Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
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Excessive alcohol consumption is a major health problem in the UK leading to both serious morbidity and mortality. This study compared newer potential biochemical markers of excessive alcohol consumption [carbohydrate-deficient transferrin (CDT), mitochondrial AST (mAST) and alpha glutathione-s-transferase (alpha-GST)] with conventional markers (AST, ALT, GGT, MCV). Patients (n = 85) were enrolled in the study and subdivided into several groups on the basis of alcohol consumption. Patients with non-alcoholic liver disease (NALD) (n = 40) were also enrolled. All the markers, with the exception of the ratio mAST/total AST were significantly higher in heavy drinkers/alcoholics compared to teetotallers/social drinkers (p < 0.05). mAST and AST/ALT ratio were significantly higher in alcoholics compared to NALD (p < 0.01), whereas ALT was higher in the NALD group (p < 0.05). Multivariate discriminant function analysis (Wilks method) demonstrated that the logarithmic functions of AST/ALT ratio and mAST could correctly classify 87.9% of cases into either the alcoholic or NALD groups. ROC plot analysis showed that AST, mAST and GGT were the best markers at distinguishing heavy consumption of alcohol from lesser levels and that AST/ALT ratio and mAST were the best in distinguishing alcoholics from NALD. In conclusion, none of the newer biochemical markers, with the exception of mAST, offers any major advantage over the conventional markers.
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PMID:Biochemical markers of alcohol abuse. 872 55

The objective of this study was to study the ability of biological markers of alcohol consumption in differentiating subjects below weekly consumption of 400 or 600 g of absolute ethanol from those above, and to study the effect of intranasal calcitonin on alcohol drinking. A prospective 12-week double-blind study that used anonymous data collection with drinking diaries was done. The drug that was studied (calcitonin or placebo) was used during study weeks 5-8. This study was performed at the research unit of a university hospital. The subjects consisted of 59-nine men aged 26 to 57 years who considered themselves as regular but modest drinkers and were recruited by advertisements. The measurements were obtained from monthly questionnaires and daily anonymous diaries for alcohol drinking data, and biological markers of alcohol consumption (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, beta hexosaminidase, and carbohydrate deficient transferrin). The results indicated intranasal calcitonin with a dose of 200 IU three times a week had no effect on alcohol use. All biological markers studied had only a modest ability to differentiate those with weekly alcohol consumption of 400 or 600 g or over from those below these limits. The areas under receiver operating characteristic (ROC) curve with the limit 400 g/week were 0.71 for aspartate aminotransferase, 0.61 for alanine aminotransferase, 0.74 for gamma-glutamyl transpeptidase, 0.68 for beta-hexosaminidase, and 0.78 for carbohydrate deficient transferrin. Respective numbers for the 600-g limit were more uniform. As evaluated by ROC analysis, carbohydrate deficient transferrin was the best biological marker to find men with weekly alcohol consumption over 400 g. Intranasal salmon calcitonin had no affect on alcohol drinking.
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PMID:Biological markers of alcohol consumption and effect of calcitonin in nonalcoholic men: a prospective, double-blind study. 886 56

The determination of serum levels of carbohydrate deficient transferrin (CDT) and transferrin ratio in the persistent abusive alcohol consumer arises with promising utility in the study of alcohol related disorders. This series shows the excellent specificity (97%), though poor sensitivity (52%), for CDT. However the CDT/Tft ratio affords a higher sensitivity, reaching 74%, maintaining the high specificity. In persistent abusive consumers (> 70 g/day) this index, which is positively correlated with serum transferrin, is capable of defining these amounts of alcohol per capita with a high frequency and provides independent information since it is not significantly correlated with the levels of traditional biological markers (AST, ALT, GGT, AGV). Although with defined methodological limitations, these indexes denote, with the improvement of technical accessibility, a practical applicability in the screening of chronic abusive consumers. In the field of hepatology the behaviour of CDT and the transferrin ratio is capable of showing the involvement of ethanol in the study of the nature of a chronic hepatic disease with a high frequency. However, the degree of liver lesion show by the PGA hepatic index, has no significant influence on the serum levels of CDT and the transferrin ratio. In this series, the circumstances and conditions of alcohol consumption seem to be the independent determinant of the informative character which these indexes reveal.
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PMID:[Asialotransferrin discriminating excessive, subacute and chronic active alcohol consumption. Clinical usefulness in hepatic disease]. 896 3

