1837 Jul 38

Synergistic therapeutic potential of ferritin (5mg/kg, i.p.) and propolis (honeybee hive product; 200mg/kg, p.o.) was analyzed to encounter the beryllium induced biochemical and ultra morphological alterations. Female albino rats were exposed to beryllium nitrate (1mg/kg, i.p.) daily for 28 days followed by treatment of above mentioned therapeutic agents either individually or in combination for five consecutive days. Exposure to beryllium increased its concentration in serum, liver and kidney and significantly altered the activities of CYP2E1 and CYP1A2 enzymes, microsomal lipid peroxidation and microsomal proteins. Activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, protein, creatinine and urea in serum as well as hemoglobin and blood glucose level; activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose-6-phosphatase and succinic dehydrogenase, total triglycerides, total cholesterol, total protein contents, glycogen contents, lipid peroxidation and glutathione level in liver and kidney were significantly altered after beryllium administration. Beryllium exposure severely altered ultramorphology of liver and kidney that proved its toxic consequences at cellular level. Ferritin in combination with propolis dramatically reversed the alterations of these variables towards control in a synergistic manner concluding its beneficial effects over monotherapy in attenuating beryllium induced systemic toxicity.
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PMID:Synergistic effects of ferritin and propolis in modulation of beryllium induced toxicogenic alterations. 1862 18

Woolly monkeys (Lagothrix sp.) are threatened species and numerous zoos have failed to sustain successful populations. The most common causes of death in captive woolly monkeys are related to pregnancy and hypertension. The objective of this retrospective study was to evaluate serum concentrations of a large number of captive woolly monkeys to establish baseline means and compare these concentrations with their closest related species to determine potential abnormalities. Serum analyses from 30 woolly monkeys housed at two institutions (Apenheul, The Netherlands and The Louisville Zoo, KY, USA) over 12 yr were collected. The statistical model included gender, age group (young, 0-4 yr of age; middle, 5-9 yr; and old, 10+ yr), and zoological institution. All panel result means were similar to previously reported concentrations for howler (Alouatta sp.) and spider monkeys (Ateles sp.) with the possible exception of alanine aminotransferase and gamma-glutamyl-transferase being higher, whereas creatinine and phosphorus were lower. The serum glucose mean of 6.7 mmol/L is above the baseline range for humans and spider monkeys. Alkaline phosphatase (ALP), alanine aminotransferase, and sodium (Na) were higher in females and magnesium (Mg) was higher in males (P<0.05). ALP, Mg, and phosphorus were highest (P<0.05) and calcium and sodium tended to be highest (P<0.10) in the oldest animals. Ferritin tended to be highest (P<0.10) in the oldest animals. Albumin, ALP, chloride, Na, and total bilirubin were higher for Zoo A, whereas gamma-glutamyl-transferase, glucose, and lactate dehydrogenase were lower for Zoo A (P<0.05). Areas of potential woolly monkey health risk were noted and discussed. Future studies are needed to determine free-ranging serum concentrations to elucidate parameters that contain aberrant concentrations and decrease health status.
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PMID:Serum chemistry concentrations of captive woolly monkeys (Lagothrix lagotricha). 1936 Jun 17


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