Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

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Lee, Linda K; Gan, Victor C; Lee, Vernon J; Tan, Adriana S; Leo, Yee Sin; Lye, David C

2012-01-01

Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

Regional adipose tissue and elevations in serum aminotransferases in HIV-infected individuals.

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Tien, Phyllis C; Kotler, Donald P; Overton, E Turner; Lewis, Cora E; Rimland, David; Bacchetti, Peter; Scherzer, Rebecca; Gripshover, Barbara

2008-06-01

The association of fat distribution with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations is not well-defined in HIV-infected individuals. Obesity is associated with hepatic steatosis, and ALT is a marker of steatosis in the general population. Cross-sectional analysis of 1119 HIV-infected and 284 control subjects. Hepatitis C virus (HCV) RNA testing determined HCV infection. Magnetic resonance imaging measured regional adipose tissue volume. After adjustment for demographic and lifestyle factors, visceral adipose tissue (VAT) was positively associated with ALT in HIV/HCV-coinfected subjects (+9.8%, 95% confidence interval [CI]: 2.8 to 17.6), HIV-monoinfected subjects (+8.0%, 95% CI: 4.2 to 12.1), and controls (+5.9%, 95% CI: 2.0 to 10.1). In contrast, lower trunk subcutaneous adipose tissue (SAT) was negatively associated with ALT in HIV/HCV-coinfected subjects (-14.3%, 95% CI: -24.7 to -4.2) and HIV-monoinfected subjects (-11.9%, 95% CI: -18.4 to -5.3); there was a trend toward an association in controls (-7.1%, 95% CI: -22.7 to 5.9). Estimated associations between regional adipose tissue and AST were small and did not reach statistical significance. More VAT and less lower trunk SAT are associated with elevated ALT, which likely reflects the presence of steatosis. There was little association with AST. HCV infection and having more VAT or less lower trunk SAT are independently associated with elevated ALT in HIV infection. Study regarding the association between VAT, trunk SAT, HCV, and progression of steatosis and fibrosis is needed in HIV-infected individuals.

Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

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Miyuki Yokoyama

2016-01-01

Full Text Available Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST to alanine aminotransferase (ALT. However, the association of AST/ALT ratio with brain natriuretic peptide (BNP levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL. There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality.

Coffee consumption is associated with lower serum aminotransferases in the general Korean population and in those at high risk for hepatic disease.

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Oh, Myueng Guen; Han, Mi Ah; Kim, Man Woo; Park, Chan Guk; Kim, Young Dae; Lee, Jun

2016-12-01

The favourable effects of coffee on liver enzymes have been reported worldwide. This study investigated the association between coffee consumption and serum aminotransferase concentration in Korean adults. Data were obtained from the fourth and fifth Korea National Health and Nutrition Examination Surveys. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentration were defined as >30 IU/L for men and >19 IU/L for women. The risk of elevated ALT and AST according to general characteristics and frequency of coffee consumption were tested by chi-square tests and multiple logistic regression analyses. The prevalence of elevated ALT was 27.4%, 27.8%, and 26.9% in subjects who drank =2 times/day, respectively. The proportions of individuals with elevated AST were 32.5%, 33.1%, and 26.7% in subjects who drank =2 times/day, respectively. The aORs for elevated ALT and AST were significantly lower in subjects who drank >=2 times of coffee/day than in those who drank =2 times/day was associated with lower ORs for elevated ALT in the high-risk group overall and in the viral hepatitis and obesity subgroups, respectively. In sensitivity analysis, reduced frequency of coffee consumption was associated with an increased risk for elevated liver enzymes, although an association between coffee consumption and elevated ALT was not observed in women or current smokers. Higher coffee consumption was associated with lower risk of elevated aminotransferase concentration in Korean adults.

Saccharomyces cerevisiae Differential Functionalization of Presumed ScALT1 and ScALT2 Alanine Transaminases Has Been Driven by Diversification of Pyridoxal Phosphate Interactions

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Erendira Rojas-Ortega

2018-05-01

Full Text Available Saccharomyces cerevisiae arose from an interspecies hybridization (allopolyploidiza-tion, followed by Whole Genome Duplication. Diversification analysis of ScAlt1/ScAlt2 indicated that while ScAlt1 is an alanine transaminase, ScAlt2 lost this activity, constituting an example in which one of the members of the gene pair lacks the apparent ancestral physiological role. This paper analyzes structural organization and pyridoxal phosphate (PLP binding properties of ScAlt1 and ScAlt2 indicating functional diversification could have determined loss of ScAlt2 alanine transaminase activity and thus its role in alanine metabolism. It was found that ScAlt1 and ScAlt2 are dimeric enzymes harboring 67% identity and intact conservation of the catalytic residues, with very similar structures. However, tertiary structure analysis indicated that ScAlt2 has a more open conformation than that of ScAlt1 so that under physiological conditions, while PLP interaction with ScAlt1 allows the formation of two tautomeric PLP isomers (enolimine and ketoenamine ScAlt2 preferentially forms the ketoenamine PLP tautomer, indicating a modified polarity of the active sites which affect the interaction of PLP with these proteins, that could result in lack of alanine transaminase activity in ScAlt2. The fact that ScAlt2 forms a catalytically active Schiff base with PLP and its position in an independent clade in “sensu strictu” yeasts suggests this protein has a yet undiscovered physiological function.

Saccharomyces cerevisiae Differential Functionalization of Presumed ScALT1 and ScALT2 Alanine Transaminases Has Been Driven by Diversification of Pyridoxal Phosphate Interactions

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Rojas-Ortega, Erendira; Aguirre-López, Beatriz; Reyes-Vivas, Horacio; González-Andrade, Martín; Campero-Basaldúa, Jose C.; Pardo, Juan P.; González, Alicia

2018-01-01

Saccharomyces cerevisiae arose from an interspecies hybridization (allopolyploidiza-tion), followed by Whole Genome Duplication. Diversification analysis of ScAlt1/ScAlt2 indicated that while ScAlt1 is an alanine transaminase, ScAlt2 lost this activity, constituting an example in which one of the members of the gene pair lacks the apparent ancestral physiological role. This paper analyzes structural organization and pyridoxal phosphate (PLP) binding properties of ScAlt1 and ScAlt2 indicating functional diversification could have determined loss of ScAlt2 alanine transaminase activity and thus its role in alanine metabolism. It was found that ScAlt1 and ScAlt2 are dimeric enzymes harboring 67% identity and intact conservation of the catalytic residues, with very similar structures. However, tertiary structure analysis indicated that ScAlt2 has a more open conformation than that of ScAlt1 so that under physiological conditions, while PLP interaction with ScAlt1 allows the formation of two tautomeric PLP isomers (enolimine and ketoenamine) ScAlt2 preferentially forms the ketoenamine PLP tautomer, indicating a modified polarity of the active sites which affect the interaction of PLP with these proteins, that could result in lack of alanine transaminase activity in ScAlt2. The fact that ScAlt2 forms a catalytically active Schiff base with PLP and its position in an independent clade in “sensu strictu” yeasts suggests this protein has a yet undiscovered physiological function. PMID:29867852

Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

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Justyna Skóra

2015-02-01

Full Text Available The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather present within the working environment stimulate or inhibit Alt a 1 production (ELISA test. Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%–16% frequency in the air. The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103–6.528 ng/mL than a ATCC strain (0.551–0.975 ng/mL. It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein.

Modifiable clinical and lifestyle factors are associated with elevated alanine aminotransferase levels in newly diagnosed type 2 diabetes patients

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Mor, Anil; Svensson, Elisabeth; Rungby, Jørgen

2014-01-01

BACKGROUND: Current literature lacks data on markers of non-alcoholic fatty liver disease (NAFLD) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. We therefore, conducted a cross-sectional study to examine modifiable clinical and lifestyle factors associated with elevated alanine...... aminotransferase (ALT) levels as a marker of NAFLD in new T2DM patients. METHODS: Alanine aminotransferase levels were measured in 1026 incident T2DM patients enrolled in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. We examined prevalence of elevated ALT (>38 IU/L for women....../L (interquartile range: 22-41 IU/L) in men. Elevated ALT was found in 16% of incident T2DM patients. The risk of elevated ALT was increased in patients who were diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14...

Plasma Levels of Alanine Aminotransferase in the First Trimester Identify High Risk Chinese Women for Gestational Diabetes

OpenAIRE

Leng, Junhong; Zhang, Cuiping; Wang, Peng; Li, Nan; Li, Weiqin; Liu, Huikun; Zhang, Shuang; Hu, Gang; Yu, Zhijie; Ma, Ronald CW; Chan, Juliana CN; Yang, Xilin

2016-01-01

Alanine aminotransferase (ALT) predicts type 2 diabetes but it is uncertain whether it also predicts gestational diabetes mellitus (GDM). We recruited 17359 Chinese women with ALT measured in their first trimester. At 24?28?weeks of gestation, all women underwent a 50-gram 1-hour glucose challenge test (GCT) followed by a 75-gram 2-hour oral glucose tolerance test if GCT result was ?7.8?mmol/L. Restricted cubic spline analysis was used to examine full-range risk associations of ALT levels wit...

Pattern of AST and ALT changes in Relation to Hemolysis in sickle cell Disease

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K. Nsiah

2011-01-01

Full Text Available Background Elevated aminotransferase levels are commonly associated with compromised hepatic integrity from various insults. In sickle cell disease, aspartate transaminase (AST is also released via intravascular hemolysis. This study was done to determine the pattern of changes in AST and alanine transaminase (ALT, in particular the AST:ALT ratio, and to relate these to the hemolytic state, which we consider to be more important than hepatic and cardiac dysfunction in some individuals with sickle cell disease. Methods Serum aminotransferase levels were measured in 330 subjects with sickle cell disease, as well as hemoglobin, reticulocytes, and lactate dehydrogenase. The AST:ALT ratio was designated as a hemolytic marker, and simple and multivariate regression analyses were carried out between this ratio and other hemolytic markers. Results Mean AST and ALT levels were 48.24 % 27.78 and 26.48 % 22.73 U/L, respectively. However, for 49 subjects without sickle cell disease, mean AST and ALT levels were the same, ie, 23.0 U/L. In the subjects with sickle cell disease, the increases in AST levels were far higher than for ALT, supporting its release via intravascular hemolysis. In 95.8% of the subjects with sickle cell disease, the AST:ALT ratio was > 1, but our results did not suggest overt malfunctioning of the liver and heart in the majority of subjects. Conclusion Regression analyses support the use of the AST:ALT ratio as a hemolytic marker, because it has an inverse association with the hemoglobin level. Whether in steady state or in crisis, provided hepatic and cardiac integrity has not been compromised, subjects with sickle cell disease would have higher AST levels due to the hemolytic nature of the condition. This is the first report highlighting the AST:ALT ratio in sickle cell disease.

Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals

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Sabin, Caroline A; Ryom, Lene; Kovari, Helen

2013-01-01

An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort ...

Associations of White Blood Cell Count,Alanine Aminotransferase,and Aspartate Aminotransferase in the First Trimester withGestational Diabetes Mellitus.

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Zhao, Li-li; Li, Wei; Ping, Fan; Ma, Liang-kun; Nie, Min

2016-06-10

Objective To explore the associations of white blood cell (WBC) count,alanine aminotransferase (ALT),and aspartate aminotransferase(AST) in the first trimester of pregnancy with gestational diabetes mellitus (GDM). Methods Totally 725 GDM women and 935 women who remained euglycemic throughout pregnancy were enrolled in this study. Pre-pregnancy weight/height were recorded. WBC,ALT,and AST levels were detected between 8 and 12 weeks of pregnancy.At 24 to 28 weeks of pregnancy,the glucose and insulin levels were measured. The WBC,ALT,and AST levels were compared between two groups,and the associations of WBC,ALT,and AST levels with the blood glucose and insulin levels were retrospectively analyzed. Meanwhile,the potential associations of those factors with the occurrence of GDM were analzyed. Results WBC count [9.41(8.15,10.84)?10(9)/L vs. 9.04 (7.64,10.37)?10(9)/L,P=1.0?10(-5)] and ALT levels [18.00(12.00,30.00)U/L vs. 16.00 (11.00,26.00)U/L,P=0.004] in the first trimester of pregnancy were significantly increased in GDM subjects than in normal glucose tolerance(NGT)subjects;however,the AST level showed no significant difference between these two groups [41.00 (26.00,43.00)U/L vs. 41.00 (23.00,43.00)U/L,P=0.588]. Logistic regression analysis illustrated that elevated WBC count was an independent risk factor for GDM after adjustment for age,pre-pregnancy body mass index,blood pressure,and family history of diabetes(OR=1.119,P=0.001). The ROC curve revealed that threshold of WBC count was 7.965?10(9)/L(AUC=0.566,P=1?10(-5)),which had a sensitivity of 79.4% and a specificity of 31.3%. Multivariate linear regression analysis showed that homeostasis model assessment of insulin resistance was positively correlated with WBC count(B=0.051,P=0.022,R(2)=0.083);1-hour blood glucose after oral 50 grams of sugar (B=0.044,P=0.001,R(2)=0.044) and fasting plasma true insulin(B=0.214,P=0.032,R(2)=0.066) were positively correlated with WBC count;1-hour true insulin after 100 grams

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus

NARCIS (Netherlands)

Schindhelm, RK; Diamant, M; Bakker, SJL; van Dijk, RAJM; Scheffer, PG; Teerlink, T; Kostense, PJ; Heine, RJ

Background Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus

NARCIS (Netherlands)

Schindhelm, R.K.; Diamant, M.; Bakker, S.J.L.; van Dijk, R.A.; Scheffer, P.G.; Teerlink, T.; Kostense, P.J.; Heine, R.J.

2005-01-01

Background: Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer

Impact of increasing alanine aminotransferase levels within normal range on incident diabetes

OpenAIRE

Chong-Shan Wang; Ting-Tsung Chang; Wei-Jen Yao; Shan-Tair Wang; Pesus Chou

2012-01-01

Abnormal alanine aminotransferase level (ALT) levels might be associated with type 2 diabetes, but whether higher ALT levels within the normal range predict the risk is unknown. Methods: We followed a community-based cohort of 3446 individuals who were ≥35 years old without diabetes and hepatitis B or C in southern Taiwan for 8 years (1997–2004) to study the risk for type 2 diabetes with different normal ALT levels. Results: Among the 337 incident diabetes cases, 16.0% were from those w...

Inhibition study of alanine aminotransferase enzyme using sequential online capillary electrophoresis analysis.

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Liu, Lina; Chen, Yuanfang; Yang, Li

2014-12-15

We report the study of several inhibitors on alanine aminotransferase (ALT) enzyme using sequential online capillary electrophoresis (CE) assay. Using metal ions (Na(+) and Mg(2+)) as example inhibitors, we show that evolution of the ALT inhibition reaction can be achieved by automatically and simultaneously monitoring the substrate consumption and product formation as a function of reaction time. The inhibition mechanism and kinetic constants of ALT inhibition with succinic acid and two traditional Chinese medicines were derived from the sequential online CE assay. Our study could provide valuable information about the inhibition reactions of ALT enzyme. Copyright © 2014 Elsevier Inc. All rights reserved.

Alt a 1 allergen homologs from Alternaria and related taxa: analysis of phylogenetic content and secondary structure.

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Hong, Soon Gyu; Cramer, Robert A; Lawrence, Christopher B; Pryor, Barry M

2005-02-01

A gene for the Alternaria major allergen, Alt a 1, was amplified from 52 species of Alternaria and related genera, and sequence information was used for phylogenetic study. Alt a 1 gene sequences evolved 3.8 times faster and contained 3.5 times more parsimony-informative sites than glyceraldehyde-3-phosphate dehydrogenase (gpd) sequences. Analyses of Alt a 1 gene and gpd exon sequences strongly supported grouping of Alternaria spp. and related taxa into several species-groups described in previous studies, especially the infectoria, alternata, porri, brassicicola, and radicina species-groups and the Embellisia group. The sonchi species-group was newly suggested in this study. Monophyly of the Nimbya group was moderately supported, and monophyly of the Ulocladium group was weakly supported. Relationships among species-groups and among closely related species of the same species-group were not fully resolved. However, higher resolution could be obtained using Alt a 1 sequences or a combined dataset than using gpd sequences alone. Despite high levels of variation in amino acid sequences, results of in silico prediction of protein secondary structure for Alt a 1 demonstrated a high degree of structural similarity for most of the species suggesting a conservation of function.

Effects of Nordic Walking and Pilates training programs on aminotransferase activity in overweight and obese elderly women

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Magdalena Hagner-Derengowska

2015-12-01

3 Chair of Vascular and Internal Diseases, Faculty of Health Sciences, Nicolaus Copernicus University in Toruń, Poland     Corresponding author: Magdalena Hagner-Derengowska, PT, PhD Chair of Clinical Neuropsychology, Nicolaus Copernicus University in Toruń M. Skłodowskiej-Curie 9 Street, 85-094 Bydgoszcz, Poland E-mail address: m_hagner-derengowska@wp.pl     ABSTRACT Background & Aims: Elevation of alanine (ALT and aspartate aminotransferase (AST activities may appear as liver injury due to fat storage and other enzyme sources, such as rhabdomyolysis. Elevated ALT is associated with all-cause and cardiovascular mortality in an elderly population. The aims of this study was to determine the effect of a 10-weeks training program on the serum activity of these enzymes in postmenopausal women with overweight and obesity. Methods: The study comprised 81 postmenopausal women with overweight and obesity: 34 (42% of whom completed a 10-weeks Nordic Walking (NW rehabilitation program, 27 (33% of whom completed a Pilates rehabilitation program, and 20 (25% of whom were the control group. Blood for testing for ALT, AST, and other parameters of metabolic syndrome was collected before the program commenced and after it finished. Results: Elevated (> 34 U/l ALT and AST activities presented in 9 (11% and 7 (9% of the patients, respectively. A reduction in ALT and AST activities was observed in 43 (53% of the subjects, and in 61%, 59% and 40%, and 47%, 63% and 50% of the individuals who completed the NW and Pilates programs and were in the control group, respectively. Conclusions: The outcome of the training programs on aminotransferase serum activities in postmenopausal women with overweight and obesity was individually different and not related to exercise type.   Keywords: alanine aminotransferase, aspartate aminotransferase, obesity, Nordic Walking, Pilates.

A Human Long Non-Coding RNA ALT1 Controls the Cell Cycle of Vascular Endothelial Cells Via ACE2 and Cyclin D1 Pathway

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Wen Li

2017-10-01

Full Text Available Background/Aims: ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2. To date, ALT1 biological roles in human vascular endothelial cells have not been reported. Methods: ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3’ rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. Results: ALT1 was expressed in human umbilical vein endothelial cells (HUVECs. The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2 was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL might be involved. Conclusion: The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.

Association between Serum Uric Acid and Elevated Alanine Aminotransferase in the General Population.

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Chen, Shuang; Guo, Xiaofan; Yu, Shasha; Sun, Guozhe; Yang, Hongmei; Li, Zhao; Sun, Yingxian

2016-08-24

Both the serum uric acid (SUA) level and elevated alanine aminotransferase (ALT) are related to metabolic syndrome. However, the association between SUA and elevated ALT has not been elucidated in the general population. The objective of this study was to investigate the association between SUA and elevated ALT in the general population of China; A total of 11,572 adults (≥35 years of age) participated in this survey. Elevated ALT was defined as >40 U/L. SUA ≥ 7.0 mg/dL in males or ≥6.0 mg/dL in females was defined as hyperuricemia. SUA within the reference range was divided into quartiles, and its associations with elevated ALT were evaluated by logistic regressions; A total of 7.4% participants had elevated ALT. The prevalence of hyperuricemia was 14.9% in males and 7.3% in females. There was a significantly positive dose-response association between SUA levels and the prevalence of elevated ALT. After adjusting for potential confounders, a positive relationship for elevated ALT was observed in subjects with hyperuricemia (odds ratio [OR]: 2.032, 95% confidence interval [CI]: 1.443-2.861 for men; OR: 2.045, 95% CI: 1.221-3.425 for women, both p < 0.05). Within the reference range, the association between SUA and elevated ALT persisted in the fourth quartile (OR: 1.467, 95% CI: 1.063-2.025 for men; OR: 1.721, 95% CI: 1.146-2.585 for women, both p < 0.05); Our results indicated that an increased SUA level, even within the reference range, was independently associated with elevated ALT in Chinese adults.

The Effects of Extra Virgin Olive Oil on Alanine Aminotransferase, Aspartate Aminotransferase, and Ultrasonographic Indices of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients Undergoing Low Calorie Diet

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Farzad Shidfar

2018-01-01

Full Text Available Background. Coronary artery disease is the most common cause of death in the patients with nonalcoholic fatty liver disease (NAFLD. Studies have shown that there is a strong relation between the increase in the aminotransferase levels and fat accumulation in the liver with cardiovascular complications, independent of all aspects of the metabolic syndrome. This study aimed to examine the effect of virgin olive oil on alanine aminotransferase (ALT and aspartate aminotransferase (AST and the severity of steatosis in the NAFLD patients undergoing a weight-loss diet. Methods. This clinical trial was carried out on 50 patients with nonalcoholic fatty liver (mean age of 45.91 ± 9.61 years, mean BMI of 29.7 ± 0.58 Kg/m2 and the subjects were randomly assigned to the olive oil group (receiving the equivalent of 20% of their total daily energy requirement from olive oil or the control group (with normal consumption of oil for 12 weeks. All the patients received a hypocaloric diet during the study. At the beginning and the end of the study, the serum levels of ALT and AST and liver steatosis were measured. Findings. A significant decrease in the level of ALT enzymes was observed in the control group at the end of the study (P = 0.004. In the olive oil group, both enzymes decreased compared to baseline measurements (P<0.01. There were significant differences in the ALT and AST levels between the two groups (P<0.02. The severity of liver steatosis did not change significantly during the study. Conclusion. The consumption of a low calorie diet enriched with olive oil, along with slight weight reduction, reinforces the desired effects of weight loss in improving the levels of the hepatic enzymes.

A Micro-Platinum Wire Biosensor for Fast and Selective Detection of Alanine Aminotransferase

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Tran Nguyen Thanh Thuy

2016-05-01

Full Text Available In this study, a miniaturized biosensor based on permselective polymer layers (overoxidized polypyrrole (Ppy and Nafion® modified and enzyme (glutamate oxidase (GlutOx immobilized micro-platinum wire electrode for the detection of alanine aminotransferase (ALT was fabricated. The proposed ALT biosensor was measured electrochemically by constant potential amperometry at +0.7 V vs. Ag/AgCl. The ALT biosensor provides fast response time (~5 s and superior selectivity towards ALT against both negatively and positively charged species (e.g., ascorbic acid (AA and dopamine (DA, respectively. The detection range of the ALT biosensor is found to be 10–900 U/L which covers the range of normal ALT levels presented in the serum and the detection limit and sensitivity are found to be 8.48 U/L and 0.059 nA/(U/L·mm2 (N = 10, respectively. We also found that one-day storage of the ALT biosensor at −20 °C right after the sensor being fabricated can enhance the sensor sensitivity (1.74 times higher than that of the sensor stored at 4 °C. The ALT biosensor is stable after eight weeks of storage at −20 °C. The sensor was tested in spiked ALT samples (ALT activities: 20, 200, 400, and 900 U/L and reasonable recoveries (70%~107% were obtained.

A quest for normal values of serum aminotransferase and its association with age and body mass index

International Nuclear Information System (INIS)

Farooq, M.A.; Farooq, Y.; Khan, M.A.

2016-01-01

Objective: To determine the reference range for serum alanine aminotransferase (ALT) levels for young healthy individuals in our population and to find out effects of age and body mass index on alanine aminotransferase. Study Design: Descriptive cross sectional study. Place and Duration of Study: Military Hospital Rawalpindi; from Dec 2009 to April 2010. Material and Methods: Five hundred and fifty three young healthy adults were included in the study. Detailed history was taken. Parameters like Age, height and weight were measured. Relevant investigations were carried out for each subject which included blood complete picture, Chest X-Ray, ECG, Urine routine examination, liver function tests, serum urea, serum creatinine, serum uric acid, plasma glucose (F), Anti HCV antibodies, HBsAg, HIV antibodies and VDRL. Data was analyzed using SPSS version 22. Results: Age of subjects ranged from 19 to 50 years (29 +- 6) years, BMI 15.59 to 29.8, (21.58 +- 2). Serum alanine aminotransferase ranged from 17 to 81 IU/l, (29.9 +- 8) IU/l. Serum alanine aminotransferase for subjects with body mass index more than 25 Kg/m2 was 29.6 +- 7 IU/L. There is no significant difference in value of mean ALT overall and in those with BMI of more than 25 (p=0.149) Conclusion: Mean serum alanine aminotransferase value in young healthy adults included in this study was 29.9 +- 8 IU/L which is lower than normal reference provided at present which is 40 IU/l. Statistical analysis revealed that serum ALT is not significantly influenced by age and BMI. (author)

Irritable Bowel Syndrome May Be Associated with Elevated Alanine Aminotransferase and Metabolic Syndrome.

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Lee, Seung Hwa; Kim, Kyu Nam; Kim, Kwang Min; Joo, Nam Seok

2016-01-01

Recent studies have revealed close relationships between hepatic injury, metabolic pathways, and gut microbiota. The microorganisms in the intestine also cause irritable bowel syndrome (IBS). The aim of this study was to examine whether IBS was associated with elevated hepatic enzyme [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], gamma-glutamyl transferase (γ-GT) levels, and metabolic syndrome (MS). This was a retrospective, cross-sectional, case-control study. The case and control groups comprised subjects who visited our health promotion center for general check-ups from June 2010 to December 2010. Of the 1127 initially screened subjects, 83 had IBS according to the Rome III criteria. The control group consisted of 260 age- and sex-matched subjects without IBS who visited our health promotion center during the same period. Compared to control subjects, patients with IBS showed significantly higher values of anthropometric parameters (body mass index, waist circumference), liver enzymes, γ-GT, and lipid levels. The prevalences of elevated ALT (16.9% vs. 7.7%; p=0.015) and γ-GT (24.1% vs. 11.5%; p=0.037) levels were significantly higher in patients with IBS than in control subjects. A statistically significant difference was observed in the prevalence of MS between controls and IBS patients (12.7% vs. 32.5%; p<0.001). The relationships between elevated ALT levels, MS, and IBS remained statistically significant after controlling for potential confounding factors. On the basis of our study results, IBS may be an important condition in certain patients with elevated ALT levels and MS.

Clinical characteristics associated with hepatic steatosis on ultrasonography in patients with elevated alanine aminotransferase

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Janaína Luz Narciso-Schiavon

Full Text Available CONTEXT AND OBJECTIVE: The main causes of hepatic steatosis (HS are alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD. Although liver biopsy is the gold standard for NAFLD diagnosis, the finding of abnormal aminotransferases in abstinent individuals, without known liver disease, suggests the diagnosis of NAFLD in 80-90% of the cases. Identification of clinical factors associated with HS on abdominal ultrasound may enable diagnoses of fatty liver non-invasively and cost-effectively. The aim here was to identify clinical variables associated with HS in individuals with elevated alanine aminotransferase (ALT levels. DESIGN AND SETTING: Cross-sectional study in a single tertiary care center. METHODS: Individuals with elevated ALT, serologically negative for hepatitis B and C, were evaluated by reviewing medical files. Patients who did not undergo abdominal ultrasonography were excluded. RESULTS: Among 94 individuals included, 40% presented HS on ultrasonography. Compared with individuals without HS, those with fatty liver were older (P = 0.043, with higher body mass index (BMI (P = 0.003, diabetes prevalence (P = 0.024, fasting glucose levels (P = 0.001 and triglycerides (P = 0.003. Multivariate analysis showed that BMI (odds ratio, OR = 1.186; 95% confidence interval, CI: 1.049-1.341; P = 0.006 and diabetes mellitus (OR = 12.721; 95% CI: 1.380-117.247; P = 0.025 were independently associated with HS. CONCLUSIONS: Simple clinical findings such as history of diabetes and high BMI may predict the presence of HS on ultrasonography in individuals with elevated ALT and negative serological tests for hepatitis.

The Effects of Extra Virgin Olive Oil on Alanine Aminotransferase, Aspartate Aminotransferase, and Ultrasonographic Indices of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients Undergoing Low Calorie Diet.

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Shidfar, Farzad; Bahrololumi, Samaneh Sadat; Doaei, Saeid; Mohammadzadeh, Assieh; Gholamalizadeh, Maryam; Mohammadimanesh, Ali

2018-01-01

Coronary artery disease is the most common cause of death in the patients with nonalcoholic fatty liver disease (NAFLD). Studies have shown that there is a strong relation between the increase in the aminotransferase levels and fat accumulation in the liver with cardiovascular complications, independent of all aspects of the metabolic syndrome. This study aimed to examine the effect of virgin olive oil on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the severity of steatosis in the NAFLD patients undergoing a weight-loss diet. This clinical trial was carried out on 50 patients with nonalcoholic fatty liver (mean age of 45.91 ± 9.61 years, mean BMI of 29.7 ± 0.58 Kg/m 2 ) and the subjects were randomly assigned to the olive oil group (receiving the equivalent of 20% of their total daily energy requirement from olive oil) or the control group (with normal consumption of oil) for 12 weeks. All the patients received a hypocaloric diet during the study. At the beginning and the end of the study, the serum levels of ALT and AST and liver steatosis were measured. A significant decrease in the level of ALT enzymes was observed in the control group at the end of the study ( P = 0.004). In the olive oil group, both enzymes decreased compared to baseline measurements ( P groups ( P < 0.02). The severity of liver steatosis did not change significantly during the study. The consumption of a low calorie diet enriched with olive oil, along with slight weight reduction, reinforces the desired effects of weight loss in improving the levels of the hepatic enzymes.

Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study

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Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

2016-01-01

Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, Pmetabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

Effect of streptococcal preparation (picibanil) on the postoperative rise in serum alanine aminotransferase activity in patients with urogenital cancer.

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Taketa, Kazuhisa; Ohmori, Hiroyuki; Matsumura, Yonesuke; Asahi, Toshihiko; Okimune, Masaaki

1980-01-01

The effect of Picibanil, a streptococcal agent, on the development of liver injury after operations for urogenital cancer was studied retrospectively in the light of serum alanine aminotransferase (ALT) activity. The series comprised 32 cases receiving Picibanil and 33 controls with otherwise comparable clinical backgrounds. Picibanil reduced the incidence of postoperative ALT rise over 50 U/l within 6 weeks but increased it thereafter. The increase in ALT activity after 6 weeks was relativel...

Effect of Phenanthrene on the Tissue Structure of Liver and Aminotransferase Enzymes in Yellowfin Seabream (Acanthopagrus latus

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Mehrnaz Shirmohammadi*

2017-06-01

Full Text Available Background: Polycyclic aromatic hydrocarbons (PAHs such as phenanthrene (Phe represent one of the most abundant forms of organic pollutants. The aim of this study was to assess changes in plasma levels of aminotransferase enzymes, total protein and liver tissue as biomarkers of yellowfin seabream (Acanthopagrus latus exposed to Phe for 14 d. Methods: The research was carried out in January 2016 at Khorramshahr University of Marine Sciences and Technology, Khorramshahr, Iran. Some 72 fish were injected with 2, 20, 40 and 70 mg/kg of Phe. Then tissue and blood samples were obtained at 1, 4, 7 and 14 d after injection. Results: Exposure of fish to Phe resulted in a significant increase of alanine aminotransferase (ALT, aspartate aminotransferase (AST and decrease of total protein after 7 d of the experiment (P<0.05. The main histopathological alteration was showed in different sampling days including nucleus margination, hypertrophy, vacuolation, melanomacrophages aggregates, sinusoid dilation, degeneration and picnotic nucleus. Degree of tissue change (DTC of liver was recorded in the Phe-exposed fish from normal range to moderate changes. Conclusion: The studied biomarkers such as changes in concentrations of ALT, AST and total protein as well as tissue damages in liver may be served as beneficial biomarker to assess Phe toxicity in yellowfin seabream.

Alanine aminotransferase, gamma-glutamyltransferase (GGT) and all-cause mortality: results from a population-based Danish twins study alanine aminotransferase, GGT and mortality in elderly twins

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Fraser, Abigail; Thinggaard, Mikael; Christensen, Kaare

2009-01-01

Abstract Background/Aims: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic...... for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings....

Comparison of blood aminotransferase methods for assessment of myopathy and hepatopathy in Florida manatees (Trichechus manatus latirostris).

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Harr, Kendal E; Allison, Kathryn; Bonde, Robert K; Murphy, David; Harvey, John W

2008-06-01

Muscle injury is common in Florida manatees (Trichechus manatus latirostris). Plasma aspartate aminotransferase (AST) is frequently used to assess muscular damage in capture myopathy and traumatic injury. Therefore, accurate measurement of AST and alanine aminotransferase (ALT) is important in managed, free-ranging animals, as well as in those rehabilitating from injury. Activities of these enzymes, however, are usually not increased in manatees with either acute or chronic muscle damage, despite marked increases in plasma creatine kinase activity. It is hypothesized that this absence of response is due to apoenzymes in the blood not detected by commonly used veterinary assays. Addition of coenzyme pyridoxal-5-phosphate (P5P or vitamin B6) should, therefore, result in higher measured enzyme activities. The objective of this study was to determine the most accurate, precise, and diagnostically useful method for aminotransferase measurement in manatees that can be used in veterinary practices and diagnostic laboratories. Additionally, appropriate collection and storage techniques were assessed. The use of an optimized commercial wet chemical assay with 100 micromol P5P resulted in a positive bias of measured enzyme activities in a healthy population of animals. However, AST and ALT were still much lower than that typically observed in domestic animals and should not be used alone in the assessment of capture myopathy and muscular trauma. Additionally, the dry chemistry analyzer, typically used in clinics, reported significantly higher and less precise AST and ALT activities with poor correlation to those measured with wet chemical methods found in diagnostic laboratories. Therefore, these results cannot be clinically compared. Overall, the optimized wet chemical method was the most precise and diagnostically useful measurement of aminotransferase in samples. Additionally, there was a statistically significant difference between paired serum and plasma measurement

PGC-1α regulates alanine metabolism in muscle cells.

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Hatazawa, Yukino; Qian, Kun; Gong, Da-Wei; Kamei, Yasutomi

2018-01-01

The skeletal muscle is the largest organ in the human body, depositing energy as protein/amino acids, which are degraded in catabolic conditions such as fasting. Alanine is synthesized and secreted from the skeletal muscle that is used as substrates of gluconeogenesis in the liver. During fasting, the expression of PGC-1α, a transcriptional coactivator of nuclear receptors, is increased in the liver and regulates gluconeogenesis. In the present study, we observed increased mRNA expression of PGC-1α and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting. In C2C12 myoblast cells overexpressing PGC-1α, ALT2 expression was increased concomitant with an increased alanine level in the cells and medium. In addition, PGC-1α, along with nuclear receptor ERR, dose-dependently enhanced the ALT2 promoter activity in reporter assay using C2C12 cells. In the absence of glucose in the culture medium, mRNA levels of PGC-1α and ALT2 increased. Endogenous PGC-1α knockdown in C2C12 cells reduced ALT2 gene expression level, induced by the no-glucose medium. Taken together, in the skeletal muscle, PGC-1α activates ALT2 gene expression, and alanine production may play roles in adaptation to fasting.

Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

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Alssema, Marjan; Rijkelijkhuizen, Josina M; Holst, Jens Juul

2013-01-01

OBJECTIVE: To i) compare incretin responses to oral glucose and mixed meal of diabetic patients with the normoglycaemic population and ii) to investigate whether incretin responses are associated with hypertriglyceridaemia and alanine aminotransferase (ALT) as liver fat marker. DESIGN: A population......-based study. METHODS: A total of 163 persons with normal glucose metabolism (NGM), 20 with intermediate hyperglycaemia and 20 with type 2 diabetes aged 40-65 years participated. Participants received a mixed meal and oral glucose load on separate occasions. Glucagon-like peptide 1 (GLP-1), glucose......-dependent insulinotropic polypeptide (GIP) and glucagon profiles were analysed as total area under the curve (tAUC) and incremental area under the curve. RESULTS: In diabetic patients compared with persons with NGM, we found increased GLP-1 secretion (tAUC per hour) following oral glucose (23.2 pmol/l (95% CI 17...

Effect of Arsenic and Chromium on the Serum Amino-Transferases Activity in Indian Major Carp, Labeo rohita

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Anjaneyulu Yerramilli

2007-09-01

Full Text Available Arsenic and hexavalent chromium toxicity results from their ability to interact with sulfahydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Alanine aminotransferase (ALT; E.C: 2.6.1.2 and Aspartate amino transferase (AST; EC 2.6.1.1 play a crucial role in transamination reactions and can be used as potential biomarkers to indicate hepatotoxicity and cellular damage. While histopathological studies in liver tissue require more time and expertise, simple and reliable biochemical analysis of ALT and AST can be used for a rapid assessment of tissue and cellular damage within 96 h. The main objective of this study was to determine the acute effects of arsenic and hexavalent chromium on the activity of ALT and AST in the Indian major carp, Labeo rohita for 24 h and 96 h. Significant increase in the activity of ALT (P < 0.01 from controls in arsenic exposed fish indicates serious hepatic damage and distress condition to the fish. However, no such significant changes were observed in chromium-exposed fish suggesting that arsenic is more toxic to the fish. These findings indicate that ALT and AST are candidate biomarkers for arsenic-induced hepatotoxicity in Labeo rohita.

Elevated alanine aminotransferase is strongly associated with incident metabolic syndrome: a meta-analysis of prospective studies.

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Zhengtao Liu

Full Text Available BACKGROUND: The incidence of metabolic syndrome (MetS is rapidly increasing worldwide and associated with alanine aminotransferase (ALT activity. However, the impact of ALT activity on MetS incidence is inconsistent in published literature. We therefore estimated the association between elevated ALT activity and incident MetS through a meta-analysis of prospective cohort studies. METHODS/PRINCIPAL FINDINGS: All published prospective cohort studies on the association between elevated ALT activity and incident MetS were retrieved from Pubmed, Embase, and the Institute for Scientific Information (ISI. In all, seven prospective cohort studies, with 31545 participants and 2873 cases of incident MetS were recruited. If there was insignificant heterogeneity (P-value>0.05 and I(2<50%, the fixed-effect model was used to calculate the pooled relative risks (RRs of incident MetS induced by raised ALT. Otherwise, the random-effect model was used. The calculated RR was 1.81 (95% confidence interval [CI]: 1.49-2.14 when the incidence of MetS was compared between the highest versus the lowest classification of ALT activities. The pooled RR was 1.13 (95% CI: 1.11-1.16 in dose-response analysis with 5 units per liter (U/l of ALT increment. Subgroup analysis suggested that gender disparity might be the main origin of heterogeneity in overall analysis (P = 0.007 between RRs of gender-specific subgroups evaluated with 5 U/l increments of ALT. Women had a higher dose-response risk of MetS incidence (1.38, 95% CI: 1.20-1.55 than men. Furthermore, sensitivity analysis confirmed the stability of results. No publication bias was found in our meta-analysis. CONCLUSIONS/SIGNIFICANCE: Current evidence from prospective studies supports the association between ALT elevation and increasing MetS incidence. This association is closer and more consistent in female population. Further studies are needed to confirm this association and to investigate the potential mechanism of

[Association between occupational stress and aminotransferase activity in patients with metabolic syndrome].

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Zhao, H; Song, L; Qiang, Y; Liu, H R; Qiu, F Y; Li, X Z; Song, H

2016-12-20

Objective: To investigate the association between occupational stress and activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with metabolic syndrome. Methods: A case-control study was performed. According to inclusion and exclusion criteria, among the staff members of enterprises and public institutions aged 20~60 years who underwent physical examination in The Affiliated Hospital of Ningxia Medical University and The People's Hospital of Wuzhong from October 2011 to October 2012, 622 patients with metabolic syndrome who did not have a blood relationship with each other were enrolled as case group, and 600 healthy staff members who also did not have a blood relationshipwith each otherwere enrolled as control group. Questionnaire investigation, chronic occupational stress investigation, physical examination, and laboratory tests were performed for all subjects. Results: Compared with the control group, the case group had significantly higher serum levels and abnormal rates of AST and ALT ( t =-4.338 and-5.485, χ(2)=11.168 and 34.302, all P occupational stresses in both groups ( F =2.192 and 2.567, χ(2)=2.694 and 5.402, all P >0.05) , but there were significant differencesbetween the subgroups in all subjects ( F =5.005, χ(2)=6.398, all P occupational stresses in the case group, the control group, and all subjects ( F =0.845, 0.450, and 1.416, χ(2)=2.564, 1.344, and 3.147, all P >0.05) . The partial correlation analysis showed that the total score of occupational stress was positively correlated withthe serum level of AST ( r =0.071, P 0.05) , and that the serum level of AST was positively correlated with that of ALT ( r =0.736, P occupational stress was positively correlated with the serum level of AST ( r =0.069, P 0.05) , and the serum level of AST was positively correlated with that of ALT ( r =0.730, P occupational stress ( b =0.131, P =0.013) . Conclusion: Occupational stress is associated with increased serum level

ELEVATED ALANINE AMINOTRANSFERASE (ALT IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

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Fernando Lopes GONÇALES Jr.

1998-07-01

Full Text Available The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH. The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87% had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1% donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9% had mild chronic active non A-G viral

The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells

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Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang, E-mail: wchai@wsu.edu

2017-06-15

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.

The Association of Elevated Serum Alanine Aminotransferase with Metabolic Syndrome in A Military Population in Southern Iran

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B Sabayan

2010-06-01

Full Text Available Background: Metabolic syndrome (MetS is rapidly rising at an alarming rate through all parts of the world. Elevated serum aminotransferase was proposed as a marker for early detection of MetS. In this investigation we primarily aimed to evaluate the prevalence of MetS and its components among army and secondly to explore the association between elevated serum aminotransferase and the components of metabolic syndrome. Methods: A total of 380 army personnel from a military camp in Southern Iran participated in this cross-sectional study. Life style related characteristics, anthropometric features, serum aminotransferase and components of MetS, based on National Cholesterol Education Program—Adult Treatment Panel III, were measured. Statistical significant was set as p value less than 0.05. Results: The mean age of participants was 35.0± 7.5 year-old and the prevalence of metabolic syndrome was 8.1%. The prevalence of the components of MetS including; central obesity, abnormal fasting blood glucose, hypertension, hypertriglycridemia and low HDL cholesterol level was 8.6%, 10.4%, 18.5%, 31%, and 45.5% respectively. MetS had significant relationship with obesity (P<0.001 and abnormal Waist Circumferance/Hip Circumference ratio (P<0.001. Twenty-six percent of subjects had ALT ≥ 41 U/L and 4.9% of them had ALT ≥ 81. Elevated serum aminotransferase had significant association with presence of MetS (P= 0.007. Conclusion: Although prevalence of metabolic syndrome among the studied army population was not high, life style modification of army members is recommended. Liver function tests should be included in routine health checkup of military personnel.

Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis

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Leib Stephen L

2011-04-01

Full Text Available Abstract Background The kynurenine (KYN pathway has been shown to be altered in several diseases which compromise the central nervous system (CNS including infectious diseases such as bacterial meningitis (BM. The aim of this study was to assess single nucleotide polymorphisms (SNPs in four genes of KYN pathway in patients with meningitis and their correlation with markers of immune response in BM. Methods One hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (IDO1 gene, kynureninase (KYNU gene, kynurenine aminotransferase I (CCBL1 gene, and kynurenine aminotransferase II (AADAT gene. SNP analyses were performed by primer-introduced restriction analysis-PCR (PIRA-PCR followed by RFLP. Cytokines were measured using multiplex bead assay while immunoglobulins (IG by immunodiffusion plates and NF-kappaB and c-Jun by dot blot assay. Results The variant allele of SNP AADAT+401C/T showed prevalent frequency in patients with BM. A significant decrease (p AADAT+401C/T. Furthermore, a significant (p p KYNU+715G/A was found with low frequency in the groups, and the SNPs in IDO1+434T/G, KYNU+693G/A, CCBL1+164T/C, and AADAT+650C/T had no frequency in this population. Conclusions This study is the first report of an association of SNP AADAT+401C/T with the host immune response to BM, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site. This finding may contribute to identifying potential targets for pharmacological intervention as adjuvant therapy for BM.