In order to evaluate the pathogenetic role of iron in Porphyria cutanea tarda (PCT), the metabolism of iron was studied in 440 patient with PCT and associated chronic liver disease (CLD) and in 91 nonporphyric CLD patients (used as a control group). The parameters considered were the following: serum iron, ferritin, Total Iron Binding Capacity (TIBC) and percent saturation of transferrin. The statistical analysis showed that the differences between the means, in the two groups, were not significant in any of the parameters examined. To investigate the possible relationships between iron metabolism and other chemico-clinical parameters concerning the porphyric disease, the associated hepatic disease and hemometry, we studied the correlations between iron parameters and total urinary and serum porphyrins, serum copper, serum albumin, hemoglobin, red blood cells, ALT, AST, CHE and GLDH. This investigation was only possible in the last 99 cases. In addition to the obvious correlations between the parameters concerning iron metabolism, the highly significant (p < 0.001) correlation between ferritin and enzyme activities which indicate cytolysis (ALT, AST, GLDH) is extremely interesting. The results seem to point to the tentative conclusion that the alterations of iron metabolism are more related to the hepatocellular necrosis than to the metabolism of porphyrins.
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PMID:Iron and porphyria cutanea tarda. 907 91

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.
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PMID:Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities. 914 69

In thalassemia after successful bone marrow transplantation (BMT), iron overload remains an important cause of morbidity. After BMT, patients have normal erythropoiesis capable of producing a hyperplastic response to phlebotomy so that this procedure can be contemplated as a method of mobilizing iron from overloaded tissues. A phlebotomy program (6 mL/kg blood withdrawal at 14-day intervals) was proposed to 48 patients with prolonged follow-up (range, 2 to 7 years) after BMT. Seven patients were not submitted to the program (five because of refusal and two because of reversible side effects). The remaining 41 patients (mean age, 16 +/- 2.9 years) were treated for a mean period of 35 +/- 18 months. All were evaluated before and after 3 +/- 0.6 years of follow-up. Values are expressed as mean +/- standard deviation (SD) or as median with a range (25 to 75 percentile). Serum ferritin decreased from 2,587 (2,129 to 4,817) to 417 (210 to 982) microg/L (P < .0001), total transferrin increased from 2.34 +/- 0.37 to 2.7 +/- 0.58 g/L (P = .0001), transferrin saturation decreased from 90% +/- 14% to 50% +/- 29% (P < .0001). Liver iron concentration evaluated on liver biopsy specimens decreased from 20.8 (15.5 to 28.1) to 4.2 (1.6 to 14.6) mg/g dry weight (P < .0001). Aspartate transaminase decreased from 2.7 +/- 2 to 1.1 +/- 0.6 (P < .0001) and alanine transaminase from 5.2 +/- 3.4 to 1.7 +/- 1.2 (P < .0001) times the upper level of normality. The Knodell score for liver histological activity decreased from 6.9 +/- 3 to 4.9 +/- 2.8 (P < .0001). These data indicate that phlebotomy is safe, efficient, and widely applicable to ex-thalassemics after BMT.
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PMID:Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients. 924 28

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcohol abuse. However, its value in patients with associated liver disease is still controversial. The aim of the study was to investigate the usefulness of CDT as a marker of alcohol consumption in patients with liver disease. We measured serum levels of CDT and those of commonly used hematological and biochemical markers, mean corpuscular volume (MCV), transaminases (AST and ALT), and gamma-glutamyltransferase in 179 male subjects divided into four groups: 45 active drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls. Serum CDT in active alcoholics was 37.5 +/- 3.6 units/liter, being significantly higher than that of abstinent alcoholics (20.3 +/- 1.5 units/liter), patients with nonalcoholic liver disease (18.1 +/- 1.1 units/liter), and controls (13.1 +/- 0.8 units/liter). Contrary to the other markers, no significant differences were observed in CDT values in relation with the presence and severity of liver disease in either the active drinkers or in the abstinent alcoholics. The sensitivity and specificity of CDT as a marker of alcoholism in the series as a whole was 64% and 82%, respectively, similar to the best conventional marker, MCV (64 and 82%). In patients with liver disease, CDT maintained good sensitivity (72%) and specificity (83%). Receiver operating characteristic analysis confirmed that CDT had a similar diagnostic value to that of MCV, but better than gamma-glutamyl-transferase and transaminases for the detection of alcohol abusers. The good diagnostic efficacy of CDT remained unchanged when analyzing only patients with liver disease. We conclude that serum CDT is a good marker of alcoholism and is less influenced than the currently used biochemical markers for associated liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse regardless of the presence of alcoholic liver disease.
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PMID:Carbohydrate-deficient transferrin as a marker of alcohol consumption in male patients with liver disease. 926 45