The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients.

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Sumida, Yoshio; Yoshikawa, Toshikazu; Tanaka, Saiyu; Taketani, Hiroyoshi; Kanemasa, Kazuyuki; Nishimura, Tekeshi; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Naito, Yuji; Itoh, Yoshito

2014-12-01

Physicians often experience difficulties in motivating patients with non-alcoholic fatty liver disease (NAFLD) to undergo lifestyle changes. The aim of this study is to examine whether 'Donations for Decreased alanine aminotransferase (ALT)' (D4D) prosocial behavior incentive can serve as an effective intrinsic motivational factor in comparison with conventional dietary and exercise intervention alone for NAFLD patients. Twenty-five NAFLD patients with elevated ALT were randomly assigned to a control group that received conventional dietary and exercise intervention alone, or a donation group whereby, as an incentive, we would make a monetary donation to the United Nations World Food Programme (WFP) based on the decrease in their ALT levels achieved over 12 weeks, in addition to receiving control intervention. In a donation group, we would donate US$1 to the WFP for every 1 IU/l of decrease in their ALT levels. There were no differences of pre-treatment clinical characteristics between the two groups. Significant reductions of ALT levels were achieved only in a donation group, although post-treatment ALT levels were not different between the two groups. These patients raised a total of $316 for the WFP. Promoting patients' intrinsic motivation by incorporating 'D4D' prosocial behavior incentive into conventional dietary and exercise intervention may provide a means to improve NAFLD. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prevalence and predictors of alanine aminotransferase elevation among normal weight, overweight and obese youth in Mexico.

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Purcell, Maura; Flores, Yvonne N; Zhang, Zuo-Feng; Denova-Gutiérrez, Edgar; Salmeron, Jorge

2013-09-01

This study aimed to determine the prevalence of and risk factors associated with elevated alanine aminotransferase (ALT) levels among a sample of normal weight, overweight and obese youth from two urban populations in Central Mexico. Baseline data from 1262 youth aged 8-19 years who participated in the Mexican Health Worker Cohort Study from March 2004 to April 2006 were reviewed, including 680 girls and 582 boys, with a total of 83 participants with elevated ALT level (>40 U/L). Information was obtained from self-administered questionnaires, anthropometric results and clinical measurements. Associations of interest were examined using multivariate logistic regression models. A total of 3.8% of girls and 9.8% of boys had elevated ALT levels. Elevated ALT was observed in 28.9% of the obese and 14.2% of the overweight participants. Metabolic syndrome (MS) occurred in 6.1% of the study population and those with MS had a high percentage of elevated ALT (14.5% of girls and 40.0% of boys, respectively). Abdominal obesity and insulin resistance were also associated with a greater risk of elevated ALT. Obesity and certain metabolic risk factors are important predictors for elevated ALT. Screening for ALT levels in obese youth could help to identify those at risk and reduce the possibility of future liver diseases. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Hb and dyslipidaemia as predicting markers of serum alanine aminotransferase elevation in Chinese adolescents.

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Chao, Kuo-Ching; Chang, Chun-Chao; Owaga, Eddy; Bai, Chyi-Huey; Huang, Tzu-chieh; Pan, Wen-Harn; Chang, Jung-Su

2016-04-01

Fe is an essential element for erythropoiesis and Hb synthesis. High Hb levels affect the blood's viscosity and are associated with cardiovascular dysfunction. The aim of the present study was to examine relationships of Hb and cardiometabolic abnormalities with the risk of alanine aminotransferase (ALT) elevation in adolescents. A population-based, cross-sectional study. National Nutrition and Health Survey in Taiwan (2010-2011, adolescents). Healthy adolescents aged 13-18 years. In total, 1941 adolescents (963 boys and 978 girls) were entered in the study. The mean age was 15·3 (sd 0·1) years (boys, 15·3 (sd 0·1) years; girls, 15·2 (sd 0·1) years). ALT tertile cut-off points for boys were 11 and 16 U/l, and for girls were 9 and 12 U/l. Girls without dyslipidaemia and presenting in the highest quartile (Q1) of Hb (>13·6 g/dl) were 1·89 and 3·76 times more likely to have raised serum ALT (9 and >12 U/l, respectively) than the reference (lowest quartile of Hb (Q1), 12 U/l) than the reference (Q1 of Hb, 15·4 g/dl), who were 7·40 times more likely to have elevated serum ALT of >16 U/l than the reference (Q1 of Hb, Hb level is a predictor of elevated serum ALT in adolescent girls with dyslipidaemia. Our study also highlights the importance of further research to establish cut-off points for Hb and its utility in diagnosing and preventing the onset of dyslipidaemia in adolescents.

Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss.

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Dawson, Alison J; Kilpatrick, Eric S; Coady, Anne-Marie; Elshewehy, Abeer M M; Dakroury, Youssra; Ahmed, Lina; Atkin, Stephen L; Sathyapalan, Thozhukat

2017-07-14

Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD). Treatment with rimonabant for 12 weeks reduced both ALT and weight (p weight. There was a significant reduction of weight with orlistat (p weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh

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Tabassum, Shahina; Ullah Munshi, Saif; Hossain, Marufa; Imam, Akhter

2014-01-01

ABSTRACT Background and aim Assessment of therapeutic response is important for monitoring the prognosis and to take decision for cessation of nucleoside analogues therapy in chronic hepatitis B patients. In addition to serum alanine aminotransferase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load and HBeAg status, identification of molecular markers associated with host immune response would be essential to assess therapeutic response. In this regard the current study was performed with the aim to detect expression of platelet endothelial cell adhesion molecule (PECAM)-I gene in peripheral blood monocytes (PBMCs) of treated chronic hepatitis B patients and also to correlate expression of this gene with serum HBV DNA load and serum ALT levels. Materials and methods The study analyzed 60 chronic hepatitis B (CHB) patients, including 30 untreated and 30 nucleoside analogs treated and 10 healthy controls. PECAM-1 gene expression/ transcripts were detected by conventional RT-PCR. Results The expression PECAM-1 mRNA in the PBMCs of CHB patients was significantly higher in untreated (3.17 ± 0.75) than the treated patients (1.64 ± 0.29) (p Tabassum S, Munshi SU, Hossain M, Imam A. Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(2):87-91. PMID:29699354

Clinical significance of elevated serum aminotransferases levels in asymptomatic individuals with hepatitis C infection

International Nuclear Information System (INIS)

Nafees, M.; Ditta, A.; Jafferi, G.

2010-01-01

Background: Hepatitis C is a common and important cause of chronic liver disease that often remains asymptomatic and most of the times discovered incidentally by routine serologic or biochemical testing. Aminotransferases (AST and ALT) reflect alterations in liver function/inflammation in liver diseases. The current study was conducted to examine the utilization and limitations of these biochemical markers in subjects with asymptomatic HCV infection. Aims and Objectives: To find out how many subjects with asymptomatic HCV infection have normal or elevated serum AST and ALT levels. Subjects and Methods: Study Design: Cross sectional. Study Duration: Seven months from November 2008 to July 2009. Study Universe: Services Hospital, Lahore. Study Population: This study included 413 subjects attending the outpatient departments of hospital with minor complaints. The random population of subjects was referred to the clinical laboratory of Services Hospital, Lahore for LFTs, HBsAg and anti-HCV screening from OPD department of the hospital. A total of 413 persons of all ages were analyzed during this study. There were 263 subjects who were sero - positive for anti-HCV (141 females, 122 males; median age 35 +- 11.34 years) and 150 in the control group (80 of them were females and 70 males with median age 32 +- 12.97 years) were sero-negative for both HBsAg and anti - HCV. Subjects Selection Criteria: In this study, only anti - HCV sero - positive subjects were included who was sero - negative for HBsAg or dual infection (both HBsAg and anti - HCV) and not on anti - viral therapy. Control group was sero - negative for both - HBsAg and anti - HCV antibodies. Data Collection: We assayed levels of serum aminotransferases (AST and ALT) and screened blood for HBsAg and anti-HCV. ELISA technique was used for viral hepatitis markers. Results: Out of 263 subjects tested positive for anti-HCV antibodies in their blood, 90.76 % and 87.45 % had elevated AST and ALT levels (ALT = 40 U

Elevated Aminotransferase Activity as an Indication of Muscular Dystrophy: Case Reports and Review of the Literature

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S Zamora

1996-01-01

Full Text Available Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT activity initiated investigation to identify the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome-linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal, an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower’s sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease - most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.

Effect of heavy metals (Cu, Cd and Pb) on aspartate and alanine aminotransferase in Ruditapes philippinarum (Mollusca: Bivalvia)

International Nuclear Information System (INIS)

Blasco, J.; Puppo, J.

1999-01-01

The accumulation of cadmium, copper and lead and their effects on aspartate and alanine aminotransferases in digestive gland, gills, foot and soft body in the clam Ruditapes philippinarum were examined. The animals were exposed to different concentrations: Cd (200-600 μg·l -1 ), Pb (350-700 μg·l -1 ) and Cu (10-20 μg·l -1 ) for 7 days. The highest concentrations were found in digestive gland for cadmium and copper, and in gills for lead, and the lowest values were observed in the foot. Aspartate aminotransferase activity (AST), in general, was not inhibited by cadmium, lead or copper during the exposure. Only in clams exposed to cadmium (600 μg·l -1 , 7 days) and copper (20 μg·l -1 , 5 days) were observed significant differences (P -1 . A significant correlation (P<0.05) was observed between ALT and metal accumulation for cadmium, copper and lead in gills. In the case of soft body, only cadmium and lead showed a significant correlation. In summary, R. philippinarum can be considered a bioindicator species for cadmium and lead accumulation and ALT could be useful as biomarker of sublethal stress for these metals in soft tissues and gills. Only gills can be considered an adequate target tissue for copper. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

High serum alanine aminotransferase is associated with the risk of colorectal adenoma in Korean men.

Science.gov (United States)

Moon, Chang Mo; Yun, Kyung Eun; Ryu, Seungho; Chang, Yoosoo; Park, Dong Il

2017-07-01

An elevated alanine aminotransferase (ALT) is frequently observed in subjects with metabolic syndrome, which is associated with the risk of colorectal adenoma (CRA). However, the relationship between ALT and CRA remains unclear. Therefore, we aimed to investigate whether high serum ALT is associated with the risk of CRA in a metabolically healthy population. We conducted this cross-sectional study in 27,717 asymptomatic Korean adults who underwent a health checkup. Subjects were categorized as adenoma-free, hyperplastic polyp, low-risk adenoma, or high-risk adenoma. High-risk adenoma was defined as three or more adenomas, any adenoma ≥ 10 mm, or adenoma with high-grade dysplasia or villous features. Among all participants, 10.3% and 1.5% of cases were categorized as low-risk and high-risk adenoma, respectively. In multivariate analyses adjusting for age, sex, body mass index, smoking habits, alcohol intake, regular exercise, aspirin and analgesics use, family history of colon cancer, education level, fatty liver, high-sensitivity C reactive protein, homeostasis model assessment of insulin resistance, total cholesterol, and triglyceride, an increase in ALT was positively associated with the prevalence of low-risk and high-risk adenoma (P for trend = 0.029 and 0.027, respectively). The highest quartile group of ALT level showed a significantly increased prevalence in low-risk (odds ratio, 1.17) and high-risk adenoma (odds ratio, 1.48) groups compared with the lowest quartile group. This phenomenon persisted in the subgroup analysis in men, but not in women. In the asymptomatic healthy population, high serum ALT is significantly associated with the risk of CRA. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Alanine aminotransferase is associated with an adverse nocturnal blood glucose profile in individuals with normal glucose regulation.

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Jian Zhou

Full Text Available OBJECTIVE: Although the association between alanine aminotransferase (ALT levels and risk of type 2 diabetes is well-studied, the effects of slightly increased ALT levels within the normal range on the temporal normal glucose profile remains poorly understood. METHODS: A total of 322 Chinese subjects without impaired glucose tolerance or previous diagnoses of diabetes were recruited for study from 10 hospitals in urban areas across China. All subjects wore a continuous glucose monitoring (CGM system for three consecutive days. The diurnal (06∶00-20∶00 and nocturnal (20∶00-06∶00 mean blood glucose (MBG levels were calculated. Subjects were stratified by ALT quartile level and correlation analyses were performed. RESULTS: The median ALT level was 17 IU/L, and subjects with ALT ≥17 IU/L had higher nocturnal MBG level than those with ALT 0.05. Multivariate stepwise regression analysis of elevated nocturnal MBG identified increased HOMA-IR, elevated ALT levels, and decreased homeostatic model assessment of ß-cell function as independent factors (all, P<0.05. CONCLUSIONS: Mildly elevated ALT levels, within the normal range, are associated with unfavorable nocturnal glucose profiles in Chinese subjects with normal glucose regulation.

Aminotransferases and Leucine Aminopeptidase Activity in Blood Plasma of Chickens

International Nuclear Information System (INIS)

Kraljevic, P.; Stojevic, Z.; Milinkovic-Tur, S.; Simpraga, M.; Miljanic, S.

1998-01-01

It has been reported that irradiation of mammals by gama-rays cause increase of some enzyme activity in their blood plasma (Miller and Gates 1949; Milch and Albaum 1959; Hughes 1958; Miholjcic et al. 1979). In our previous papers (Kraljevic et al., 1982; Kraljevic and Emanovic 1993) it has been shown that activities of some enzymes in the blood plasma of chickens after an intramuscular injection of radioactive isotope 32 P. In this paper an attempt has been made to investigate the influence of gamma-ray irradiation of the whole body of chickens upon activity of some enzymes in their blood plasma. We also wanted to investigate whether the activity of aspartate-aminotransferase (AST), alanine aminotransferase (ALT) and leucine-aminopeptidase (LAP) may serve as an additional test for functional liver damage in chickens caused by gamma-ray. Fifty day old hybrid male chickens of heavy Jata breeds were irradiated by gamma-ray in the dose of 7,23±0,95 Gy. Blood samples were taken from the wing vein on days 1, 3, 5, 7, 9 and 15 after irradiation. Activity of AST, ALT, and LAP in the blood plasma were determined spectrophotometrically using Boehringer Mannheim GmbH optimized kits. At the end of the experiment all birds were sacrificed and, as well as died birds were photomorphologically and histologically investigated. The obtained results showed decrease of activity of all three enzymes during the whole period of investigation, but significant decrease showed only AST and LAP. It seems that both enzymes may serve as additional test for functional liver damage in chickens by external gamma-rays. (author)

Influence of gender, BMI, and ethnicity on serum ALT levels of healthy students of a medical school

International Nuclear Information System (INIS)

Bilal, M.; Tariq, A.; Khan, S.; Quratulain, A.; Tariq, A.; Shahid, M.F.; Khan, M.W.; Naveed, A.K.

2011-01-01

Background: Alanine Aminotransferase (ALT) is an enzyme found in Liver and indicates injury to Hepatocytes. It is influenced by various factors. The objectives of this study were to identify the correlates of ALT activity among healthy medical students of Army Medical College, National University of Sciences and Technology, aged 18-22 years. This was to establish the mean ALT levels of the students and compare them with those in various parts of the world and observe various correlations that exist and factors that may influence ALT levels. Methods: This population included 143 volunteer students (93 men and 50 women) selected on the basis of negative answers to a detailed medical questionnaire including past medical history, drug and alcohol consumption, on the absence of clinical signs of liver disease, on the negativity of serological testing for Hepatitis B and C virus. Results: The mean ALT level of the entire population was 28.7 IU/L. A major sex-difference in ALT value was observed, the mean ALT value being higher in men than in women (32.1+- 21.7 vs. 22.6 +- 9.7 IU/L, p<0.004). According to WHO criteria for Asians, normal BMI was taken from 18.5-23.0 Kg/m/sup 2/. There was a positive significant correlation between serum ALT level and BMI (p<0.002). ALT level strongly correlates with body mass index and gender. There was no significant variation in ALT levels among Punjabis and Sindhis, Balochis, Pathans, and Kashmiris. Conclusion: We suggest the need of taking into account these parameters in a clinical interpretation of ALT level. (author)

A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

DEFF Research Database (Denmark)

Andersen, Gorm; Andersen, Birgit; Dobritzsch, D.

2007-01-01

and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity.......In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue...... to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V...

Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

Science.gov (United States)

Kechagias, S; Ernersson, A; Dahlqvist, O; Lundberg, P; Lindström, T; Nystrom, F H

2008-05-01

To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Prospective interventional study with parallel control group. University Hospital of Linköping, Sweden. 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.

Science.gov (United States)

Zelber-Sagi, S; Toker, S; Armon, G; Melamed, S; Berliner, S; Shapira, I; Halpern, Z; Santo, E; Shibolet, O

2013-12-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Sex-Specific Association between Metabolic Abnormalities and Elevated Alanine Aminotransferase Levels in a Military Cohort: The CHIEF Study

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Kai-Wen Chen

2018-03-01

Full Text Available The association of metabolic syndrome (MetS components with elevated serum alanine aminotransferase (ALT levels, a marker of hepatic injury, may differ between men and women. However, the sex-specific association in a military young population which has a low prevalence of MetS was unclear. We conducted a cross-sectional examination in 6738 men and 766 women, aged 18–50 years, from the cardiorespiratory fitness study in armed forces (CHIEF in eastern Taiwan. The components of MetS were defined according to the updated International Diabetes Federation (IDF ethnic criteria for Asians. Elevated ALT levels were defined as ≥40 U/L for both sexes and ≥30 U/L for women alternatively. Multivariate logistic regression analysis was performed to determine the sex-specific association between MetS components and elevated ALT. The prevalence of MetS and elevated ALT in men were 11.9% and 12.7% respectively, and in women were 3.5%, and 3.8% respectively. In men, high-density lipoprotein < 40 mg/dL, blood pressures ≥ 130/85 mmHg, serum triglycerides ≥ 150 mg/dL, and waist size ≥ 90 cm were associated with elevated ALT (odds ratios (OR and 95% confidence intervals: 1.59 (1.34–1.90, 1.40 (1.19–1.65, 2.00 (1.68–2.39, and 1.68 (1.38–2.04; all p < 0.001; whereas in women, only fasting plasma glucose ≥ 100 mg/dL was associated with elevated ALT ≥ 40 U/L (OR: 7.59 (2.35–24.51, p = 0.001 and ALT ≥ 30 U/L (2.67 (0.89–7.95, p = 0.08. Our findings suggest that the relationship between metabolic abnormalities and elevated ALT may differ by sex, possibly due to the MetS more prevalent in young adult men than in women.

Influence of convulsants on rat brain activities of alanine aminotransferase and aspartate aminotransferase

Czech Academy of Sciences Publication Activity Database

Netopilová, M.; Haugvicová, Renata; Kubová, Hana; Dršata, J.; Mareš, Pavel

2001-01-01

Roč. 26, č. 12 (2001), s. 1285-1291 ISSN 0364-3190 Institutional research plan: CEZ:AV0Z5011922 Keywords : alanine aminotransferase * aspartale aminotransferase Subject RIV: FH - Neurology Impact factor: 1.638, year: 2001

Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

Science.gov (United States)

Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

2017-06-01

The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

Simple serum markers for significant liver inflammation in chronic hepatitis B patients with an alanine aminotransferase level lower than 2 times upper limit of normal

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LI Qiang

2016-06-01

Full Text Available ObjectiveTo investigate the simple serum markers for significant liver inflammation in chronic hepatitis B (CHB patients with an alanine aminotransferase (ALT level of ＜2 times upper limit of normal (ULN. MethodsThe clinical data of 278 CHB patients with ALT ＜2×ULN (ULN=40 U/L were analyzed retrospectively. Significant liver inflammation was defined as a liver inflammatory activity grade (G ≥2. The t-test was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis rank sum test was used for non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. Multivariate logistic regression analysis was used to identify independent predictors for significant liver inflammation in CHB patients with ALT ＜2×ULN. The receiver operating characteristic (ROC curve was used to evaluate the diagnostic value of serum markers in significant liver inflammation. ResultsOf the 278 CHB patients enrolled, 175 (62.9% had no significant liver inflammation (G0-1 group and 103 (37.1% had significant liver inflammation (G2-4 group. There were significant differences in ALT, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT, albumin, globulin, prothrombin time (PT, platelet, absolute neutrophil count, hyaluronic acid (HA, glycocholic acid, precollagen Ⅲ, and collagen type Ⅳ(ⅣC between the two groups (all P＜0.05. The multivariate regression analysis showed that GGT, PT, ⅣC, and HA were independent predictors for significant liver inflammation in CHB patients with ALT＜2×ULN (OR=1.015, 1.600, 1.151, and 1.014, P=0.008, 0.021, 0.003, and 0.018. The areas under the ROC curve for GGT, PT, IVC, and HA to diagnose significant liver inflammation were 0.804, 0.722, 0.707, and 0.632, respectively. The cut-off value of 48.5 U/L for GGT to predict significant liver inflammation had a specificity of 90.3% and a negative

An assessment of racial differences in the upper limits of normal ALT levels in children and the effect of obesity on elevated values.

Science.gov (United States)

Kliethermes, S; Ma, M; Purtell, C; Balasubramanian, N; Gonzalez, B; Layden, T J; Cotler, S J

2017-10-01

Childhood obesity is a risk factor for non-alcoholic fatty liver disease and poses important public health issues for children. Racial differences in alanine aminotransferase (ALT) levels among children have not been described. This study aimed to identify racial differences in upper limit normal (ULN) ALT levels and evaluate the effect of obesity on elevated levels in children without other metabolic risk factors. National Health and Nutrition Examination Surveys and clinical data from the Loyola University Health System were used to determine ULN ALT by race and gender. Quantile regression was used to evaluate the impact of obesity on elevated ALT and to identify potential risk factors for ALT above the ULN. Upper limit normal (ULN) ALT was approximately 28.0 and 21.0-24.0 U/L for boys and girls, respectively. No significant difference in ULN ALT across race was observed. Obesity was significantly associated with elevated ALT; obese children with elevated ALT had values 10 U/L higher than normal-weight children. Racial differences in ALT levels among adults are not evident in children. Obesity, in the absence of metabolic risk factors and other causes of liver disease, is associated with elevated ALT, providing evidence against the concept of healthy obesity in children. © 2016 World Obesity Federation.

Liver stiffness becomes stable in patients with chronic hepatitis C three months after ALT normalization due to antiviral therapy

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CHEN Feikai

2013-10-01

Full Text Available ObjectiveTo investigate the time for liver stiffness measurement (LSM to become stable in chronic hepatitis C (CHC patients with elevated alanine aminotransferase (ALT levels after ALT normalization due to antiviral therapy. MethodsCHC patients who sought initial treatment at Peking University People′s Hospital were screened for elevated ALT levels from May 2011. Liver stiffness was determined by FibroScan. A total of 29 patients had been included in the study by September 2012, who were followed up regularly after antiviral treatment. ALT tests were repeated every four weeks and LSM every eight weeks until their medians did not change significantly. Comparisons of matched data at two adjacent time points were made with the non-parametric Wilcoxon test, while multiple comparisons of repeated measurements were performed using Bonferroni correction. Correlation between two variables was analyzed with the Spearman rank test. ResultsPatients were followed up until 24 weeks after antiviral treatment, and 24 patients were included in analysis. The median ALT levels were 64, 26, 21, 20, and 22 U/L at baseline and 4, 8, 12, and 24 weeks, respectively (P= 0.000, 0.006, 0.337, and 0.109 for comparisons between two adjacent values. ALT decreased significantly below 1 ULN at 4 weeks after antiviral therapy and stabilized at 8 weeks. The median LSM values were 8.7, 7.8, 6.8, and 6.7 kPa at baseline and 8, 16, and 24 weeks, respectively (P= 0.009, 0.001, and 0188 for comparisons between two adjacent values. LSM decreased significantly within 16 weeks after antiviral therapy and stabilized afterwards. LSM stabilized 12 weeks after ALT normalization. ConclusionLSM becomes stable in CHC patients with elevated ALT levels three months after ALT normalization due to antiviral therapy.

Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.

Science.gov (United States)

Yang, Jiezuan; Yan, Dong; Guo, Renyong; Chen, Jiajia; Li, Yongtao; Fan, Jun; Fu, Xuyan; Yao, Xinsheng; Diao, Hongyan; Li, Lanjuan

2017-03-01

Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4CD25 regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients.

Perfil da aspartato aminotransferase e alanina aminotransferase e biometria do fígado de codornas japonesas

OpenAIRE

Barbosa,Anderson de Almeida; Müller,Elisa Sialino; Moraes,George Henrique Kling de; Umigi,Regina Tie; Barreto,Sergio Luiz de Toledo; Ferreira,Ronaldo Martins

2010-01-01

Objetivou-se determinar o perfil da aspartato aminotransferase e alanina aminotransferase e a biometria do fígado de codornas poedeiras (Coturnix coturnix japonica) de 1 a 25 dias de idade. Avaliaram-se o peso vivo e o peso do fígado e as atividades das aspartato e alanina aminotransferases no fígado utilizando-se 90 codornas de 1 dia de idade. O delineamento experimental foi inteiramente casualizado com seis idades e cinco repetições, considerando cada animal uma unidade experimental. Aos 1,...

Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

Science.gov (United States)

Thulin, Petra; Nordahl, Gunnar; Gry, Marcus; Yimer, Getnet; Aklillu, Eleni; Makonnen, Eyasu; Aderaye, Getachew; Lindquist, Lars; Mattsson, C Mikael; Ekblom, Björn; Antoine, Daniel J; Park, B Kevin; Linder, Stig; Harrill, Alison H; Watkins, Paul B; Glinghammar, Björn; Schuppe-Koistinen, Ina

2014-03-01

There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identificação de ponto de corte no nível sérico da alanina aminotransferase para rastreamento da hepatite C em pacientes com insuficiência renal crônica em hemodiálise Identification of the cutoff value for serum alanine aminotransferase in hepatitis C screening of patients with chronic renal failure on hemodialysis

Directory of Open Access Journals (Sweden)

Ericson Cavalcanti Gouveia

2004-02-01

Full Text Available Pacientes com insuficiência renal crônica em hemodiálise apresentam níveis séricos mais baixos de alanina aminotransferase. Para estabelecer melhor ponto de corte nos níveis de ALT, no diagnóstico da hepatite C, avaliaram-se mensalmente, durante 6 meses os níveis desta enzima em 235 pacientes em hemodiálise, sendo excluídos aqueles que apresentassem média acima do limite superior da normalidade. O ponto de corte foi identificado através da construção de curva ROC. Entre 202 pacientes, 15 (7,4% apresentavam anti-VHC positivo e 187 (92,6% negativo, com média de ALT de 0,7 e de 0,5 do limite superior (p The patients with chronic renal failure in hemodialysis present low levels of serum alanine aminotransferases. In order to establish a better cutoff value for ALT in hepatitis C screening of hemodialysis patients, the ALT levels were measured monthly in 235 patients, being excluded those that presented average above the upper limit of normality. The cutoff value was identified by construction of a ROC curve (receiver operating characteristic. Among 202 patients, 15 (7.4% presented antibodies to hepatitis C virus (anti-HCV and 187 (92.6% were anti-HCV negative , with an ALT average of 0.7 and of 0.5 from ULN (p <0.0001, respectively. The better cutoff value for ALT was at 0.6 from ULN, with sensitivity of 67% and specificity of 75% in anti-HCV screening. These results suggest that ULN of ALT could be reduced for 60% from conventional limit, when we are evaluating patients with CRF in hemodialysis.

Longitudinal association of obesity, metabolic syndrome and diabetes with risk of elevated aminotransferase levels in a cohort of Mexican health workers.

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Flores, Yvonne N; Auslander, Allyn; Crespi, Catherine M; Rodriguez, Michael; Zhang, Zuo-Feng; Durazo, Francisco; Salmerón, Jorge

2016-05-01

In Mexico, chronic liver disease have been increasingly found along with the rapidly growing prevalence of obesity, diabetes and metabolic syndrome (MS). We aimed to investigate the longitudinal association between these three factors and risk of elevated alanine aminotransferase (ALT) levels (>40 U/L), a marker for liver damage, in a cohort of Mexican adults. Data were obtained from two separate waves of the Mexican Health Worker Cohort Study: Wave 1 (2004-2006) and Wave 2 (2011-2013). Unconditional logistic regression models were employed to determine the cross-sectional and longitudinal association between these risk factors and elevated ALT levels. The prevalence of elevated ALT was significantly higher among men, individuals aged under 60 years, those who were overweight or obese, diabetic, with MS or heavy/binge drinkers. The longitudinal results indicated that weight gain between waves that resulted in a change in body mass index, along with remaining overweight or obese, were significantly associated with an increased risk of elevated ALT levels. A significantly increased risk of developing elevated ALT was also observed among those who acquired diabetes or MS from Wave 1 to Wave 2. Weight gain and acquiring diabetes or MS are associated with a significant risk of having elevated ALT. These results, within the context of the rapid increase in global obesity rates, call urgently for programs to help to prevent chronic liver disease. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Prevalence of metabolic syndrome and risks of abnormal serum alanine aminotransferase in Hispanics: a population-based study.

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Jen-Jung Pan

Full Text Available Study the prevalence of metabolic syndrome (MS and risk factors for and association with elevated alanine aminotransferase (ALT as markers of hepatic injury in a large Hispanic health disparity cohort with high rates of obesity.Analysis of data from a prospective cross-sectional population based study. From 2004-7, we randomly recruited 2000 community participants to the Cameron County Hispanic Cohort collecting extensive socioeconomic, clinical and laboratory data. We excluded 153 subjects due to critical missing data. Pearson chi-square tests and Student's t-tests were used for categorical and continuous variable analysis, respectively. Logistic regression analysis was performed to determine the risk factors for elevated ALT.The mean age of the cohort was 45 years and 67% were females. The majority of the cohort was either overweight (32.4% or obese (50.7%. Almost half (43.7% had MS and nearly one-third diabetes. Elevated ALT level was more prevalent in males than females. Obesity was a strong risk for abnormal ALT in both genders. Hypertriglyceridemia, hypercholesterolemia and young age were risks for elevated ALT in males only, whereas increased fasting plasma glucose was associated with elevated ALT in females only.We identified high prevalence of MS and markers of liver injury in this large Mexican American cohort with gender differences in prevalence and risk factors, with younger males at greatest risk.

Identification and Partial Characterization of an L-Tyrosine Aminotransferase (TAT from Arabidopsis thaliana

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Pranav R. Prabhu

2010-01-01

Full Text Available The aminotransferase gene family in the model plant Arabidopsis thaliana consists of 44 genes. Twenty six of these enzymes are classified as characterized meaning that the reaction(s that the enzyme catalyzes are documented using experimental means. The remaining 18 enzymes are uncharacterized and are therefore deemed putative. Our laboratory is interested in elucidating the function(s of the remaining putative aminotransferase enzymes. To this end, we have identified and partially characterized an aminotransferase (TAT enzyme from Arabidopsis annotated by the locus tag At5g36160. The full-length cDNA was cloned and the purified recombinant enzyme was characterized using in vitro and in vivo experiments. In vitro analysis showed that the enzyme is capable of interconverting L-Tyrosine and 4-hydroxyphenylpyruvate, and L-Phenylalanine and phenylpyruvate. In vivo analysis by functional complementation showed that the gene was able to complement an E. coli with a background of aminotransferase mutations that confers auxotrophy for L-Tyrosine and L-Phenylalanine.

Clinical implications in the prevalence and associated cardiovascular factors of elevated serum alanine aminotransferase levels among elderly agricultural and fishing population in Taipei, Taiwan: experience at a teaching hospital.

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Chen, Yu-Fen; Hu, Yi-Chun; Shen, Hsi-Che; Chang, Hui-Te; Tung, Tao-Hsin

2014-01-01

To discuss the prevalence and associated factors related to an elevated serum alanine aminotransferase (ALT) level among the elderly agricultural and fishing population. A total of 6542 (3989 males and 2553 females) healthy adults voluntarily admitted to a teaching hospital for a physical checkup in 2010 in Taipei, Taiwan. Fasting blood samples were drawn via venipuncture, and clinical nurses interviewed the study participants using a structured questionnaire from. The overall prevalence of an elevated serum ALT level was 18.2% and revealed a statistically significant decrease with increasing age (P < 0.001). The men exhibited a higher prevalence than the women (19.7% vs 15.9%; P < 0.001). Male sex; younger age; and presence of obesity, hypertension, hyperuricemia, and hypoalbuminemia were significantly associated with an elevated serum ALT level. Sex-related differences were also revealed. For the men, type 2 diabetes (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02-1.57), hypercholesterolemia (OR, 1.78; 95% CI, 1.22-2.83), hypertriglyceridemia (OR, 1.32; 95% CI, 1.04-1.73), and low high-density lipoprotein (OR, 1.26; 95% CI, 1.05-1.51) were significantly related to an elevated serum ALT level, but this was not so for the women. The disparity of ALT in age groups was revealed. Several sex-related differences were indicated pertaining to the prevalence of an elevated serum ALT level among elderly specific occupational population.

Structure Expression and Function of kynurenine Aminotransferases in Human and Rodent Brains

Energy Technology Data Exchange (ETDEWEB)

Q Han; T Cai; D Tagle; J Li

2011-12-31

Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-D: -aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer's disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup Iepsilon. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.

The helicase domain of Polθ counteracts RPA to promote alt-NHEJ.

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Mateos-Gomez, Pedro A; Kent, Tatiana; Deng, Sarah K; McDevitt, Shane; Kashkina, Ekaterina; Hoang, Trung M; Pomerantz, Richard T; Sfeir, Agnel

2017-12-01

Mammalian polymerase theta (Polθ) is a multifunctional enzyme that promotes error-prone DNA repair by alternative nonhomologous end joining (alt-NHEJ). Here we present structure-function analyses that reveal that, in addition to the polymerase domain, Polθ-helicase activity plays a central role during double-strand break (DSB) repair. Our results show that the helicase domain promotes chromosomal translocations by alt-NHEJ in mouse embryonic stem cells and also suppresses CRISPR-Cas9- mediated gene targeting by homologous recombination (HR). In vitro assays demonstrate that Polθ-helicase activity facilitates the removal of RPA from resected DSBs to allow their annealing and subsequent joining by alt-NHEJ. Consistent with an antagonistic role for RPA during alt-NHEJ, inhibition of RPA1 enhances end joining and suppresses recombination. Taken together, our results reveal that the balance between HR and alt-NHEJ is controlled by opposing activities of Polθ and RPA, providing further insight into the regulation of repair-pathway choice in mammalian cells.

Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
.

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Maeda, Akimitsu; Ando, Hitoshi; Ura, Takashi; Komori, Azusa; Hasegawa, Ayako; Taniguchi, Hiroya; Kadowaki, Shigenori; Muro, Kei; Tajika, Masahiro; Kobara, Makiko; Matsuzaki, Masahide; Hashimoto, Naoya; Maeda, Mieko; Kojima, Yasushi; Aoki, Masahiro; Kondo, Eisaku; Mizutani, Akiyoshi; Fujimura, Akio

2017-05-01

Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings.
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Potential of Red Spinach Leaves Ethanolic Extract (Amaranthus tricolor L. as a Complementary Therapy For Hiperlipidemia: Study in Vivo of Histopathologic and Activity of Alanin Aminotransferase (ALT

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Dimas Adhi Pradana

2016-12-01

Full Text Available This study was conducted to determine the potential of ethanolic extract of red spinach leaves (Amaranthus tricolor L. with control quality as a complementary treatment of hyperlipidemic based on histopathology and activity of alanin aminotrasferase (ALT. A total of 24 male Wistar rats were randomized in 6 groups: normal group; positive control group were given the drug simvastatin; negative control group; 1st treatment group was given extract at dose of 400mg/kgBW rat, 2nd group was given extract at dose of 400mg/kgBW rat and simvastatin dose 0.18 mg/kgBW rat; 3rd treatment groups were given extract at dose of 800mg/kgBW rat and simvastatin dose 0.18 mg/kgBW rat. Induction hyperlipidemic using high fat diet and poloxamer. The data obtained were tested normality with the Shapiro-Wilk test. Statistical analysis using Oneway ANOVA and Post-Hoc Tukey HSD to determine the significance of differences between groups for ALT parameter. Result show the use of ethanolic extract of red spinach leaves can reduce fatty liver condition based on decreased level of ALT and liver histopathologic. It is concluded that the ethanolic extract of red spinach leaves dose 400mg/kgBW rat combine with simvastatin can reduce activity of ALT until 31.57 U1-1.

Activity of aminotransferases in organs of rats during hypoxia of enclosed space of the action of thiamine bromide

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Сніжана Сергіївна Чернадчук

2015-05-01

Full Text Available It is studied an aminotransferase activity during injection of thiamin bromide in rat tissues in normal and hypoxic enclosed space. After injection of thiamine bromide we have set reduction of AST and ALT activity, relative to control, except by the brain tissue, where there was an increase of investigated indicators. The decrease of activity of the investigated elements is occurred in animals which before hypoxia were injection of thiamine bromide

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

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Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza

2016-11-01

We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cloning and inactivation of a branched-chain-amino-acid aminotransferase gene from Staphylococcus carnosus and characterization of the enzyme

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Madsen, Søren M; Beck, Hans Christian; Ravn, Peter

2002-01-01

. The first step in the catabolism is most likely a transamination reaction catalyzed by BCAA aminotransferases (IlvE proteins). In this study, we cloned the ilvE gene from S. carnosus by using degenerate oligonucleotides and PCR. We found that the deduced amino acid sequence was 80% identical...... were essential for optimal cell growth....

A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

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Lafferty-Whyte, K; Cairney, C J; Will, M B

2009-01-01

Telomere length is maintained by two known mechanisms, the activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular le......TERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalization in cell lines and mesenchymal tissues....

Enhancement of solubility in Escherichia coli and purification of an aminotransferase from Sphingopyxis sp. MTA144 for deamination of hydrolyzed fumonisin B1

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Hartinger Doris

2010-08-01

Full Text Available Abstract Background Fumonisin B1 is a cancerogenic mycotoxin produced by Fusarium verticillioides and other fungi. Sphingopyxis sp. MTA144 can degrade fumonisin B1, and a key enzyme in the catabolic pathway is an aminotransferase which removes the C2-amino group from hydrolyzed fumonisin B1. In order to study this aminotransferase with respect to a possible future application in enzymatic fumonisin detoxification, we attempted expression of the corresponding fumI gene in E. coli and purification of the enzyme. Since the aminotransferase initially accumulated in inclusion bodies, we compared the effects of induction level, host strain, expression temperature, solubility enhancers and a fusion partner on enzyme solubility and activity. Results When expressed from a T7 promoter at 30°C, the aminotransferase accumulated invariably in inclusion bodies in DE3 lysogens of the E. coli strains BL21, HMS174, Rosetta 2, Origami 2, or Rosetta-gami. Omission of the isopropyl-beta-D-thiogalactopyranoside (IPTG used for induction caused a reduction of expression level, but no enhancement of solubility. Likewise, protein production but not solubility correlated with the IPTG concentration in E. coli Tuner(DE3. Addition of the solubility enhancers betaine and sorbitol or the co-enzyme pyridoxal phosphate showed no effect. Maltose-binding protein, used as an N-terminal fusion partner, promoted solubility at 30°C or less, but not at 37°C. Low enzyme activity and subsequent aggregation in the course of purification and cleavage indicated that the soluble fusion protein contained incorrectly folded aminotransferase. Expression in E. coli ArcticExpress(DE3, which co-expresses two cold-adapted chaperonins, at 11°C finally resulted in production of appreciable amounts of active enzyme. Since His tag-mediated affinity purification from this strain was hindered by co-elution of chaperonin, two steps of chromatography with optimized imidazole concentration in the

Effect of Orthodontic Tooth Movement on Salivary Aspartate Aminotransferase Activity

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Steiven Adhitya

2013-07-01

Full Text Available 72 1024x768 Aspartate aminotransferase is one of biological indicator in gingival crevicular fluid (CGF. Force orthodontic application could increase activity of aspartate aminotransferase in CGF. However, the increase activity of aspartate aminotransferase in saliva due to orthodontic force and its correlation between aspartate aminotransferase activity and tooth movement remains unclear. Objectives: To evaluate application orthodontic force on the aspartate aminotransferase activity in saliva based on the duration of force and finding correlation between tooth movement and aspartate aminotransferase activity. Methods: Twenty saliva samples collected before extraction of first premolar, at the time of force application for canine retraction and after force application. The canines retraction used 100 grams of interrupted force (module chain for thirty days. The collection of saliva and the measurement of tooth movement were carried out 1 day, 7 days, 14 days, 21 days, and 28 days after force application. The measurement of aspartate aminotransferase activity in saliva was done using spectrophotometer. Results: Application of orthodontic force influences the salivary aspartate aminotransferase activity (F=25.290, p=0.000. Furthermore, tooth movement correlated with aspartate aminotransferase activity (F=0.429, p=0.000. Conclusion: Aspartate aminotransferase activity could be used as tooth movement indicator that related to the duration of force application.DOI : 10.14693/jdi.v20i1.128

Serum Alanine Aminotransferase Levels within Normal Range Have Different Associations with Augmentation Index and Other Cardiometabolic Risk Factors in Nondrinkers and Drinkers: A Chinese Community-Based Analysis

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Shihui Fu

2017-01-01

Full Text Available Background. To investigate whether serum alanine aminotransferase (ALT levels within normal range were associated with augmentation index (AIx and cardiometabolic risk factors in nondrinkers and drinkers in Chinese community-dwelling population. Methods. There were 4165 participants with serum ALT levels within normal range. Results. Alcohol drinking was observed in 1173 participants (28.2%. In multivariate analysis, serum ALT levels of nondrinkers were independently associated with age, sex, body mass index (BMI, hypertension, diabetes mellitus, diastolic blood pressure, triglyceride, low-density lipoprotein-cholesterol (LDL-c, and AIx, while serum ALT levels of drinkers were independently associated with age, sex, BMI, triglyceride, and LDL-c (p<0.05 for all. Conclusions. Associations of serum ALT levels within normal range with age, sex, body height and weight, and blood lipid were simultaneously present in participants with and without alcohol drinking, while associations of serum ALT levels within normal range with AIx, blood pressure, and glucose were seen in nondrinkers rather than in drinkers. These findings not only provide the evidence that serum ALT levels, even within the normal range, have different associations with arteriosclerosis and cardiometabolic risk factors in nondrinkers and drinkers but also are helpful in understanding the underlying pathophysiologic mechanisms linking the hepatic function to arteriosclerosis and cardiometabolic risk factors.

Serum alanine aminotransferase predicts interventricular septum thickness and left ventricular mass in patients with nonalcoholic fatty liver disease.

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Ybarra, Juan; Fernández, Sandra; Sánchez-Hernández, Joan; Romeo, June H; Ballesta-Lopez, Carlos; Guell, Javier; Mearin, Fermin

2014-06-01

Alanine aminotransferase (ALT) is a marker of nonalcoholic fatty liver disease (NAFLD) and predicts type 2 diabetes mellitus (DM2) as well as coronary events independently of traditional risk factors and the features of the metabolic syndrome. The extent to which interventricular septum thickness (IVS) and left ventricular mass (LVM) are associated with ALT levels in cohorts of individuals with body weights ranging from overweight to morbid obesity and NAFLD remains still unknown. This was a cross-sectional pilot study involving 151 young White participants with liver ultrasound-proven NAFLD. Standard echocardiograms were used to define LVM, IVS, and left ventricle diastolic function [mitral inflow velocity pattern (E/A ratio) and mitral annulus velocity by tissue Doppler imaging (Em/Am ratio)]. Participants were classified according to ALT quartiles: p25, p50, p75, and p100. The study included 36 men and 115 women with an age of 38.4 ± 0.7 years and BMI of 43.9 ± 0.6 kg/m2. p100 participants disclosed significantly higher homeostasis model assessment (P=0.003), DM2 (P=0.002), and hypertension (P=0.01) prevalence, whereas LVM, IVS, E/A, and Em/Am ratios were significantly higher in this group when compared with their p25 peers (PDM2. ALT levels predict both IVS and LVM in NAFLD individuals irrespective of their BMI, DM2, hypertension, age, and sex. ALT levels behave as a surrogate marker of left ventricular hypertrophy in overweight and/or obese NAFLD patients. Hence, it seems worth obtaining cardiac ultrasounds in NAFLD patients with elevated ALT levels.

Mutational analysis of the activator of late transcription, Alt , in the lactococcal bacteriophage TP901-1

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Pedersen, Margit; Hammer, Karin

2007-01-01

An activator protein, Alt, synthesized during the early state of lytic infection is required for transcription of the late operon in the lactococcal phage TP901-1. In order to identify amino acid residues in the Alt protein required for activation of the TP901-1 late promoter, Plate, hydroxylamine...

Alanine transaminase (ALT) blood test

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... gov/ency/article/003473.htm Alanine transaminase (ALT) blood test To use the sharing features on this page, please enable JavaScript. The alanine transaminase (ALT) blood test measures the level of the enzyme ALT in ...

Aspartate aminotransferase (AST) blood test

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... gov/ency/article/003472.htm Aspartate aminotransferase (AST) blood test To use the sharing features on this page, please enable JavaScript. The aspartate aminotransferase (AST) blood test measures the level of the enzyme AST in ...

PLASMA INSULIN AND IGF-1 AND HEPATIC ACTIVITY IN SAANEN GOAT KIDS, AROUND WEANING

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Damiano Magistrelli

2009-02-01

Full Text Available Weaning is a crucial event in the life of young ruminants. At weaning ruminal and digestive activity are still incomplete, so weaning may coincide with a period of growth stasis. Since insulin and insulin-like growth factor 1 (IGF-1 can play a fundamental role in post-natal development, the aim of the present study was to evaluate plasma variations of insulin and IGF-1 levels and their relationships with the hepatic activity, around weaning.For this purpose, eleven 3-days-old Saanen goat kids were randomly divided into MILK (6 animals and WMIX (5 animals groups. All kids were fed goat milk to age 29 days. After that, MILK kids continued to receive milk, while WMIX ones underwent weaning, based on the progressive replacement of milk with solid feed. WMIX kids were completely weaned on day 48. Blood samples were weekly analyzed for metabolic traits, insulin and IGF-1 levels, alanine aminotransferase (ALT and aspartate aminotransferase (AST activities. On day 50, all animals were slaughtered, liver weight was recorded and liver samples were analyzed for DNA, RNA, phospholipids, glicogen and soluble protein content, ALT and AST activity.On day 50, plasma insulin and IGF-1 were lower in WMIX group, as possible consequence of the lower plasma glucose and amino acids levels. Liver weight was not different between groups, but liver weight expressed as percentage of body weight was lower in WMIX kids and highly correlated to plasma IGF-1. Liver glycogen was also lower in WMIX kids, as possible consequence of the lower plasma glucose.Hepatic ALT and AST activities were not different between groups and both were strongly correlated to plasma insulin. Moreover, insulin was positively correlated to the proteosynthetic capability per cell (RNA/DNA of the liver.Our results indicate that the adopted livestock practice permitted the normal development of the animal used, avoiding growth stasis. Anyway, weaning altered plasma insulin and IGF-1, without affecting

Relaxed evolution in the tyrosine aminotransferase gene tat in old world fruit bats (Chiroptera: Pteropodidae).

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Shen, Bin; Fang, Tao; Yang, Tianxiao; Jones, Gareth; Irwin, David M; Zhang, Shuyi

2014-01-01

Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid) catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene) is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae) and two New World fruit bats (Phyllostomidae). Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats) formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet.

High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

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Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

2016-04-01

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

The major Alternaria alternata allergen, Alt a 1: A reliable and specific marker of fungal contamination in citrus fruits.

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Gabriel, M F; Uriel, N; Teifoori, F; Postigo, I; Suñén, E; Martínez, J

2017-09-18

The ubiquitously present spores of Alternaria alternata can spoil a wide variety of foodstuffs, including a variety of fruits belonging to the Citrus genus. The major allergenic protein of A. alternata, Alt a 1, is a species-specific molecular marker that has been strongly associated with allergenicity and phytopathogenicity of this fungal species. This study aimed to evaluate the potential of the detection of Alt a 1 as a reliable indicator of A. alternata contamination in citrus fruits. To accomplish this aim, sixty oranges were artificially infected with a spore suspension of A. alternata. Internal fruit material was collected at different incubation times (one, two and three weeks after the fungal inoculation) and used for both total RNA extraction and protein extraction. Alt a 1 detection was then performed by polymerase chain reaction (PCR) amplification using Alt a 1 specific primers and by enzyme-linked immunosorbent assay (ELISA). The experimental model presented in this work was effective to simulate the typical Alternaria black rot phenotype and its progression. Although both PCR and ELISA techniques have been successfully carried out for detecting Alt a 1 allergen in A. alternata infected oranges, the PCR method was found to be more sensitive than ELISA. Nevertheless, ELISA results were highly valuable to demonstrate that considerable amounts of Alt a 1 are produced during A. alternata fruit infection process, corroborating the recently proposed hypothesis that this protein plays a role in the pathogenicity and virulence of Alternaria species. Such evidence suggests that the detection of Alt a 1 by PCR-based assay may be used as a specific indicator of the presence of pathogenic and allergenic fungal species, A. alternata, in fruits. This knowledge can be employed to control the fungal infection and mitigate agricultural losses as well as human exposure to A. alternata allergens and toxins. Copyright © 2017 Elsevier B.V. All rights reserved.

A Styrene-alt-Maleic Acid Copolymer Is an Effective Inhibitor of R5 and X4 Human Immunodeficiency Virus Type 1 Infection

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Vanessa Pirrone

2010-01-01

Full Text Available An alternating copolymer of styrene and maleic acid (alt-PSMA differs from other polyanionic antiviral agents in that the negative charges of alt-PSMA are provided by carboxylic acid groups instead of sulfate or sulfonate moieties. We hypothesized that alt-PSMA would have activity against human immunodeficiency virus type 1 (HIV-1 comparable to other polyanions, such as the related compound, poly(sodium 4-styrene sulfonate (PSS. In assays using cell lines and primary immune cells, alt-PSMA was characterized by low cytotoxicity and effective inhibition of infection by HIV-1 BaL and IIIB as well as clinical isolates of subtypes A, B, and C. In mechanism of action assays, in which each compound was added to cells and subsequently removed prior to HIV-1 infection (“washout” assay, alt-PSMA caused no enhancement of infection, while PSS washout increased infection 70% above control levels. These studies demonstrate that alt-PSMA is an effective HIV-1 inhibitor with properties that warrant further investigation.

[Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

Science.gov (United States)

Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

2016-09-20

Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT liver biopsy to the certain degree.

The Role of ATRX in the Alternative Lengthening of Telomeres (ALT Phenotype

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João P. Amorim

2016-09-01

Full Text Available Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT. The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX or Death-Domain Associated Protein (DAXX genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype.

Relaxed evolution in the tyrosine aminotransferase gene tat in old world fruit bats (Chiroptera: Pteropodidae.

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Bin Shen

Full Text Available Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae and two New World fruit bats (Phyllostomidae. Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet.

The Magnaporthe oryzae Alt A 1-like protein MoHrip1 binds to the plant plasma membrane.

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Zhang, Yi; Liang, Yingbo; Dong, Yijie; Gao, Yuhan; Yang, Xiufen; Yuan, Jingjing; Qiu, Dewen

2017-10-07

MoHrip1, a protein isolated from Magnaporthe oryzae, belongs to the Alt A 1 (AA1) family. mohrip1 mRNA levels showed inducible expression throughout the infection process in rice. To determine the location of MoHrip1 in M. oryzae, a mohrip1-gfp mutant was generated. Fluorescence microscopy observations and western blotting analysis showed that MoHrip1 was both present in the secretome and abundant in the fungal cell wall. To obtain MoHrip1 protein, we carried out high-yield expression of MoHrip1 in Pichia pastoris. Treatment of tobacco plants with MoHrip1 induced the formation of necrosis, accumulation of reactive oxygen species and expression of several defense-related genes, as well as conferred disease resistance. By fusion to green fluorescent protein, we showed that MoHrip1 was able to bind to the tobacco and rice plant plasma membrane, causing rapid morphological changes at the cellular level, such as cell shrinkage and chloroplast disorganization. These findings indicate that MoHrip1 is a microbe-associated molecular pattern that is perceived by the plant immune system. This is the first study on an AA1 family protein that can bind to the plant plasma membrane. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of the different spectral forms of glutamate 1-semialdehyde aminotransferase by mass spectrometry

DEFF Research Database (Denmark)

Brody, S; Andersen, Jens S.; Kannangara, C G

1995-01-01

Glutamate 1-semialdehyde aminotransferase produces delta-aminolevulinate for the synthesis of chlorophyll, heme, and other tetrapyrrole pigments. The native enzyme from Synechococcus is pale yellow and has absorption maxima at 338 and 418 nm from vitamin B6. Yellow, colorless, and pink forms...

Alternative Liquid Fuels Simulation Model (AltSim).

Energy Technology Data Exchange (ETDEWEB)

Williams, Ryan; Baker, Arnold Barry; Drennen, Thomas E.

2009-12-01

The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production and end use costs, greenhouse gas emissions, and energy balances of several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol from various feedstocks (switchgrass, corn stover, forest residue, and farmed trees), biodiesel, and diesels derived from natural gas (gas to liquid, or GTL), coal (coal to liquid, or CTL), and coal with biomass (CBTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion ratio, financial assumptions, tax credits, CO{sub 2} taxes, and plant capacity factor. This paper summarizes the structure and methodology of AltSim, presents results, and provides a detailed sensitivity analysis. The Energy Independence and Security Act (EISA) of 2007 sets a goal for the increased use of biofuels in the U.S., ultimately reaching 36 billion gallons by 2022. AltSim's base case assumes EPA projected feedstock costs in 2022 (EPA, 2009). For the base case assumptions, AltSim estimates per gallon production costs for the five ethanol feedstocks (corn, switchgrass, corn stover, forest residue, and farmed trees) of $1.86, $2.32, $2.45, $1.52, and $1.91, respectively. The projected production cost of biodiesel is $1.81/gallon. The estimates for CTL without biomass range from $1.36 to $2.22. With biomass, the estimated costs increase, ranging from $2.19 per gallon for the CTL option with 8% biomass to $2.79 per gallon for the CTL option with 30% biomass and carbon capture and sequestration. AltSim compares the greenhouse gas emissions (GHG) associated with both the production and consumption of the various fuels. EISA allows fuels emitting 20% less greenhouse gases (GHG) than conventional gasoline and diesels to qualify as renewable fuels. This allows several of the

Independent predictive factors for significant liver histological changes in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal alanine aminotransferase level

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LI Qiang

2016-07-01

Full Text Available Objective To investigate the independent predictive factors for significant liver histological changes (SLHCs in patients with HBeAg-positive high-viral-load chronic hepatitis B virus (HBV infection and a normal alanine aminotransferase (ALT level. MethodsA retrospective analysis was performed on the clinical data of 116 previously untreated patients with HBeAg-positive high-viral-load (HBV DNA≥105 copies/ml chronic HBV infection and a normal ALT level (＜50 U/L who were hospitalized in Shanghai Public Health Clinical Center Affiliated to Fudan University from June 2013 to August 2015. The definition of SLHCs was inflammation ≥G2 and/or fibrosis≥S2. The t-test or Mann-Whitney U rank sum test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate regression analyses were used to determine independent predictive factors for SLHCs. ResultsOf all the 116 patients, 47(40.5% had SLHCs. The multivariate analysis showed that age (OR=2.828, P＜0.05, ALT (OR=1.011, P＜0.05, and gamma-glutamyl transpeptidase (GGT (OR=1.089, P＜0.05 were independent predictors for SLHCs in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level. The patients aged ≤30 years had a significantly lower incidence rate of SLHCs than those aged＞30 years (21.6% vs 49.4%, χ2=6.42, P=0.015, the patients with ALT ≤30 U/L had a significantly lower incidence rate of SLHCs than those with 30 U/L＜ALT≤50 U/L (17.6% vs 50.0%, χ2=19.86, P＜0.001, and the patients with GGT≤40 U/L had a significantly lower incidence rate of SLHCs than those with GGT＞40 U/L (28.8% vs 66.7%, χ2=28.63, P＜0.001. ConclusionIn patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level, those with an age of＞30 years, ALT＞30 U/L, and GGT＞40 U/L tend to develop SLHCs and need liver biopsy.

Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.

Science.gov (United States)

Sookoian, Silvia; Castaño, Gustavo O; Scian, Romina; Fernández Gianotti, Tomas; Dopazo, Hernán; Rohr, Cristian; Gaj, Graciela; San Martino, Julio; Sevic, Ina; Flichman, Diego; Pirola, Carlos J

2016-02-01

Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown. We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS. Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included. Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3' untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations. In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and

Effect of Capreolus capreolus and Sus scrofa excreta on alanine aminotransferase activity in Glechoma hederacea leaves in conditions of Cd pollution

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O. M. Vasilyuk

2015-06-01

Full Text Available The paper reflects the analysis of Cd impact on the total activity (nM pyruvic acid/ml s of alanine aminotransferase (ALT, EC 2.6.1.2 nitrogen metabolism and the content (mg/ml of water-soluble protein fraction (albumin in Glechoma hederacea L. leaves subject, which dominated in the research area (natural floodplain oak with Stellaria holostea L.. Cd was introduced in the form of salts Cd(NO32 in the concentrations of 0.25, 1.25 and 2.50 g/m2, equivalent to Cd in 1, 5 and 10 doses of MAC. The content of doses of MAC of Cd (5 mg/kg soil was taken into account during introduction. We observed the inhibition of the activity of ALT 3–4 times (with adding the Cd salts at a dose of 1 and 5 МAС compared to controls (area without pollution of Cd and excreta of mammals. This stress reaction took place in the protein complex as well. Thus, albumin content was equal to 72% and 80% (with Cd 1 and 5 MAC compared to control (the area without pollution and excretory functions of mammals. It proved nonspecific response to stress. Using excreta of Capreolus capreolus L. and Sus scrofa L. shows the reduction of Cd effects and increasing the metabolic activity of ALT by 41% and 105%, respectively (with adding of Cd 1 MAC compared to control (pollution by Cd at a dose 1 MAC. The effect of Cd 5 MAC is offset (only with the introduction of C. capreolus excreta compared to control (pollution by Cd at a dose 5 MAC. Normalization of the albumin content (with adding of Cd 1 and 5 MAC compared to control (сontrol of Cd at a dose 1 MAC and сontrol of Cd at a dose 5 MAC with using of excreta of C. capreolus was observed. In conditions of Cd at a doze 10 MAC the ALT activity was reduced 2 times with the introduction of excreta of C. capreolus as S. scrofa compared to control (Cd at a dose 10 MAC. The introduction of excreta of S. scrofa compared with C. capreolus restored the albumin content by 10% to the control. Thus, the feasibility of using different biological

Characterization of a bordetella pertussis diaminopimelate (DAP) biosynthesis locus identifies dapC, a novel gene coding for an N-succinyl-L,L-DAP aminotransferase.

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Fuchs, T M; Schneider, B; Krumbach, K; Eggeling, L; Gross, R

2000-07-01

The functional complementation of two Escherichia coli strains defective in the succinylase pathway of meso-diaminopimelate (meso-DAP) biosynthesis with a Bordetella pertussis gene library resulted in the isolation of a putative dap operon containing three open reading frames (ORFs). In line with the successful complementation of the E. coli dapD and dapE mutants, the deduced amino acid sequences of two ORFs revealed significant sequence similarities with the DapD and DapE proteins of E. coli and many other bacteria which exhibit tetrahydrodipicolinate succinylase and N-succinyl-L,L-DAP desuccinylase activity, respectively. The first ORF within the operon showed significant sequence similarities with transaminases and contains the characteristic pyridoxal-5'-phosphate binding motif. Enzymatic studies revealed that this ORF encodes a protein with N-succinyl-L,L-DAP aminotransferase activity converting N-succinyl-2-amino-6-ketopimelate, the product of the succinylase DapD, to N-succinyl-L,L-DAP, the substrate of the desuccinylase DapE. Therefore, this gene appears to encode the DapC protein of B. pertussis. Apart from the pyridoxal-5'-phosphate binding motif, the DapC protein does not show further amino acid sequence similarities with the only other known enzyme with N-succinyl-L,L-DAP aminotransferase activity, ArgD of E. coli.

Saccharomyces cerevisiae Bat1 and Bat2 aminotransferases have functionally diverged from the ancestral-like Kluyveromyces lactis orthologous enzyme.

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Maritrini Colón

Full Text Available BACKGROUND: Gene duplication is a key evolutionary mechanism providing material for the generation of genes with new or modified functions. The fate of duplicated gene copies has been amply discussed and several models have been put forward to account for duplicate conservation. The specialization model considers that duplication of a bifunctional ancestral gene could result in the preservation of both copies through subfunctionalization, resulting in the distribution of the two ancestral functions between the gene duplicates. Here we investigate whether the presumed bifunctional character displayed by the single branched chain amino acid aminotransferase present in K. lactis has been distributed in the two paralogous genes present in S. cerevisiae, and whether this conservation has impacted S. cerevisiae metabolism. PRINCIPAL FINDINGS: Our results show that the KlBat1 orthologous BCAT is a bifunctional enzyme, which participates in the biosynthesis and catabolism of branched chain aminoacids (BCAAs. This dual role has been distributed in S. cerevisiae Bat1 and Bat2 paralogous proteins, supporting the specialization model posed to explain the evolution of gene duplications. BAT1 is highly expressed under biosynthetic conditions, while BAT2 expression is highest under catabolic conditions. Bat1 and Bat2 differential relocalization has favored their physiological function, since biosynthetic precursors are generated in the mitochondria (Bat1, while catabolic substrates are accumulated in the cytosol (Bat2. Under respiratory conditions, in the presence of ammonium and BCAAs the bat1Δ bat2Δ double mutant shows impaired growth, indicating that Bat1 and Bat2 could play redundant roles. In K. lactis wild type growth is independent of BCAA degradation, since a Klbat1Δ mutant grows under this condition. CONCLUSIONS: Our study shows that BAT1 and BAT2 differential expression and subcellular relocalization has resulted in the distribution of the

Efeitos da farinha de folhas de mandioca sobre a atividade das enzimas AST, ALT, FA e lipídios hepáticos de ratos Wistar Effects of cassava leaves flour on the AST, ALT, ALP enzymes activity and hepatic lipids of Wistar rats

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Daniela Séfora de Melo

2008-12-01

Full Text Available Folhas de mandioca possuem substâncias como ligninas e saponinas que podem apresentar efeito hipolipidêmico. Todavia, um estudo recente relatou aumento no peso do fígado de ratos alimentados com dietas contendo farinha de folhas de mandioca (FFM - Manihot esculenta Crantz cv. Cacao, tornando-se necessário um estudo mais aprofundado dos efeitos desta farinha sobre os parâmetros hepáticos. Para este estudo, um ensaio biológico com 32 ratos machos Wistar foi conduzido por um período de 7 semanas, sendo os tratamentos: dieta controle e dietas contendo 5, 10 e 15% de FFM. As dietas contendo FFM não apresentaram efeitos sobre as atividades das enzimas Aspartato Aminotransferase (AST e Fosfatase Alcalina (FA, mas aumentaram significativamente a atividade da enzima alanina aminotransferase (ALT. O estudo histopatológico revelou vacuolização do citoplasma dos hepatócitos para todos os grupos. No entanto, a freqüência de animais com vacuolização acentuada foi superior nos grupos que receberam dietas com FFM, apresentando também maiores teores de lipídios e colesterol total hepáticos e maior relação peso fígado/peso corporal. Estes resultados indicam que os antinutrientes presentes nas folhas de mandioca, como taninos, cianeto e saponinas, podem ser responsáveis pela redução da função hepática nos animais alimentados com FFM.Cassava leaves contain substances such as lignins and saponins that can present the hypolipidemic effect. However, a recent study has reported an increase in liver weight of rats fed diet containing cassava leaves flour (CLF - Manihot esculenta Crantz cv. Cacao. Thus, a further study of the effect of this flour on the hepatic parameters is necessary. For the development of this study, a biological assay with 32 male Wistar rats was conducted for a period of 7 weeks with the following treatments: control diet and diets containing 5, 10, and 15% of CLF. The diets containing CLF showed no effects on the

Tyrosine Aminotransferase Contributes to Benzylisoquinoline Alkaloid Biosynthesis in Opium Poppy1[W

Science.gov (United States)

Lee, Eun-Jeong; Facchini, Peter J.

2011-01-01

Tyrosine aminotransferase (TyrAT) catalyzes the transamination of l-Tyr and α-ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and l-glutamate. The decarboxylation product of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural products known collectively as benzylisoquinoline alkaloids (BIAs). We have isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum), which remains the only commercial source for several pharmaceutical BIAs, including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5′-phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between PLP and a specific Lys residue. The amino acid sequence of TyrAT showed considerable homology to other putative plant TyrATs, although few of these have been functionally characterized. Purified, recombinant TyrAT displayed a molecular mass of approximately 46 kD and a substrate preference for l-Tyr and α-ketoglutarate, with apparent Km values of 1.82 and 0.35 mm, respectively. No specific requirement for PLP was detected in vitro. Liquid chromatography-tandem mass spectrometry confirmed the conversion of l-Tyr to 4-hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and stems of mature opium poppy plants. Virus-induced gene silencing was used to evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT transcript levels were reduced by at least 80% in silenced plants compared with controls and showed a moderate reduction in total alkaloid content. The modest correlation between transcript levels and BIA accumulation in opium poppy supports a role for TyrAT in the generation of alkaloid precursors, but it also suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde. PMID:21949209

Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population

DEFF Research Database (Denmark)

Tolstrup, J.S.; Gronbaek, M.; Tybjaerg-Hansen, A.

2009-01-01

the Copenhagen City Heart Study. Biochemical tests for the detection of liver damage were specific for alanine aminotransferase (ALT), aspartate aminotransferase (AST)-to-ALT ratio (AST/ALT), gamma-glutamyl transpeptidase (gamma-GT), albumin, bilirubin, alkaline phosphatase, coagulation factors, and erythrocyte...... volume. RESULTS: Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were...

Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

Science.gov (United States)

Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

2015-01-01

The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats.

PISCES and ALT-II: Juelich PSI papers

International Nuclear Information System (INIS)

Conn, R.W.; Hirooka, Y.; LaBombard, B.

1988-08-01

This publication comprises papers from the PISCES and ALT-II Programs at UCLA which were presented at the International Plasma Surface Interactions Meeting held in Juelich, FRG, on May 2-6, 1988. A list of publications from the PISCES and ALT-II contained in this report are: Deuterium pumping and erosion behavior of selected graphite materials under high flux plasma bombardment in PISCES; Erosion and redeposition behavior of selected NET-candidate materials under high-flux hydrogen, deuterium plasma bombardment in PISCES; Presheath profiles in simulated tokamak edge plasmas; Boundary asymmetries and plasma flow to the ALT-II toroidal belt pump limiter; ALT-II toroidal belt pump limiter performance in TEXTOR; and An in-situ spectroscopic erosion yield measurement with applications to sputtering and surface morphology alterations

LIMITED ELEVATIONS IN ANTITUBERCULOSIS DRUG-INDUCED SERUM ALANINE AMINOTRANSFERASE (ALT) LEVELS IN A COHORT OF NIGERIANS ON TREATMENT FOR PULMONARY TUBERCULOSIS AND HIV INFECTION IN YENAGOA

NARCIS (Netherlands)

Ikuabe, Peter Ogie; Ebuenyi, Ikenna Desmond; Harry, Tubonye Clement

2015-01-01

BACKGROUND: This study, undertaken in a major tertiary hospital in the Niger Delta region of Nigeria was designed to examine the incidence of elevation in serum alanine aminotransference (ALT) in our patients who were on treatment for HIV/AIDS with some of them on antituberculosis drugs. METHOD:

Dinámica del virus de la hepatitis C con carga viral y ALT y monitoreo del daño hepático libre de biopsias Dinámica del virus de la hepatitis C con carga viral y ALT y monitoreo del daño hepático libre de biopsias

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Justino Alavez Domínguez

2006-12-01

Full Text Available Se compara el modelo estándar reducido de tres poblaciones (hepatocitos sanos y enfermos, y carga viral para el estudio de la dinámica del virus de la hepatitis C (VHC, con el modelo de la dinámica viral con alanina aminotransferasa (ALT. En términos del parámetro umbral que es el mismo para ambos modelos, se determina la existencia y estabilidad del estado de equilibrio endémico, así como la estabilidad global del estado de equilibrio del individuo sano. Por otro lado, se presenta un estudio experimental que muestra que es posible monitorear el daño hepático sin biopsias, mediante la estimación numérica de los parámetros de los modelos, considerando solamente mediciones de la carga viral, de los niveles de ALT y una valoración razonable del daño hepático pretratamiento.aThe standard model of three populations (healthy and unhealthy hepatocytes, and viral load for the study of the dynamics of hepatitis C virus (HCV, is compared with viral dynamic model with alanine aminotransferase (ALT. In terms of the threshold parameter that it’s the same for both models, the existence and local asymptotic stability of the endemically infected equilibrium steady state, and the global stability of the healthy individual equilibrium steady state are established. Furthermore, an experimental study is presented showing that it’s possible to carry out the monitoring of hepatic damage biopsies free by numerical parameter estimation, considering only viral load and ALT levels measurements and a reasonable assessment of pretreatment hepatic damage.

Activation of the ALT pathway for telomere maintenance can affect other sequences in the human genome.

Science.gov (United States)

Jeyapalan, Jennie N; Varley, Helen; Foxon, Jenny L; Pollock, Raphael E; Jeffreys, Alec J; Henson, Jeremy D; Reddel, Roger R; Royle, Nicola J

2005-07-01

Immortal human cells maintain telomere length by the expression of telomerase or through the alternative lengthening of telomeres (ALT). The ALT mechanism involves a recombination-like process that allows the rapid elongation of shortened telomeres. However, it is not known whether activation of the ALT pathway affects other sequences in the genome. To address this we have investigated, in ALT-expressing cell lines and tumours, the stability of tandem repeat sequences known to mutate via homologous recombination in the human germline. We have shown extraordinary somatic instability in the human minisatellite MS32 (D1S8) in ALT-expressing (ALT+) but not in normal or telomerase-expressing cell lines. The MS32 mutation frequency varied across 15 ALT+ cell lines and was on average 55-fold greater than in ALT- cell lines. The MS32 minisatellite was also highly unstable in three of eight ALT+ soft tissue sarcomas, indicating that somatic destabilization occurs in vivo. The MS32 mutation rates estimated for two ALT+ cell lines were similar to that seen in the germline. However, the internal structures of ALT and germline mutant alleles are very different, indicating differences in the underlying mutation mechanisms. Five other hypervariable minisatellites did not show elevated instability in ALT-expressing cell lines, indicating that minisatellite destabilization is not universal. The elevation of MS32 instability upon activation of the ALT pathway and telomere length maintenance suggests there is overlap between the underlying processes that may be tractable through analysis of the D1S8 locus.

Essential roles of aspartate aminotransferase 1 and vesicular glutamate transporters in β-cell glutamate signaling for incretin-induced insulin secretion.

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Naoya Murao

Full Text Available Incretins (GLP-1 and GIP potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS that requires two critical processes: 1 generation of cytosolic glutamate through the malate-aspartate (MA shuttle in glucose metabolism and 2 glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1, a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively, which participate in glutamate transport into secretory vesicles. Got1 knockout (KO β-cell lines were defective in cytosolic glutamate production from glucose and showed impaired IIIS. Unexpectedly, different from the previous finding that global Slc17a7 KO mice exhibited impaired IIIS from pancreatic islets, β-cell specific Slc17a7 KO mice showed no significant impairment in IIIS, as assessed by pancreas perfusion experiment. Single Slc17a7 KO β-cell lines also retained IIIS, probably due to compensatory upregulation of Slc17a6. Interestingly, triple KO of Slc17a7, Slc17a6, and Slc17a8 diminished IIIS, which was rescued by exogenously introduced wild-type Slc17a7 or Slc17a6 genes. The present study provides direct evidence for the essential roles of AST1 and VGLUTs in β-cell glutamate signaling for IIIS and also shows the usefulness of the CRISPR/Cas9 system for studying β-cells by simultaneous disruption of multiple genes.

Army AL&T, July-September 2008

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2008-09-01

Northern Region — Wanda Reed (PCO), Joann Langston (PARC), Debbie Emerson (Alt. to PARC) Southern Region — Julie Silva (PCO), Carol Lowman (Direc- tor/PARC...Charles Jaber (PCO), Roger Engebretson, (Director/PARC), Sharon Oishi (Alt. to PARC) U.S. Army Contracting Command, Southwest Asia — Carol Estes (PCO...Robyn Villafranco, Margarita Ramirez, Diana Fernandez, Donna Reed, Michely Walton, Elisa Mendez , Cynariah Wilkins, Deinor Bolanos, Belinda Kent

Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci

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Guillermo Hugo Peralta

Full Text Available ABSTRACT Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor.

Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

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Inoue, Motoki; Tazuma, Susumu; Kanno, Keishi; Hyogo, Hideyuki; Igarashi, Kazuhiko; Chayama, Kazuaki

2011-03-01

Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

Alanine-aminotransferase: an early marker for insulin resistance? Alanino-aminotransferasa: ¿un marcador temprano de resistencia a la insulina?

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Martín R. Salazar

2007-04-01

Full Text Available In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis Band C infected, we investigated if alanine-aminotransferase (ALT was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD. The sample (432 female and 119 male was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P (female ≤ 15 and ≤ 19 U/L; male ≤ 17 and ≤ 23 U/l, respectively. Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc, triglyceride (TG, TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029, glycemia (p=0.028, and homeostasis model assessment of insulin resistance, (p=0.045, and above the 75th P had higher SBP (p=0.036, DBP (p=0.018, TG (p=0.024, TG/HDLc ratio (p=0.028, glycemia (p=0.004 and HOMA-IR (p=0.0014. Male placed above the 50th P of ALT had higher BMI (p=0.017 and TG/HDLc ratio (p=0.048, and above the 75th P had lower values of HDLc (p=0.042. Only 16.5% of women and 14.5% of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.En una muestra poblacional, luego de excluir a quienes consumían alcohol y drogas hepatotóxicas y a los infectados con virus B y C de la hepatitis, investigamos si la alanino-aminotransferasa (ALT, o transaminasa glutámico pirúvica (TGP, se asociaba con el síndrome metabólico y con resistencia a la insulina y si esta asociación se explicaba por enfermedad hep

Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis.

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Eun Young Yu

2015-10-01

Full Text Available A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR. These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs. The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and "trapped" the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes, suggesting that these factors process ALT intermediates or products. Notably, the antagonism of Ku and Mre11 in the induction of ALT is reminiscent of their roles in DSB resection, in which Blm is also known to play a key role. We suggest that an aberrant resection reaction may constitute an early trigger for ALT telomeres, and that the outcomes of ALT are distinct from DSB because of the unique telomere nucleoprotein structure.

Gender difference of alanine aminotransferase elevation may be associated with higher hemoglobin levels among male adolescents.

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Solomon Chih-Cheng Chen

Full Text Available BACKGROUND: To explore the gender difference of ALT elevation and its association with high hemoglobin levels. METHODS: A cross-sectional study of 3547 adolescents (2005 females, mean age of 16.5?.3 years who were negative for hepatitis B surface antigen received health checkups in 2006. Body mass index (BMI, levels of hemoglobin, ALT and cholesterol were measured. ALT >42 U/L was defined as elevated ALT. Elevated ALT levels were detected in 112 of the 3547 participants (3.3%, more prevalent in males than in females (5.4% vs. 1.4%, p11 g/dl in females or >13.5 g/dl in males, but the cumulative cases of elevated ALT increased more quickly in males. Proportion of elevated ALT increased as either the BMI or hemoglobin level rise, more apparent in male adolescents. Logistic regression modeling showed odds ratio (95% confidence interval were 24.7 (15.0-40.6 for BMI ≥27 kg/m(2; 5.5 (2.9-10.4 for BMI 24-27 kg/m(2; 2.7 (1.3-5.5 for Q5 (top 20th percentile hemoglobin level; and 2.6 (1.6-4.1 for male gender. Further separately fitting the logistic models for two genders, the significance of Q5 hemoglobin level only appeared in the males. CONCLUSIONS: High hemoglobin level is a significant risk factor of ALT elevation after control hepatitis B, obesity and gender. Males have greater risk of abnormal liver function which may be associated with higher hemoglobin levels.

Peroxisomal alanine: glyoxylate aminotransferase AGT1 is indispensable for appressorium function of the rice blast pathogen, Magnaporthe oryzae.

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Vijai Bhadauria

Full Text Available The role of β-oxidation and the glyoxylate cycle in fungal pathogenesis is well documented. However, an ambiguity still remains over their interaction in peroxisomes to facilitate fungal pathogenicity and virulence. In this report, we characterize a gene encoding an alanine, glyoxylate aminotransferase 1 (AGT1 in Magnaporthe oryzae, the causative agent of rice blast disease, and demonstrate that AGT1 is required for pathogenicity of M. oryzae. Targeted deletion of AGT1 resulted in the failure of penetration via appressoria; therefore, mutants lacking the gene were unable to induce blast symptoms on the hosts rice and barley. This penetration failure may be associated with a disruption in lipid mobilization during conidial germination as turgor generation in the appressorium requires mobilization of lipid reserves from the conidium. Analysis of enhanced green fluorescent protein expression using the transcriptional and translational fusion with the AGT1 promoter and open reading frame, respectively, revealed that AGT1 expressed constitutively in all in vitro grown cell types and during in planta colonization, and localized in peroxisomes. Peroxisomal localization was further confirmed by colocalization with red fluorescent protein fused with the peroxisomal targeting signal 1. Surprisingly, conidia produced by the Δagt1 mutant were unable to form appressoria on artificial inductive surfaces, even after prolonged incubation. When supplemented with nicotinamide adenine dinucleotide (NAD(++pyruvate, appressorium formation was restored on an artificial inductive surface. Taken together, our data indicate that AGT1-dependent pyruvate formation by transferring an amino group of alanine to glyoxylate, an intermediate of the glyoxylate cycle is required for lipid mobilization and utilization. This pyruvate can be converted to non-fermentable carbon sources, which may require reoxidation of NADH generated by the β-oxidation of fatty acids to NAD(+ in

Serum alanine aminotransferase levels, hematocrit rate and body weight correlations before and after hemodialysis session

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Edmundo Pessoa Lopes

2009-01-01

Full Text Available PURPOSE: To evaluate alanine aminotransferase levels before and after a hemodialysis session and to correlate these values with the hematocrit rate and weight loss during hemodialysis. PATIENTS AND METHODS: The serum alanine aminotransferase levels, hematocrit rate and body weight were measured and correlated before and after a single hemodialysis session for 146 patients with chronic renal failure. An receiver operating characteristic (ROC curve for the serum alanine aminotransferase levels collected before and after hemodialysis was plotted to identify hepatitis C virus-infected patients. RESULTS: The mean weight loss of the 146 patients during hemodialysis was 5.3% (p < 0.001. The mean alanine aminotransferase levels before and after hemodialysis were 18.8 and 23.9 IU/, respectively, denoting a significant 28.1% increase. An equally significant increase of 16.4% in the hematocrit rate also occurred after hemodialysis. The weight loss was inversely correlated with the rise in both the alanine aminotransferase level (r = 0.3; p < 0.001 and hematocrit rate (r = 0.5; p < 0.001. A direct correlation was found between the rise in alanine aminotransferase levels and the hematocrit during the hemodialysis session (r = 0.4; p < 0.001. Based on the ROC curve, the upper limit of the normal alanine aminotransferase level should be reduced by 40% relative to the upper limit of normal if the blood samples are collected before the hemodialysis session or by 60% if blood samples are collected after the session. CONCLUSION: In the present study, significant elevations in the serum alanine aminotransferase levels and hematocrit rates occurred in parallel to a reduction in body weight after the hemodialysis session. These findings suggest that one of the factors for low alanine aminotransferase levels prior to hemodialysis could be hemodilution in patients with chronic renal failure.

Study on pretreatment of FPS-1 in rats with hepatic ischemia-reperfusion injury.

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Lin, Shiqing; Liu, Kexuan; Wu, Weikang; Chen, Chao; Wang, Zhi; Zhang, Xuanhong

2009-01-01

This study was designed to determine whether FPS-1, the water-soluble polysaccharide isolated from fuzi, protected against hepatic damage in hepatic ischemia-reperfusion injury in rats, and its mechanism. SD rats were subjected to 60 min of hepatic ischemia, followed by 120 min reperfusion. FPS-1 (160 mg/kg/day) was administered orally for 5 days before ischemia-reperfusion injury in treatment group. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) were assayed to evaluate liver functions. Liver samples were taken for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), that catalase (CAT) in liver. Na(+)-K(+)-ATPase and Ca(2+)-ATPase in mitochondria were measured with colorimetry method. Morphological changes were also investigated by using both light microscopy and electron microscopy (EM). In addition, apoptosis and oncosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. Serum AST and ALT levels were elevated in groups exposed to ischemia-reperfusion (p FPS-1 reversed all these biochemical parameters as well as histological alterations, evidently by increased SOD, CAT, reduced MDA and histological scores compared to the model group (p FPS-1 could attenuate the necrotic states by the detection of immunofluorescent flow cytometry analysis. Pretreatment with FPS-1 reduced hepatic ischemia-reperfusion injury through its potent antioxidative effects and attenuation of necrotic states.

Barium chloride induces redox status unbalance, upregulates cytokine genes expression and confers hepatotoxicity in rats-alleviation by pomegranate peel.

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Elwej, Awatef; Grojja, Yousri; Ghorbel, Imen; Boudawara, Ons; Jarraya, Raoudha; Boudawara, Tahia; Zeghal, Najiba

2016-04-01

The present study was performed to establish the therapeutic efficacy of pomegranate peel against barium chloride induced liver injury. Adult rats were divided into four groups of six animals each: group I, serving as controls, received distilled water; group II received by their drinking water 67 ppm of BaCl2; group III received both 67 ppm of BaCl2 by the same way than group II and 5 % of pomegranate peel (PP) via diet; group IV received 5 % of PP. Analysis by HPLC/MS of PP showed its rich composition in flavonoids such as gallic acid, castalin, hyperin, quercitrin, syringic acid, and quercetin. The protective effects of pomegranate peel against hepatotoxicity induced by barium chloride were assessed using biochemical parameters and histological studies. Exposure of rats to barium caused oxidative stress in the liver as evidenced by an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOHs), H2O2 and advanced oxidation protein product (AOPP) levels, and lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities, a decrease in catalase (CAT) and glutathione peroxidase (GPx) activities, glutathion (GSH), non-protein thiol (NPSH), vitamin C levels, and Mn-SOD gene expression. Liver total MT levels, MT-1, and MT-2 and pro-inflammatory cytokine genes expression like TNF-α, IL-1β and IL-6 were increased. Pomegranate peel, supplemented in the diet of barium-treated rats, showed an improvement of all the parameters indicated above.The present work provided ethnopharmacological relevance of pomegranate peel against the toxic effects of barium, suggesting its beneficial role as a potential antioxidant.

Correlation between alanine aminotransferase level, HCV-RNA titer ...

African Journals Online (AJOL)

In contrast, an insignificant correlation was found between ALT level and grade of necroinflammation. In conclusion neither ALT level nor HCV viremia can reflect the histological liver change accurately. As a result, liver biopsy or other noninvasive procedures that measure liver stiffness (i.e., Fibroscan) remain essential for ...

Lingmao Formula Combined with Entecavir for HBeAg-Positive Chronic Hepatitis B Patients with Mildly Elevated Alanine Aminotransferase: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

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Xiao-Jun Zhu

2013-01-01

Full Text Available Objective. To determine the efficacy and safety of Lingmao Formula combined with entecavir for HBeAg-positive chronic hepatitis B patients with mildly elevated alanine aminotransferase (ALT. Methods. 301 patients were randomly assigned to receive Lingmao Formula combined with entecavir (treatment group or placebo combined with entecavir (control group for 52 weeks. The outcomes of interest included the reduction of serum HBV DNA level, HBeAg loss, HBeAg seroconversion, ALT normalization, and histological improvement. Results. The mean decrease of serum HBV DNA level from baseline and the percentage of patients who had reduction in serum HBV DNA level ≥2 lg copies/mL in treatment group were significantly greater than that in control group (5.5 versus 5.4 lg copies/mL, P=0.010; 98.5% versus 92.6%, P=0.019. The percentage of HBeAg loss in treatment group was 22.8%, which was much higher than a percentage of 12.6% in control group (P=0.038. There was no significant difference between the two groups in histological improvement. Safety was similar in the two groups. Conclusions. The combination of Lingmao Formula with entecavir could result in significant decrease of serum HBV DNA and increase of HBeAg loss for HBeAg-positive chronic hepatitis B patients with mildly elevated ALT without any serious adverse events. Clinical trial registration number is ChiCTR-TRC-09000594.

Avaliação hematológica e dosagem bioquímica de ALT, AST e creatinina em elefante-marinho-do-sul, Mirounga leonina (linnaeus, 1758, encontrado no litoral de Salvador, Bahia

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Bruno Lopes Bastos

2006-02-01

Full Text Available Since 1999 the Aquatic Mammals Rescue Center - AMRC has been working in the rescue and rehabilitation of stranded cetaceans and pinnipeds on the coast of Bahia, Brazil. This paper presents and analyses the blood cells count and clinical chemistry of alanine aminotransferase (ALT, aspartate aminotransferase (AST and creatinine of a southern elephant seal, Mirounga leonina (LINNAEUS, 1758, found on February the 11th at Barra Beach, Salvador, BA. The specimen was an orphan male calf, with 137cm of length and estimated weight of 49kg. It presented bad nutritional conditions and a shark bite on the right shoulder area. Clinical management was performed for 56 days, anthelmintic Febendazole was utilized, and the bite was treated with iodined alcohol, Nitrofurazone solution and Kethanserin, simultaneously with Enrofloxacin 10%, Potenay®, Vitamin B Complex and Benerva®. On the 16th the animal presented a right unilateral conjuntivitis, treated with Cloranphenicol oftalmic pomade until the end of its stay in the captive. During this period a total of six blood samples were collected, three for total blood counts and the others for the biochemistry determination of ALT, AST and creatinine. According to the haematological analysis the seal developed an anaemia which was classified as microcytic and normochromic. Lymphopenia, eosinopenia and monocytopenia were also observed, possibly due to its handling and stress conditions. The clinical chemistry presented low values for AST and creatinine, although this did not represent the existence of any pathologic context or disease with clinical significance.

Clinical value of spleen acoustic radiation force impulse, aspartate aminotransferase-to-platelet ratio index, and aspartate aminotransferase/alanine aminotransferase ratio in predicting esophageal varices in patients with liver cirrhosis

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ZHANG Dakun

2018-03-01

Full Text Available ObjectiveTo investigate the spleen stiffness of patients with chronic hepatitis and liver cirrhosis by spleen acoustic radiation force impulse (ARFI, aspartate aminotransferase-to-platelet ratio index (APRI, and aspartate aminotransferase/alanine aminotransferase ratio (AAR, as well as the clinical value of these three noninvasive techniques in predicting esophageal varices (EV in patients with liver cirrhosis. MethodsA total of 247 patients with chronic hepatitis and liver cirrhosis were enrolled, and ARFI was used to measure real-time spleen stiffness. APRI and AAR were calculated. Gastroscopy was performed within one week before and after measurement to clarify the degree of EV. With the results of gastroscopy as the gold standard, the receiver operating characteristic (ROC curve was used to compare the clinical value of spleen ARFI value, APRI, and AAR in the diagnosis of EV in patients with liver cirrhosis. The t-test was used for comparison of continuous data between two groups. ResultsThere were significant differences between the EV group (n=169 and the non-EV group (n=78 in spleen ARFI stiffness (3.64±0.53 m/s vs 2.97±0.65 m/s, t=-7.93, P＜0.001, APRI (0.87±091 vs 0.52±0.80, t=-2.90, P=0.004, and AAR (1.54±0.67 vs 1.29±0.55, t=-2.93, P=0.004. Spleen ARFI, APRI, and AAR had an area under the ROC curve of 0.80, 0.72, and 0.63, respectively, in predicting EV in patients with liver cirrhosis, there was a significant difference between spleen ARFI stiffness and AAR (P=0.005, while there was no significant difference between spleen ARFI stiffness and APRI (P=0.10. ConclusionARFI is a real-time ultrasound elastography technique, and compared with APRI and AAR, spleen stiffness measured by ARFI can predict EV in patients with chronic hepatitis and liver cirrhosis more accurately and noninvasively and thus holds promise for clinical application.