To investigate Fe nutritional indices in malaria infection in children, haematology (blood haemoglobin, plasma ferritin, transferrin, Fe, and transferrin saturation), acute phase markers (albumin and caeruloplasmin) and liver function tests were studied in fifty consecutive cases of severe and mild falciparum malaria, fifty matched controls and twenty-three cases of asymptomatic malaria. Blood haemoglobin and transferrin were lower, while ferritin and transferrin saturation were higher, in groups with symptomatic malaria in comparison with the control group. The differences were greatest with the severest form of the disease. There were no differences between any of the groups in plasma Fe. Plasma transferrin correlated directly with albumin in asymptomatic, mild and severe malaria groups (r 0.48, 0.65 and 0.83; P < 0.05, P < 0.05, P < 0.01 and P < 0.001 respectively), and inversely with caeruloplasmin (r -0.65, -0.34 and -0.43; P < 0.01, P < 0.05 and P < 0.01 respectively). For ferritin, the correlation was inverse with albumin (r -0.65, -0.57 and -0.64; P < 0.01, P < 0.001 and P < 0.001 respectively and direct with caeruloplasmin (r 0.83, 0.21 and 0.49, P < 0.001, NS and P < 0.001 respectively). Multiple regression analysis on data from all patients combined indicated that albumin, and to a lesser extent alanine aminotransferase (EC 2.6.1.2) activity, explained 62 % of the variance in transferrin. Caeruloplasmin, parasite count and albumin explained 59 % of the variance in ferritin, and transferrin and unconjugated bilirubin explained 62 % of the variance in Fe values. In conclusion, these data suggest that low transferrin and high ferritin values are primarily due to the acute phase response. High transferrin saturation and lack of differences in plasma Fe between the groups are probably due to Fe released from lysed erythrocytes. Finally, in both symptomatic and asymptomatic malaria, indices of Fe status can be misleading and may be especially problematic in community studies in malaria-endemic areas where asymptomatic malaria may be common.
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PMID:Influence of malaria on markers of iron status in children: implications for interpreting iron status in malaria-endemic communities. 938 98

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.
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PMID:Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse. 946 24

The stage of human African trypanosomiasis (HAT) is important to define precisely as far as it is directly related to the type of treatment used. The beginning of the neurological involvement is difficult to find out because there is no known specific clinical or biological sign. This study is trying to look for a precise marker and has been realized in Congo. 70 subjects with parasitologically confirmed HAT and 70 controls are included. The stage of HAT is determined according to the classical definition on the field using the cerebrospinal fluid (CSF) cell count: less than 5 cells/microliters for the first stage (P1), more than 5 cells/microliters for the second stage (P2). The blood analysis has included: glucose, urea, creatinine, sodium, potassium, calcium, chloride, phosphorus, uric acid, total bilirubin, unconjugated bilirubin, total cholesterol, triglycerides, total proteins, aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, alkaline phosphatase, gamma-glutamyltransferase, immunoglobulins M and G, C3c fraction of complement, transferrin, seromucoid alpha 1, haptoglobin and albumin. In CSF we have analyzed IgM, IgG, protein levels and the bloodbrain barrier (BBB) impairment. The comparison between the subjects and their controls, the subjects in P1 and in P2, the CSF cell count and the other CSF alterations show the interest of the IgM level in CSF and the BBB impairment to identify subjects in P2. However there is a low gradation in the biological disturbances and not a precise threshold point. Nevertheless it seems reasonable to raise the CSF cell count level to 20 cells/microliters to define the beginning of the nervous involvement.
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PMID:[Contribution of biochemical tests in the diagnosis of the nervous phase of human African trypanosomiasis]. 950 61


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