Biocatalytic potential of vanillin aminotransferase from Capsicum chinense

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2014-01-01

Background The conversion of vanillin to vanillylamine is a key step in the biosynthetic route towards capsaicinoids in pungent cultivars of Capsicum sp. The reaction has previously been annotated to be catalysed by PAMT (putative aminotransferase; [GenBank: AAC78480.1, Swiss-Prot: O82521]), however, the enzyme has previously not been biochemically characterised in vitro. Results The biochemical activity of the transaminase was confirmed by direct measurement of the reaction with purified recombinant enzyme. The enzyme accepted pyruvate, and oxaloacetate but not 2-oxoglutarate as co-substrate, which is in accordance with other characterised transaminases from the plant kingdom. The enzyme was also able to convert (S)-1-phenylethylamine into acetophenone with high stereo-selectivity. Additionally, it was shown to be active at a broad pH range. Conclusions We suggest PAMT to be renamed to VAMT (vanillin aminotransferase, abbreviation used in this study) as formation of vanillin from vanillylamine could be demonstrated. Furthermore, due to high stereoselectivity and activity at physiological pH, VAMT is a suitable candidate for biocatalytic transamination in a recombinant whole-cell system. PMID:24712445

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase.

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Young-Il Kim

Full Text Available The role of serum alpha-fetoprotein (AFP levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment.A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4-8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence.The etiology of HCC was related to chronic hepatitis B virus (HBV infection in 562 patients (77.8%, chronic hepatitis C virus (HCV infection in 74 (10.2%, and non-viral cause in 86 (11.9%. There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001 and non-viral causes (p<0.05, and limited only to patients who had normal alanine aminotransferase (ALT levels.Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT.

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

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Park, Joong-Won

2016-01-01

Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

Associated factors and clinical implications of serum aminotransferase elevation in scrub typhus.

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Su, Tung-Hung; Liu, Chun-Jen; Shu, Pei-Yun; Fu, Yang-Hsien; Chang, Chi-Hsien; Jao, Ping; Kao, Jia-Horng

2016-12-01

Timely diagnosis and prompt treatment can reduce the complications of scrub typhus. It is thus important to find easy laboratory tests to help in the diagnosis, especially in patients without eschar at initial presentation. Because serum aminotransferase elevation is common in scrub typhus, its associated factors and clinical implications need further investigations. We conducted a retrospective study in Kinmen, Taiwan, to collect clinically suspected scrub typhus patients notified to Taiwan Centers for Disease Control for confirmation during 2005-2010. Scrub typhus was diagnosed and Orientia tsutsugamushi was genotyped by serological or molecular assays. The laboratory data and clinical information were recorded for analysis. Overall, 344 suspected scrub typhus patients were reported to Taiwan Centers for Disease Control and 288 of them were certified scrub typhus. Scrub typhus patients had significantly more thrombocytopenia, serum aminotransferase elevation (76% vs. 54%, p = 0.001), higher frequency of fever, eschar, and lymphadenopathy, compared with nontyphus patients. Hepatic dysfunction in scrub typhus was associated with older age, longer fever duration, and absence of lymphadenopathy, but seemed to be unrelated to the rickettsial genotypes. Multivariate analysis showed that serum aminotransferase elevation (odds ratio: 3.75; p = 0.003; 95% confidence interval: 1.56-9.01) independently predicted scrub typhus. Furthermore, in suspected scrub typhus patients without eschar, 92% of true typhus patients had serum aminotransferase elevation compared with the nontyphus ones (odds ratio: 6.47; p = 0.028, 95% confidence interval: 1.23-34.11). Hepatic dysfunction in scrub typhus patients is associated with older age, longer fever duration, and absence of lymphadenopathy. Serum aminotransferase elevation can aid in the diagnosis of scrub typhus, especially in suspected patients without eschar. Copyright © 2014. Published by Elsevier B.V.

Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.

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Joanne M Kingsbury

2015-12-01

Full Text Available The conserved target of rapamycin complex 1 (TORC1 integrates nutrient signals to orchestrate cell growth and proliferation. Leucine availability is conveyed to control TORC1 activity via the leu-tRNA synthetase/EGOC-GTPase module in yeast and mammals, but the mechanisms sensing leucine remain only partially understood. We show here that both leucine and its α-ketoacid metabolite, α-ketoisocaproate, effectively activate the yeast TORC1 kinase via both EGOC GTPase-dependent and -independent mechanisms. Leucine and α-ketoisocaproate are interconverted by ubiquitous branched-chain aminotransferases (BCAT, which in yeast are represented by the mitochondrial and cytosolic enzymes Bat1 and Bat2, respectively. BCAT yeast mutants exhibit severely compromised TORC1 activity, which is partially restored by expression of Bat1 active site mutants, implicating both catalytic and structural roles of BCATs in TORC1 control. We find that Bat1 interacts with branched-chain amino acid metabolic enzymes and, in a leucine-dependent fashion, with the tricarboxylic acid (TCA-cycle enzyme aconitase. BCAT mutation perturbed TCA-cycle intermediate levels, consistent with a TCA-cycle block, and resulted in low ATP levels, activation of AMPK, and TORC1 inhibition. We propose the biosynthetic capacity of BCAT and its role in forming multicomplex metabolons connecting branched-chain amino acids and TCA-cycle metabolism governs TCA-cycle flux to activate TORC1 signaling. Because mammalian mitochondrial BCAT is known to form a supramolecular branched-chain α-keto acid dehydrogenase enzyme complex that links leucine metabolism to the TCA-cycle, these findings establish a precedent for understanding TORC1 signaling in mammals.

Enzyme characteristics of aminotransferase FumI of Sphingopyxis sp. MTA144 for deamination of hydrolyzed fumonisin B₁.

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Hartinger, Doris; Schwartz, Heidi; Hametner, Christian; Schatzmayr, Gerd; Haltrich, Dietmar; Moll, Wulf-Dieter

2011-08-01

Fumonisins are carcinogenic mycotoxins that are frequently found as natural contaminants in maize from warm climate regions around the world. The aminotransferase FumI is encoded as part of a gene cluster of Sphingopyxis sp. MTA144, which enables this bacterial strain to degrade fumonisin B(1) and related fumonisins. FumI catalyzes the deamination of the first intermediate of the catabolic pathway, hydrolyzed fumonisin B(1). We used a preparation of purified, His-tagged FumI, produced recombinantly in Escherichia coli in soluble form, for enzyme characterization. The structure of the reaction product was studied by NMR and identified as 2-keto hydrolyzed fumonisin B(1). Pyruvate was found to be the preferred co-substrate and amino group receptor (K (M) = 490 μM at 10 μM hydrolyzed fumonisin B(1)) of FumI, but other α-keto acids were also accepted as co-substrates. Addition of the co-enzyme pyridoxal phosphate to the enzyme preparation enhanced activity, and saturation was already reached at the lowest tested concentration of 10 μM. The enzyme showed activity in the range of pH 6 to 10 with an optimum at pH 8.5, and in the range of 6°C to 50°C with an optimum at 35°C. The aminotransferase worked best at low salt concentration. FumI activity could be recovered after preincubation at pH 4.0 or higher, but not lower. The aminotransferase was denatured after preincubation at 60°C for 1 h, and the residual activity was also reduced after preincubation at lower temperatures. At optimum conditions, the kinetic parameters K (M) = 1.1 μM and k (cat) = 104/min were determined with 5 mM pyruvate as co-substrate. Based on the enzyme characteristics, a technological application of FumI, in combination with the fumonisin carboxylesterase FumD for hydrolysis of fumonisins, for deamination and detoxification of hydrolyzed fumonisins seems possible, if the enzyme properties are considered.

21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alanine amino transferase (ALT/SGPT) test system... Test Systems § 862.1030 Alanine amino transferase (ALT/SGPT) test system. (a) Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended to measure the activity of the...

Effect of ionising radiation and salt of cadmium on the activity enzymes in serum of chickens

International Nuclear Information System (INIS)

Kafka, I.; Danova, D.; Kalenicova, Z.; Toropila, M.

2008-01-01

The present study investigated changes of activities alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of broiler chickens exposed to single of whole-body dose of 3 Gy gamma rays and concentration of cadmium 6 mg · kg -1 live weight. Samples of our experiment was analyse on the 7, 14. and 21 day after irradiation. (authors)

ALT-II armor tile design for upgraded TEXTOR operation

International Nuclear Information System (INIS)

Newberry, B.L.; McGrath, R.T.; Watson, R.D.

1994-01-01

The upgrade of the TEXTOR tokamak at KFA Julich will be completed in the spring of 1994. The upgrade will extend the TEXTOR pulse length from 5 seconds to 10 seconds. The auxiliary heating systems are also scheduled to be upgraded so that eventually a total of 8.0 MW auxiliary heating will be available through a combination of neutral beam injection and radio frequency heating. Originally, the inertially cooled armor tiles on the full toroidal belt Advanced Limiter Test - II (ALT-II) were designed for 5-second operation with a total heating power of 6.0 MW. The upgrade of TEXTOR will increase the energy deposited per pulse onto ALT-II by more than 300%. Consequently, the graphite armor tiles for ALT-II had to be redesigned in order to increase their thermal inertia and, thereby, avoid excessively high graphite armor surface temperatures that would lead to unacceptable contamination of the plasma. The armor tile thermal inertia had been increase primarily by expanding the radial thickness of the tiles from 17 mm to 20 mm. This increase in radial tile dimension will reduce the overall pumping efficiency of the ALT-II pump limiter by about 30%. The final armor tile design was a compromise between increasing the power handling capability and reducing the particle exhaust efficiency of ALT-II. The reduction in exhaust efficiency is unfortunate, but could only be avoided by active cooling of the ALT-II armor tiles. The active cooling option was too complicated and expensive to be considered at this time

Serine:glyoxylate aminotransferase mutant of barley

International Nuclear Information System (INIS)

Blackwell, R.; Murray, A.; Joy, K.; Lea, P.

1987-01-01

A photorespiratory mutant of barley (LaPr 85/84), deficient in both of the major peaks of serine:glyoxylate aminotransferase activity detected in the wild type, also lacks serine:pyruvate and asparagine:glyoxylate aminotransferase activities. Genetic analysis of the mutation demonstrated that these three activities are all carried on the same enzyme. The mutant, when placed in air, accumulated a large pool of serine, showed the expected rate (50%) of ammonia release during photorespiration but produced CO 2 at twice the wild type rate when it was fed [ 14 C] glyoxylate. Compared with the wild type, LaPr 85/84 exhibited abnormal transient changes in chlorophyll a fluorescence when the CO 2 concentration of the air was altered, indicating that the rates of the fluorescence quenching mechanisms were affected in vivo by the lack of this enzyme

Hepatoprotective and Hypolipidemic Effects of Carthamus tinctorius oil in Alloxan-induced Type 1 Diabetic Rats

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Rahimi Parivash

2014-04-01

Full Text Available Introduction: Hepatoprotective and hypolipidemic effects of Carthamus tinctorius Linn.(Safflower seed oil was investigated in diabetic rats. Methods: Diabetes was induced by administration of 120 mg/kg alloxan monohydrate. The seed oil of safflower at dose of 200 mg/kg was administered as single dose per day to diabetic rats for a period of 28 days. The effect of oil on blood glucose level was measured in the diabetic rats. Serum lipid profile [total cholesterol (TC, triglycerides (TGs, low density (LDL and high density lipoprotein (HDL and enzymes such as alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP were also determined. Results: Levels of blood glucose, TC, TGs, LDL, ALT, AST and ALP decreased and HDL increased in alloxan induced diabetic rats after treatment with 200 mg/kg safflower seed oil for 28 days. Conclusion: The present study demonstrates that seed oil of safflower seems to be useful for the prevention of diabetes complications.

Análise sérica das enzimas aspartato aminotransferase, alanina aminotransferase e gama glutamiltranspeptidase de coelhos adultos tratados com extrato bruto de própolis

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J. N. Ribeiro

2009-01-01

Full Text Available

Diversos trabalhos têm atribuído a própolis inúmeras propriedades farmacológicas, dentre elas podemos citar, como exemplo, efeitos antibacteriano, antiviral, antiinflamatório, regenerador do tecido cartilaginoso, inibidor da formação de radicais livres e redutor de níveis sangüíneo de glicose e triacilglicerol. Alguns efeitos colaterais são atribuídos à própolis principalmente em doses elevadas. Muitos efeitos tóxicos da própolis são atribuídos ao álcool etílico presente no extrato.Dentre alguns efeitos tóxicos citados em literatura como realmente da própolis temos a dermatite e o aumento da uréia sangüínea. O presente estudo teve como objetivo investigar se o extrato bruto de própolis ocasiona algum efeito adverso nos níveis séricos de alanina aminotransferase, aspartato aminotransferase e gama – glutamiltranspeptidase de coelhos saudáveis. O experimento teve 30 dias de duração, sendo as dosagens dos constituintes do sangue (alanina aminotransferase, aspartato aminotransferase e gama – glutamiltranspeptidase realizadas a 0, 15 e 30 dias. Os resultados indicaram que, de o extrato bruto de própolis na forma testadea, não ocasionou alteração relevante nos níveis séricos das enzimas marcadoras de metabolismo hepático. Palavras-chave: Própolis, alanina aminotransferase, aspartato aminotransferase, gama glutamiltranpeptidase, toxicologia.

Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes.

Science.gov (United States)

Spraggs, C F; Parham, L R; Briley, L P; Warren, L; Williams, L S; Fraser, D J; Jiang, Z; Aziz, Z; Ahmed, S; Demetriou, G; Mehta, A; Jackson, N; Byrne, J; Andersson, M; Toi, M; Harris, L; Gralow, J; Zujewski, J A; Crescenzo, R; Armour, A; Perez, E; Piccart, M

2017-08-08

HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10 -26 , n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers. A higher ALT case incidence plus weaker HLA association observed during concurrent administration of lapatinib and taxane suggested a subset of liver injury in this combination group that was HLA-DRB1*07:01 independent. Furthermore, the incidence of ALT elevation demonstrated an expected correlation with geographic HLA-DRB1*07:01 carriage frequency. Robust ALT elevation risk estimates for HLA-DRB1*07:01 may support causality discrimination and safety risk management during the use of lapatinib combination therapy for the treatment of metastatic breast cancer.The Pharmacogenomics Journal advance online publication, 8 August 2017; doi:10.1038/tpj.2017.39.

Modification of nanocellulose by poly-lysine can inhibit the effect of fumonisin B1 on mouse liver cells.

Science.gov (United States)

Jebali, Ali; Yasini Ardakani, Seyed Ali; Shahdadi, Hossein; Balal Zadeh, Mohammad Hossein; Hekmatimoghaddam, Seyedhossein

2015-02-01

Fumonisin B1 is an important mycotoxin, mainly produced by Fusarium verticillioides. It has toxic effects on liver, brain, and kidney cells. The first aim of this study was to synthesize nanocellulose modified with poly-lysine (NMPL), and the second aim was to evaluate the adsorption of fumonisin B1 by NMPL. As third aim, the function of mouse liver cells was investigated after exposure to fumonisin B1, and fumonisin B1+ NMPL. In this study, NMPL was prepared using cross-linker, and then incubated with fumonisin B1 at controlled conditions. After incubation, the adsorption and release of fumonisin B1 were evaluated in each condition. Next, mouse liver cells were separately exposed to fumonisin B1, NMPL, and (fumonisin B1+NMPL). Then, the level of aniline aminotransferase (ALT) and aspartate aminotransferase (AST) was evaluated. It was found that both adsorption and release of fumonisin B1 were not affected by temperature and incubation time, but affected by pH and concentration of NMPL. Also, this study showed NMPL could adsorb fumonisin B1 in different foodstuffs. Importantly, although the levels of ALT and AST were increased when the cells were treated with fumonisin B1 alone, they were not affected when exposed to NMPL or (fumonisin B1+NMPL). The authors suggest that NMPL is a good adsorbent to remove and inhibit fumonisin B1. Copyright © 2015 Elsevier B.V. All rights reserved.

Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway

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Qiong-Hui Huang

2017-01-01

Full Text Available Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH in the serum, suppressed the malonaldehyde (MDA and triglyceride (TG content and the production of reactive oxygen species (ROS, and enhanced the activities of superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, andalcohol dehydrogenase (ADH, and aldehyde dehydrogenase (ALDH, paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1 and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2 and its target gene haem oxygenase-1 (HO-1. Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6 via downregulating toll-like receptor 4 (TLR4 and nuclear factor kappa B (NF-κB p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium.

Science.gov (United States)

Hossen, Muhammad Jahangir; Kim, Mi-Yeon; Cho, Jae Youl

2016-01-01

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

Effects of fumonisin B1 on selected biological responses and performance of broiler chickens

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Ricardo H. Rauber

2013-09-01

Full Text Available The objective of this study was to determine the effects of three doses of fumonisin B1 (0, 100, and 200mg/kg of feed on biological variables (relative weight of liver [RWL], total plasma protein [TPP], albumin [Alb], calcium [Ca], phosphorus [P], uric acid [UA], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma glutamyltransferase [GGT], alkaline phosphatase [AP], total cholesterol [Chol], triglycerides [Tri], sphinganine-to-sphingosine ratio [SA:SO], and C-reactive protein [CRP], morphological evaluation of the small intestine (villus height [VH], crypt depth [CD], and villus-to-crypt ratio [V:C], histological evaluation, and on performance (body weight [BW], feed intake [FI], and feed conversion rate [FCR] of broiler chickens. Significant effects of FB were observed on BW and FI (reduced, on RWL, TPP, Ca, ALT, AST, GGT, Chol, and Tri (increased at both 14 and 28 days evaluations. In addition, significant increase was observed on FCR, Alb, P, SA:SO, and CRP and significant reduction in UA, VH, and V:C only at the 28 days evaluation. Significant histological lesions were observed on liver and kidney of FB inoculated broilers at 14 and 28 days. Those results show that FB has a significant effect on biological and histological variables and on performance of broiler chickens.

Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

Science.gov (United States)

Shirpoor, Alireza; Heshmati, Elaheh; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini; Chodari, Leila; Naderi, Roya; Majd, Farideh Nezami; Samadi, Mahrokh

2018-05-28

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

General Time-Division AltBOC Modulation Technique for GNSS Signals

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Z. Zhou

2018-04-01

Full Text Available In this paper, a general time-division alternate binary offset carrier (GTD-AltBOC modulation method is proposed, which is an extension of TD-AltBOC and time-multiplexed offset-carrier quadrature phase shift keying (TMOC-QPSK with high design flexibility. In this method, binary complex subcarriers and a time-division technique with flexible time slot assignment are used to achieve constant envelope modulation of the signal components with a variable power allocation ratio (PAR. The underlying principle of GTD-AltBOC and the constraints related to the PAR are investigated. For the generation of GTD-AltBOC signals, a lookup table (LUT-based scheme is presented; the minimum required clock rate is half or less of that for existing non-time-division methods. The receiver processing complexities are analyzed for three typical receiving modes, and the power spectral densities (PSDs, cross-correlation functions, multiplexing efficiencies and code-tracking performance are simulated; the results show that GTD-AltBOC enables a significant decrease in receiving complexity compared with existing methods while maintaining high performance in terms of multiplexing efficiency and code tracking.

Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair.

Science.gov (United States)

Chatterjee, Nimrat; Lin, Yunfu; Yotnda, Patricia; Wilson, John H

2016-07-31

Multiple pathways modulate the dynamic mutability of trinucleotide repeats (TNRs), which are implicated in neurodegenerative disease and evolution. Recently, we reported that environmental stresses induce TNR mutagenesis via stress responses and rereplication, with more than 50% of mutants carrying deletions or insertions-molecular signatures of DNA double-strand break repair. We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and NHEJ, which have no effect. Thus, alt-NHEJ, which contributes to genetic mutability in cancer cells, also plays a novel role in environmental stress-induced TNR mutagenesis. Published by Elsevier Ltd.

Editorial ALT-J non-electronica

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Gabriel Jacobs

1997-12-01

Full Text Available The ALT Executive Committee has discussed on a number of occasions the question of making ALT-J wholly available in electronic form on our Web site (at present only the editorial and abstracts of papers appear, and even of turning it into a full-blown electronic journal. I have gently but consistently opposed this move, on occasions to the intense irritation of some of my fellow members, and always at the risk of appearing to be a Luddite. Explicitly ('Who, if not we as learning technologists, should be in the forefront of the soon-to-happen electronic-journal revolution?' and implicitly ('It is estimated that within two years, paper-based journals will be considered the dinosaurs of the academic world', I have increasingly come under pressure to accede to an apparently unstoppable, apparently imminent change in the method and form of scholarly publication. I set out here my reasons for my continued resistance.

Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular injury in mice.

Science.gov (United States)

Oarada, Motoko; Tsuzuki, Tsuyoshi; Nikawa, Takeshi; Kohno, Shohei; Hirasaka, Katsuya; Gonoi, Tohru

2012-05-01

Elucidating the effects of refeeding a high-protein diet after fasting on disease development is of interest in relation to excessive protein ingestion and irregular eating habits in developed countries. The objective of the present study was to address the hepatic effects of refeeding a high-protein diet after fasting. Mice were fasted for 48 h and then refed with a test diet containing 3, 15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and liver immediate-early gene expression levels were sequentially measured for the first 24 h after initiation of refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid (within 2-3 h) and abnormal elevation in serum ALT (P = 0·006) and AST (P = 0·001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ) osteosarcoma oncogene (P = 0·007) and nuclear receptor subfamily 4, group A, member 1 (P = 0·002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 % casein diets produced no substantial increases in serum ALT and AST activities in mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly increased. We conclude from these data that the consumption of a high-protein diet after fasting causes acute hepatocellular injury in healthy animals, and propose that careful attention should be paid to the use of such diets.

Sensitive non-radioactive determination of aminotransferase stereospecificity for C-4' hydrogen transfer on the coenzyme.

Science.gov (United States)

Jomrit, Juntratip; Summpunn, Pijug; Meevootisom, Vithaya; Wiyakrutta, Suthep

2011-02-25

A sensitive non-radioactive method for determination of the stereospecificity of the C-4' hydrogen transfer on the coenzymes (pyridoxal phosphate, PLP; and pyridoxamine phosphate, PMP) of aminotransferases has been developed. Aminotransferase of unknown stereospecificity in its PLP form was incubated in (2)H(2)O with a substrate amino acid resulted in PMP labeled with deuterium at C-4' in the pro-S or pro-R configuration according to the stereospecificity of the aminotransferase tested. The [4'-(2)H]PMP was isolated from the enzyme protein and divided into two portions. The first portion was incubated in aqueous buffer with apo-aspartate aminotransferase (a reference si-face specific enzyme), and the other was incubated with apo-branched-chain amino acid aminotransferase (a reference re-face specific enzyme) in the presence of a substrate 2-oxo acid. The (2)H at C-4' is retained with the PLP if the aminotransferase in question transfers C-4' hydrogen on the opposite face of the coenzyme compared with the reference aminotransferase, but the (2)H is removed if the test and reference aminotransferases catalyze hydrogen transfer on the same face. PLP formed in the final reactions was analyzed by LC-MS/MS for the presence or absence of (2)H. The method was highly sensitive that for the aminotransferase with ca. 50 kDa subunit molecular weight, only 2mg of the enzyme was sufficient for the whole test. With this method, the use of radioactive substances could be avoided without compromising the sensitivity of the assay. Copyright © 2011 Elsevier Inc. All rights reserved.

Ethylene and 1-MCP regulate major volatile biosynthetic pathways in apple fruit.

Science.gov (United States)

Yang, Xiaotang; Song, Jun; Du, Lina; Forney, Charles; Campbell-Palmer, Leslie; Fillmore, Sherry; Wismer, Paul; Zhang, Zhaoqi

2016-03-01

The effects of ethylene and 1-methylcyclopropene (1-MCP) on apple fruit volatile biosynthesis and gene expression were investigated. Statistical analysis identified 17 genes that changed significantly in response to ethylene and 1-MCP treatments. Genes encoding branched-chain amino acid aminotransferase (BCAT), aromatic amino acid aminotransferase (ArAT) and amino acid decarboxylases (AADC) were up-regulated during ripening and further enhanced by ethylene treatment. Genes related to fatty acid synthesis and metabolism, including acyl-carrier-proteins (ACPs), malonyl-CoA:ACP transacylase (MCAT), acyl-ACP-desaturase (ACPD), lipoxygenase (LOX), hydroperoxide lyase (HPL), alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC2), β-oxidation, acyl-CoA synthetase (ACS), enoyl-CoA hydratase (ECHD), acyl-CoA dehydrogenase (ACAD), and alcohol acyltransferases (AATs) also increased during ripening and in response to ethylene treatment. Allene oxide synthase (AOS), alcohol dehydrogenase 1 (ADH1), 3-ketoacyl-CoA thiolase and branched-chain amino acid aminotransferase 2 (BCAT2) decreased in ethylene-treated fruit. Treatment with 1-MCP and ethylene generally produced opposite effects on related genes, which provides evidence that regulation of these genes is ethylene dependent. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Increased liver alkaline phosphatase and aminotransferase ...

African Journals Online (AJOL)

The effect of daily, oral administration of ethanolic extract of Khaya senegalensis stem bark (2mg/kg body weight) for 18days on the alkaline phosphatase, aspartate and alanine aminotransferase activities of rat liver and serum were investigated. Compared with the control, the activities of liver alkaline phosphatase (ALP), ...

Langmuir probe measurements in the TEXTOR tokamak during ALT-I pump limiter experiments

International Nuclear Information System (INIS)

Goebel, D.M.; Campbell, G.A.; Conn, R.W.; Leung, W.K.; Dippel, K.H.; Finken, K.H.; Thomas, G.J.; Pontau, A.E.

1986-04-01

Langmuir probes have been used to characterize the edge plasma of the TEXTOR tokamak and measure the parameters of the plasma incident on the ALT-I pump limiter during ohmic and ICRH heating. Probes mounted directly on the ALT limiter, and a scanning probe located 90 0 toroidally from the limiter, provide data for the evaluation of pump limiter performance and its effect on the edge plasma. The edge plasma is characterized by density and flux e-folding lengths of about 1.8cm when ALT is the main limiter. These scrape-off lengths do not vary significantly as ALT is moved between the normal 42-46cm minor radii, but increase to over 2.2cm when ALT is inserted to 40cm. The flux to probes at a fixed position in the limiter shadow varies by less than 25% for core density changes of a factor of five. This suggests that the global particle confinement time tau/sub p/, scales as the core density. Estimates from the probes indicate that tau/sub p/ is on the order of the energy confinement time, tau/sub E/. The edge electron temperature, T/sub e/, typically decreases by a factor of two when the core density is raised from 1 to 4 x 10 13 cm -3 . The T/sub e/ profile is essentially flat in the limiter shadow, with values of 10-25 eV depending on the core plasma density and ICRH power. ICRH heating increases the electron temperature and flux in proportion to the coupled power. With ALT as the primary limiter and no direct shadowing, the ion side receives 2 to 3 times the flux of the electron side during both ohmic and ICRH heating. The edge plasma is not directly modified by pump limiter operation, but changes with the core plasma density as particle removal lowers the recycling of neutrals in the boundary

Kynurenine aminotransferase III and glutamine transaminase L are identical enzymes that have cysteine S-conjugate β-lyase activity and can transaminate L-selenomethionine.

Science.gov (United States)

Pinto, John T; Krasnikov, Boris F; Alcutt, Steven; Jones, Melanie E; Dorai, Thambi; Villar, Maria T; Artigues, Antonio; Li, Jianyong; Cooper, Arthur J L

2014-11-07

Three of the four kynurenine aminotransferases (KAT I, II, and IV) that synthesize kynurenic acid, a neuromodulator, are identical to glutamine transaminase K (GTK), α-aminoadipate aminotransferase, and mitochondrial aspartate aminotransferase, respectively. GTK/KAT I and aspartate aminotransferase/KAT IV possess cysteine S-conjugate β-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome data banks as CCBL1 (cysteine conjugate beta-lyase 1). Also listed, despite the fact that no β-lyase activity has been assigned to the encoded protein in the genome data bank, is a CCBL2 (synonym KAT III). We show that human KAT III/CCBL2 possesses cysteine S-conjugate β-lyase activity, as does mouse KAT II. Thus, depending on the nature of the substrate, all four KATs possess cysteine S-conjugate β-lyase activity. These present studies show that KAT III and glutamine transaminase L are identical enzymes. This report also shows that KAT I, II, and III differ in their ability to transaminate methyl-L-selenocysteine (MSC) and L-selenomethionine (SM) to β-methylselenopyruvate (MSP) and α-ketomethylselenobutyrate, respectively. Previous studies have identified these seleno-α-keto acids as potent histone deacetylase inhibitors. Methylselenol (CH3SeH), also purported to have chemopreventive properties, is the γ-elimination product of SM and the β-elimination product of MSC catalyzed by cystathionine γ-lyase (γ-cystathionase). KAT I, II, and III, in part, can catalyze β-elimination reactions with MSC generating CH3SeH. Thus, the anticancer efficacy of MSC and SM will depend, in part, on the endogenous expression of various KAT enzymes and cystathionine γ-lyase present in target tissue coupled with the ability of cells to synthesize in situ either CH3SeH and/or seleno-keto acid metabolites. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Preliminary design analysis of the ALT-II limiter for TEXTOR

International Nuclear Information System (INIS)

Koski, J.A.; Boyd, R.D.; Kempka, S.M.; Romig, A.D. Jr.; Smith, M.F.; Watson, R.D.; Whitley, J.B.; Conn, R.W.; Grotz, S.P.

1983-01-01

Installation of a large toroidal belt pump limiter, Advanced Limiter Test II (ALT-II), on the TEXTOR tokamak at Juelich, FRG is anticipated for early 1986. This paper discusses the preliminary mechanical design and materials considerations undertaken as part of the feasibility study phase for ALT-II

Effects of lixisenatide on elevated liver transaminases

DEFF Research Database (Denmark)

Gluud, Lise L; Knop, Filip K; Vilsbøll, Tina

2014-01-01

) on lixisenatide versus placebo or active comparators for type 2 diabetes were included. PARTICIPANTS: Individual patient data were retrieved to calculate outcomes for patients with elevated liver blood tests. MAIN OUTCOME MEASURES: Normalisation of alanine aminotransferase (ALT) and aspartate aminotransferase......OBJECTIVE: To evaluate the effects of the glucagon-like peptide-1 receptor agonist lixisenatide on elevated liver blood tests in patients with type 2 diabetes. DESIGN: Systematic review. DATA SOURCES: Electronic and manual searches were combined. STUDY SELECTION: Randomised controlled trials (RCTs...... the proportion of obese or overweight patients with type 2 diabetes who achieve normalisation of ALT. Additional research is needed to determine if the findings translate to clinical outcome measures. TRIAL REGISTRATION NUMBER: PROSPERO; CRD42013005779....

ALT-II armor tile design for upgraded TEXTOR operation

International Nuclear Information System (INIS)

Newberry, B.L.; McGrath, R.T.; Watson, R.D.; Kohlhaas, W.; Finken, K.H.

1994-01-01

The upgrade of the TEXTOR tokamak at KFA Juelich was recently completed. This upgrade extended the TEXTOR pulse length from 5 seconds to 10 seconds. The auxiliary heating was increased to a total of 8.0 MW through a combination of neutral beam injection and radio frequency heating. Originally, the inertially cooled armor tiles of the full toroidal belt Advanced Limiter Test -- II (ALT-II) were designed for a 5-second operation with total heating of 6.0 MW. The upgrade of TEXTOR will increase the energy deposited per pulse onto the ALT-II by about 300%. Consequently, the graphite armor tiles for the ALT-II had to be redesigned to avoid excessively high graphite armor surface temperatures that would lead to unacceptable contamination of the plasma. This redesign took the form of two major changes in the ALT-II armor tile geometry. The first design change was an increase of the armor tile thermal mass, primarily by increasing the radial thickness of each tile from 17 mm to 20 mm. This increase in the radial tile dimension reduces the overall pumping efficiency of the ALT-II pump limiter by about 30%. The reduction in exhaust efficiency is unfortunate, but could be avoided only by active cooling of the ALT-II armor tiles. The active cooling option was too complicated and expensive to be considered at this time. The second design change involved redefining the plasma facing surface of each armor tile in order to fully utilize the entire surface area. The incident charged particle heat flux was distributed uniformly over the armor tile surfaces by carefully matching the radial, poloidal and toroidal curvature of each tile to the plasma flow in the TEXTOR boundary layer. This geometry redefinition complicates the manufacturing of the armor tiles, but results in significant thermal performance gains. In addition to these geometry upgrades, several material options were analyzed and evaluated

GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

Energy Technology Data Exchange (ETDEWEB)

Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

2011-04-01

Highlights: {yields}We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. {yields} Deletion of the UGA1 or GAD1 genes extends replicative lifespan. {yields} Addition of GABA to wild-type cultures has no effect on lifespan. {yields} Intracellular GABA levels do not differ in longevity mutants and wild-type cells. {yields} Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for {gamma}-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The {Delta}uga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for {Delta}uga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of {sup 1}H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan

GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

International Nuclear Information System (INIS)

Kamei, Yuka; Tamura, Takayuki; Yoshida, Ryo; Ohta, Shinji; Fukusaki, Eiichiro; Mukai, Yukio

2011-01-01

Highlights: →We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. → Deletion of the UGA1 or GAD1 genes extends replicative lifespan. → Addition of GABA to wild-type cultures has no effect on lifespan. → Intracellular GABA levels do not differ in longevity mutants and wild-type cells. → Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for γ-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The Δuga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for Δuga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of 1 H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan extension. These results strongly suggest

Developing an Alternanthera mosaic virus vector for efficient clonging of Whitefly cDNA RNAi to screen gene function

Science.gov (United States)

Alternanthera mosaic virus (AltMV; genus Potexvirus) is distinguished from the type member of the genus, Potato virus X by features of viral movement and variation within triple gene block protein 1 (TGB1). AltMV TGB1 variants TGB1L88 and TGB1P88 confer strong and weak silencing suppression, respect...

The effect of isotretinoin on triglycerides and liver aminotransferases Influência da isotretinoína nas transaminases hepáticas e triglicerídeos

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Andreia Salezze Vieira

2012-06-01

Full Text Available BACKGROUND: Isotretinoin has been used to treat the most severe cases of acne; however, it may provoke adverse events in mucocutaneous and hepatic tissues, lead to alterations in lipid levels and cause teratogenicity. OBJECTIVE: The objective of this study was to evaluate the profile of changes in alanine aminotransferase (ALT, aspartate aminotransferase (AST and triglyceride levels in patients who had been treated with oral isotretinoin dispensed by the São Mateus/ES pharmacy for special drugs. METHODS: A retrospective, observational, longitudinal study was conducted by carrying out a secondary analysis of each patient's data. RESULTS: Of the 130 patients who received isotretinoin between January and December 2009, only 70 were actually treated for 3 months or more and handed in the results of their laboratory tests. Of these 70 patients, 39 (55.7% were female. The mean age of the women (23.9 years was higher than the mean age of the men (20.1 years. There was a statistically significant increase in the levels of triglycerides (87.01 ± 48.25 versus 105.32 ± 48.76 mg/dL, AST (20.44 ± 6.26 versus 24.38 ± 11.92 U/L and ALT (18.24 ± 8.31 versus 23.34 ± 20.03 U/L performed prior to and 3 months or more after oral isotretinoin treatment. After treatment with oral isotretinoin, triglyceride levels had increased beyond the normal range in 11% of the patients, while 8.6% had elevated AST levels and 7.3% had increased ALT levels. CONCLUSION: The results in this population show that the use of oral isotretinoin for the treatment of acne may result in altered triglyceride, AST and ALT levels. These findings are in accordance with data published previously in the scientific literature, confirming the need to monitor these patients.FUNDAMENTOS: A isotretinoína tem sido usada no tratamento dos casos mais graves de acne, embora possa induzir reações adversas nos tecidos mucocutâneos e hepáticos, alterações nos níveis lipídicos e

Preoperative Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Perioperative Liver-Related Complications Following Liver Resection for Colorectal Cancer Metastases

DEFF Research Database (Denmark)

Amptoulach, S.; Gross, G.; Sturesson, C.

2017-01-01

-related). In multivariate regression analysis, the aspartate aminotransferase-to-platelet ratio index was independently associated with liver-related complications (odds ratio: 1.149, p = 0.003) and perioperative liver failure (odds ratio: 1.155, p = 0.012). The latter was also true in the subcohort of patients......Background and Aims: There are limited data on the potential role of preoperative non-invasive markers, specifically the aspartate-to-alanine aminotransferase ratio and the aspartate aminotransferase-to-platelet ratio index, in predicting perioperative liver-related complications after hepatectomy...... collected from medical records. The nontumorous liver parenchyma in the surgical specimens of 31 patients was re-evaluated. Results: Overall, 215 patients were included. In total, 40% underwent neoadjuvant chemotherapy and 47% major resection, while 47% had perioperative complications (6% liver...

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

Science.gov (United States)

Chen, Shuhua; Hoffman, Rosemary A; Scott, Melanie; Manson, Joanna; Loughran, Patricia; Ramadan, Mostafa; Demetris, Anthony J; Billiar, Timothy R

2017-07-01

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1 + cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1 + cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1 + cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1 + cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut. © Society for Leukocyte Biology.

Antidiabetic and Hypolipidemic Activities of Curculigo latifolia Fruit:Root Extract in High Fat Fed Diet and Low Dose STZ Induced Diabetic Rats

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Nur Akmal Ishak

2013-01-01

Full Text Available Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD and 40 mg streptozotocin (STZ induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT, gamma glutamyltransferase (GGT, urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P<0.05 increase in body weight, high density lipoprotein (HDL, insulin, and adiponectin levels and decreased glucose, total cholesterol (TC, triglycerides (TG, low density lipoprotein (LDL, urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPARα, PPARγ, AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.

Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

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He Peiyuan

2017-01-01

Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

Alte Harfe. Vollständige Sammlung alter estnischer Volkslieder : Vorrede / Jakob Hurt

Index Scriptorium Estoniae

Hurt, Jakob, 1839-1907

2005-01-01

Eessõna rmt. : Hurt, Jakob. Vana kannel. 1. kogu : täieline kogu vanu eesti rahvalaulusid = Alte Harfe : vollständige Sammlung alter estnischen Volkslieder. Tartu, 1875-1886. - (Eesti Kirjameeste Seltsi toimetised ; 3)

Clinico-biochemical factors to early predict biliary etiology of acute pancreatitis: age, female gender, and ALT.

Science.gov (United States)

Zarnescu, N O; Costea, R; Zarnescu Vasiliu, E C; Neagu, S

2015-01-01

Background/ Aims: Despite the existence of an easy tool to diagnose biliary tract disease as an etiology for acute pancreatitis (AP), the sensitivity of abdominal ultrasound is around 80%, which can be even lower in certain conditions. We have retrospectively reviewed data of 146 patients admitted for acute pancreatitis between 1999 and 2013. Bivariate analysis for clinical and biochemical variables was performed with respect to etiology of AP (biliary versus non-biliary). Multivariate analysis was performed by using binary logistic regression. There were 87 males (59.6%) and 59 females (40.4%), with a median age of 51. The etiology of acute pancreatitis was biliary in 71 patients (48.6%). Bivariate analysis found the following as significant association (p=0.001) with biliary pancreatitis: older age, female gender, and elevated AST, ALT. A binary logistic regression analysis identified as predictor factors for biliary etiology of acute pancreatitis: age OR = 1.031 (95% CI 1.004 - 1.059, p = 0.024), sex (female) OR = 2.34 (95% CI 1.022 - 5.359, p = 0.044) and ALT OR = 1.004 (95% CI 1.001 - 1.007, p =0.004). The two clinical scores included the three variables (A.S.ALT scores) in categorical format were generated and then checked with the ROC curves (areas under curve are 0.768 and 0.778). Age, female gender, and elevated ALT can help identifying cases with biliary etiology of acute pancreatitis.

Body weight changes, haematological and serum biochemical ...

African Journals Online (AJOL)

Daily weight gain, feed conversion ratio, platelet, lymphocytes, neutrophil, cholesterol, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline Phosphatase (ALP) values of the rams fed ammonium sulphate fortified diets were significantly (p<0.05) higher than the control. Haemoglobin concentration ...

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

Science.gov (United States)

2012-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. Methods Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. Results Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. Conclusions These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver. PMID:22569330

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

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Zhang Bei

2012-05-01

Full Text Available Abstract Background Nonalcoholic fatty liver disease (NAFLD is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC extracted from Acaudina molpadioides in fatty liver rats. Methods Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT and aspartate aminotransferase (AST activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. Results Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS, malic enzyme (ME and glucose-6-phosphatedehydrogenase (G6PDH were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP activity was observed in SCC-feeding rats. Conclusions These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.

Rescue excavations on Alt-Laari settlement site, Tartumaa / Anti Lillak, Heiki Valk

Index Scriptorium Estoniae

Lillak, Anti

2009-01-01

Alt-Laari linnusasula tekkis nähtavasti rooma rauaajal. Kui Alt-Laari linnus oli kasutused arvatavasti I aastatuhandest II aastatuhandeni pKr. siis asula kestis edasi keskajal ning jäeti maha hiljemalt 14. sajandil

Sarcopenia is a risk factor for elevated aminotransferase in men independently of body mass index, dietary habits, and physical activity.

Science.gov (United States)

Yoo, Ki Deok; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon

2015-04-01

Aminotransferase activity is a surrogate marker of liver injury showing strong correlations with obesity and metabolic syndrome. However, elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic patients in clinical practice. To examine the relationship between sarcopenia and aminotransferase activity in a large population-based cohort. Data from the Korean National Health and Nutrition Examinations were used. A total of 13,431 subjects were included. A whole-body dual X-ray absorptiometry scan was performed on each patient to measure total and regional muscle mass. Appendicular skeletal muscle mass indices were also obtained. The prevalence of sarcopenia was significantly higher in the group with elevated aminotransferase levels than in the normal liver enzyme group (males: 26.5% vs. 16.9%; females: 38.3% vs. 22.1%, plevels. The frequency of elevated aminotransferase increased in male patients with sarcopenia after adjusting for potential confounding factors including age, body mass index, fasting glucose level, dietary, and exercise habits. However, the correlation was no longer observed in women after adjusting for body mass index. Sarcopenia is a risk factor for elevated aminotransferase in men, independently of body mass index, dietary habits, and physical activity. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Identification of (R)-selective ω-aminotransferases by exploring evolutionary sequence space.

Science.gov (United States)

Kim, Eun-Mi; Park, Joon Ho; Kim, Byung-Gee; Seo, Joo-Hyun

2018-03-01

Several (R)-selective ω-aminotransferases (R-ωATs) have been reported. The existence of additional R-ωATs having different sequence characteristics from previous ones is highly expected. In addition, it is generally accepted that R-ωATs are variants of aminotransferase group III. Based on these backgrounds, sequences in RefSeq database were scored using family profiles of branched-chain amino acid aminotransferase (BCAT) and d-alanine aminotransferase (DAT) to predict and identify putative R-ωATs. Sequences with two profile analysis scores were plotted on two-dimensional score space. Candidates with relatively similar scores in both BCAT and DAT profiles (i.e., profile analysis score using BCAT profile was similar to profile analysis score using DAT profile) were selected. Experimental results for selected candidates showed that putative R-ωATs from Saccharopolyspora erythraea (R-ωAT_Sery), Bacillus cellulosilyticus (R-ωAT_Bcel), and Bacillus thuringiensis (R-ωAT_Bthu) had R-ωAT activity. Additional experiments revealed that R-ωAT_Sery also possessed DAT activity while R-ωAT_Bcel and R-ωAT_Bthu had BCAT activity. Selecting putative R-ωATs from regions with similar profile analysis scores identified potential R-ωATs. Therefore, R-ωATs could be efficiently identified by using simple family profile analysis and exploring evolutionary sequence space. Copyright © 2017 Elsevier Inc. All rights reserved.

Ornithine aminotransferase deficiency: Diagnostic difficulties in neonatal presentation

NARCIS (Netherlands)

Cleary, M. A.; Dorland, L.; de Koning, T. J.; Poll-The, B. T.; Duran, M.; Mandell, R.; Shih, V. E.; Berger, R.; Olpin, S. E.; Besley, G. T. N.

2005-01-01

We describe two unrelated cases of ornithine aminotransferase (OAT) deficiency with rare neonatal presentation of hyperammonaemia. The diagnosis in the neonatal presentation of OAT deficiency is hampered as hyperornithinaemia is absent. Enzyme and mutation studies confirmed the diagnosis. OAT

Assessment the effect of N Acetyl Cysteine on liver function test in patient with elective Coronary Artery Bypass Grafting with cardiopulmonary bypass

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Mohammad Fathi

2016-07-01

Full Text Available Background: Liver ischemic insults are important sources of liver injuries leading to production of reactive oxygen species (ROS and mediating liver cell injury. Glutathione mediated mechanisms are among the most important defense mechanisms of the liver; N-acetylcysteine (NAC provides cysteine for glutathione defense mechanisms. Patients undergoing cardiac surgery are at increased risk of liver ischemia. This study was performed to assess the role of NAC in prevention of liver ischemia.Materials and Methods: In a double blind, randomized clinical trial, 90 patients entered the study in two groups (45 in each. Patients in the NAC group received 150 mg/Kg NAC after induction of anesthesia and the other group, the same volume of placebo. Serum levels of aspartate aminotransferase (AST, Alanine aminotransferase (ALT and bilirubin were checked before and after the surgery. ANOVA was used for data analysis and p value less than 0.05 was considered statistically significant.Results: No difference between the two groups regarding basic variables; however, the postoperative values of AST and ALT were lower in the NAC group with statistically significant difference. Also, postoperative levels of total bilirubin were lower in the NAC group compared with the control group; a statistically significant difference.Conclusion: Patients undergoing CABG are advised to receive prophylactic 150 mg/Kg NAC to improve their postoperative levels of AST, ALT and bilirubin.Keywords: glutathione antioxidant mechanism, N-acetylcysteine; Aspartate aminotransferase (AST, Alanine aminotransferase (ALT, bilirubin, liver ischemia.

Biochemical assessement of liver enzymes in immunocompromised ...

African Journals Online (AJOL)

Aim: This study aims at the estimation of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and glutmyltransferase GGT (Liver enzymes) in Human immunodeficiency virus(HIV) and/or Acquired immune deficiency syndrome(AIDS) patients in parts of Edo State, Nigeria.

Evaluation of liver marker enzymes and biochemical indices of ...

African Journals Online (AJOL)

Liver marker enzymes, total protein, amylase and glucose were evaluated in alloxan-induced diabetic wistar rats treated with aqueous extract of Pennisetum purpureum. The liver marker enzymes evaluated were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Sixteen wistar rats were grouped into ...

Comparative study of C-Reactive Protein and other biochemical ...

African Journals Online (AJOL)

Serum levels of C-reactive proteins (CRP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total protein, albumin and globulins were investigated using high sensitivity Immunoturbidometric and colorimetric techniques in individuals with hepatitis (n=50), Malaria (n=50) and 40 control subjects in age ...

Serum biochemical profile of laying hens in the region of Araçatuba, SPPerfil bioquímico das galinhas poedeiras na região de Araçatuba-SP.

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Paulo César Ciarlini

2011-10-01

Full Text Available The establishment of reference values is extremely important for successful diagnosis and treatament. Considering that in most species the serum chemistry profile is influenced by race, climate and management, we decided to determine the values of aspartate aminotransferase (AST, alanine aminotransferase (ALT, uric acid, creatinine, creatine kinase (CK, phosphatase alkaline (ALP, gamma-glutamyltransferase (GGT, total protein (TP and albumin of Dekalb hens in the region of Araçatuba - SP. All samples were processed soon after harvesting in an automatic biochemical analyzer calibrated and monitored with control serum levels I and II. The following confidence intervals were obtained: 44-65,5 U / L (AST; 18,4-21,2 U / L (ALT, 2.1-2.5 mg / dL (uric acid; 1.7 to 5.7 U / L (CK; CI 1.2-2.2 mg / dL (creatinine, 1276-1506 U / L (FA; 18-23,4 U / L (GGT; 27.12 to 29 g / L (PT, from 11.4 to 12.16 g / L (albumin.O estabelecimento de valores bioquímicos de referência é de extrema importância para o sucesso do diagnóstico e do tratamento. Considerando que na maioria das espécies o perfil bioquímico sérico sofre influência de raça, clima e manejo, decidiu-se determinar os valores de aspartato aminotransferase (AST, alanina aminotransferase (ALT, ácido úrico, creatinina, creatina quinase (CK, fostatase alcalina (FA, gama-glutamiltransferase (GGT, proteína total (PT e albumina de galinhas poedeiras da linhagem Dekalb da região de Araçatuba – SP. Todas as amostras foram processadas logo após a colheita em um analisador bioquímico automatizado previamente calibrado e monitorado com soros controles nível I e II. Obtiveram-se os seguintes intervalos de confiança: 44-65,5 U/L (AST; 18,4-21,2 U/L (ALT; 2,1–2,5 mg/dL (ácido úrico ; 1,7– 5,7 U/L (CK ; 1,2–2,2 mg/dL (creatinina; 1276–1506 U/L (FA; 18-23,4 U/L (GGT; 27,12– 29 g/L (PT; 11,4 – 12,16 g/L (albumina.

Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children.

Science.gov (United States)

Bortolotti, Flavia; Muratori, Luigi; Jara, Paloma; Hierro, Loreto; Verucchi, Gabriella; Giacchino, Raffaella; Barbera, Cristiana; Zancan, Lucia; Guido, Maria; Resti, Massimo; Pedditzi, Sabrina; Bianchi, Francesco; Gatta, Angelo

2003-02-01

To evaluate the clinical pattern and evolution of chronic hepatitis C in children with liver/kidney microsomal antibody type 1 autoantibodies (LKM1). A multicenter, retrospective study, including the following groups of children with hepatitis C virus infection: (1). 21 consecutive LKM1-positive patients, (2). 42 age- and sex- matched LKM1-negative patients, and (3). 4 interferon-induced LKM1-positive cases. LKM1 reactivity to human microsomes and recombinant cytochrome P450IID6 (CYP2D6) was assayed by immunoblotting. Clinical and biochemical features overlapped in LKM1-positive and LKM1-negative children, but a fibrosis score >3 (range 0-6) was significantly more frequent (P =.04) in the former. Reactivity to microsomal protein and CYP2D6 was significantly (P =.02) associated with LKM1 titers >or=1:320 and was found in 39% of patients, including severe cases and both children (of 4 treated) who achieved a sustained alanine aminotransferase (ALT) normalization after steroid treatment. Five of 7 LKM1-positive children treated with interferon had an ALT exacerbation. LKM1-positive hepatitis C in children is characterized by a wide spectrum of biochemical, serologic, and histologic features. Whether autoimmunity may contribute to liver damage in a subgroup of patients with more severe liver disease, high LKM1 titers, and reactivity to CYP2D6 is a question deserving further investigation.

Synthesis and photophysical and electroluminescent properties of poly(1,4-phenylene–ethynylene)-alt-poly(1,4-phenylene–vinylene)s with various dissymmetric substitution of alkoxy side chains

Czech Academy of Sciences Publication Activity Database

Bouguerra, N.; Růžička, Aleš; Ulbricht, C.; Enengl, C.; Enengl, S.; Pokorná, Veronika; Výprachtický, Drahomír; Tordin, E.; Aitout, R.; Cimrová, Věra; Egbe, D. A. M.

2016-01-01

Roč. 49, č. 2 (2016), s. 455-464 ISSN 0024-9297 R&D Projects: GA ČR(CZ) GA13-26542S; GA ČR(CZ) GAP106/12/0827 Institutional support: RVO:61389013 Keywords : poly(1,4-phenylene-ethynylene)-alt-poly(1,4-phenylene-vinylene)s * dissymmetric side chains * synthesis Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.835, year: 2016

ALT-I pump limiter results on TEXTOR

International Nuclear Information System (INIS)

Dippel, K.H.; Finken, K.H.; Guthrie, S.E.; Malinowski, M.E.; Pontau, A.E.; Campbell, G.A.; Goebel, D.M.; Conn, R.W.

1985-01-01

The ALT-I pump limiter is used to control hydrogen fluxes from the TEXTOR tokamak. The performance of two different modules, the open fixed geometry (FG) and the closed variable geometry (VG) is discussed. In unpumped scoop limiter operation, the pressure in the ALT-I chamber increases to 3x10 -4 torr(FG) and 2x10 -3 torr(VG). With pumping, the fraction of particles incident on the neutralizer plate that is removed is 25-50%(FG) and 50-80%(VG). These removed particles are estimated to be 2-4(8)%(FG) and 6-13%(VG) of the total plasma outflux (Nsub(e)/tausub(p)). The collection of helium from the plasma using the FG module is approximately half as effective as hydrogen collection. The higher particle removal efficiency for the VG module is attributed to lower neutral backstreaming. (author)

Weight reduction improves markers of hepatic function and insulin ...

African Journals Online (AJOL)

Results: There was a 26.99%, 40.8%, 33.81%, 32.73%, 37.8% and 15 % reduction in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma – Glutamyltransferase (GGT) and Homeostasis Model Assessment-Insulin Resistance- index (HOMA-IR) and BMI ...

Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport

Science.gov (United States)

Day, Pricilla E.; Ntani, Georgia; Crozier, Sarah R.; Mahon, Pam A.; Inskip, Hazel M.; Cooper, Cyrus; Harvey, Nicholas C.; Godfrey, Keith M.; Hanson, Mark A.; Lewis, Rohan M.; Cleal, Jane K.

2015-01-01

Introduction Maternal environment and lifestyle factors may modify placental function to match the mother’s capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. Methods RNA was extracted from 102 term Southampton Women’s Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. Results Increased placental LAT2 (p = 0.01), y + LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). Conclusion A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of

Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport.

Directory of Open Access Journals (Sweden)

Pricilla E Day

Full Text Available Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content on a selection of metabolic and amino acid transporter genes and their associations with fetal growth.RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR.Increased placental LAT2 (p = 0.01, y+LAT2 (p = 0.03, aspartate aminotransferase 2 (p = 0.02 and decreased aspartate aminotransferase 1 (p = 0.04 mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01, ASCT1 (p = 0.03, mitochondrial branched chain aminotransferase (p = 0.02 and glutamine synthetase (p = 0.05 was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05 associated with higher maternal diet quality (prudent dietary pattern pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05 and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01 associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01. Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001.A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking

Effect of nitrate poisoning on some biochemical parameters in rats

OpenAIRE

M. B. Mahmood; O. H. Azeez; J. S. Hassan

2011-01-01

The present study was conducted to investigate the toxicity of potassium nitrate on glucose, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the possible ameliorative effect of ascorbic acid (Vitamin C). Male Wister rats are used as experimental model divided into three groups (each of 6-8 rats) and treated for six weeks as follows: Group 1: served as control; Group 2: received 2 % potassium nitrate added to the forage and Group 3: received 2 % potassium nit...

ALT-II toroidal belt limiter biasing experiments on TEXTOR

International Nuclear Information System (INIS)

Doerner, R.; Boedo, J.A.; Gray, D.S.

1991-01-01

Edge electric fields have been related to H-mode-like behaviour. The experiments reported here are an attempt to control the SOL profiles by electrostatic biasing of the full toroidal-belt limiter ALT-II. The specific goals are: influencing the edge particle flows, particle removal, power deposition and the global confinement. The ALT-II pump limiter is a full toroidal belt located at 45 o below the outer midplane and consisting of eight graphite covered blades which can be independently biased. Particle scoops located behind the limiter neutralize and direct the incoming plasma into the pumping ducts. (author) 5 refs., 3 figs

Preliminary design analysis of the ALT-II limiter for TEXTOR

International Nuclear Information System (INIS)

Koski, J.A.; Boyd, R.D.; Kempka, S.M.; Romig, A.D. Jr.; Smith, M.F.; Watson, R.D.; Whitley, J.B.; Conn, R.W.; Grotz, S.P.

1984-01-01

Installation of a large toroidal belt pump limiter, Advanced Limiter Test II (ALT-II), on the TEXTOR tokamak at Juelich, FRG is anticipated for early 1986. This paper discusses the preliminary mechanical design and materials considerations undertaken as part of the feasibility study phase for ALT-II. Since the actively cooled limiter blade is the component in direct contact with the plasma edge, and thus subject to the severe plasma environment, most preliminary design efforts have concentrated on analysis of the blade. The screening process which led to the recommended preliminary design consisting of a dispersion strenghthened copper or OFHC copper cover plate over an austenitic stainless steel base plate is discussed. A 1 to 3 mm thick low atomic number coating consisting of a graded plasma-sprayed Silicon Carbide-Aluminium composite is recommended subject to further experiment and evaluation. Thermal-hydraulic and stress analyses of the limiter blade are also discussed. (orig.)

( Myrciaria jaboticaba ) peel on blood glucose and cholesterol levels ...

African Journals Online (AJOL)

Berg) peel was lyophilized and the proximate composition, total anthocyanins and polyphenolic content were determined. The effect of the freeze-dried jaboticaba peels (FJP) in the plasmatic levels of glucose, lipid fractions, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in Wistar adult male rats was ...

Effects of adenosine on the organ injury and dysfunction caused by hemorrhagic shock

International Nuclear Information System (INIS)

Soliman, M.M.

2009-01-01

Objectives: Adenosine has been shown in animal and human studies to decrease the post-ischemic myocardial injury by lowering the levels of tumor necrosis factor-a. The objectives of the study was to examine the protective effects of adenosine on the organ injury (liver, kidney, pancreas) associated with hemorrhagic shock in rats. Methodology: The study was conducted at Cardiovascular Physiology laboratory, King Saud University, Riyadh in 2007-2008. Anesthetized male Sprague- Dawley rats were assigned to hemorrhage and resuscitation treated with 20mM adenosine , untreated, or similar time matched control groups (n=6 per group). Rats were hemorrhaged for one hour using a reservoir model. Arterial blood pressure was monitored for one hour, and maintained at a mean arterial blood pressure of 40 mmHg. Adenosine 20mM was injected intra-arterially, before resuscitation in the adenosine treated group. Resuscitation was performed by re infusion of the sheded blood for 30 minutes. Arterial blood samples were analyzed for biochemical indicators of multiple organ injury: 1) liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), 2) renal function: urea and creatinine, 3) pancreatic function: amylase. Results: In the control group there was no significant rise in the serum levels of (i) urea and creatinine, (ii) aspartate aminotransferase (AST) and alanine aminotransferase (ALT), (iii) amylase. While in the adenosine treated group, resuscitation from one hour of hemorrhagic shock resulted in significant rises in the serum levels of (i) urea and creatinine, (ii) aspartate aminotransferase (AST) and alanine aminotransferase (ALT), (iii) amylase. Treatment of rats with 20mM adenosine before resuscitation following one hour of hemorrhagic shock decreased the multiple organ injury and dysfunction caused by hemorrhagic shock. Conclusion: Adenosine attenuated the renal, liver and pancreatic injury caused by hemorrhagic shock and resuscitation in rats. Thus

Impact of grape pomace consumption on the blood lipid profile and liver genes associated with lipid metabolism of young rats.

Science.gov (United States)

Yu, Jianmei; Bansode, Rishipal R; Smith, Ivy N; Hurley, Steven L

2017-08-01

Herein, we investigated the effects of grape pomace (GP) in diet on body weight, blood lipid profile, and expression of liver genes associated with lipid metabolism using a young rat model. In this study, twenty female Sprague-Dawley rats at 7 weeks of age were randomly divided into 4 groups, which were fed modified AIN-93G diets containing 0% (control), 6.9%, 13.8%, and 20.7% of GP for 10 weeks. Feed consumption and body weight were weekly determined. Blood samples were obtained at the beginning and end of the feeding period for cholesterol, alanine aminotransferase (ALT), and glucose analysis. At the end of the feeding period, all rats were fasted overnight and euthanized. Heart, kidney, and liver samples were obtained and weighed. Liver tissues were used for gene expression analysis. GP-containing diet did not influence the body weight of the rats. As GP content increased, blood triglyceride and very low density lipoprotein (VLDL) decreased (P consumption of a diet containing appropriate amount of GP may help in the reduction of body fat accumulation and prevention of obesity. This is the first study revealing the change in gene expression caused by long-term consumption of GP-containing diet.

Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates a2ß1 integrin-mediated cell adhesion, migration and proliferation

Directory of Open Access Journals (Sweden)

Selistre-de-Araujo H.S.

2005-01-01

Full Text Available The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C, a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of ~10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.

Apoenzyme of aspartate aminotransferase isozymes in serum and its diagnostic usefullness for hepatic diseases.

Science.gov (United States)

Kamei, S; Ohkubo, A; Yamanaka, M

1979-08-15

Aspartate aminotransferase in the sera of normal subjects and of patients with hepatic diseases has been immunologically separated into two isoenzymes, cytosolic aspartate aminotransferase and mitochondrial aspartate aminotransferase. The activity of the isoenzymes was measured in three different buffer solutions with or without pyridoxal 5'-phosphate. To attain maximal activation, the apoenzyme of mitochondrial fraction must be preincubated with pyridoxal 5'-phosphate longer than that of the cytosolic fraction in either of the three reaction mixtures. In most sera the activity of both isoenzymes increased substantially in the presence of pyridoxal 5'-phosphate regardless of the type of buffer solutions. Both the apoenzymatic activity and the ratio of apo- to holo-enzymatic activity of each of the isoenzymes varied among samples from the patients with hepatic diseases. However, significantly high ratios of apo- to holo-enzymatic activity of both isoenzymes were observed in the patients with hepatoma in contrast with those with other hepatic diseases. These findings suggest that the simultaneous measurement of both apo- and holo-enzyme activities of aspartate aminotransferase isoenzymes may be useful in the clinical assessment of hepatic diseases.

Preliminary Studies on Some Haematological and Serum ...

African Journals Online (AJOL)

The mean serum values of sodium, potassium, chloride and bicarbonate, as well as urea, creatinine and alanine aminotransferase(ALT) enzyme did not differ from the normal values, while the mean aspartate aminotransferase (AST) enzyme value appeared to be lower than the normal range.In conclusion, the RBC, PCV ...

Effect of subchronic administration of ethanolic leaf extract of croton ...

African Journals Online (AJOL)

The biochemical effcts of ethanolic leaf extract of Croton zambesicus on serum alkaline phosphatase(SAP),aspartate aminotransferase (AST) ,alanine aminotransferase(ALT),serum total protein and albumin were studied.The levels of these enzymes and that of total protein and albumin in the extract treated rats were not ...

Acute toxicity study of methanolic extract of Asparagus pubescens ...

African Journals Online (AJOL)

The acute toxicity study of methanolic extract of Asparagus pubescens root was studied on rats. The indices of the study were the liver enzymes (transaminases), cholesterol, creatinine and urea serum levels as well as the ionic analysis. Both alanine aminotransferase (ALT) and. Aspartate aminotransferase (AST) showed a ...

Kui kapital veab alt, siis turvaliselt / Aleksander Tsapov

Index Scriptorium Estoniae

Tsapov, Aleksander

2006-01-01

Kuraatorinäitus "Kapital (see veab meid alt)" Tallinna Kunstihoones. Kuraator Simon Sheikh. Fia-Stina Sandlundi, Katya Sanderi, Oliver Ressleri, Ashley Hunti ja Susan Kelly&Stephen Mortoni töödest näitusel

Antioxidant and Antifatigue Activities of Polygonatum Alte-lobatum Hayata Rhizomes in Rats

Directory of Open Access Journals (Sweden)

Chi-Ting Horng

2014-11-01

Full Text Available Polygonatum alte-lobatum Hayata, a rhizomatous perennial herb, belongs to the Liliaceae family and is endemic to Taiwan. We investigated the antioxidant and anti-fatigue activities of P. alte-lobatum in exercised rats. Levels of polyphenols, flavonoids and polysaccharides and 2,2-diphenyl-1-picrylhydrazyl (DPPH free-radical scavenging activity were measured in extracts of P. alte-lobatum (EPA. Sprague-Dawley rats were randomly divided into four groups for 8-week treatment with vehicle (control and low-, medium-, and high-dose EPA (LEPA, MEPA, HEPA; 0, 75, 150, and 375 mg/kg/day, respectively. Exercise performance was evaluated by exhaustive treadmill exercise time and by changes in body composition and biochemical variables at the end of the experiment. EPA contained polyphenols, flavonoids and polysaccharides, with polysaccharide content at least 26 times greater than that of polyphenols and flavonoids. Trend analysis revealed that EPA dose-dependently scavenged DPPH free radicals. EPA treatment dose-dependently increased endurance running time to exhaustion and superoxide dismutase activity and total antioxidant ability of blood. EPA dose-dependently decreased serum urea nitrogen and malondialdehyde levels after exercise. Hepatic glycogen content, an important energy source for exercise, was significantly increased with EPA treatment. EPA could be a potential agent with an anti-fatigue pharmacological function.

The association between dietary lifestyles and hepatocellular injury in Japanese workers.

Science.gov (United States)

Iwata, Toyoto; Arai, Kaori; Saito, Norimitsu; Murata, Katsuyuki

2013-12-01

Elevated alanine aminotransferase (ALT) in serum, relevant to nonalcoholic fatty liver disease, has been often reported from Asian countries and the U.S., and it may be associated with lifestyle behavior. To clarify whether specific dietary behavior is associated with hepatocellular injury, we explored liver markers and dietary lifestyles (e.g., breakfast-skipping, eating for lunch, and snacking) in 1,809 male employees, aged 19-59 years, belonging to a health insurance union of automobile dealerships in Japan. ALT, γ-glutamyltransferase, and asparate aminotransferase (AST) were positively correlated with age and body mass index (BMI) (P instant noodle ingestion for lunch to ALT elevation (> 30 IU/L), after adjusting for possible confounders including age, BMI, and drinking, were 1.33 (95% confidence interval, 1.01-1.75) at 1-2 times/week and 1.47 (1.07-2.01) at ≥ 3 times/week, compared to those who seldom ate instant noodles. Likewise, the OR of the ingestion at ≥ 3 times/week to γ-glutamyltransferase elevation (> 50 IU/L) was 1.42 (1.02-1.99), but the OR to elevated AST (> 30 IU/L) was not statistically significant. Habitual ethanol intake was significantly associated with hepatocellular injury, though the threshold of daily ethanol intake differed among liver markers. Despite the low OR, habitual instant noodle ingestion for lunch is associated with ALT elevation. Since the average content of saturated fatty acids in instant noodles is considerably high among cereal foods in Japan, workers with this habit should be advised to avoid having unbalanced diets.

Correlation between alanine aminotransferase level, HCV-RNA titer ...

African Journals Online (AJOL)

Reham Al Swaff

2012-04-04

Apr 4, 2012 ... RNA titer and/or serum ALT level in patients with chronic hepatitis C (genotype 4) infection. .... Other liver diseases such as alcoholic liver disease, non- .... Insulin resistance, obesity, and steatosis are associated with a.

HCV carriers with normal aminotransferase levels: “normal” does not always mean “healthy”

Directory of Open Access Journals (Sweden)

Claudio Puoti

2013-04-01

Full Text Available BACKGROUND Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels (PNALT, and another 40% have minimally raised ALT values. Although formerly referred to as “healthy” or “asymptomatic” HCV carriers, it has now become clear that the majority of these patients have some degree of histological liver damage. Controversies still exist regarding the definition of “persistent” ALT normality, the virological and histological features of these subjects, and the natural history and optimal management of chronic hepatitis C (CHC with normal ALT. Most patients with normal ALT have histologically proven liver damage that may be significant (> F2 in up to 20% of patients, and might progress toward more severe degree of liver fibrosis. A significant proportion of patients (≥ 20% experiences periods of increased serum ALT (flare associated with disease progression. AIM OF THE STUDY The introduction of the new combination therapy of PEG-IFN plus ribavirin allowed response rates higher than 50%, with a favourable risk-benefit ratio also in patients with benign or slow progressive disease. Given the efficacy of the new treatments, which soon became the standard of care for CHC, it has been suggested that the issue of whether or not to treat subjects with PNALT should be re-evaluated. ALT levels may have less importance in deciding who should be treated. Many other factors might influence the decision to treat, such as the age of the patient, HCV genotype, liver histology, patient’s motivation, symptoms, extrahepatic manifestations, comorbid illness. The role of non-invasive tools for the assessment of liver fibrosis (transient hepatic elastography remains to be further validated.

Early changes in GABA and dlutamine levels and aminotransferase activity in rat brain after total-body γ-irradiation with absolutely lethal doses

International Nuclear Information System (INIS)

Rozanov, V.A.; Karpovich, G.A.

1985-01-01

The contents of gaama-aminobutyric acid (GABA) and glutamate (GL) as well as GABA-aspartate- and alanine aminotransferase activities were measured in rat cerebellum, cerebral cortex and truncus cerebri 1, 3, 6, 24 and 48 hr following total-body γ-irradiation ( 60 Co) with a dose of 30 Gy. All the indices under study changed in a similar way in the cortex and truncus cerebri while in the cerebellum, GABA level increased and GABA-α-ketoglutarate aminotransfearse activity decreased 60 min after irradiation. The levels of GABA and GL in the cortex and truncus cerebri decreased immediately and increased 24 hr after irradiation. Activity of aminotransferases changed in a phase manner: changes in aspartate- and alanine aminotransferase activity were more pronounced than those of GABA-α-ketoglutarate aminotransferase activity and correlated with the glutamate level changes

Identification of DNA-binding sites for the activator involved in late transcription of the temperate lactococcal phage TP901-1

DEFF Research Database (Denmark)

Pedersen, Margit; Kilstrup, Mogens; Hammer, Karin

2006-01-01

Alt, encoded by the lactococcal phage TP901-1, is needed for late transcription. We identify Alt as a DNA-binding protein, and footprint analysis shows that Alt binds to a region containing four imperfect direct repeats (ALT boxes) located -76 to -32 relative to the P-late transcriptional start...... site. The importance of the ALT boxes was confirmed by deletion of one or two ALT boxes and by introducing mutations in ALT boxes 1 and 4. Alt is proposed to act as a tetramer or higher multimer activating transcription of TP901-1 late genes by binding to the four ALT boxes, and bending of the DNA may...... be important for transcriptional activation of P-late. Furthermore, our results suggest that DNA replication may be required for late transcription in TP901-1. Additionally, we identify gp28 of the related lactococcal phage Tuc2009 as an activator and show that the activators required for late transcription...

Antiatherogenic, hepatoprotective, and hypolipidemic effects of coenzyme Q10 in alloxan-induced type 1 diabetic rats

Directory of Open Access Journals (Sweden)

Hassan Ahmadvand

2014-07-01

Full Text Available BACKGROUND: Diabetes mellitus, one of the leading metabolic syndromes, accounts for highest morbidity and mortality worldwide. In this study, we examined possible protective effect of coenzyme Q10 on lipid profile, atherogenic index, and liver enzyme markers in alloxan-induced type 1 diabetic rats. METHODS: A total of 30 male rats were randomly divided into three groups; group 1 as control, group 2 diabetic untreatment, and group 3 treatments with coenzyme Q10 by 15 mg/kg i.p. daily, respectively .Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of fasting blood glucose (FBG, triglyceride (TG, total cholesterol (TC, low density lipoprotein (LDL, very low-density lipoprotein (VLDL, high density lipoprotein (HDL, atherogenic index, atherogenic coefficient, cardiac risk ratio, and the activities of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP of all groups were analyzed. Data were analyzed using non-parametric Mann-Whitney test (using SPSS and P < 0.05 was considered as significant. RESULTS: Coenzyme Q10 inhibited significantly the activities of ALT (11.17%, AST (19.35% and ALP (36.67% and decreased FBG (21.19%, TG (37.24%, TC (17.15%, LDL (30.44%, VLDL (37.24%, atherogenic index (44.24%, atherogenic coefficient (49.69%, and cardiac risk ratio (37.97%, HDL level was significantly (33.38% increased when treated with coenzyme Q10. CONCLUSION: The findings of this study suggest that coenzyme Q10 exert beneficial effects on the lipid profile, atherogenic index, and liver enzymes activity in alloxan-induced type 1 diabetic rats.   Keywords: Diabetes, Lipid Profile, Atherogenic Index, Rats, Liver Enzymes, Coenzyme Q10 

Characterization of Potential Antimicrobial Targets in Bacillus spp. II. Branched-Chain Aminotransferase and Methionine Regeneration in B. cereus and B. anthracis

National Research Council Canada - National Science Library

Berger, B

2002-01-01

.... Four putative family III aminotransferases, two with homology to branched-chain amino acid aminotransferases and two with homology to D- amino acid aminotransferases, were cloned from B. cereus...

4-aminobutyrate aminotransferase (ABAT: genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

Directory of Open Access Journals (Sweden)

Johan Jirholt

Full Text Available Gastro-esophageal reflux disease (GERD is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0 on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT (P(adj = 0.027. This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs by 57.3 ± 11.4 % (p = 0.007 and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007. Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES control and identifies ABAT as a genetic risk factor for GERD.

4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

Science.gov (United States)

Jirholt, Johan; Asling, Bengt; Hammond, Paul; Davidson, Geoffrey; Knutsson, Mikael; Walentinsson, Anna; Jensen, Jörgen M; Lehmann, Anders; Agreus, Lars; Lagerström-Fermer, Maria

2011-04-28

Gastro-esophageal reflux disease (GERD) is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0) on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents) and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP) markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT) (P(adj) = 0.027). This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA) in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs) by 57.3 ± 11.4 % (p = 0.007) and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007). Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control and identifies ABAT as a genetic risk factor for GERD.

ALT-I pump limiter experiments

International Nuclear Information System (INIS)

Goebel, D.M.; Conn, R.W.; Campbell, G.A.

1987-09-01

Results from the ALT-I pump limiter experiments in TEXTOR are presented. ALT-I has demonstrated control of the plasma density in a high recycling tokamak by pumping up to 15% of the core efflux. The closed pump limiter designs with restricted entrance geometries to reduce the backflow of neutral gas to the plasma remove over 50% of the ion flux incident on the collection slot. Up to 80% of the entrance ion flux is removed when the edge electron temperature is less than 10 eV and plasma-neutral gas interactions are minimized inside the limiter. Results from a 3-D Monte Carlo neutral gas transport code agree closely with these experimental results. The compound curvature of the head is found to distribute the heat over the surface as predicted in the original designs. Impurity removal experiments demonstrate that significant helium exhaust can be achieved with a pump limiter. During ohmic heating in TEXTOR, the energy and particle confinement times are proportional to the line averaged core density. With ICRH auxiliary heating, tau/sub E/ follow L-mode scaling independent of particle removal by the pump limiter. Pump limiter operation does not directly modify the SOL plasma density and electron temperature, but controls the core plasma density by changing the global recycling at the boundary. The global particle confinement, the particle flux to the limiter, and the edge electron temperature follow the changes in the core density and auxiliary heating power. 25 refs

ALT Strategy, February 2017 - January 2020

OpenAIRE

Deepwell, Maren

2017-01-01

The Association for Learning Technology (ALT) represents individual and organisational Members from all sectors and parts of the UK. Our Membership includes practitioners, researchers and policy makers with an interest in Learning Technology. Our community grows more diverse as Learning Technology has become recognised as a fundamental part of learning, teaching and assessment. Our charitable objective is "to advance education through increasing, exploring and disseminating knowledge in t...

Effects of the Dietary Probiotic Clostridium butyricum on Intestine Digestive and Metabolic Capacities, SCFA Content and Body Composition in Marsupenaeus japonicus

Science.gov (United States)

Duan, Yafei; Dong, Hongbiao; Wang, Yun; Zhang, Yue; Zhang, Jiasong

2018-06-01

A 56-day feeding trial was performed to evaluate the effects of dietary probiotic Clostridium butyricum (CB) on intestine digestive and metabolic capacities, intestine short-chain fatty acids (SCFA) content and body composition of kuruma shrimp Marsupenaeus japonicus. Shrimps were randomly allocated into 9 tanks, 30 each, and fed with diets containing different levels of C. butyricum (1 × 109 cfu g-1): 0 mg g-1 feed (Control), 100 mg g-1 feed (CB-100), 200 mg g-1 feed (CB-200), while each level was triplicated. The results indicated that compared with the control group, the intestine pepsin (Pep) activity and 5-hydroxytryptamine (5-HT) concentration of two C. butyricum groups were both increased. Amylase (AMY) and lipase (LPS) activities were only induced in CB-200 group. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities of two C. butyricum groups showed no significant change. The α-amylase (AMY) gene expression was induced in CB-200 group, and trypsin gene expression of two C. butyricum treated groups were both induced. Intestine SCFA content and body composition analysis showed that the contents of propionic acid, butyric acid and the crude protein of two C. butyricum groups were all higher than those of control. These results revealed that C. butyricum can modulate intestine digestive and metabolic capacities, improve intestine SCFA content and body crude protein content in M. japonicus.

Respiratory toxicity of cyanobacterial aphantoxins from Aphanizomenon flos-aquae DC-1 in the zebrafish gill

Energy Technology Data Exchange (ETDEWEB)

Zhang, De Lu, E-mail: deluzh@163.com [Department of Lifescience and Biotechnology, College of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070 (China); Liu, Si Yi [Department of Lifescience and Biotechnology, College of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Zhang, Jian Kun [Department of Lifescience and Biotechnology, College of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070 (China); Hu, Chun Xiang, E-mail: cxhu@ihb.ac.cn [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Liu, Yong Ding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)

2016-07-15

Highlights: • Aphantoxin causes physiological and histological changes in zebrafish gills. • Changes in gill enzymes (ALT, AST) and ultrastructure demonstrate injury. • Reduced AChE and MAO activity suggest altered neurotransmitter inactivation. - Abstract: Aphantoxins from Aphanizomenon flos-aquae are frequently identified in eutrophic waterbodies worldwide. These toxins severely endanger environmental safety and human health due to the production of paralytic shellfish poisons (PSPs). Although the molecular mechanisms of aphantoxin neurotoxicity have been studied, many questions remain to be resolved such as in vivo alterations in branchial histology and neurotransmitter inactivation induced by these neurotoxins. Aphantoxins extracted from a naturally isolated strain of A. flos-aquae DC-1 were determined by high performance liquid chromatography. The basic components of the isolated aphantoxins identified were gonyautoxin 1 (GTX1), gonyautoxin 5 (GTX5), and neosaxitoxin (neoSTX), which comprised 34.04, 21.28, and 12.77% of the total, respectively. Zebrafish (Danio rerio) was administrated 5.3 or 7.61 mg STX equivalents (eq)/kg (low and high doses, respectively) of the A. flos-aquae DC-1 aphantoxins by intraperitoneal injection. Histological alterations and changes in neurotransmitter inactivation in the gills of zebrafish were investigated for 24 h following exposure. Aphantoxin exposure significantly increased the activities of gill alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and resulted in histological alterations in the gills during the first 12 h of exposure, indicating the induction of functional and structural damage. Gill acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities were inhibited significantly, suggesting an alteration of neurotransmitter inactivation in zebrafish gills. The observed alterations in gill structure and function followed a time- and dose-dependent pattern. The results demonstrate that

Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients.

Science.gov (United States)

Khodadadi, Iraj; Abdi, Mohammad; Ahmadi, Abbas; Wahedi, Mohammad Saleh; Menbari, Shahoo; Lahoorpour, Fariba; Rahbari, Rezgar

2011-08-01

To determine adenosine deaminase (ADA) activity as a possible diagnostic marker in HIV and HIV-HBV co-infected patients. Blood samples were collected from 72 healthy, 33 HIV positive and 30 HIV-HBV co-infected subjects. Blood CD4+ cell count was recorded and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total ADA, and ADA1 and ADA2 isoenzyme activities were determined. Serum ALT, AST, total ADA and ADA2 isoenzyme activities were significantly higher in HIV positive and HIV-HBV co-infected groups compare to the control (pADA activities (R(2)=0.589, pADA was significantly increased in HIV and HIV-HBV co-infections. Therefore, because of its low cost and simplicity to perform, ADA activity might be considered as a useful diagnostic tool among the other markers in these diseases. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Sub-Acute Hepatoxicity of Aqueous Leaf Extract of Eucalyptus ...

African Journals Online (AJOL)

Sub–acute toxicity study of the aqueous leaf extract of Eucalyptus camaldulensis was carried out on albino rats. Doses of 250mg, 500mg, 750mg and 1000mg per kilogram body weight of the extract were administered orally for 21 days. The activities of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), ...

Protective effect of diallyl disulfide against the irradiation damage in mice induced by "1"2C"6"+ ion beams

International Nuclear Information System (INIS)

Xu Shuai; Ma Xiaofei; Zhang Hong; Liu Yang

2013-01-01

The radioprotective effect of Diallyl disulfide (DADS) on "1"2C"6"+ ion irradiation was studied. Pretreated with DADS of different concentration, male Kung-Ming mice were exposed to whole body irradiation with dosage of 4 Gy "1"2C"6"+ ion. The animals were sacrificed after irradiation. Then the bone marrow cells micronucleus rate, malondialdehyde (MDA) levels, content of protein carbonylation, total antioxidant capacity (T-AOC) and alanine aminotransferase (ALT) activity were measured. As compared with those in irradiated group, the ratio of micronucleus cells in marrow and the hepatic ALT activity in the pretreatment group with low dose DADS decreased significantly (p < O.OOl). Similarly, the content of protein carbonylation and the levels of MDA dropped dramatically in the group with middle dose DADS treatment (p < 0.05). On the contrary, the hepatic T-AOC increased markedly in the group of pretreatment with low dose DADS (p < 0.05). The results showed that DADS protect lipoid, protein and genetic material from "1"2C"6"+ ion irradiation by right of resisting oxidative stress. (authors)

Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy.

Science.gov (United States)

Lee, Eun-Jeong; Facchini, Peter J

2011-11-01

Tyrosine aminotransferase (TyrAT) catalyzes the transamination of L-Tyr and α-ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and L-glutamate. The decarboxylation product of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural products known collectively as benzylisoquinoline alkaloids (BIAs). We have isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum), which remains the only commercial source for several pharmaceutical BIAs, including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5'-phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between PLP and a specific Lys residue. The amino acid sequence of TyrAT showed considerable homology to other putative plant TyrATs, although few of these have been functionally characterized. Purified, recombinant TyrAT displayed a molecular mass of approximately 46 kD and a substrate preference for L-Tyr and α-ketoglutarate, with apparent K(m) values of 1.82 and 0.35 mm, respectively. No specific requirement for PLP was detected in vitro. Liquid chromatography-tandem mass spectrometry confirmed the conversion of L-Tyr to 4-hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and stems of mature opium poppy plants. Virus-induced gene silencing was used to evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT transcript levels were reduced by at least 80% in silenced plants compared with controls and showed a moderate reduction in total alkaloid content. The modest correlation between transcript levels and BIA accumulation in opium poppy supports a role for TyrAT in the generation of alkaloid precursors, but it also suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde.

High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

Science.gov (United States)

Portillo-Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

Variation in metabolic enzymatic activity in white muscle and liver of blue tilapia, Oreochromis aureus, in response to long-term thermal acclimatization

Science.gov (United States)

Younis, Elsayed M.

2015-05-01

The effects of rearing temperature on white muscle and hepatic phosphofructokinase (PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined in fingerlings of blue tilapia, Oreochromis aureus. The experiment was conducted for 14 weeks at temperatures of 18, 22, 26, 30, and 34°C. The activity of the glycolytic enzymes PFK, PK, and LDH in white muscle increased significantly with increase in water temperature. A reverse trend was observed for these enzymes in the liver, except for LDH, which behaved in the same manner as in white muscle. Cytosolic AST and ALT activity increased in both white muscle and liver in response to warm thermal acclimatization, while a reduction in mitochondrial AST and ALT activity was noticed at high temperatures in comparison with those at a lower temperature.

The Advanced Limiter Test-I (ALT-I) variable-geometry pump limiter module

International Nuclear Information System (INIS)

Pontau, A.E.; Malinowski, M.E.; Ver Berkmoes, A.A.; Guthrie, S.E.; Watson, R.D.; Goebel, D.M.; Campbell, G.A.

1984-01-01

The ALT-I variable geometry module has been designed to address many of the issues not previously settled by earlier experiments. The goal is to study the basic processes involved in pump limiter operation as well as demonstrate its utility and effect on the plasma. The flexibility and extensive instrumentation of ALT-I will offer a unique opportunity to parameterize operation and facilitate the engineering design of future pump limiters. (orig.)

Hepatoprotective effect of fermented ginseng and its major constituent compound K in a rat model of paracetamol (acetaminophen)-induced liver injury.

Science.gov (United States)

Igami, Kentaro; Shimojo, Yosuke; Ito, Hisatomi; Miyazaki, Toshitsugu; Kashiwada, Yoshiki

2015-04-01

This work aimed at evaluating the effect of fermented ginseng (FG) and fermented red ginseng (FRG) against rat liver injury caused by paracetamol (acetaminophen (APAP)). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum and histopathological changes in the liver were analysed to determine the degree of liver injury. Deoxyribonucleic acid (DNA) microarray analysis was performed to compare gene expression levels altered in the rat livers. Phosphorylated Jun-N-terminal kinase (JNK) in human hepatocellular carcinoma (HepG2) cells were detected using western blot analysis to investigate the anti-inflammatory activity of compound K. Pretreatment with FG, containing compound K at high concentration, attenuated AST as well as ALT levels in rats, while no obvious effect was observed in the group that received FRG, whose content of compound K was lower than that of FG. In addition, the results of our histopathological analysis were consistent with changes in the serum biochemical analysis. DNA microarray analysis indicated that JNK- and glutathione S-transferase (GST)-related genes were involved in the hepatotoxicity. Notably, compound K, a major ginsenoside in FG, inhibited the phosphorylation of JNK in HepG2 cells. FG was shown to possess hepatoprotective activity against paracetamol (APAP)-induced liver injury better than FRG. Compound K might play an important role for an anti-inflammatory activity of FG by inhibiting JNK signalling in the liver. © 2014 Royal Pharmaceutical Society.

Evaluation of metabolic enzymes in response to Excel Mera 71, a glyphosate-based herbicide, and recovery pattern in freshwater teleostean fishes.

Science.gov (United States)

Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

2014-01-01

Metabolic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in Indian teleostean fishes, namely, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch), for an exposure to 30 days of Excel Mera 71 (17.2 mg/L), a glyphosate formulation, and subsequent depuration under Liv.52, a plant extract at a dose of 187.5 mg/d/250 L for the same period in the same tissues under laboratory condition. ALT activity was significantly increased (PExcel Mera 71 caused alterations in the metabolic enzymatic activities in fish tissues and AST showed the highest alteration in both the fishes, while lowest in ALP and ALT in A. testudineus and H. fossilis, respectively. During depuration under Liv.52, all the enzyme activities came down towards the control condition which indicated the compensatory response by the fish against this herbicidal stress and it was in the following order: AST>ALT>ALP, in A. testudineus, while H. fossilis showed the following trend: ALT>AST>ALP. Therefore, these parameters could be used as indicators of herbicidal pollution in aquatic organisms and were recommended for environmental monitoring for investigating the mechanism involved in the recovery pattern.

Influence of Prescribed Herbal and Western Medicine on Patients with Abnormal Liver Function Tests: A Retrospective Quasi-Experimental Study

Science.gov (United States)

Lee, Ah-Ram; Yim, Je-Min; Kim, Won-Il

2012-01-01

Objectives: The aim of this study was to investigate the safety and the efficacy of Korean herbal, western and combination medicine use in patients with abnormal liver function tests. Methods: We investigated nerve disease patients with abnormal liver function tests who were treated with Korean herbal, western and combination medicine at Dong-Eui University Oriental Hospital from January 2011 to August 2011. We compared aspartic aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (T-bil) levels before and after taking medicine and excluded patients who had liver-related disease when admitted. Results: AST and ALT were decreased significantly in patients who had taken herbal, western medicine. AST, ALT and ALP were decreased significantly in patients who had taken combination medicine. Compare to herbal medicine, AST, ALT and ALP were decreased significantly in patients who had taken western medicine, and ALT and ALP were decreased significantly in patients who had taken combination medicine. There were no significant differences between western and combination medicine. Conclusions: This study suggests that prescribed Korean herbal medicine, at least, does not injure liver function for patients’, moreover, it was shown to be effective in patients with abnormal liver function tests. PMID:25780634

Possible protective role of palm oil and beef liver on the kidney and ...

African Journals Online (AJOL)

We investigated the effects of eight weeks of a diesel-contaminated diet on liver and kidney of Wistar Albino rats, as well as the possible protective role of palm oil and beef liver. There was a significant increase in serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of rats fed with ...

An ll-Diaminopimelate Aminotransferase Defines a Novel Variant of the Lysine Biosynthesis Pathway in Plants1[W

Science.gov (United States)

Hudson, André O.; Singh, Bijay K.; Leustek, Thomas; Gilvarg, Charles

2006-01-01

Although lysine (Lys) biosynthesis in plants is known to occur by way of a pathway that utilizes diaminopimelic acid (DAP) as a central intermediate, the available evidence suggests that none of the known DAP-pathway variants found in nature occur in plants. A new Lys biosynthesis pathway has been identified in Arabidopsis (Arabidopsis thaliana) that utilizes a novel transaminase that specifically catalyzes the interconversion of tetrahydrodipicolinate and ll-diaminopimelate, a reaction requiring three enzymes in the DAP-pathway variant found in Escherichia coli. The ll-DAP aminotransferase encoded by locus At4g33680 was able to complement the dapD and dapE mutants of E. coli. This result, in conjunction with the kinetic properties and substrate specificity of the enzyme, indicated that ll-DAP aminotransferase functions in the Lys biosynthetic direction under in vivo conditions. Orthologs of At4g33680 were identified in all the cyanobacterial species whose genomes have been sequenced. The Synechocystis sp. ortholog encoded by locus sll0480 showed the same functional properties as At4g33680. These results demonstrate that the Lys biosynthesis pathway in plants and cyanobacteria is distinct from the pathways that have so far been defined in microorganisms. PMID:16361515

Evidence for alternative lengthening of telomeres in liposarcomas in the absence of ALT-associated PML bodies.

Science.gov (United States)

Jeyapalan, Jennie N; Mendez-Bermudez, Aaron; Zaffaroni, Nadia; Dubrova, Yuri E; Royle, Nicola J

2008-06-01

Immortalized and cancer cells maintain their telomeres by activation of a telomere maintenance mechanism (TMM). In approximately 85% of cancers telomerase is activated (TA) but in some tumours, in particular sarcomas, an alternative lengthening of telomeres (ALT) pathway is used. Liposarcomas are the most common soft-tissue sarcoma in adults and they activate ALT or telomerase with equal frequency, however no TMM has been identified in approximately 50% of liposarcomas. In our study, we have shown that instability at the minisatellite MS32, usually associated with ALT activation, aids the identification of liposarcomas that have recombination-like activity at telomeres in absence of ALT associated PML-bodies (APBs). Furthermore, using single molecule telomere analysis, we have detected complex telomere mutations directly in ALT positive liposarcomas and interestingly in some liposarcomas with an unknown TMM but high MS32 instability. We have shown by sequence analysis that some of these complex telomere mutations must arise by an inter-molecular recombination-like process rather than by deletion caused by t-loop excision or by unequal telomere-sister-chromatid-exchange (T-SCE), which is known to be elevated in ALT cell lines. Preliminary evidence also suggests that inter-molecular recombination events may be processed differently in liposarcomas with APBs compared to those without. In conclusion, we have shown for the first time, that some telomerase negative liposarcomas without APBs have other features associated with ALT, indicating that the incidence of ALT in these tumours has previously been under-estimated. This has major implications for the use of cancer treatments targeted at TMMs. (c) 2008 Wiley-Liss, Inc.

Prevalence of abnormal serum liver enzymes in patients with type 2 diabetes mellitus: a cross-sectional study from China.

Science.gov (United States)

Chen, Shuang; Guo, Xiaofan; Chen, Yintao; Dong, Siyuan; Sun, Yingxian

2016-11-01

This cross-sectional study aimed to determine the prevalence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in Chinese type 2 diabetic patients and identify contributing risk factors. This cross-sectional study was conducted in rural areas of China, and 1,198 type 2 diabetic patients with complete data were recruited. Elevated ALT and AST levels were defined as >40 U/L. Prevalence of abnormal liver enzymes was analyzed and multivariable analysis was used to identify independent risk factors. 10.3% and 6.1% diabetic patients had elevated ALT and elevated AST, respectively. The prevalence of elevated liver enzymes was gender-related; it was 13.8% in men and 7.5% in women for elevated ALT, and 7.4% in men and 3.1% in women for elevated AST. High triglyceride was positively associated with both elevated ALT (OR 1.80, 95% CI 1.08-3.01, p = 0.024) and elevated AST (OR 2.24, 95%CI 1.08-4.65, p = 0.031), while taking anti-diabetes medicine was inversely related to both elevated ALT (OR 0.48, 95% CI 0.29-0.80, p = 0.005) and elevated AST (OR 0.37, 95% CI 0.17-0.82, p = 0.014). The risk of elevated ALT in diabetic patients increased with the presence of obesity (OR 2.54, 95% CI 1.07-6.01, p = 0.034), and was lower in women (OR 0.37, 95% CI 0.19-0.72, p = 0.003). Hypertension (OR 4.33, 95% CI 1.41-13.30, p = 0.011), current drinking status (OR 2.90, 95% CI 1.21-6.96, p = 0.017) and national minority (OR 3.26, 95%CI 1.31-8.12, p = 0.011) were risk factors for elevated AST. A relatively high prevalence of abnormal serum liver enzymes in diabetic patients was demonstrated in China, especially in males. More attention should be paid to preventing liver injuries in diabetic patients.

Presentation and demonstration at Alt-i-lab 2005

NARCIS (Netherlands)

Tattersall, Colin

2005-01-01

These documents were used to accompany the Learning Design presentation and demonstration at Alt-i-lab 2005. The slides were shown during a plenary session describing the interoperability demo. The scenario was used to guide the demonstration process, and the UNFOLD handout was used to illustrate

In vitro effects of sodium benzoate on the activities of aspartate and ...

African Journals Online (AJOL)

The in vitro effects of varying concentrations sodium benzoate on the activities of aspartate (E.C. 2.6.1.1) and alanine (E.C. 2.6.1.2) aminotransferases (AST and ALT, respectively) and alkaline phosphatase (E.C. 3.1.3.1; abbreviated as ALP) from human erythrocytes of different genotypes (HbAA, HbAS and HbSS) were ...

Effect of quality protein maize diet on liver integrity and serum ...

African Journals Online (AJOL)

The study was designed to evaluate the effect of quality protein maize (QPM) diet on the histology of the liver and on the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in albino wistar rats. The AST level in rats fed QPM diet was 57.4 ± 8.92U/L which compared favourably with that ...

Biochemical changes in the kidney and liver of rats following administration of ethanolic extract of Psidium guajava leaves.

Science.gov (United States)

Adeyemi, O S; Akanji, M A

2011-09-01

Furtherance to a previous report on the anti-trypanosomal properties of Psidium guajava aqueous leaf extract in rats experimentally infected with Trypanosoma brucei brucei, we have evaluated the effects of the daily intraperitoneal administration of P. guajava leaf extract to rats on the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) in the kidney, liver and serum. The results obtained revealed that the administration of the extract produced significant increase in the serum activities of AST, ALT, ALP and ACP when compared with the control (p < 0.05). Also AST, ALT and ALP and ACP activities in the tissues of animals administered the extract revealed inconsistent changes (p < 0.05) relative to control. The increase in the serum activity of ALP may be an indicator that there was a likely compromise to the integrity of the plasma membrane as a result of the ethanolic extract administration. This could have caused leakages of the other enzymes investigated, which may explain the corresponding increases in the serum activities of AST, ALT and ACP observed.

Die Altäre von Selinunt

OpenAIRE

Voigts, Clemens

2014-01-01

In der Dissertation wurden die Altäre von Selinunt, einer griechischen Kolonie auf Sizilien, mit den Methoden der Bauforschung untersucht. Die neun behandelten Brandopferaltäre sind monumentale Quaderbauten, die bis zu 20 m Länge erreichen. Sie stammen aus der Blütezeit Selinunts, dem 6. und 5. Jh. v. Chr. Die Bauten waren bereits im 19. und 20. Jh. freigelegt worden und wurden nun in Bauaufnahmen dokumentiert, zeichnerisch rekonstruiert und zeitlich eingeordnet. Dabei ließ sich an ihnen eine...

The effect of dietary folic acid on biochemical parameters and gene expression of three heat shock proteins (HSPs) of blunt snout bream (Megalobrama amblycephala) fingerling under acute high temperature stress.

Science.gov (United States)

Sesay, Daniella Fatmata; Habte-Tsion, Habte-Michael; Zhou, Qunlan; Ren, Mingchun; Xie, Jun; Liu, Bo; Chen, Ruli; Pan, Liangkun

2017-08-01

The effects of dietary folic acid on biochemical parameters and gene expression of three heat shock proteins (HSPs) of blunt snout bream (Megalobrama amblycephala) fingerling under acute high temperature stress. Six dietary folic acid groups (0.0, 0.5, 1.0, 2.0, 5.0, and 10.0) mg/kg diets were designed and assigned into 18 tanks in three replicates each (300 l/tank) and were administered for 10 weeks in a re-circulated water system. The fingerlings with an initial weight of 27.0 ± 0.03 g were fed with their respective diets four times daily. At the end of the experiment, samples were collected before challenge, 0, 24, 72 h, and 7 days. Serum total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cortisol, glucose, complement C3 (C3), complement C4 (C4, immunoglobulin M (IgM) hepatic superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and the expression of heat shock protein 60 (HSP60), 70 (HSP70), and 90 (HSP90) were studied. The results showed that fish fed with dietary folic acid between 1.0, 2.0, and 5.0 mg/kg significantly (P stress, 0, 24, 72 h, and 7 days significantly (P  0.05) of the three HSPs. However, there were statistical significant interactive effect between dietary folic acid inclusion level and temperature duration on serum C3 and C4 (P  0.05). The present results indicate that supplementation of basal diet from 1.0 mg/kg; 2.0 and 5.0 mg/kg can enhance acute high temperature resistance ability in M. amblycephala fingerling to some degree and improve physiological response, immune and antioxidant capacities, and expression level of three HSPs.

Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential

Directory of Open Access Journals (Sweden)

Dae Hoon Kim

2016-01-01

Full Text Available Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR as the substrate. Cudrania tricuspidata leaves (CTe had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity.

Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential

Science.gov (United States)

Kim, Dae Hoon; Lee, Sooung; Chung, Youn Wook; Kim, Byeong Mo; Kim, Hanseul; Kim, Kunhong; Yang, Kyung Mi

2016-01-01

Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. PMID:26989693

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

Science.gov (United States)

Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

2016-01-01

MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

Genel Anestezi Altında Çocukta Diş Tedavisi

OpenAIRE

Gülhan, A.; Sandallı, N.

2013-01-01

ÖZETBu makalede çocuklarda genel anestezi altında diş tedavisinin koşulları anlatıldı ve normal tedavi koşulları sağlanamadığı takdirde, genel anesteziye başvurmanın yararlarına ve sakıncalarına değinildi. Genel anestezi indikasyonları sıralanarak, bunlar arasında en sık rastladığımız «Güç çocuklarım" genci anesteziye başvurmadan Önce hangi yollara başvurularak normal tedavinin deneneceğinden bahsedildi.Bir hastane ortamında genel anestezi altında çalışmaya karar verildikten sonra, bir a...

Peek ja Lepik soovisid varade aresti alt vabastamist

Index Scriptorium Estoniae

2005-01-01

LHV endine töötaja Oliver Peek väidab, et tema vastu esitatud süüdistused on alusetud ja tõendamata ning nõuab oma varade aresti alt vabastamist. Kristjan Lepingu kohtuasja arutamine lükati edasi 21. detsembrile. Endiselt käib uurimine, kui palju väidetavalt teabevargusega raha teeniti

L,L-diaminopimelate aminotransferase, a trans-kingdom enzyme shared by Chlamydia and plants for synthesis of diaminopimelate/lysine.

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McCoy, Andrea J; Adams, Nancy E; Hudson, André O; Gilvarg, Charles; Leustek, Thomas; Maurelli, Anthony T

2006-11-21

The synthesis of meso-diaminopimelic acid (m-DAP) in bacteria is essential for both peptidoglycan and lysine biosynthesis. From genome sequencing data, it was unclear how bacteria of the Chlamydiales order would synthesize m-DAP in the absence of dapD, dapC, and dapE, which are missing from the genome. Here, we assessed the biochemical capacity of Chlamydia trachomatis serovar L2 to synthesize m-DAP. Expression of the chlamydial asd, dapB, and dapF genes in the respective Escherichia coli m-DAP auxotrophic mutants restored the mutants to DAP prototrophy. Screening of a C. trachomatis genomic library in an E. coli DeltadapD DAP auxotroph identified ct390 as encoding an enzyme that restored growth to the Escherichia coli mutant. ct390 also was able to complement an E. coli DeltadapD DeltadapE, but not a DeltadapD DeltadapF mutant, providing genetic evidence that it encodes an aminotransferase that may directly convert tetrahydrodipicolinate to L,L-diaminopimelic acid. This hypothesis was supported by in vitro kinetic analysis of the CT390 protein and the fact that similar properties were demonstrated for the Protochlamydia amoebophila homologue, PC0685. In vivo, the C. trachomatis m-DAP synthesis genes are expressed as early as 8 h after infection. An aminotransferase activity analogous to CT390 recently has been characterized in plants and cyanobacteria. This previously undescribed pathway for m-DAP synthesis supports an evolutionary relationship among the chlamydiae, cyanobacteria, and plants and strengthens the argument that chlamydiae synthesize a cell wall despite the inability of efforts to date to detect peptidoglycan in these organisms.

(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

DEFF Research Database (Denmark)

Pan, Yue; Gerasimov, Madina R; Kvist, Trine

2012-01-01

Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target...

Antioxidant activity of lycopene extracted from tomato pomace toward gamma irradiation hazards in male albino rats

International Nuclear Information System (INIS)

Saad, T.M.M.; EL MASRY, F.S.

2005-01-01

The present study aims to evaluate the anti oxidative activity of lycopene extracted from tomato pomace against hazards induced by gamma irradiation. Male Swiss albino rats were orally administered by lycopene (1.2 mg/rat/day) using suitable stomach tube 7 days before exposure to a sublethal single dose (6.5 Gy) of whole body gamma radiation. Lipid peroxides (MDA) levels in plasma, reduced glutathione (GSH) content and superoxide dismutase activity in blood were determined, as well as serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase activity (GGT) were investigated 7 and 15 days post-irradiation and/or lycopene administration. The results revealed that exposure to ionizing radiation resulted in significant elevation in plasma levels of MDA, serum ALT, AST, ALP and GGT, as well as significant reduction in GSH content and superoxide dismutase activity in blood. Administration of lycopene by using suitable stomach tube pre-irradiation has significantly ameliorated the radiation-induced disturbances in all the investigated parameters

A COMPARATIVE STUDY ON THE ACTIVITY OF ALANIN-AMINOTRANSFERASE IN HYPOPHTHALMICHTHYS MOLITRIX AND ARISTICHTHYS NOBILIS

Directory of Open Access Journals (Sweden)

Gabriela Vasile

2006-08-01

Full Text Available The present paper represents a comparative study on the activity of one aminotransferase - alaninaminotransferase, in the digestive tube of Hypophthalmichthys molitrix (silver carp and Aristichthys nobilis (bighead carp. The enzymatic activity has been determined colorimetrically, with 2, 4 - dinitrophenyl hydrazine, the results obtained being expressed as UE / g / min. It was observed that, comparatively with the alanin-aminotransferase activity recorded in silver carp, in the case of bighead carp, the values recorded are much lower.

SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation.

Science.gov (United States)

Pan, Zhen-Guo; An, Xu-Sheng

2018-04-06

SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory response caused by HFD was alleviated by SARM1-deletion through inactivating TLR4/7/9 and nuclear factor kappa B (NF-κB) pathways. Of note, SARM1-deletion also reduced the expressions of inflammation-associated molecules in hypothalamus of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was also attenuated by SARM1-deficiency through enhancing the activation of liver Akt/glycogen synthase kinase-3β (GSK3β) and insulin receptor substrate-1 (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine-and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of mice after HFD administration. In vitro, we found that the reduction of inflammatory response, oxidative stress and dyslipidemia induced by SARM1-knockout in primary hepatocytes after fructose stimulation was largely attributed to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1 might be an effective target for developing effective therapeutic strategies against NAFLD. Copyright © 2018

Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

Science.gov (United States)

Jessen, Holly Jean [Chanhassen, MN; Liao, Hans H [Eden Prairie, MN; Gort, Steven John [Apple Valley, MN; Selifonova, Olga V [Plymouth, MN

2011-10-04

The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

The usefulness of physical examination and laboratory data in pediatric patients with blunt abdominal trauma

International Nuclear Information System (INIS)

Muramori, Katsumi; Kondo, Tsuyoshi; Zaizen, Yoshio; Tsuno, Shinsuke

2007-01-01

To evaluate the usefulness of clinical and laboratory data in pediatric patients with abdominal blunt trauma, the case records of 43 pediatric cases with blunt trauma who were admitted to our hospital were reviewed retrospectively. Among these patients, 23 were determined to have intraabdominal injury. Abdominal physical examination was not statistically identified to be a predictor of intraabdominal injury, however, the hematocrit and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were significantly aberrant in these cases. Furthermore, the mean AST and ALT values in the non-hepatic injury cases were also apt to be higher than those in the no-injury group. These findings suggested that the serum AST and ALT may be possible predictors of intraabdominal injury, not only that restricted to the liver. Additionally, in our cases, abdominal CT examination was more diagnostic than ultrasound examination. Accordingly, in cases of pediatric abdominal blunt trauma with aberrant serum values of the liver transaminases, CT san should be performed electively. (author)

Analysis of the Variability of Epstein-Barr Virus Genes in Infectious Mononucleosis: Investigation of the Potential Correlation with Biochemical Parameters of Hepatic Involvement.

Science.gov (United States)

Banko, Ana; Lazarevic, Ivana; Stevanovic, Goran; Cirkovic, Andja; Karalic, Danijela; Cupic, Maja; Banko, Bojan; Milovanovic, Jovica; Jovanovic, Tanja

2016-09-01

Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1 , and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1 , and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala , as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers.

Phase 1 trial of ALT-801, an interleukin-2/T cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies

Science.gov (United States)

Fishman, Mayer N.; Thompson, John A.; Pennock, Gregory K.; Gonzalez, Rene; Diez, Luz M.; Daud, Adil I.; Weber, Jeffery S.; Huang, Bee Y.; Tang, Shamay; Rhode, Peter R.; Wong, Hing C.

2014-01-01

Purpose ALT-801 is a bifunctional fusion protein comprising interleukin-2 (IL-2) linked to a soluble, single-chain T cell receptor domain that recognizes a peptide epitope (aa264-272) of the human p53 antigen displayed on cancer cells in the context of HLA-A*0201 (p53+/HLA-A*0201). We evaluated the safety, pharmacokinetics and pharmacodynamics of ALT-801 in p53+/HLA-A*0201 patients with metastatic malignancies. Experimental Design p53+/HLA-A*0201 patients were treated with ALT-801 on a schedule of 4 daily 15-minute intravenous infusions, then 10 days rest and 4 more daily infusions. Cohorts of patients were treated at 0.015, 0.040, and 0.080 mg/kg/dose. Results Four, sixteen, and six patients were treated at the 0.015, 0.04 and 0.08 mg/kg cohorts, respectively. Two dose limiting toxicities (a grade 4 transient thrombocytopenia and a myocardial infarction) in the 0.08 mg/kg cohort established the maximum tolerated dose (MTD) at 0.04 mg/kg. Patients treated at the MTD experienced toxicities similar to those associated with high-dose IL-2 but of lesser severity. The serum half-life of ALT-801 was 4 hours and ALT-801 serum recovery was as expected based on the dose administered. ALT-801 treatment induced an increase of serum interferon-γ but not tumor necrosis factor-α. Response assessment showed 10 subjects with stable disease at at least 11 weeks, and in one who had melanoma metastasis, there is an ongoing complete absence of identifiable disease after resection of radiographically identified lesions. Conclusion This first-in-man study defines an ALT-801 regimen that can be administered safely and is associated with immunological changes of potential antitumor relevance. PMID:21994418

Characterization and vaccine potential of Fasciola gigantica saposin-like protein 1 (SAP-1).

Science.gov (United States)

Kueakhai, Pornanan; Changklungmoa, Narin; Waseewiwat, Pinkamon; Thanasinpaiboon, Thanaporn; Cheukamud, Werachon; Chaichanasak, Pannigan; Sobhon, Prasert

2017-01-15

The recombinant Fasciola gigantica Saposin-like protien-1 (rFgSAP-1) was cloned by polymerase chain reaction (PCR) from NEJ cDNA, expressed in Escherichia coli BL21 (DE3) and used for production of a polyclonal antibody in rabbits (anti-rFgSAP-1). By immunoblotting and immunohistochemistry, rabbit IgG anti-rFgSAP-1 reacted with rFgSAP-1 at a molecular weight 12kDa, but not with rFgSAP-2. The rFgSAP-1 reacted with antisera from mouse infected with F. gigantica metacercariae collected at 2, 4, and 6 weeks after infection. The FgSAP-1 protein was expressed at a high level in the caecal epithelium of metacercariae and NEJs. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rFgSAP-1 combined with Alum adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae per mouse by the oral route. The percents protection of rFgSAP-1 vaccine were estimated to be 73.2% and 74.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. The levels of IgG1 and IgG2a specific to rFgSAP-1 in the immune sera, which are indicative of Th2 and Th1 immune responses, were inversely and significantly correlated with the numbers of worm recoveries. The rFgSAP-1-vaccinated mice showed significantly reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and liver damage. These indicated that rFgSAP-1 has strong potential as a vaccine candidate against F. gigantica, whose efficacy will be studied further in large economic animals including cattle, sheep, and goat. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of branched-chain amino acid aminotransferases active towards (R)-(+)-1-phenylethylamine among PLP fold type IV transaminases.

Science.gov (United States)

Bezsudnova, Ekaterina Yu; Dibrova, Daria V; Nikolaeva, Alena Yu; Rakitina, Tatiana V; Popov, Vladimir O

2018-04-10

New class IV transaminases with activity towards L-Leu, which is typical of branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)-(+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)-amine:pyruvate transaminases, were identified by bioinformatics analysis, obtained in recombinant form, and analyzed. The values of catalytic activities in the reaction with L-Leu and (R)-PEA are comparable to those measured for characteristic transaminases with the corresponding specificity. Earlier, (R)-selective class IV transaminases were found to be active, apart from (R)-PEA, only with some other (R)-primary amines and D-amino acids. Sequences encoding new transaminases with mixed type of activity were found by searching for changes in the conserved motifs of sequences of BCAT by different bioinformatics tools. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.

Science.gov (United States)

Siqueira, Erika Rabelo Forte de; Pereira, Luciano Beltrao; Stefano, Jose Tadeu; Patente, Thiago; Cavaleiro, Ana Mercedes; Silva Vasconcelos, Luydson Richardson; Carmo, Rodrigo Feliciano; Moreira Beltrao Pereira, Leila Maria; Carrilho, Flair Jose; Corrêa-Giannella, Maria Lucia; Oliveira, Claudia P

2015-03-28

Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV. One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T → A in CYBA. No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025). The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.

Analysis of the enzymatic properties of a broad family of alanine aminotransferases.

Directory of Open Access Journals (Sweden)

Chandra H McAllister

Full Text Available Alanine aminotransferase (AlaAT has been studied in a variety of organisms due to the involvement of this enzyme in mammalian processes such as non-alcoholic hepatocellular damage, and in plant processes such as C4 photosynthesis, post-hypoxic stress response and nitrogen use efficiency. To date, very few studies have made direct comparisons of AlaAT enzymes and fewer still have made direct comparisons of this enzyme across a broad spectrum of organisms. In this study we present a direct kinetic comparison of glutamate:pyruvate aminotransferase (GPAT activity for seven AlaATs and two glutamate:glyoxylate aminotransferases (GGAT, measuring the K(M values for the enzymes analyzed. We also demonstrate that recombinant expression of AlaAT enzymes in Eschericia coli results in differences in bacterial growth inhibition, supporting previous reports of AlaAT possessing bactericidal properties, attributed to lipopolysaccharide endotoxin recognition and binding. A probable lipopolysaccharide binding region within the AlaAT enzymes, homologous to a region of a lipopolysaccharide binding protein (LBP in humans, was also identified in this study. The AlaAT enzyme differences identified here indicate that AlaAT homologues have differentiated significantly and the roles these homologues play in vivo may also have diverged significantly. Specifically, the differing kinetics of AlaAT enzymes and how this may alter the nitrogen use efficiency in plants is discussed.

Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview.

Science.gov (United States)

Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

2015-09-01

Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44) catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder characterized by the deposition of calcium oxalate crystals primarily in the urinary tract. Here we describe the results obtained on the biochemical features of AGT as well as on the molecular and cellular effects of polymorphic and pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1 emerges in which the co-inheritance of polymorphic changes and the condition of homozygosis or compound heterozygosis are two important factors that determine the enzymatic phenotype of PH1 patients. All the reported data represent relevant steps toward the understanding of genotype/phenotype correlations, the prediction of the response of the patients to the available therapies, and the development of new therapeutic approaches. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatotoxicity and genotoxicity of gasoline fumes in albino rats

Directory of Open Access Journals (Sweden)

Folarin O. Owagboriaye

2017-09-01

Full Text Available Toxic effects of gasoline fumes have been reported, but evidence of its hepatotoxicity and genotoxicity are rare. Therefore, this study assesses hepatotoxicity and genotoxicity of gasoline fumes on forty Albino rats randomly assigned to five experimental treatments (T with eight rats per treatment (T1, T2, T3, T4 and T5. T1(Control was housed in a section of experimental animal house free from gasoline fumes while T2, T3, T4 and T5 were exposed to gasoline fumes in exposure chambers for one, three, five and nine hours daily respectively for twelve weeks. Serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and histopathological examination of the liver tissues were used as diagnostic markers to assess liver dysfunction. Genotoxicity test was conducted on the lung tissues using randomly amplified polymorphic DNA fingerprinting polymerase chain reaction (RAPD PCR technique. Significant increase (p < 0.05 in the level of ALT, AST and ALP for T2, T3, T4 and T5 compared to T1 were recorded. Photomicrograph examination of the liver sections of T1 showed hepatic tissue with normal liver cell architecture while that of T2, T3, T4 and T5 revealed degenerative changes in the ultrastructural integrity of the hepatic cells. Genotoxicity test revealed DNA bands at a reducing intensity from T1 to T5. Dendrogram showed DNA damage in the lungs of T3, T4 and T5 were closely similar and the genotoxic impact was more in T3. Frequent exposure to gasoline fumes was observed to induce hepatoxicity and genotoxicity, hence impairing the normal liver function and gene structure.

Diversification of Transcriptional Regulation Determines Subfunctionalization of Paralogous Branched Chain Aminotransferases in the Yeast Saccharomyces cerevisiae.

Science.gov (United States)

González, James; López, Geovani; Argueta, Stefany; Escalera-Fanjul, Ximena; El Hafidi, Mohammed; Campero-Basaldua, Carlos; Strauss, Joseph; Riego-Ruiz, Lina; González, Alicia

2017-11-01

Saccharomyces cerevisiae harbors BAT1 and BAT2 paralogous genes that encode branched chain aminotransferases and have opposed expression profiles and physiological roles . Accordingly, in primary nitrogen sources such as glutamine, BAT1 expression is induced, supporting Bat1-dependent valine-isoleucine-leucine (VIL) biosynthesis, while BAT2 expression is repressed. Conversely, in the presence of VIL as the sole nitrogen source, BAT1 expression is hindered while that of BAT2 is activated, resulting in Bat2-dependent VIL catabolism. The presented results confirm that BAT1 expression is determined by transcriptional activation through the action of the Leu3-α-isopropylmalate (α-IPM) active isoform, and uncovers the existence of a novel α-IPM biosynthetic pathway operating in a put3 Δ mutant grown on VIL, through Bat2-Leu2-Leu1 consecutive action. The classic α-IPM biosynthetic route operates in glutamine through the action of the leucine-sensitive α-IPM synthases. The presented results also show that BAT2 repression in glutamine can be alleviated in a ure2 Δ mutant or through Gcn4-dependent transcriptional activation. Thus, when S. cerevisiae is grown on glutamine, VIL biosynthesis is predominant and is preferentially achieved through BAT1 ; while on VIL as the sole nitrogen source, catabolism prevails and is mainly afforded by BAT2 . Copyright © 2017 by the Genetics Society of America.

Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

Directory of Open Access Journals (Sweden)

Angel L. Pey

2013-01-01

Full Text Available Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.

Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260

International Nuclear Information System (INIS)

Harrill, Alison H.; Eaddy, John S.; Rose, Kelly; Cullen, John M.; Ramanathan, Lakshmi; Wanaski, Stephen; Collins, Stephen; Ho, Yu; Watkins, Paul B.; LeCluyse, Edward L.

2014-01-01

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABA A receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog > human > rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity. - Highlights: • NP260 caused ALT elevations in dogs without evidence of hepatocellular injury. • SDH, GLDH, and miRNA-122 elevations occurred, confirming hepatocellular necrosis. • NP260 toxicity is greater in dog and human hepatocytes than in rat hepatocytes. • Species sensitivity may explain why the rodent studies failed to indicate risk. • Diagnostic biomarkers and hepatocyte studies aid interpretation of hepatotoxicity

Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart.

Science.gov (United States)

Monteiro, D A; Kalinin, A L; Selistre-de-Araujo, H S; Vasconcelos, E S; Rantin, F T

2016-02-01

Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traíra, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) exchanger); 4) abolishment of the typical negative force-frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca(2+) handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

The medical laboratory issues about recommendation on uniform cutoff values of “normal” ALT in the ACG guidelines

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YU Qian

2018-01-01

Full Text Available In the recent American clinical guidelines dealing with laboratory tests for evaluation of liver disease, the American College of Gastroenterology (ACG recommends ALT upper reference limits of 33 U/L for males and 25 U/L for females respectively, and that individuals with ALT above these “normal” cutoffs should be further investigated. Considering the differences between laboratory assays measuring ALT in our country, the standardization of methods and the consistency of results can not be completely ensured. The uniform “normal” range of ALT recommended by the ACG guidelines is largely based on findings from foreign studies and may not be suitable to Chinese population. On the other hand, reference upper/lower limits should not simply be equated with clinical decision thresholds. However, due to improper application of the related concepts of the above medical laboratory issues, simply recommending the uniform reference range of the ALT may lead to overdiagnosis and unnecessary follow-up examinations.

Occupational coke oven emissions exposure and risk of abnormal liver function: modifications of body mass index and hepatitis virus infection

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Y. Hu; B. Chen; J. Qian; L. Jin; T. Jin; D. Lu [Fudan University, Shanghai (China). Department of Occupational and Environmental Health

2010-03-15

Occupational coke oven emissions (COEs) have been considered an important health issue. However, there are no conclusive data on human hepatic injury due to COE exposure. The association of COE exposure with liver function was explored and the effects of modification of potential non-occupational factors were assessed. 705 coke oven workers and 247 referents were investigated. Individual cumulative COE exposure was quantitatively estimated. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), {gamma}-glutamyl transferase, alkaline phosphatase, hepatitis B surface antigen and anti-hepatitis C antibody were measured. Among those with high COE exposure, the adjusted ORs of abnormal ALT and AST were 5.23 (95% CI 2.66 to 10.27) and 1.95 (95% CI 1.18 to 3.52), respectively. Overweight individuals (body mass index (BMI) {>=}25 kg/m{sup 2}) with high COE exposure had elevated risks of abnormal ALT (adjusted OR 23.93, 95% CI 8.73 to 65.62) and AST (adjusted OR 5.18, 95% CI 2.32 to 11.58). Risk of liver damage in hepatitis B virus- or hepatitis C virus-positive individuals with COE exposure was also elevated. Long-term exposure to COE increases the risk of liver dysfunction, which is more prominent among those with higher BMI and hepatitis virus infection. The risk assessment of liver damage associated with COE exposure should take BMI and hepatitis virus infection into consideration.

Biochemical and phylogenetic characterization of a novel diaminopimelate biosynthesis pathway in prokaryotes identifies a diverged form of LL-diaminopimelate aminotransferase.

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Hudson, André O; Gilvarg, Charles; Leustek, Thomas

2008-05-01

A variant of the diaminopimelate (DAP)-lysine biosynthesis pathway uses an LL-DAP aminotransferase (DapL, EC 2.6.1.83) to catalyze the direct conversion of L-2,3,4,5-tetrahydrodipicolinate to LL-DAP. Comparative genomic analysis and experimental verification of DapL candidates revealed the existence of two diverged forms of DapL (DapL1 and DapL2). DapL orthologs were identified in eubacteria and archaea. In some species the corresponding dapL gene was found to lie in genomic contiguity with other dap genes, suggestive of a polycistronic structure. The DapL candidate enzymes were found to cluster into two classes sharing approximately 30% amino acid identity. The function of selected enzymes from each class was studied. Both classes were able to functionally complement Escherichia coli dapD and dapE mutants and to catalyze LL-DAP transamination, providing functional evidence for a role in DAP/lysine biosynthesis. In all cases the occurrence of dapL in a species correlated with the absence of genes for dapD and dapE representing the acyl DAP pathway variants, and only in a few cases was dapL coincident with ddh encoding meso-DAP dehydrogenase. The results indicate that the DapL pathway is restricted to specific lineages of eubacteria including the Cyanobacteria, Desulfuromonadales, Firmicutes, Bacteroidetes, Chlamydiae, Spirochaeta, and Chloroflexi and two archaeal groups, the Methanobacteriaceae and Archaeoglobaceae.

Efeitos genotóxicos e alterações de enzimas hepáticas em trabalhadores do refino de petróleo Genotoxic effects and hepatic enzymes alterations among petroleum refinery workers

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Rozana Oliveira Gonçalves

2005-10-01

Full Text Available Um estudo de casos e controles, aninhado num estudo de coorte, investigou a associação entre efeitos genotóxicos e alteração de enzimas hepáticas em trabalhadores de uma refinaria de petróleo do Nordeste. Foram examinados todos os dez novos casos de alterações de enzimas hepáticas - gama-glutamil transferase (GGT e alanina aminotransferase (ALT - ocorridos em 2002. Dez trabalhadores sem alterações de GGT ou ALT foram selecionados como controles. Os efeitos do fumo, sexo, idade e consumo de café foram controlados. O efeito genotóxico foi avaliado pela técnica de trocas entre cromátides irmãs (TCI e alterações cromossômicas (AC estruturais. As médias de TCI por célula (3,92 ± 1,04 versus 4,25 ± 1,47 e de ACE (8,85 ± 3,4 versus 9,1 ± 3,7 não diferiram de forma significante entre casos e controles respectivamente.A case-control study, nested in a cohort study, investigated the association between genotoxic effects and hepatic enzymes alterations among workers in a petroleum refinery, Northeast Brazil. Ten cases of hepatic enzymes alterations - gamma-glutamyltransferase (GGT and Alanine aminotransferase (ALT - representing all incident cases occurring in the refinery during 2002, were examined. Ten workers without GGT and ALT alterations were selected as controls. The effects of smoking, sex, age and coffee consumption were controlled. The genotoxic effects were evaluated by the sister chromatid exchange (SCE and by the chromosomal aberrations (CA techniques. Mean SCE per cell (3.92 ± 1.04 versus 4.25 ± 1.47 and CA per cell (8.85 ± 3.4 versus 9.1 ± 3.7 did not differ significantly between cases and controls respectively.

Effect of Ramadan fasting on alanine transferase (ALT in nonalcoholic fatty liver disease (NAFLD

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Hojjatolah Rahimi

2017-09-01

Full Text Available Background: The effects of Ramadan fasting on NAFLD are unknown and there are very limited studies have done in this area. Some nutritional and behavioral changes of fasting people in Ramadan can affect NAFLD. These include nutrition with high fat and calories, altering in weight and sleep and low physical activity. We decided to evaluate the effects of these changes on one of the important indicators of deterioration of NAFLD, ALT.Methods: Sixty patients with fatty liver disease performed two consecutive ALT exams before and after Ramadan month of whom finally 34 were fasting and 26 nonfasting. After collecting data they were divided in two groups of fasting and nonfasting and compared using SPSS software.Results: Mean ALT change from before to after Ramadan was higher and positive in fasting (+7.38±8.47 IU/L compared to nonfastng patients that was negative (-0.12±10.15 IU/L (P=0.002 and this change was mainly in patients who had fasted 21-30 days.Conclusion: Ramadan fasting may increase ALT. It is needed to perform more studies in patients with NAFLD during Ramadan fasting with larger sample size and in various conditions especially weight loss with patients’ education for observing dietary regimen.

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

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Liu, Junxi; Au Yeung, Shiu Lun; Lin, Shi Lin; Leung, Gabriel M.; Schooling, C. Mary

2016-01-01

We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT ...

Serum ALT levels as a surrogate marker for serum HBV DNA levels in HBeAg-negative pregnant women.

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Sangfelt, Per; Von Sydow, Madeleine; Uhnoo, Ingrid; Weiland, Ola; Lindh, Gudrun; Fischler, Björn; Lindgren, Susanne; Reichard, Olle

2004-01-01

In Stockholm, Sweden, the majority of pregnant women positive for hepatitis B surface antigen (HBsAg) are hepatitis Be antigen (HBeAg) negative. Newborns to HBeAg positive mothers receive vaccination and hepatitis B immunoglobulin (HBIg). Newborns to HBeAg negative mothers receive vaccine and HBIg only if the mothers have elevated ALT levels. The aim of this study was to retrospectively evaluate ALT levels as a surrogate marker for HBV DNA levels in HBeAg negative carrier mothers. Altogether 8947 pregnant women were screened for HBV markers from 1999 to 2001 at the Virology Department, Karolinska Hospital. Among mothers screened 192 tested positive for HBsAg (2.2%). 13 of these samples could not be retrieved. Of the remaining 179 sera, 8 (4%) tested positive for HBeAg and 171 (95.5%) were HBeAg negative. Among the HBeAg negative mothers, 9 had HBV DNA levels > 10(5) copies/ml, and of these 7 had normal ALT levels indicating low sensitivity of an elevated ALT level as a surrogate marker for high HBV DNA level. Furthermore, no correlation was found between ALT and HBV DNA levels. Hence, it is concluded that the use of ALT as a surrogate marker for high viral replication in HBeAg negative mothers could be questioned.

Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis.

Science.gov (United States)

Mattos, A Z; Mattos, A A

Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity

International Nuclear Information System (INIS)

Sayer, Christopher; Isupov, Michail N.; Westlake, Aaron; Littlechild, Jennifer A.

2013-01-01

The X-ray structures of two ω-aminotransferases from P. aeruginosa and C. violaceum in complex with an inhibitor offer the first detailed insight into the structural basis of the substrate specificity of these industrially important enzymes. The crystal structures and inhibitor complexes of two industrially important ω-aminotransferase enzymes from Pseudomonas aeruginosa and Chromobacterium violaceum have been determined in order to understand the differences in their substrate specificity. The two enzymes share 30% sequence identity and use the same amino acceptor, pyruvate; however, the Pseudomonas enzyme shows activity towards the amino donor β-alanine, whilst the Chromobacterium enzyme does not. Both enzymes show activity towards S-α-methylbenzylamine (MBA), with the Chromobacterium enzyme having a broader substrate range. The crystal structure of the P. aeruginosa enzyme has been solved in the holo form and with the inhibitor gabaculine bound. The C. violaceum enzyme has been solved in the apo and holo forms and with gabaculine bound. The structures of the holo forms of both enzymes are quite similar. There is little conformational difference observed between the inhibitor complex and the holoenzyme for the P. aeruginosa aminotransferase. In comparison, the crystal structure of the C. violaceum gabaculine complex shows significant structural rearrangements from the structures of both the apo and holo forms of the enzyme. It appears that the different rigidity of the protein scaffold contributes to the substrate specificity observed for the two ω-aminotransferases

Frederick W. Alt received the 2015 Szent-Györgi Prize for Progress in Cancer Research.

Science.gov (United States)

Scully, Peter; Zhao, Jie; Ba, Sujuan

2016-02-03

The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award established by the National Foundation for Cancer Research (NFCR)--a leading cancer research charitable organization in the United States that is committed to supporting scientific research and public education relating to the prevention, early diagnosis, better treatments, and ultimately, a cure for cancer. Each year, the Szent-Györgyi Prize honors an outstanding researcher, nominated by colleagues or peers, who has contributed outstanding, significant research to the fight against cancer, and whose accomplishments have helped improve treatment options for cancer patients. The Prize also promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. This report highlights the pioneering work led by the 2015 Prize winner, Dr. Frederick Alt. Dr. Alt's work in the area of cancer genetics over four decades has helped to shape the very roots of modern cancer research. His work continues to profoundly impact the approaches that doctors around the globe use to diagnose and treat cancer. In particular, his seminal discoveries of gene amplification and his pioneering work on molecular mechanisms of DNA damage repair have helped to usher in the era of genetically targeted therapy and personalized medicine.

[Impact analysis of shuxuetong injection on abnormal changes of ALT based on generalized boosted models propensity score weighting].

Science.gov (United States)

Yang, Wei; Yi, Dan-Hui; Xie, Yan-Ming; Yang, Wei; Dai, Yi; Zhi, Ying-Jie; Zhuang, Yan; Yang, Hu

2013-09-01

To estimate treatment effects of Shuxuetong injection on abnormal changes on ALT index, that is, to explore whether the Shuxuetong injection harms liver function in clinical settings and to provide clinical guidance for its safe application. Clinical information of traditional Chinese medicine (TCM) injections is gathered from hospital information system (HIS) of eighteen general hospitals. This is a retrospective cohort study, using abnormal changes in ALT index as an outcome. A large number of confounding biases are taken into account through the generalized boosted models (GBM) and multiple logistic regression model (MLRM) to estimate the treatment effects of Shuxuetong injections on abnormal changes in ALT index and to explore possible influencing factors. The advantages and process of application of GBM has been demonstrated with examples which eliminate the biases from most confounding variables between groups. This serves to modify the estimation of treatment effects of Shuxuetong injection on ALT index making the results more reliable. Based on large scale clinical observational data from HIS database, significant effects of Shuxuetong injection on abnormal changes in ALT have not been found.

Canine stage 1 periodontal disease: a latent pathology.

Science.gov (United States)

Whyte, A; Bonastre, C; Monteagudo, L V; Les, F; Obon, J; Whyte, J; Tejedor, M T

2014-07-01

To evaluate the potential health issues associated with periodontal disease (PD) in dogs, 1004 teeth from 25 dogs were examined. The dogs were randomly selected, aged 2-14 years, and had at least 95% of their teeth at the first PD stage. Significant positive correlations between plaque grade (PG) and gum inflammation, gingival regression, periodontal pocket, age and serum alanine aminotransferase (ALT) activity were identified. In contrast, PG was negatively correlated to total platelet count. Altogether, these findings suggest that prevention and therapy at the first PD stages can have an important impact on the general health condition of dogs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ephedra alte (Joint Pine: An Invasive, Problematic Weedy Species in Forestry and Fruit Tree Orchards in Jordan

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Jamal R. Qasem

2012-01-01

Full Text Available A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008–2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked.

Ephedra alte (Joint Pine): An Invasive, Problematic Weedy Species in Forestry and Fruit Tree Orchards in Jordan

Science.gov (United States)

Qasem, Jamal R.

2012-01-01

A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008–2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked. PMID:22645486

Ephedra alte (joint pine): an invasive, problematic weedy species in forestry and fruit tree orchards in Jordan.

Science.gov (United States)

Qasem, Jamal R

2012-01-01

A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008-2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked.

INTERNAL MILIEAU OF DAIRY COWS AT THE BEGINNING OF LACTATION AND ITS INFLUENCE ON COMPOSITION OF RAW MILK

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Tušimová Eva

2015-02-01

Full Text Available The aim of this work was to evaluate selected blood biochemical parameters and milk composition of dairy cows at the beginning of lactation and to observe the correlations between blood and milk parameters. In total, 15 Holstein cows at the beginning of lactation were chosen. Blood and milk samples were collected. Energetic (glucose - GLU, d-beta-hydroxybutyrate - D-BHB, triglycerides - TG, nitrogenous (total proteins - TP, UREA, hepatic (aspartate aminotransferase - AST, alanine aminotransferase - ALT, gamma-glutamyltransferase - GGT, alkaline phosphatase - ALP, bilirubin - BILI, cholesterol - CHOL and mineral (sodium - Na, potassium - K, chlorides - Cl-, calcium – Ca, phosphorus – P, magnesium - Mg profiles were determined in the blood serum. Levels of lactose, fat, proteins and minerals (sodium - Na, potassium – K, calcium – Ca, phosphorus – P, magnesium - Mg were determined in milk. Most of the parameters outside physiological limits were found among mineral and hepatic profile. Levels of calcium, phosphorus and sodium were decreased in comparison to reference values. Average concentration of urea was also lower. On the other hand, increase of aspartate aminotransferase and gamma-glutamyltransferase were observed. Levels of lactose (4.82 g.100g-1, fat (4.21 g.100g-1, protein (3.14 g.100g-1 and calcium (4.82 g.l-1 in milk complied with Slovak national standard (STN 57 0529. In our study, ratio of fat to protein lower than 0.75 was observed in 13 % of cows (risk of ketosis and higher than 1.4 in 40 % (NEB. Strong negative correlation between serum cholesterol and milk fat (-0.716; P<0.01 and middle strong negative correlation between cholesterol and milk protein (-0.397; P<0.01 were observed. ALT affected negatively amount of phosphorus in milk (-0.417; P<0.001, which complied with demineralization of the organism and following restriction of liver detoxification activity. On the other hand, strong positive correlation was observed

Evolutionary Diversification of Alanine Transaminases in Yeast: Catabolic Specialization and Biosynthetic Redundancy

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Ximena Escalera-Fanjul

2017-06-01

Full Text Available Gene duplication is one of the major evolutionary mechanisms providing raw material for the generation of genes with new or modified functions. The yeast Saccharomyces cerevisiae originated after an allopolyploidization event, which involved mating between two different ancestral yeast species. ScALT1 and ScALT2 codify proteins with 65% identity, which were proposed to be paralogous alanine transaminases. Further analysis of their physiological role showed that while ScALT1 encodes an alanine transaminase which constitutes the main pathway for alanine biosynthesis and the sole pathway for alanine catabolism, ScAlt2 does not display alanine transaminase activity and is not involved in alanine metabolism. Moreover, phylogenetic studies have suggested that ScALT1 and ScALT2 come from each one of the two parental strains which gave rise to the ancestral hybrid. The present work has been aimed to the understanding of the properties of the ancestral type Lacchancea kluyveri LkALT1 and Kluyveromyces lactis KlALT1, alanine transaminases in order to better understand the ScALT1 and ScALT2 evolutionary history. These ancestral -type species were chosen since they harbor ALT1 genes, which are related to ScALT2. Presented results show that, although LkALT1 and KlALT1 constitute ScALT1 orthologous genes, encoding alanine transaminases, both yeasts display LkAlt1 and KlAlt1 independent alanine transaminase activity and additional unidentified alanine biosynthetic and catabolic pathway(s. Furthermore, phenotypic analysis of null mutants uncovered the fact that KlAlt1 and LkAlt1 have an additional role, not related to alanine metabolism but is necessary to achieve wild type growth rate. Our study shows that the ancestral alanine transaminase function has been retained by the ScALT1 encoded enzyme, which has specialized its catabolic character, while losing the alanine independent role observed in the ancestral type enzymes. The fact that ScAlt2 conserves 64

Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABA{sub A} receptor antagonist NP260

Energy Technology Data Exchange (ETDEWEB)

Harrill, Alison H., E-mail: ahharrill@uams.edu [College of Public Health, The University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); The Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Eaddy, John S. [The Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Rose, Kelly [The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Cullen, John M. [College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607 (United States); Ramanathan, Lakshmi [QPS, Newark, DE 19711 (United States); Wanaski, Stephen; Collins, Stephen; Ho, Yu [NeuroTherapeutics Pharma, Inc., Chicago, IL 60631 (United States); Watkins, Paul B. [The Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Schools of Pharmacy and Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); LeCluyse, Edward L. [The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

2014-06-01

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABA{sub A} receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog > human > rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity. - Highlights: • NP260 caused ALT elevations in dogs without evidence of hepatocellular injury. • SDH, GLDH, and miRNA-122 elevations occurred, confirming hepatocellular necrosis. • NP260 toxicity is greater in dog and human hepatocytes than in rat hepatocytes. • Species sensitivity may explain why the rodent studies failed to indicate risk. • Diagnostic biomarkers and hepatocyte studies aid interpretation of hepatotoxicity.

Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle

OpenAIRE

Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

2015-01-01

The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid conten...

Effects of different levels of protein supplements in the diet of early-weaned yaks on growth performance, intestinal development, and immune response to tuberculosis

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Haibo Zhang

2015-06-01

Full Text Available This study was conducted to determine the effects of different levels of crude protein (CP supplements to the diet of early-weaned yaks on their growth performance, intestinal development, and immune response. Forty 3-month-old weaned yaks were selected and assigned to four dietary groups (Control, 17, 19 and 21% CP. Dietary CP supplements had a significant effect on average daily gain (ADG, crypt depth (CD (duodenum, jejunum and ileum, villous height (VH (duodenum, jejunum and ileum and CD/VH (jejunum and ileum. Average daily gain, CD (duodenum, jejunum and ileum and VH (ileum showed quadratic increases as the dietary CP increased, whereas CD/VH (jejunum and ileum ratios showed quadratic decreases. Blood urea nitrogen (BUN, glucose (GLU, immunoglobulin G (IgG, IgM, interleukin-1 (IL-1, IL-2, tumor necrosis factor (TNF-α, and interferon (IFN-γ concentrations increased significantly, whereas albumin (ALB, alanine aminotransferase (ALT and aspartate aminotransferase (AST decreased significantly with dietary CP supplements. Dietary CP supplements significantly increased the concentrations of IL-6, TNF-α, IFN-γ and the nuclear factor of activated T cell transcription factor (NFAT for gene expression. As the dietary CP supplements increased, IL-6, IFN-γ and NF-AT gene expression showed quadratic increases. These results showed that the appropriate dietary CP supplementation improved the growth performance and intestinal development of earlyweaned yaks and thus that the CP supplements were beneficial and enhanced the humoral immunity response of yaks.

nvj 34 4 corrected.cdr

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Brommer et al, 2001) Errors that affect the results of biochemical tests may be ... pH. Total protein and albumin. Vitamins. Lactate. Aminotransferases. (ALT and ... inappropriate container, handling, storage ... undetected failure in quality control) or.

Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

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Zhang, De Lu, E-mail: deluzh@163.com [Department of Lifescience and Biotechnology, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Hu, Chun Xiang, E-mail: cxhu@ihb.ac.cn [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)

2014-12-15

Highlights: • Aphantoxins induced zebrafish hepatic physiological and morphological changes. • AChE and MAO inhibition reflected abnormality of neurotransmitter inactivation. • ROS advance and T-AOC reduction suggested oxidative stress. • ALT, AST, histological and ultrastructural alterations indicated hepatic damage. - Abstract: Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1–24 h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3–12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish

Jasmonate is involved in the induction of tyrosine aminotransferase and tocopherol biosynthesis in Arabidopsis thaliana.

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Sandorf, Iris; Holländer-Czytko, Heike

2002-11-01

Coronatine-inducible tyrosine aminotransferase (TAT), which catalyses the transamination from tyrosine to p-hydroxyphenylpyruvate, is the first enzyme of a pathway leading via homogentisic acid to plastoquinone and tocopherols, the latter of which are known to be radical scavengers in plants. TAT can be also induced by the octadecanoids methyl jasmonate (MeJA) and methyl-12-oxophytodienoic acid (MeOPDA), as well as by wounding, high light, UV light and the herbicide oxyfluorfen. In order to elucidate the role of octadecanoids in the process of TAT induction in Arabidopsis thaliana (L.) Heynh., the jasmonate-deficient mutant delayed dehiscence (dde1) was used, in which the gene for 12-oxophytodienoic acid reductase 3 is disrupted. The amount of immunodetectable TAT was low. The enzyme was still fully induced by coronatine as well as by MeJA although induction by the latter was to a lesser extent and later than in the wild type. Treatment with MeOPDA, wounding and UV light, however, had hardly any effects. Tocopherol levels that showed considerable increases in the wild type after some treatments were much less affected in the mutant. However, starting levels of tocopherol were higher in non-induced dde1 than in the wild type. We conclude that jasmonate plays an important role in the signal transduction pathway regulating TAT activity and the biosynthesis of its product tocopherol.

Standardization of clinical enzyme analysis using frozen human serum pools with values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures.

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Tong, Qing; Chen, Baorong; Zhang, Rui; Zuo, Chang

Variation in clinical enzyme analysis, particularly across different measuring systems and laboratories, represents a critical but long-lasting problem in diagnosis. Calibrators with traceability and commutability are imminently needed to harmonize analysis in laboratory medicine. Fresh frozen human serum pools were assigned values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK) and lactate dehydrogenase (LDH) by six laboratories with established International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures. These serum pools were then used across 76 laboratories as a calibrator in the analysis of five enzymes. Bias and imprecision in the measurement of the five enzymes tested were significantly reduced by using the value-assigned serum in analytical systems with open and single-point calibration. The median (interquartile range) of the relative biases of ALT, AST, GGT, CK and LDH were 2.0% (0.6-3.4%), 0.8% (-0.8-2.3%), 1.0% (-0.5-2.0%), 0.2% (-0.3-1.0%) and 0.2% (-0.9-1.1%), respectively. Before calibration, the interlaboratory coefficients of variation (CVs) in the analysis of patient serum samples were 8.0-8.2%, 7.3-8.5%, 8.1-8.7%, 5.1-5.9% and 5.8-6.4% for ALT, AST, GGT, CK and LDH, respectively; after calibration, the CVs decreased to 2.7-3.3%, 3.0-3.6%, 1.6-2.1%, 1.8-1.9% and 3.3-3.5%, respectively. The results suggest that the use of fresh frozen serum pools significantly improved the comparability of test results in analytical systems with open and single-point calibration.

Effect of nitrate poisoning on some biochemical parameters in rats

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M. B. Mahmood

2011-01-01

Full Text Available The present study was conducted to investigate the toxicity of potassium nitrate on glucose, cholesterol, alanine aminotransferase (ALT, aspartate aminotransferase (AST, and the possible ameliorative effect of ascorbic acid (Vitamin C. Male Wister rats are used as experimental model divided into three groups (each of 6-8 rats and treated for six weeks as follows: Group 1: served as control; Group 2: received 2 % potassium nitrate added to the forage and Group 3: received 2 % potassium nitrate together with 1 % ascorbic acid added to rat's forage. Nitrate treatment in group 2 leads to high significant increase levels of glucose in 3rd, 4th, and 5th weeks, cholesterol level increased significantly in both 4th and 5th weeks, while ALT levels increased in the 4th, 5th and 6th weeks, and AST increased significantly in the 5th and 6th weeks. Addition of ascorbic acid with potassium nitrate, lead to reverse all the parameters nearly to normal. It was concluded that potassium nitrate causes significant toxic effect on some biochemical parameters which was ameliorated by ascorbic acid.

Hepatic necro-inflammation and elevated liver enzymes: Evaluation with MRI perfusion imaging with gadoxetic acid in chronic hepatitis patients

International Nuclear Information System (INIS)

Chen, B.-B.; Hsu, C.-Y.; Yu, C.-W.; Kao, J.-H.; Lee, H.-S.; Liang, P.-C.; Wei, S.-Y.; Hwang, R.-M.; Shih, T.T.-F.

2014-01-01

Aim: To evaluate liver necro-inflammation and function by using gadoxetic acid-enhanced dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with histological analysis as the reference standard. Materials and methods: Seventy-nine subjects (21 healthy subjects; 58 chronic hepatitis patients) who received gadoxetic acid-enhanced DCE-MRI were divided into three subgroups: no (A0, n = 31), mild (A1, n = 27), and moderate–severe (A2–A3, n = 21) activities. Two DCE-MRI models were measured: (1) a dual-input single-compartment model to obtain absolute arterial, portal venous, and total blood flow, arterial fraction (ART), distribution volume, and mean transit time; (2) a curve analysis method to obtain peak, slope, and AUC (area under curve). The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels also obtained. Statistical testing included Kruskal–Wallis tests for continuous data, Pearson's correlation tests, and multiple linear regression analyses. Results: Hepatic necro-inflammatory activity grades were significantly correlated with fibrotic stages, serum ALT level, ART and AUC. ART was helpful to predict the mild activity (≤A1 versus >A1; Az = 0.728), whereas AUC could differentiate no activity from any activity (A0 versus >A0; Az = 0.703). Peak, slope and AUC were all associated with AST and ALT (p < 0.05). Conclusion: Gadoxetic acid-enhanced DCE-MRI parameters may be used to evaluate the severity of hepatic necro-inflammation and function

Disk suspension method: a novel and safe technique for the retraction of the liver during laparoscopic surgery (with video).

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Shibao, Kazunori; Higure, Aiichiro; Yamaguchi, Koji

2011-08-01

A good operative field is important for safe operations, but it is sometimes difficult to obtain a satisfactory operative field in laparoscopic upper abdominal surgery. We developed a novel and safe technique for the retraction of the liver and falciform ligament during laparoscopic surgery, and evaluated its technical feasibility and safety. Forty-three patients with gastric cancer were divided into two groups: disk suspension group (DS group; snake retractor and elastic band fixation with a silicon disk), and fixed retractor group (FR group; snake retractor and nonelastic band fixation without a silicon disk). To evaluate liver damage during retraction, we measured the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels preoperatively and on postoperative day (POD) 1. In the DS group, all liver lobes were adequately retracted and the hepatoduodenal and gastrohepatic ligaments were fully exposed. This procedure took less than 3 min. On the other hand, 5 of 18 patients of the FR group had insufficient surgical fields for laparoscopic gastrectomy because of soft and/or large livers. Although the preoperative AST and ALT levels were not different between the two groups, the DS group did not display increases in both AST and ALT levels, whereas the FR group showed increases in both on POD 1 (AST: 50.2 ± 8.4 IU/l vs. 124.2 ± 37.7 IU/l, P = 0.07; and ALT: 35.6 ± 6.4 IU/l vs. 106.1 ± 36.2 IU/l, P = 0.07). No complications related to the liver retraction were observed in the DS group. However, liver congestion was evident in six patients and minor liver injury in two patients of the FR group during the esophagojejunostomy. The DS method is a simple and safe and provides a better surgical field during laparoscopic surgery of the upper abdomen without damaging the liver.

Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice.

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Abdel-Salam, Omar M E; Salem, Neveen A; Hussein, Jihan Seid

2012-04-01

This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS; 100 μg/kg) in mice. Aspartame (0.625-45 mg/kg) was given via subcutaneous route at the time of endotoxin administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis factor-alpha (TNF-α) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7-32.8%, decreased GSH by 25.6-31.6%, and increased TNF-α by 16.7-44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline, and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration of LPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by 21.6 and 31.1%, respectively; increased brain TNF-α by 340.4%, and glucose by 39.9%, and caused marked increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%, respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5-16.9%, nitrite by 12.6-20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS, nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mild systemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver.

Simple synthesis of P(Cbz-alt-TBT) and PCDTBT by combining direct arylation with suzuki polycondensation of heteroaryl chlorides.

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Lombeck, Florian; Matsidik, Rukiya; Komber, Hartmut; Sommer, Michael

2015-01-01

Direct arylation (DA) of 2-chlorothiophene and 2-chloro-3-hexylthiophene with 4,7-dibromo-2,1,3-benzothiadiazole is used to synthesize 4,7-bis(5-chloro-2-thienyl)-2,1,3-benzothiadiazole (TBTCl2) and 4,7-bis(5-chloro-4-hexyl-2-thienyl)-2,1,3-benzothiadiazole (DH-TBTCl2) in one step. Suitable conditions of the Suzuki polycondensations (SPC) of TBTCl2 and DH-TBTCl2 with the carbazole comonomer CbzPBE2 are established, furnishing PCDTBT and P(Cbz-alt-TBT) with high molecular weight and yield. Compared with control samples made from the corresponding dibromides, high-temperature NMR and UV-vis spectroscopy indicate similar properties for PCDTBT but an increased content of Cbz-Cbz homocouplings for P(Cbz-alt-TBT). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular characterization and expression study of a histidine auxotrophic mutant (his1-) of Nicotiana plumbaginifolia.

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El Malki, F; Jacobs, M

2001-01-01

The histidine auxotroph mutant his 1(-) isolated from Nicotiana plumbaginifolia haploid protoplasts was first characterized to be deficient for the enzyme histidinol phosphate aminotransferase that is responsible for one of the last steps of histidine biosynthesis. Expression of the mutated gene at the RNA level was assessed by northern analysis of various tissues. Transcriptional activity was unimpaired by the mutation and, in contrast, a higher level of expression was obtained when compared to the wild-type. The cDNA sequence encoding the mutated gene was isolated by RT-PCR and compared to the wild-type gene. A single point mutation corresponding to the substitution of a G nucleotide by A was identified at position 1212 starting from the translation site. The alignment of the deduced amino acid sequences from the mutated and wild-type gene showed that this mutation resulted in the substitution of an Arg by a His residue at position 381. This Arg residue is a conserved amino acid for histidinol phosphate aminotransferase of many species. These results indicate that the identified mutation results in an altered histidinol phosphate aminotransferase enzyme that is unable to convert the substrate imidazole acetol phosphate to histidinol phosphate and thereby leads to the blockage of histidine biosynthesis. Possible consequences of this blockage on the expression of other amino acid biosynthesis genes were evaluated by analysing the expression of the dhdps gene encoding dihydrodipicolinate synthase, the first key enzyme of the lysine pathway.

Crystallization and preliminary X-ray diffraction analysis of l,l-diaminopimelate aminotransferase (DapL) from Chlamydomonas reinhardtii

International Nuclear Information System (INIS)

Hudson, André O.; Girón, Irma; Dobson, Renwick C. J.

2010-01-01

A variant of the diaminopimelate/lysine pathway has recently been defined following the discovery of the enzyme l,l-diaminopimelate aminotransferase (DapL). The cloning of the cDNA, recombinant expression, purification and preliminary diffraction analysis of DapL from the alga C. reinhardtii are presented. In the anabolic synthesis of diaminopimelate and lysine in plants and in some bacteria, the enzyme l,l-diaminopimelate aminotransferase (DapL; EC 2.6.1.83) catalyzes the conversion of tetrahydrodipicolinic acid (THDPA) to l,l-diaminopimelate, bypassing the DapD, DapC and DapE enzymatic steps in the bacterial acyl pathways. Here, the cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DapL from the alga Chlamydomonas reinhardtii are presented. Protein crystals were grown in conditions containing 25%(w/v) PEG 3350 and 200 mM lithium sulfate and initially diffracted to ∼1.35 Å resolution. They belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 58.9, b = 91.8, c = 162.9 Å. The data were processed to 1.55 Å resolution with an R merge of 0.081, an R p.i.m. of 0.044, an R r.i.m of 0.093 and a V M of 2.28 Å 3 Da −1

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital.

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Anjos, Alessandra Marques dos; Nunes, Magda Lahorgue

2009-09-01

To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. During the study, 30 (4.2%) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73%) and term infants (70%). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

Carboxylesterase 1 genes

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Rasmussen, Henrik Berg; Madsen, Majbritt Busk

2018-01-01

The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2...

miR-380-5p-mediated repression of TEP1 and TSPYL5 interferes with telomerase activity and favours the emergence of an “ALT-like” phenotype in diffuse malignant peritoneal mesothelioma cells

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Graziella Cimino-Reale

2017-07-01

Full Text Available Abstract Background Understanding the molecular/cellular underpinnings of diffuse malignant peritoneal mesothelioma (DMPM, a fatal malignancy with limited therapeutic options, is of utmost importance for the fruitful management of the disease. In this context, we previously found that telomerase activity (TA, which accounts for the limitless proliferative potential of cancer cells, is prognostic for disease relapse and cancer-related death in DMPM patients. Consequently, the identification of factors involved in telomerase activation/regulation may pave the way towards the development of novel therapeutic interventions for the disease. Here, the capability of miR-380-5p, a microRNA negligibly expressed in telomerase-positive DMPM clinical specimens, to interfere with telomerase-mediated telomere maintenance and, hence, with cancer cell growth was assessed on preclinical models of DMPM. Methods DMPM cells were transfected with a miR-380-5p synthetic precursor, and the effects of miRNA replacement were evaluated in terms of growing capability, induction of apoptosis and interference with TA. Reiterated weekly transfections were also performed in order to analyse the phenotype arising upon prolonged miR-380-5p reconstitution in DMPM cells. Results The ectopic expression of miR-380-5p elicited a remarkable inhibition of TA and resulted in DMPM cell growth impairment and apoptosis induction. In particular, we demonstrated for the first time that these effects were the result of a molecular circuitry converging on telomerase associated protein 1 (TEP1, where the miRNA was able to target the gene both directly in unconventional targeting modality and indirectly via p53 accumulation consequent to miRNA-mediated downregulation of testis-specific protein, Y-encoded-like 5 gene. Moreover, miR-380-5p did not cause telomere attrition and cell growth arrest in long-term DMPM transfectants, which in turn showed slightly elongated telomeres and molecular

Hepatic enzyme decline after pediatric blunt trauma: a tool for timing child abuse?

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Baxter, Amy L; Lindberg, Daniel M; Burke, Bonnie L; Shults, Justine; Holmes, James F

2008-09-01

Previous research in adult patients with blunt hepatic injuries has suggested a pattern of serum hepatic transaminase concentration decline. Evaluating this decline after pediatric blunt hepatic trauma could establish parameters for estimating the time of inflicted injuries. Deviation from a consistent transaminase resolution pattern could indicate a developing complication. Retrospective review of pediatric patients with injuries including blunt liver trauma admitted to one of four urban level 1 trauma centers from 1990 to 2000. Cases were excluded for shock, death within 48 h, complications, or inability to determine injury time. Transaminase concentration decline was modeled by individual patients, by injury grade, and as a ratio with regard to injury time. One hundred and seventy-six patients met inclusion criteria. The rate of aspartate aminotransferase (AST) clearance changed significantly over time. Alanine aminotransferase (ALT) fell more slowly. Of the 118 patients who had multiple measurements of AST, for 112 (95%) the first concentration obtained was the highest. When ALT was greater than AST, the injury was older than 12h (97% specificity (95% CI, 95-99%), sensitivity 42% (95% CI, 33-50%)). Patients with enzymes that rose after 14 h post-injury were more likely to develop complications (RR=24, 95% CI 10-58). Hepatic transaminases rise rapidly after uncomplicated blunt liver injury, then fall predictably. Persistently stable or increasing concentrations may indicate complications. ALT>AST indicates subacute injury.

Assessment of Dengue Fever Severity Through Liver Function Tests

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Ahmed, A.; Alvi, A. H.; Nawaz, A. A.; Butt, A.; Hanif, A.

2014-01-01

Objective: To assess the utility of liver function tests (LFTs) for early recognition and prediction of severity of Dengue fever in hospitalized patients. Study Design: An analytical study. Place and Duration of Study: Services Institute of Medical Science and Fatima Memorial Hospital, Lahore, from September - December 2010. Methodology: Admitted cases of Dengue fever were divided into 3 groups; mild, moderate and severe increases in aminotransferases. Elevation in LFTs was co-related with good or bad outcome i.e. (survival or complication free stay) or (death or complications). Results were analyzed in SPSS version 18. Results: Out of the 353 patients with mean age of 37.12 +- 15.45 years, 245 (69.4%) were males and 108 (30.6%) were females. Seventy five patients (21.2%) had mild elevation of aminotransferases (2 fold increases), 265 patients (75.1%) had moderate increases (3 to 4 fold) and 13 (3.7%) had severe (> 4 fold increase). ALT was statistically higher in patients with septicemia, hepatic and renal failure (p-value 0.05). AST was higher in almost all complications. Prolonged hospital stay was associated with raised LFTs and greater complications and mortality. AST was found to be twice as much raised as ALT. Conclusion: AST and ALT were statistically higher in patients with worse outcome thus can lead to early recognition of high risk cases. (author)

Sensitive, specific radioisotope assay for L-glutamine-D-fructose-6- phosphat aminotransferase

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Callahan, M.; Tourian, A.; Hung, W.Y.

1981-01-01

A sensitive and specific radioassay for L-glutamine-D-fructose-6-phosphate aminotransferase (EC 5.3.1.19) activity is presented. Picomoles of product are measurable, and the assay can be applied to systems having limited quantities of available protein, particularly in extracts of either cell or organ cultures. The assay is at least 10,000 times more sensitive under K 1 concentrations of fructose 6-phosphate than the modified Elson-Morgan colorimetric assay and 20 times more sensitive under saturating conditions of fructose 6-phosphate. As little as 0.5 μg of cell-extract protein will yield measurable product. In contrast, 280 μg of crude-extract protein from colon is required with the modified Elson-Morgan colorimetric assay

Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia

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Alizée Latour

2015-03-01

Full Text Available Hyperhomocysteinemia results from hepatic metabolism dysfunction and is characterized by a high plasma homocysteine level, which is also an independent risk factor for cardiovascular disease. Elevated levels of homocysteine in plasma lead to hepatic lesions and abnormal lipid metabolism. Therefore, lowering homocysteine levels might offer therapeutic benefits. Recently, we were able to lower plasma homocysteine levels in mice with moderate hyperhomocysteinemia using an adenoviral construct designed to restrict the expression of DYRK1A, a serine/threonine kinase involved in methionine metabolism (and therefore homocysteine production, to hepatocytes. Here, we aimed to extend our previous findings by analyzing the effect of hepatocyte-specific Dyrk1a gene transfer on intermediate hyperhomocysteinemia and its associated hepatic toxicity and liver dysfunction. Commensurate with decreased plasma homocysteine and alanine aminotransferase levels, targeted hepatic expression of DYRK1A in mice with intermediate hyperhomocysteinemia resulted in elevated plasma paraoxonase-1 and lecithin:cholesterol acyltransferase activities and apolipoprotein A–I levels. It also rescued hepatic apolipoprotein E, J, and D levels. Further, Akt/GSK3/cyclin D1 signaling pathways in the liver of treated mice were altered, which may help prevent homocysteine-induced cell cycle dysfunction. DYRK1A gene therapy could be useful in the treatment of hyperhomocysteinemia in populations, such as end-stage renal disease patients, who are unresponsive to B-complex vitamin therapy.

THE CHIMERIC ALT-VASTUS LATERALIS FREE FLAP IN RECONSTRUCTION OF ADVANCED BRONJ OF THE MAXILLA

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Francesca Toia

2015-04-01

Full Text Available ntroduction Bisphosphonate-related osteonecrosis of the jaw (BRONJ is a dangerous complication of bisphosphonates, a class of pharmaceutical agents used in numerous bone disorders. No gold standard therapy exists, but recent literature suggests that, in advanced stages, the best results are achieved with aggressive debridement. In this paper, we report our experience of treatment of stage 3 BRONJ of the maxilla with extensive surgical debridement and reconstruction with a chimeric ALT-Vastus lateralis flap. Methods Five selected patients with stage 3 BRONJ underwent partial maxillectomy with disease-free margins followed by immediate reconstruction with a chimeric ALT-Vastus lateralis free flap. Results Only two patients experienced minor complications. All other patients healed uneventfully within two weeks and donor site morbidity was minimal. Conclusions Our data suggest that aggressive debridement and reconstruction with a chimeric ALT -Vastus lateralis flap is an effective option for the treatment of stage III BRONJ of the maxilla.

Type 1 Diabetes and Non-Alcoholic Fatty Liver Disease: When Should We Be Concerned? A Nationwide Study in Brazil †

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de Melo, Laura Gomes Nunes; Brito Gomes, Marilia

2017-01-01

Obesity is increasing worldwide, affecting even patients with type 1 diabetes (T1D). A higher prevalence of associated comorbidities is expected, such as non-alcoholic fatty liver disease (NAFLD). This paper reports a cross-sectional multicenter study on a population with T1D (n = 1662), which aimed to evaluate the prevalence of metabolic syndrome (MS), a known risk factor for NAFLD, and to investigate predisposing factors associated with MS, as well as factors associated with elevated alanine aminotransferase (ALT), as it correlates to liver fat content. Patients were from 14 public clinics of 10 cities from all geographical regions of Brazil. A high prevalence of MS was found, especially among adults (32.3%), and this was related to age, female gender, acid uric levels, and the presence of acanthosis nigricans. ALT above the normal range was associated with triglyceride levels (especially above 129.5 mg/dL), serum uric acid, age, male gender, HbA1c, and non-Caucasian ethnicity. Patients with T1D, metabolic syndrome, and the aforementioned factors may be at a higher risk of NAFLD and should be referred to ultrasound for NAFLD evaluation. Further studies are necessary to establish the prevalence of NAFLD in individuals with T1D and to determine the disease’s progression in these patients. PMID:28809804

The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats

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Nishiya, Takayoshi; Mori, Kazuhiko; Hattori, Chiharu; Kai, Kiyonori; Kataoka, Hiroko; Masubuchi, Noriko; Jindo, Toshimasa; Manabe, Sunao

2008-01-01

To investigate the hepatotoxic potential of tienilic acid in vivo, we administered a single oral dose of tienilic acid to Sprague-Dawley rats and performed general clinicopathological examinations and hepatic gene expression analysis using Affymetrix microarrays. No change in the serum transaminases was noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and bilirubin, and very mild hepatotoxic changes in morphology were observed. In contrast to the marginal clinicopathological changes, marked upregulation of the genes involved in glutathione biosynthesis [glutathione synthetase and glutamate-cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H dehydrogenase quinone 1] and phase II drug metabolism (glutathione S-transferase and UDP glycosyltransferase 1A6) were noted after 3 or 6 h post-dosing. The hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or 48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated gene and the late increase in hepatic glutathione are protective responses against the oxidative and/or electrophilic stresses caused by tienilic acid. In a subsequent experiment, tienilic acid in combination with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of Gcl caused marked elevation of serum alanine aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was observed at the same dose levels of tienilic acid as the upregulation of the Nrf2-regulated genes by tienilic acid alone. In conclusion, these results suggest that the impairment of glutathione biosynthesis may play a critical role in the development of tienilic acid hepatotoxicity through extensive oxidative and/or electrophilic stresses

Liver histology in hepatitis C virus positive patients with normal and elevated alanine amino transferase levels

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Bhatty, S.A.; Shaikh, N.A.; Akhter, S.S.

2009-01-01

To compare liver histology in HCV RNA positive patients with normal and elevated Alanine Aminotransferase Level (AST). This Cohort (prospective) study was conducted at Civil Hospital Karachi from Jan 2007 to July 2007. Forty patients with positive HCV RNA were included. Their liver function tests were followed for three months. Those having normal ALT on three occasions were taken as controls and those having elevated ALT were taken as cases. Liver biopsy was performed, Specimens were reviewed by single pathologist. Scheuer's scoring for grading of inflammation and staging of fibrosis of chronic hepatitis was used. Out of Forty patients having positive HCV RNA, 14 (35%) were male and 26 (65%) were female. Mean ALT in control group was 27.3 +- 6.1mu/l, mean ALT in cases was 91.7 +- 39.95 mu/l. Mean age in controls was 34.2 +- 10.75 years and in cases was 33.6 +- 9.40 years. On histopathology, the mean grade of inflammation in controls was 1.40 +- 0.681 while in cases was 1.20 +- 0.834, which was not statistically significantly different in the two groups (p= 0.411). Similarly mean staging of fibrosis in controls was 1.20 +- 0.768 and in cases was 1.35 +- 1.348 which was also not statistically different in the two groups (p=0.668). Stage 3 and 4 fibrosis was seen only in raised ALT group and not in the controls. Patients with persistently normal ALT and elevated ALT, although had similar grading of inflammation but the fibrosis score was more in elevated ALT group. None of the patients with normal ALT had normal histology, so decision for antiviral treatment should be individualized in this group also (JPMA 59:832; 2009). (author)

Structure and mechanism of a cysteine sulfinate desulfinase engineered on the aspartate aminotransferase scaffold.

Science.gov (United States)

Fernandez, Francisco J; de Vries, Dominique; Peña-Soler, Esther; Coll, Miquel; Christen, Philipp; Gehring, Heinz; Vega, M Cristina

2012-02-01

The joint substitution of three active-site residues in Escherichia coli (L)-aspartate aminotransferase increases the ratio of l-cysteine sulfinate desulfinase to transaminase activity 10(5)-fold. This change in reaction specificity results from combining a tyrosine-shift double mutation (Y214Q/R280Y) with a non-conservative substitution of a substrate-binding residue (I33Q). Tyr214 hydrogen bonds with O3 of the cofactor and is close to Arg374 which binds the α-carboxylate group of the substrate; Arg280 interacts with the distal carboxylate group of the substrate; and Ile33 is part of the hydrophobic patch near the entrance to the active site, presumably participating in the domain closure essential for the transamination reaction. In the triple-mutant enzyme, k(cat)' for desulfination of l-cysteine sulfinate increased to 0.5s(-1) (from 0.05s(-1) in wild-type enzyme), whereas k(cat)' for transamination of the same substrate was reduced from 510s(-1) to 0.05s(-1). Similarly, k(cat)' for β-decarboxylation of l-aspartate increased fromcat)' for transamination was reduced from 530s(-1) to 0.13s(-1). l-Aspartate aminotransferase had thus been converted into an l-cysteine sulfinate desulfinase that catalyzes transamination and l-aspartate β-decarboxylation as side reactions. The X-ray structures of the engineered l-cysteine sulfinate desulfinase in its pyridoxal-5'-phosphate and pyridoxamine-5'-phosphate form or liganded with a covalent coenzyme-substrate adduct identified the subtle structural changes that suffice for generating desulfinase activity and concomitantly abolishing transaminase activity toward dicarboxylic amino acids. Apparently, the triple mutation impairs the domain closure thus favoring reprotonation of alternative acceptor sites in coenzyme-substrate intermediates by bulk water. Copyright © 2011 Elsevier B.V. All rights reserved.

The current state of serum biomarkers of hepatotoxicity.

Science.gov (United States)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-03-20

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

The current state of serum biomarkers of hepatotoxicity

International Nuclear Information System (INIS)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-01-01

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

Nutritional prognostic scores in patients with hilar cholangiocarcinoma treated by percutaneous transhepatic biliary stenting combined with 125I seed intracavitary irradiation: A retrospective observational study.

Science.gov (United States)

Cui, Peiyuan; Pang, Qing; Wang, Yong; Qian, Zhen; Hu, Xiaosi; Wang, Wei; Li, Zongkuang; Zhou, Lei; Man, Zhongran; Yang, Song; Jin, Hao; Liu, Huichun

2018-06-01

We mainly aimed to preliminarily explore the prognostic values of nutrition-based prognostic scores in patients with advanced hilar cholangiocarcinoma (HCCA).We retrospectively analyzed 73 cases of HCCA, who underwent percutaneous transhepatic biliary stenting (PTBS) combined with I seed intracavitary irradiation from November 2012 to April 2017 in our department. The postoperative changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) were observed. The preoperative clinical data were collected to calculate the nutrition-based scores, including controlling nutritional status (CONUT), C-reactive protein/albumin ratio (CAR), and prognostic nutritional index (PNI). Kaplan-Meier curve and Cox regression model were used for overall survival (OS) analyses.The serum levels of TBIL, DBIL, ALT, AST, and ALP significantly reduced, and ALB significantly increased at 1 month and 3 months postoperatively. The median survival time of the cohort was 12 months and the 1-year survival rate was 53.1%. Univariate analysis revealed that the statistically significant factors related to OS were CA19-9, TBIL, ALB, CONUT, and PNI. Multivariate analysis further identified CA19-9, CONUT, and PNI as independent prognostic factors.Nutrition-based prognostic scores, CONUT and PNI in particular, can be used as predictors of survival in unresectable HCCA.

A Retrospective Mid- and Long-term Follow-up Study on the Changes in Hematologic Parameters in the Highly Exposed Residents of the Hebei Spirit Oil Spill in Taean, South Korea

Science.gov (United States)

Choi, Young-Hyun; Hong, Jee-Young; Lee, Moo-Sik

2017-01-01

Objectives This study aimed to analyze changes in hematologic parameters in the residents of the areas highly contaminated by the Hebei Spirit Oil Spill in 2007 and those who participated in the clean-up activities. Methods According to demographic characteristics, health status and behavior, and level of exposure to oil, we compared the hematologic results in 2009 and 2012 among 701 residents. The hematologic parameters were composed of white blood cell (WBC) count, and levels of hemoglobin, hematocrit (Hct), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine (Cr), total cholesterol (T-chol), high-density lipoprotein (HDL), and triglyceride (TG). Results Paired t-test revealed that the WBC count and levels of Hct, AST, ALT, glucose, and HbA1c significantly increased, whereas the BUN, Cr, HDL, and TG levels significantly decreased. Multiple linear regression modelling showed a relationship between the level of exposure to oil and temporal changes in Hct, glucose, HbA1c, and BUN levels. Conclusion Our results suggest a relationship between level of exposure to oil and changes in hematologic parameters over 3 years. Further studies should be conducted to determine the impact of oil spill on health such as the occurrence of diseases. PMID:29164048

Biomaterial properties evaluation of poly(vinyl acetate- alt-maleic anhydride)/chitosan nanocapsules

Science.gov (United States)

Raţă, Delia Mihaela; Popa, Marcel; Chailan, Jean-François; Zamfir, Carmen Lăcrămioara; Peptu, Cătălina Anişoara

2014-08-01

Nanocapsules with diameter around 100 nm based on a natural polymer (chitosan) and a synthetic polymer poly(vinyl acetate- alt-maleic anhydride) [poly(MAVA)] by interfacial condensation method were prepared. The present study proposes a new type of biocompatible nanocapsules based on poly(vinyl acetate- alt-maleic anhydride-chitosan) (MCS) able to become a reliable support for inclusion and release of drugs. The spherical shape of the nanocapsules was evidenced by scanning electron microscopy. Nanocapsules presented a good Norfloxacin loading and release capacity. Haemocompatibility tests have demonstrated that the nanocapsules present a low toxicity and a good compatibility with sanguine medium. The biocompatibility properties of the nanocapsules after their intraperitoneal administration in rats were evidenced by histopathological examination of different organs (brain, liver, kidney, and lung). The results are encouraging and the nanocapsules can be used as controlled drug delivery systems.

Possible Ameliorative Effect of Chicory Extract (Cichorium Intybus) on Radiation-Induced Oxidative Damage in Rats Heart

International Nuclear Information System (INIS)

Osman, N. N; Farag, M. F. S.; Darwish, M. M

2011-01-01

The radioprotective effect of aqueous leaf extract of Chicorium intybus (Chicory) against radiation induced-oxidative stress and changes in the levels of 150-180 g were divided into four groups. Group 1: control animals, group 2: animals orally administrated with chicory extract at a daily dose of 250 mg/kg b.wt/day for four weeks, group 3: animals exposed to whole body gamma irradiation (6.5 Gy), group 4: animals orally administrated with chicory extract two weeks before and two weeks after irradiation. Serum level of creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipid profile was measured.also concentration of superoxide dismutase (SOD), glutathione (GSH), Catalase (CAT) and TBARS level was estimated in the cardiac tissue. The results showed decreased body weight and heart weight in irradiated animals. Compared to the control normal rats, irradiated rats had higher total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), serum creatinine phosphokinase(CPK), lactate dehydrogenase (LDH), serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lower high-density lipoprotein-cholesterol (HDL-C) levels. Moreover, cardiac tissue TBARS was markedly increased while SOD, GSH and CAT were significantly decreased. Oral and heart weights, serum cardiac enzymes and lipid profile. Cardiac GSH, SOD and CAT were significantly increased while TBARS was markedly reduced, membrane bound enzymes in rats' heart was investigated. Rats weighing about administration of chicory extract at doses of 250 mg/kg b.wt. improved the body compared to irradiated rats. These results may suggest a strong antioxidant effect of chicory, which was effective in mitigating adverse effect of γ irradiation on animals

Transferases activity in blood plasma of chickens hatched from eggs irradiated during incubation by low dose gamma rays

International Nuclear Information System (INIS)

Kraljevic, P.; Vilic, M.; Miljanic, S.; Simpraga, M.

2005-01-01

In our earlier studies chickens hatched from eggs irradiated with 0.15 Gy gamma rays before incubation showed a significantly higher growth than controls during the fattening period (1-42 days). The activity of aspartate-aminotransferase (AST), alanine-aminotransferase (ALT) and plasma glucose in the same chickens were also significantly higher. These results suggested that low-dose gamma-radiation stimulated certain metabolic processes in chickens hatched from eggs irradiated before incubation. The goal of this study was to determine the effects of low-dose ionising radiation on AST and ALT activity in the blood plasma of chickens hatched from eggs irradiated during incubation. The eggs of heavy breeding chickens (Avian, line 34) were exposed to 0.15 Gy of gamma-radiation (6 0C o) on the seventh day of incubation, i.e. at the time when the organogenesis in chickens is completed. The control group of chickens hatched from non-irradiated eggs. All other conditions were the same for both groups. After hatching, blood samples were taken from the wing vein on days 1, 3, 5, 7, 10, 20, 32 and 42. The activity of both enzymes was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. On day 10, AST and ALT activity were significantly higher in the blood plasma of chickens hatched from irradiated eggs, but it significantly dropped for both enzymes on day 20. Our results indicate that exposure of eggs to low-dose gamma-radiation on the seventh day of incubation affects AST and ALT activity in the blood plasma of chickens hatched from irradiated eggs. However, this effect is somewhat different from the effects of egg exposure to low-dose gamma radiation before incubation.(author)

measurements of iron status and survival in african iron overload

African Journals Online (AJOL)

Serum concentrations of lactate dehydrogenase (LDH), AST, alanine aminotransferase (ALT), garnma-glutamyl transpeptidase. (-yGT), bilirubin, glucose and sodi~ were measured using an automated clinical chemistry analyser. Erythrocyte sedimentation rate (ESR) was determined using the Westergren method. C-reactive ...

Partial amino acid sequence of the branched chain amino acid aminotransferase (TmB) of E. coli JA199 pDU11

International Nuclear Information System (INIS)

Feild, M.J.; Armstrong, F.B.

1987-01-01

E. coli JA199 pDU11 harbors a multicopy plasmid containing the ilv GEDAY gene cluster of S. typhimurium. TmB, gene product of ilv E, was purified, crystallized, and subjected to Edman degradation using a gas phase sequencer. The intact protein yielded an amino terminal 31 residue sequence. Both carboxymethylated apoenzyme and [ 3 H]-NaBH-reduced holoenzyme were then subjected to digestion by trypsin. The digests were fractionated using reversed phase HPLC, and the peptides isolated were sequenced. The borohydride-treated holoenzyme was used to isolate the cofactor-binding peptide. The peptide is 27 residues long and a comparison with known sequences of other aminotransferases revealed limited homology. Peptides accounting for 211 of 288 predicted residues have been sequenced, including 9 residues of the carboxyl terminus. Comparison of peptides with the inferred amino acid sequence of the E. coli K-12 enzyme has helped determine the sequence of the amino terminal 59 residues; only two differences between the sequences are noted in this region

Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level.

Science.gov (United States)

Duan, Xiangke; Li, Yunsong; Du, Qinglin; Huang, Qinqin; Guo, Siyao; Xu, Mengmeng; Lin, Yanping; Liu, Zhidong; Xie, Jianping

2016-01-25

Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation, and possibly through altering the intracellular amino acid metabolism balance.

Changes of basic metabolic parameters after single gamma irradiation in broiler chickens

International Nuclear Information System (INIS)

Falis, M.; Benova, K.; Toropila, M.; Sesztakova, E.; Vargova, M.

2004-01-01

Investigation of the effect of radiation on animal organisms helps us to develop methods of protection against its unfavourable influences. The presented study focused on changes in the concentration of corticosterone, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of broilers irradiated with gamma rays. The serum corticosterone had increased on day one after irradiation. The increase in serum corticosterone can be ascribed to the stress action of ionizing radiation on the broilers. (authors)

Diorganosilacetylene-alt-diorganosilvinylene polymers and a process densifying porous silicon-carbide bodies

Science.gov (United States)

Barton, Thomas J.; Ijadi-Maghsoodi, Sina; Pang, Yi

1994-05-17

The present invention provides linear organosilicon polymers including acetylene and vinylene moieties, and a process for their preparation. These diorganosilacetylene-alt-diorganosilvinylene linear polymers can be represented by the formula: --[--(R.sup.1)(R.sup.2)Si--C.tbd.C--(R.sup.3)(R.sup.4)Si--CH=CH--].sub.n-- , wherein n.gtoreq.2; and each R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, aryl, and aralkyl radicals. The polymers are soluble in organic solvents, air stable, and can be pulled into fibers or cast into films. They can be thermally converted into silicon carbide ceramic materials.

A comparative study of hepatitis caused by scrub typhus and viral hepatitis A in South Korea.

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Lee, Jun; Kim, Dong-Min; Yun, Na Ra; Byeon, Yu Mi; Kim, Young Dae; Park, Chan Guk; Kim, Man Woo; Han, Mi Ah

2011-11-01

We compared clinical features and laboratory findings of 104 patients with hepatitis A and 197 patients with scrub typhus. Nausea, vomiting, abdominal pain, hepatomegaly, and jaundice were common in patient with hepatitis A, and fever and headache were significantly more common in patients with scrub typhus. At presentation, an alanine aminotransferase (ALT) level ≥ 500 U/L was observed in 1% of scrub typhus patients and in 87.5% of hepatitis A patients (P hepatitis A patients. The ALT:lactate dehydrogenase ratio was ≤ 5 in 97.4% of the patients with scrub typhus and > 5 in 95.2% of those with hepatitis A (P 5, and hepatomegaly are indications of viral hepatitis A.

A Comparative Study of Hepatitis Caused by Scrub Typhus and Viral Hepatitis A in South Korea

Science.gov (United States)

Lee, Jun; Kim, Dong-Min; Yun, Na Ra; Byeon, Yu Mi; Kim, Young Dae; Park, Chan Guk; Kim, Man Woo; Han, Mi Ah

2011-01-01

We compared clinical features and laboratory findings of 104 patients with hepatitis A and 197 patients with scrub typhus. Nausea, vomiting, abdominal pain, hepatomegaly, and jaundice were common in patient with hepatitis A, and fever and headache were significantly more common in patients with scrub typhus. At presentation, an alanine aminotransferase (ALT) level ≥ 500 U/L was observed in 1% of scrub typhus patients and in 87.5% of hepatitis A patients (P hepatitis A patients. The ALT:lactate dehydrogenase ratio was ≤ 5 in 97.4% of the patients with scrub typhus and > 5 in 95.2% of those with hepatitis A (P 5, and hepatomegaly are indications of viral hepatitis A. PMID:22049041

Genetic Mapping of Novel Loci Affecting Canine Blood Phenotypes.

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Michelle E White

Full Text Available Since the publication of the dog genome and the construction of high-quality genome-wide SNP arrays, thousands of dogs have been genotyped for disease studies. For many of these dogs, additional clinical phenotypes are available, such as hematological and clinical chemistry results collected during routine veterinary care. Little is known about the genetic basis of variation in blood phenotypes, but this variation may play an important role in the etiology and progression of many diseases. From a cohort of dogs that had been previously genotyped on a semi-custom Illumina CanineHD array for various genome-wide association studies (GWAS at Cornell University Hospital for Animals, we chose 353 clinically healthy, adult dogs for our analysis of clinical pathologic test results (14 hematological tests and 25 clinical chemistry tests. After correcting for age, body weight and sex, genetic associations were identified for amylase, segmented neutrophils, urea nitrogen, glucose, and mean corpuscular hemoglobin. Additionally, a strong genetic association (P = 8.1×10-13 was evident between a region of canine chromosome 13 (CFA13 and alanine aminotransferase (ALT, explaining 23% of the variation in ALT levels. This region of CFA13 encompasses the GPT gene that encodes the transferase. Dogs homozygous for the derived allele exhibit lower ALT activity, making increased ALT activity a less useful marker of hepatic injury in these individuals. Overall, these associations provide a roadmap for identifying causal variants that could improve interpretation of clinical blood tests and understanding of genetic risk factors associated with diseases such as canine diabetes and anemia, and demonstrate the utility of holistic phenotyping of dogs genotyped for disease mapping studies.

Genetic Mapping of Novel Loci Affecting Canine Blood Phenotypes.

Science.gov (United States)

White, Michelle E; Hayward, Jessica J; Stokol, Tracy; Boyko, Adam R

2015-01-01

Since the publication of the dog genome and the construction of high-quality genome-wide SNP arrays, thousands of dogs have been genotyped for disease studies. For many of these dogs, additional clinical phenotypes are available, such as hematological and clinical chemistry results collected during routine veterinary care. Little is known about the genetic basis of variation in blood phenotypes, but this variation may play an important role in the etiology and progression of many diseases. From a cohort of dogs that had been previously genotyped on a semi-custom Illumina CanineHD array for various genome-wide association studies (GWAS) at Cornell University Hospital for Animals, we chose 353 clinically healthy, adult dogs for our analysis of clinical pathologic test results (14 hematological tests and 25 clinical chemistry tests). After correcting for age, body weight and sex, genetic associations were identified for amylase, segmented neutrophils, urea nitrogen, glucose, and mean corpuscular hemoglobin. Additionally, a strong genetic association (P = 8.1×10-13) was evident between a region of canine chromosome 13 (CFA13) and alanine aminotransferase (ALT), explaining 23% of the variation in ALT levels. This region of CFA13 encompasses the GPT gene that encodes the transferase. Dogs homozygous for the derived allele exhibit lower ALT activity, making increased ALT activity a less useful marker of hepatic injury in these individuals. Overall, these associations provide a roadmap for identifying causal variants that could improve interpretation of clinical blood tests and understanding of genetic risk factors associated with diseases such as canine diabetes and anemia, and demonstrate the utility of holistic phenotyping of dogs genotyped for disease mapping studies.

Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

Science.gov (United States)

Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

2017-04-01

For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Indole-3-acetic acid biosynthetic pathway and aromatic amino acid aminotransferase activities in Pantoea dispersa strain GPK.

Science.gov (United States)

Kulkarni, G B; Nayak, A S; Sajjan, S S; Oblesha, A; Karegoudar, T B

2013-05-01

This investigation deals with the production of IAA by a bacterial isolate Pantoea dispersa strain GPK (PDG) identified by 16S rRNA gene sequence analysis. HPLC and Mass spectral analysis of metabolites from bacterial spent medium revealed that, IAA production by PDG is Trp-dependent and follows indole-3-pyruvic acid (IPyA) pathway. Substrate specificity study of aromatic amino acid aminotransferase (AAT) showed high activities, only when tryptophan (Trp) and α-ketoglutarate (α-kg) were used as substrates. AAT is highly specific for Trp and α-kg as amino group donor and acceptor, respectively. The effect of exogenous IAA on bacterial growth was established. Low concentration of exogenous IAA induced the growth, whereas high concentration decreased the growth of bacterium. PDG treatment significantly increased the root length, shoot length and dry mass of the chickpea and pigeon pea plants. © 2013 The Society for Applied Microbiology.

Evaluation of hepatocyte-derived microRNA-122 for diagnosis of acute and chronic hepatitis of dogs

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S. R. Eman

2018-05-01

Full Text Available Aim: This study was performed to evaluate the diagnostic value of hepatocyte-derived microRNA (miRNA-122 in acute and chronic hepatitis of dogs. Materials and Methods: A total of 26 dogs presented at Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Cairo University, 16 dogs out of 26 showing clinical signs of hepatic insufficiency were subjected to clinical, ultrasonographic, hematobiochemical and ultrasound-guided fine-needle biopsy for cytological and histopathological investigations. On the basis of these results, 7 dogs out of 16 dogs were found to be suffering from acute hepatitis and 9 dogs suffering from chronic hepatitis. 10 clinically healthy dogs were kept as control. Serum hepatocyte-derived miRNA-122 was analyzed by real-time quantitative polymerase chain reaction in all dogs. Results: The dogs suffering from acute hepatitis manifested jaundice, vomiting, and depression while dogs with chronic hepatitis manifested anorexia, abdominal distension, weight loss, and melena. Hematological parameters showed normocytic normochromic anemia and thrombocytopenia in both acute and chronic hepatitis groups. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and total bilirubin were significantly higher than control values in acute hepatitis. In chronic hepatitis, total protein and albumin were significantly lower than control values with normal ALT, AST, ALP, and gamma-glutamyltransferase values. Ultrasonography revealed a diffuse decrease in hepatic echogenicity in acute hepatitis while the increase in hepatic echogenicity and anechoic ascetic fluid in chronic hepatitis. Cytology revealed hepatic vacuolar degeneration and histopathology revealed necrosis and apoptosis of hepatocyte in acute hepatitis while revealed massive fibrous tissue proliferation in hepatic parenchyma in chronic hepatitis. Serum miRNA-122 analysis, normalized for glyceraldehyde-3- phosphate dehydrogenase expression

Evaluation of liver function tests of HIV positive patients on ...

African Journals Online (AJOL)

Liver enzymes-alanine and aspartate aminotransferases and alkaline phosphatase (AST, ALT and ALP), bilirubin and serum proteins were determined using standard laboratory methods and these parameters were used to evaluate the liver function of human immunodeficiency virus (HIV)- positive patients receiving ...

Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

Science.gov (United States)

Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

2016-03-01

Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

Relationships between cerebral autoregulation and markers of kidney and liver injury in neonatal encephalopathy and therapeutic hypothermia.

Science.gov (United States)

Lee, J K; Perin, J; Parkinson, C; O'Connor, M; Gilmore, M M; Reyes, M; Armstrong, J; Jennings, J M; Northington, F J; Chavez-Valdez, R

2017-08-01

We studied whether cerebral blood pressure autoregulation and kidney and liver injuries are associated in neonatal encephalopathy (NE). We monitored autoregulation of 75 newborns who received hypothermia for NE in the neonatal intensive care unit to identify the mean arterial blood pressure with optimized autoregulation (MAP OPT ). Autoregulation parameters and creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed using adjusted regression models. Greater time with blood pressure within MAP OPT during hypothermia was associated with lower creatinine in girls. Blood pressure below MAP OPT related to higher ALT and AST during normothermia in all neonates and boys. The opposite occurred in rewarming when more time with blood pressure above MAP OPT related to higher AST. Blood pressures that optimize cerebral autoregulation may support the kidneys. Blood pressures below MAP OPT and liver injury during normothermia are associated. The relationship between MAP OPT and AST during rewarming requires further study.

Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice

Directory of Open Access Journals (Sweden)

Nancy Sayuri Uchida

2017-01-01

Full Text Available High doses of acetaminophen (APAP lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and gamma-glutamyl transferase (γGT were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO activity and nitric oxide (NO production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP.

Estimation of liver parameters and oxidative stress in chronic renal failure patients on hemodialysis in Erbil governorate

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Kakey, Musher Ismail Salih; Abdoulrahman, Kamaran Kaiani

2017-09-01

The present study aims to evaluate iron related parameters in chronic renal failure (CRF) patients on hemodialysis (HD). The study was carried out in Kidney Dialysis Center of Hawler Teaching Hospital in Erbil governorate. This study comprised (76) patients with chronic renal failure on hemodialysis and 41 healthy subjects as a control group of same ages. All hemodialysis patients were taking erythropoietin. The blood samples were taken from the patients before and after the process of hemodialysis for liver parameters and oxidative stress estimations. The results of this study showed lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, total protein and total antioxidant capacity (TAC), while higher levels of alkaline phosphatase (ALP), direct bilirubin and malondialdeyhde (MDA) before analysis was seen. Hemodialysis causes increasing in AST, ALT, albumin, total bilirubin, total protein and decreasing in ALP, direct bilirubin MDA and TAC.

[Hydroxyurea (hydroxycarbamide)-induced hepatic dysfunction confirmed by drug-induced lymphocyte stimulation test].

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Shimizu, Takayuki; Mori, Takehiko; Karigane, Daiki; Kikuchi, Taku; Koda, Yuya; Toyama, Takaaki; Nakajima, Hideaki; Okamoto, Shinichiro

2014-01-01

A 62-year-old man with refractory leukemia transformed from myelodysplastic syndrome was placed on hydroxyurea (hydroxycarbamide) at a daily dose of 500 mg. Because of insufficient cytoreductive efficacy, the dose was increased to 1,500 mg five days later. Eight days after the initiation of hydroxyurea, the patient started complaining of chills, fever, and vomiting. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly elevated to 5,098 and 3,880 IU/l from 44 and 59 IU/l in one day, respectively. Tests for hepatitis viruses were all negative. With the discontinuation of hydroxyurea, AST and ALT returned to their former levels within two weeks. A drug-induced lymphocyte stimulation test for hydroxyurea was positive with a stimulating index of 2.0. Hepatic dysfunction has been recognized as one of the side effects of hydroxyurea. However, there have been only a limited number of reports demonstrating drug allergy to have a role in hepatic dysfunction accompanied by fever and gastrointestinal symptoms. The findings of our case strongly suggest that all presentations could be explained by drug allergy. Physicians should be mindful of the potential for acute and severe hepatic dysfunction due to allergic reaction against hydroxyurea.

Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats.

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Young, Shun-Chieh; Wang, Chau-Jong; Lin, Jing-Jing; Peng, Pei-Ling; Hsu, Jui-Ling; Chou, Fen-Pi

2007-01-01

Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.

Association between hepatic steatosis and serum liver enzyme levels with atrial fibrillation in the general population: The Study of Health in Pomerania (SHIP).

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Markus, Marcello Ricardo Paulista; Meffert, Peter J; Baumeister, Sebastian Edgar; Lieb, Wolfgang; Siewert, Ulrike; Schipf, Sabine; Koch, Manja; Kors, Jan A; Felix, Stephan Burkhard; Dörr, Marcus; Targher, Giovanni; Völzke, Henry

2016-02-01

Hepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample. We analyzed data from 3090 women and men, aged 20-81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software. The prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF. Our findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effects of Crataegus aronia var. dentata Browicz extract on biochemical indices and apoptosis in partially hepatectomized liver in rats

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Nazan Keskin

2012-08-01

Full Text Available Crataegus species have been widely used in herbal medicine, especially for the hearth diseases. In the present study, the effect of Crataegus aronia var. dentata Browicz extract on partially hepatectomized rats was investigated with biochemical and TUNEL apoptosis assays. The extracts of the plant at the concentrations of 0.5 and 1 ml/100 g body weight/day were administered orally to the two experimental groups including partially hepatectomized rats for 42 days. At the end of the experimental period, animals were sacrificed, blood was collected for the assessment of serum levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST and gamma-glutamyltransferase (GGT, and the liver tissue was used for TUNEL assay.In biochemical assay, it was found a significant decrease in the levels of serum ALT and AST in the experimental groups. On the other hand, the plant extract did not cause any significant changes in the level of GGT in these groups. In apoptosis assay, TUNEL positive hepatocytes could not be detected in both experimental groups.The present findings can suggest that Crataegus aronia var. dentata Browicz extract can decrease the levels of serum ALT and AST and play a role in apoptosis of hepatocytes in the liver of partially hepatectomized rats. However, further studies are required to confirm the effects of the plant extract on hepatoprotection and apoptosis in the regenerating liver after partial hepatectomy in animal models. 

Neural correlate of autistic-like traits and a common allele in the oxytocin receptor gene.

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Saito, Yuki; Suga, Motomu; Tochigi, Mamoru; Abe, Osamu; Yahata, Noriaki; Kawakubo, Yuki; Liu, Xiaoxi; Kawamura, Yoshiya; Sasaki, Tsukasa; Kasai, Kiyoto; Yamasue, Hidenori

2014-10-01

Sub-clinical autistic-like traits (ALTs) are continuously distributed in the general population and genetically linked to autism. Although identifying the neurogenetic backgrounds of ALTs might enhance our ability to identify those of autism, they are largely unstudied. Here, we have examined the neuroanatomical basis of ALTs and their association with the oxytocin receptor gene (OXTR) rs2254298A, a known risk allele for autism in Asian populations which has also been implicated in limbic-paralimbic brain structures. First, we extracted a four-factor structure of ALTs, as measured using the Autism-Spectrum Quotient, including 'prosociality', 'communication', 'details/patterns' and 'imagination' in 135 neurotypical adults (79 men, 56 women) to reduce the genetic heterogeneity of ALTs. Then, in the same population, voxel-based morphometry revealed that lower 'prosociality', which indicates strong ALTs, was significantly correlated to smaller regional grey matter volume in the right insula in males. Males with lower 'prosociality' also had less interregional structural coupling between the right insula and the ventral anterior cingulate cortex. Furthermore, males with OXTR rs2254298A had significantly smaller grey matter volume in the right insula. These results show that decreased volume of the insula is a neuroanatomical correlate of ALTs and a potential intermediate phenotype linking ALTs with OXTR in male subjects. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Níveis séricos de enzimas de função hepática em frangos de corte de criação industrial clinicamente saudáveis Serum levels of hepatic enzyme function in clinically healthy broiler chickens

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A. Borsa

2006-08-01

Full Text Available The values for the main hepatic enzymes included in the profiles of screen clinical biochemistry, alanine-aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (FA, lactate desidrogenase (LDH and gamaglutamiltransferase (GGT, in samples of serum of broiler chickens in industrial system, clinically healthy, starting from the seventh day of life, until the slaughter (42 days in weekly intervals were determined. Significant variations were not observed in the analyses in relation to the age of the birds for none of the appraised enzymes.

A multiple mediator analysis approach to quantify the effects of the ADH1B and ALDH2 genes on hepatocellular carcinoma risk.

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Shih, Stephannie; Huang, Yen-Tsung; Yang, Hwai-I

2018-06-01

Previous work suggested a genetic component affecting the risk of hepatocellular carcinoma (HCC) and mediation analyses have elucidated potential indirect pathways of these genetic effects. Specifically, the effects of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes on HCC risk vary based on alcohol consumption habits. However, alcohol consumption may not be the only mediator in the identified pathway: factors related to alcohol consumption may contribute to the same indirect pathway. Thus, we developed a multimediator model to quantify the genetic effects on HCC risk through sequential dichotomous mediators under the counterfactual framework. Our method provided a closed form formula for the mediation effects through different indirect paths, which requires no assumption for the rarity of outcome. In simulation studies of a finite sample, we presented the utility of the method with the variance of the effects estimated using the delta method and bootstrapping. We applied our method to data from participants in Taiwan (580 cases and 3,207 controls) and quantified the mediation effects of single nucleotide polymorphisms (SNPs) in the ADH1B and ALDH2 genes on HCC through alcohol consumption (yes/no) and high alanine transaminase (ALT) levels (greater than or equal to 45 U/L or below 45 U/L). Assuming a dominant risk model, we identified that the SNPs' effects through alcohol consumption is more significant than through ALT levels on HCC risk. This new method provides insight to the magnitude of various casual mechanisms as a closed form solution and can be readily applied in other genomic studies. © 2018 WILEY PERIODICALS, INC.

NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants

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Jie Liu

2013-01-01

Full Text Available To investigate the role of Nrf2 as a master defense against the hepatotoxicity produced by various chemicals, Nrf2-null, wild-type, Keap1-knock down (Keap1-Kd and Keap1-hepatocyte knockout (Keap1-HKO mice were used as a “graded Nrf2 activation” model. Mice were treated with 14 hepatotoxicants at appropriate doses, and blood and liver samples were collected thereafter (6 h to 7 days depending on the hepatotoxicant. Graded activation of Nrf2 offered a Nrf2-dependent protection against the hepatotoxicity produced by carbon tetrachloride, acetaminophen, microcystin, phalloidin, furosemide, cadmium, and lithocholic acid, as evidenced by serum alanine aminotransferase (ALT activities and by histopathology. Nrf2 activation also offered moderate protection against liver injury produced by ethanol, arsenic, bromobenzene, and allyl alcohol but had no effects on the hepatotoxicity produced by D-galactosamine/endotoxin and the Fas ligand antibody Jo-2. Graded Nrf2 activation reduced the expression of inflammatory genes (MIP-2, mKC, IL-1β, IL-6, and TNFα, oxidative stress genes (Ho-1, Egr1, ER stress genes (Gadd45 and Gadd153, and genes encoding cell death (Noxa, Bax, Bad, and caspase3. Thus, this study demonstrates that Nrf2 prevents the liver from many, but not all, hepatotoxicants. The Nrf2-mediated protection is accompanied by induction of antioxidant genes, suppression of inflammatory responses, and attenuation of oxidative stress.

Melatonin mitigates thioacetamide-induced hepatic fibrosis via antioxidant activity and modulation of proinflammatory cytokines and fibrogenic genes.

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Lebda, Mohamed A; Sadek, Kadry M; Abouzed, Tarek K; Tohamy, Hossam G; El-Sayed, Yasser S

2018-01-01

The potential antifibrotic effects of melatonin against induced hepatic fibrosis were explored. Rats were allocated into four groups: placebo; thioacetamide (TAA) (200mg/kg bwt, i.p twice weekly for two months); melatonin (5mg/kgbwt, i.p daily for a week before TAA and continued for an additional two months); and melatonin plus TAA. Hepatic fibrotic changes were evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative indices were assessed. The expression of hepatic proinflammatory cytokines (tumor necrosis factor-α, and interleukin-1β), fibrogenic-related genes (transforming growth factor-1β, collagen I, collagen, III, laminin, and autotaxin) and an antioxidant-related gene (thioredoxin-1) were detected by qRT-PCR. In fibrotic rats, melatonin lowered serum aspartate aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin, hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed hepatoprotective and antifibrotic potential as indicated by mild hydropic degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced the depletion of glutathione, glutathione s-transferase, glutathione peroxidase, superoxide dismutase, catalase, and paraoxonase-1 (PON-1), while inducing the accumulation of malondialdehyde, protein carbonyl (C=O) and nitric oxide (NO), and DNA fragmentation. These effects were restored by melatonin pretreatment. Furthermore, melatonin markedly attenuated the expression of proinflammatory cytokines and fibrogenic genes via the upregulation of thioredoxin-1 mRNA transcripts. Melatonin exhibits potent anti-inflammatory, antioxidant and fibrosuppressive activities against TAA-induced hepatic fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the antifibrotic activity of melatonin is mediated by the induction of thioredoxin-1 with attenuation of autotaxin expressions

DSLR Double Star Astrometry Using an Alt-Az Telescope

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Frey, Thomas; Haworth, David

2014-07-01

The goal of this project was to determine if the double star's angular separation and position angle measurements could be successfully measured with a motor driven, alt-azimuth Dobsonian-mounted Newtonian telescope (without a field rotator), and a digital single-lens reflex (DSLR) camera. Additionally, the project was constrained by using as much existing equipment as much as possible, including an Apple MacBook Pro laptop and a Canon T2i camera. This project was additionally challenging because the first author had no experience with astrophotography.

Safety and protective effect of Lactobacillus acidophilus and ...

African Journals Online (AJOL)

The protective effect of Lactobacillus acidophilus and Lactobacillus casei, isolated from fresh cow milk, was studied in vivo. Toxicological data of rat serum revealed that the Lactobacillus isolates had liver improvement functions. Serum alanine aminotransferase (ALT) activities of the rats dosed with Lactobacillus isolates ...

The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes

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Radhia M’kacher

2018-05-01

Full Text Available Background: We analyzed telomere maintenance mechanisms (TMMs in lymph node samples from HL patients treated with standard therapy. The TMMs correlated with clinical outcomes of patients. Materials and Methods: Lymph node biopsies obtained from 38 HL patients and 24 patients with lymphadenitis were included in this study. Seven HL cell lines were used as in vitro models. Telomerase activity (TA was assessed by TRAP assay and verified through hTERT immunofluorescence expression; alternative telomere lengthening (ALT was also assessed, along with EBV status. Results: Both TA and ALT mechanisms were present in HL lymph nodes. Our findings were reproduced in HL cell lines. The highest levels of TA were expressed in CD30−/CD15− cells. Small cells were identified with ALT and TA. Hodgkin and Reed Sternberg cells contained high levels of PML bodies, but had very low hTERT expression. There was a significant correlation between overall survival (p < 10−3, event-free survival (p < 10−4, and freedom from progression (p < 10−3 and the presence of an ALT profile in lymph nodes of EBV+ patients. Conclusion: The presence of both types of TMMs in HL lymph nodes and in HL cell lines has not previously been reported. TMMs correlate with the treatment outcome of EBV+ HL patients.

Assessment of Growth and Development in Children With Hepatitis B Positivity.

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Sari, Tugba; Eren, Erdal; Koruk, Suda Tekin

2014-12-01

Chronic infections and liver diseases may influence the growth and development of children by leading to malnutrition. In this study, demographic characteristics, anthropometric measurements and laboratory findings for children with hepatitis B positivity were analyzed. A total of 43 cases were admitted to our clinic between January 2012 and February 2013 and detected to have HBsAg positivity. Malnutrition was detected in 11 cases (25.6%) and obesity in three cases (6.9%). Aspartate aminotransferase (AST) levels were significantly higher in malnourished patients compared to those without malnutrition. The weight to height was significantly higher in patients with positive HBeAg compared to children with negative HBeAg. We found that the weight standard deviation scores (SDS) ratios dropped as alanine aminotransferase (ALT) and AST levels increased and height SDS ratios decreased. In addition, body mass index (BMI) decreased as AST and alpha feto protein (AFP) values increased. While a significant relationship was not detected between insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) and ALT, a significantly negative correlation was detected between IGFBP-3 and IGF-1 and AST. We found a malnutrition rate of 25.6% in children with HBsAg positivity. We also found that weight and height SDS rates decreased as ALT and AST levels increased. In addition, we detected that BMI decreased as AST and AFP values increased. We consider that hepatic inflammation is the factor that affects growth. Monitoring of growth and development during follow-up of children who are detected to have HBsAg positivity would be beneficial to determine the mechanism and causes of growth retardation.

Association of the components of the metabolic syndrome with non- alcoholic fatty liver disease among normal-weight, overweight and obese children and adolescents

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Kelishadi Roya

2009-12-01

Full Text Available Abstract Objectives This study aimed to determine the prevalence of the metabolic syndrome, abnormalities of liver enzymes and sonographic fatty liver, as well as the inter-related associations in normal weight, overweight and obese children and adolescents. Methods This cross-sectional study was conducted among a sample of 1107 students (56.1% girls, aged 6-18 years in Isfahan, Iran. In addition to physical examination, fasting blood glucose, serum lipid profile and liver enzymes were determined. Liver sonography was performed among 931 participants. These variables were compared among participants with different body mass index (BMI categories. Results From lower to higher BMI category, alanine aminotransferase (ALT, total cholesterol, LDL-cholesterol, triglycerides and systolic blood pressure increased, and HDL-cholesterol decreased significantly. Elevated ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP were documented in respectively 4.1%, 6.6% and 9.8% of normal weight group. The corresponding figure was 9.5%, 9.8% and 9.1% in overweight group, and 16.9%, 14.9% and 10.8% in obese group, respectively. In all BMI categories, ALT increased significantly by increasing the number of the components of the metabolic syndrome. Odds ratio for elevated liver enzymes and sonographic fatty liver increased significantly with higher number of the components of the metabolic syndrome and higher BMI categories before and after adjustment for age. Conclusions Because of the interrelationship of biochemical and sonographic indexes of fatty liver with the components of the metabolic syndrome, and with increase in their number, it is suggested to determine the clinical impact of such association in future longitudinal studies.

Effect of Milk Thistle (Silybum marianum L. on Biochemical Parameters and Immunity of Broiler Chicks Fed Aflatoxin B1 after Three Weeks

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Maliheh Amiri Dumari

2014-09-01

Full Text Available Background: This study was conducted to determine the efficacy of milk thistle seeds (MTSs in counteracting the toxic effects of aflatoxin B1 (AFB1 in a contaminated diet fed to broilers. Methods: Two dietary inclusion rates of AFB1 (0, 0.250 and 500 ppb and MTS (0, 0.5 and 1% were tested in a 3×3 factorial manner. The effect of nine experimental treatments was assessed using 216 one-d-old Ross 308 male broiler chicks in a randomized complete design with 4 replicates of 6 birds each from one to 21 days of age. The effects of dietary AFB1 and MTS on serum biochemistry factors, antibody titer against Newcastle disease (ND and influenza disease (ID in broilers were evaluated at the end of this period. Results: Statistical analysis of the main effects of diets indicated no significant changes in uric acid, cholesterol, triglycerides, low density lipoprotein (LDL, ID, and phosphorus compared to the control (P>0.01. Also, addition of 500 ppb of dietary AFB1 into the diet was associated with significant decreases in serum glucose, calcium, high density lipoprotein (HDL, and ND compared to the control group (P<0.01. The contaminated diet significantly increased the activities of aspartate aminotransferase (AST and alanine aminotransferase (ALT (P<0.05. Conclusion: Milk thistle showed protective effects and resulted in some serum enzyme activities and serum biochemical changes associated with aflatoxin toxicity.

Concentrações de creatino quinase, aspartato aminotransferase e desidrogenase lática em potros do nascimento até os seis meses de idade Concentration of creatine kinase, aspartate aminotransferase and lactate dehydrogenase in foals from birth up to sixth month

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Elisiane Lourdes Da Cás

2001-12-01

Full Text Available Dez potros da raça Puro Sangue de Corrida (PSC, de ambos os sexos, foram avaliados quanto à concentração das enzimas séricas creatino quinase (CK, aspartato aminotransferase (AST e deshidrogenase lática (DHL. Foram colhidas amostras sangüíneas diariamente do 1º ao 7ºdia de vida e depois aos 15, 30, 60, 90, 120, 150 e 180 dias de idade. A concentração da CK mostrou um decréscimo significativo (pTen Thoroughbred foals, male and female, had the seric concentration of creatine kinase (CK, aspartate aminotransferase (AST and lactate dehydrogenase (LDH determined. Blood samples were collected every day from days 1 to 7 and on days 15, 30, 60, 90, 120, 150 and 180 of age. CK activity decreased significantly (p< 0.0003 in the first week and showed significant variation between day 15 and 6 months of age. AST showed a significant (p< 0.0001 increase in its values until 102 days of age, decreasing subsequently until 6 months of age. LDH values decreased significantly (p< 0.0002 between days 15 and 120, increasing subsequently until 6 months of age. At 6 months of age CK, AST and LDH activities were close to those of adult horses.

Gene expression profiles reveal key pathways and genes associated with neuropathic pain in patients with spinal cord injury.

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He, Xijing; Fan, Liying; Wu, Zhongheng; He, Jiaxuan; Cheng, Bin

2017-04-01

Previous gene expression profiling studies of neuropathic pain (NP) following spinal cord injury (SCI) have predominantly been performed in animal models. The present study aimed to investigate gene alterations in patients with spinal cord injury and to further examine the mechanisms underlying NP following SCI. The GSE69901 gene expression profile was downloaded from the public Gene Expression Omnibus database. Samples of peripheral blood mononuclear cells (PBMCs) derived from 12 patients with intractable NP and 13 control patients without pain were analyzed to identify the differentially expressed genes (DEGs), followed by functional enrichment analysis and protein‑protein interaction (PPI) network construction. In addition, a transcriptional regulation network was constructed and functional gene clustering was performed. A total of 70 upregulated and 61 downregulated DEGs were identified in the PBMC samples from patients with NP. The upregulated and downregulated genes were significantly involved in different Gene Ontology terms and pathways, including focal adhesion, T cell receptor signaling pathway and mitochondrial function. Glycogen synthase kinase 3 β (GSK3B) was identified as a hub protein in the PPI network. In addition, ornithine decarboxylase 1 (ODC1) and ornithine aminotransferase (OAT) were regulated by additional transcription factors in the regulation network. GSK3B, OAT and ODC1 were significantly enriched in two functional gene clusters, the function of mitochondrial membrane and DNA binding. Focal adhesion and the T cell receptor signaling pathway may be significantly linked with NP, and GSK3B, OAT and ODC1 may be potential targets for the treatment of NP.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE in children admitted to a tertiary hospital Prevalência de epilepsia e crises epilépticas como causa de eventos com aparente risco de vida (ALTE em crianças internadas em hospital terciário

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Alessandra Marques dos Anjos

2009-09-01

Full Text Available OBJECTIVE: To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE in children admitted at the emergency and followed in a tertiary hospital. METHOD: Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. RESULTS: During the study, 30 (4.2% children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73% and term infants (70%. Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. CONCLUSION: Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.OBJETIVO: Determinar a prevalência e características clínicas de crises epilépticas e epilepsia como causa de eventos com aparente risco de vida (ALTE em crianças atendidas na emergência e acompanhadas em hospital terciário. MÉTODO: Estudo transversal com coleta prospectiva de dados através de protocolo específico para identificação da etiologia de ALTE. RESULTADOS: Foram diagnosticadas 30 crianças com ALTE perfazendo 4.2% das crianças internadas no período do estudo. Houve predominância no sexo masculino (73% e em neonatos a termo (70%. História prévia de doenças neurológicas no período neonatal e atraso no desenvolvimento neuropsicomotor ocorreram respectivamente em 13.4% e 10% dos casos. A investigação etiológica identificou 13.4% dos casos relacionados a epilepsia ou crise convulsivas e 50% idiopáticos. Apesar destes pacientes terem apresentados episódios recorrentes em nenhum caso havia a suspeita prévia de epilepsia. CONCLUSÃO: Ao investigar

Changes in biochemical proxy indicators for nutritional stress resilience from Boran and Nguni cows reared in dry arid rangeland.

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Mapfumo, Lizwell; Muchenje, Voster; Mupangwa, John F; Scholtz, Michiel M

2017-10-01

The objective of this study was to determine the changes in biochemical indicators for nutritional stress from a herd of Boran and Nguni cows. A total of 40 cows (20 from each herd) were randomly selected for the study. The animals were identified according to their parities as follows: parity 1 (n = 8), parity 2 (n = 16), parity 3 (n = 8) and parity 4 (n = 8). Serum chemistry levels of glucose, total cholesterol, urea, creatinine, albumin, globulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutylaminotransferase (GGT), leukocytes, erythrocytes, haemoglobin, packed cell volume (PCV) and platelet counts were determined for 12 consecutive months spanning across the wet and dry seasons. The Boran cows had different creatinine concentration levels at different parities. The Boran cows in parity 1 had the highest (P cows in different parities within the herd. There were significant differences in enzymes such as AST, ALP and ALT among the herd and parities. Boran cows in parity 3 had the lowest (P cows in parity 4 had the highest concentration of ALP of 161.3 ± 8.10 U/L while Nguni cows in parity 1 had the highest concentration level of ALT 55.1 ± 1.56 U/L than all the cows within the same herd. The Nguni herd had significantly higher (P Cows from the Nguni herd maintained significantly higher amount of urea, creatinine, albumin and total protein in both the wet and dry seasons as compared with cows from the Boran herd. Cows from the Nguni herd maintained significantly higher amount of urea, creatinine, albumin and total protein in both the wet and dry seasons as compared with those from the Boran herd.

Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP)

DEFF Research Database (Denmark)

Fattovich, G; Giustina, G; Realdi, G

1997-01-01

The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion...... criteria were biopsy-proven cirrhosis, hepatitis B e antigen (HBeAg) positivity, abnormal serum aminotransferase levels, exclusion of hepatitis delta virus, and absence of complications of cirrhosis. Of the 40 IFN-treated patients, 27 (67%) showed sustained HBeAg loss with alanine aminotransferase (ALT...

Effect of Eight Weeks Forced Swimming Training with Methadone Supplementation on Aspartate Aminotransferase, Alanine Aminotransferase, and Alkaline Phosphatase of Rats

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Seyed Ali Hoseini

2016-12-01

Full Text Available Background & Objective: Narcotics abuse can induce liver disorders; nevertheless, exercises improve liver disorders. The present research aimed to review the effect of eight weeks forced swimming training with methadone supplementation on liver enzymes of rats. Material & Method: In this experimental research, 48 rats were selected, and after one week adaptation to lab environment, they were randomly divided into four groups of 12 rats including (1 forced swimming training, (2 methadone supplementation, (3 forced swimming training with methadone supplementation, and (4 control. Groups 2 and 3 used 2 mg/kg methadone daily for 8 weeks. Also, groups 1 and 3 swam for 8 weeks, three sessions per week and each session for 30 minutes. For statistical analysis of data, one way ANOVA and Tukey post hoc tests were used (α≤0.05. Results: Findings showed that forced swimming training, methadone supplementation, and forced swimming training with methadone supplementation had no significant effect on AST (P=0.90 and ALT (P=0.99 enzymes; forced swimming training had significant effect on increase of ALP (P=0.001; also, forced swimming training, compared with methadone supplementation and combination of forced swimming training with methadone supplementation, had significant effect on increase of ALP (P=0.001. Conclusion: Accordingly, 8 weeks of forced swimming training with methadone has possibly no significant effect on liver enzymes.

High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

DEFF Research Database (Denmark)

Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S

2002-01-01

-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver...... with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat...... 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO...

CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

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Crockett Elahé T

2007-05-01

Full Text Available Abstract Background Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R. P-selectin and the intercellular adhesion molecule (ICAM-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. Methods Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study. Liver injury was assessed by plasma level of alanine aminotransferase (ALT and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. Results Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. Conclusion While ICAM-1 and P

Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

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Andreas Buness

Full Text Available Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI using transcriptomics, metabolite profiling (metabolomics and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine, classical clinical chemistry markers like AST (aspartate aminotransferase, ALT (alanine aminotransferase, and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1 and Egr1 (early growth response protein 1. The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

STATUS OF ANTIOXIDANT AND LIVER FUNCTION IN TYPE-2 DIABETIC PATIENTS ATTENDING NEPALGUNJ MEDICAL COLLEGE

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C Thanpari

2013-01-01

Full Text Available Objective: Diabetes mellitus (DM is one of the most common metabolic disorders characterized by hyperglycemia due to defects in insulin secretion, insulin action or both. This study aims to investigate the status of antioxidants and liver function in type-2 diabetic patients among patients attending OPD of Nepalgunj Medical College, Banke, Nepal.Methods: A total of 280 samples were recruited to evaluate aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, total bilirubin (TB, glutathione (GSH, and superoxide dismutase (SOD.Determination of all biochemical parameters were carried out using Kit Methods.Results: AST level was elevated in maximum number of patients, 64 (36.57% out of175 males and 59 (56.19% out of 105 females followed by ALT elevation in females and ALP elevation in males, 50 (47.61% out of 105 and 57(32.57% out of 175 respectively.Conclusion: Antioxidants & LFTs were found to be statistically significant when compared with healthy controls.

[Effect of Low-Intensity 900 MHz Frequency Electromagnetic Radiation on Rat Brain Enzyme Activities Linked to Energy Metabolism].

Science.gov (United States)

Petrosyan, M S; Nersesova, L S; Gazaryants, M G; Meliksetyan, G O; Malakyan, M G; Bajinyan, S A; Akopian, J I

2015-01-01

The research deals with the effect of low-intensity 900 MHz frequency electromagnetic radiation (EMR), power density 25 μW/cm2, on the following rat brain and blood serum enzyme activities: creatine kinase (CK), playing a central role in the process of storing and distributing the cell energy, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) that play a key role in providing the conjunction of carbohydrate and amino acid metabolism. The comparative analysis of the changes in the enzyme activity studied at different times following the two-hour single, as well as fractional, radiation equivalent of the total time showed that the most radiosensitive enzyme is the brain creatine kinase, which may then be recommended as a marker of the radio frequency radiation impact. According to the analysis of the changing dynamics of the CK, ALT and AST activity level, with time these changes acquire the adaptive character and are directed to compensate the damaged cell energy metabolism.

Efficiency of lycopene extracted from tomato pomace as antioxidant against gamma irradiation hazards in male albino rats

International Nuclear Information System (INIS)

Abdallah, I.Z.A.; Kattab, H.A.H.; Sheashea, E.A.R.

2003-01-01

Nowadays, increasing attention has been given to the roles of free radicals generated through oxidative stres. The present study aims to evaluate the antioxidative role lycopene extracted from tomato processing wastes or pomace against hazards induced by gamma irradiation. Male rats were adminstered lycopene by a daily intragastric gavage(0.24mg/rat/day) or supplemented in a standard casein diet (6.5 Gy) of whole body gamma radiation. Lipid peroxides (MDA) reduced ghutathione (GSH) and superoxide dismutase activity (SOD) were determined in liver homogenate, as well as serum levels of alanine aminotransferase (ALT). asparate aminotransferase (AST), toral protein, albumin, globulin and A/G ratio were investigated 2 and 13 days post irradiation and/or lycopene administration. The results revealed that exposure to ionizing radiation resulted in significant elevation in MDA, ALT,AST, albumin levels and A/G ratio. Meanwhile, radiation exposure caused significant reduction in weight gain, SOD activity, GSH, total protein and globulin levels

Biochemical changes and manifestations of envenomation produced by Odonthobuthus doriae venom in rabbits

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A. Z. Mirakabadi

2006-01-01

Full Text Available Many toxins from scorpion venoms cause neurotransmitters release by activating the autonomic system. The aim of the present work was to determine osmotic fragility of red blood cells (RBCs and serum biochemical changes produced by the venom of Odonthobuthus doriae (O. doriae, a dangerous species of scorpion in Iran. For this study we selected 2 groups, each one containing 10 New Zealand white rabbits weighing 2 ± 0.2 kg. In vivo and in vitro osmotic fragilities as well as packed cell volume (PCV were determined. Serum was separated and used for determination of glucose, blood urea nitrogen (BUN, creatinine, uric acid (UA, triglycerides, cholesterol, aspartate aminotransferase (AST, EC 2.6.1.1, and alanine aminotransferase (ALT, EC 2.6.1.2. Results indicate that Odonthobuthus doriae venom (0.5 mg/kg, IV causes a significant increase (p<0.05 of serum glucose, UA, PCV, ALT, and AST. Increase was also observed in BUN, but it was not statistically significant. On the other hand a significant decrease (p<0.05 was observed in triglycerides and cholesterol levels. Increased in vivo osmotic fragility of RBCs was significant too, but in vitro osmotic fragility did not show a significant change. These results support the hypothesis that the biochemical variation caused by scorpion venom can be due to an autonomic storm and release of catecholamines.

Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis

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Zenya Saito

2016-11-01

Full Text Available Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST and/or alanine aminotransferase (ALT of more than twice the upper limit of normal (ULN. We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN, moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN, and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN. We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin. Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97. In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046. Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

TIM1 (HAVCR1 Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

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Anshuman Das

2017-09-01

Full Text Available Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1 is widely accepted to be the receptor for hepatitis A virus (HAV, an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer residues on the eHAV membrane. Both Tim1−/− Ifnar1−/− and Tim4−/− Ifnar1−/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT elevations similar to those in Ifnar1−/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1−/−Ifnar1−/− mice compared to Ifnar1−/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice.

Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

DEFF Research Database (Denmark)

Fealy, Ciaran E; Haus, Jacob M; Solomon, Thomas

2012-01-01

and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P vs. 24.3 ± 4.8 U/l, P vs. 69...... changes in fat oxidation and circulating sFasL (rho = -0.65, P vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes....... We therefore examined the effect of a short-term exercise program on markers of apoptosis-plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese individuals with NAFLD [body mass index 35.2 ± 1...

Altın Fiyatlarının Yapay Sinir Ağları ile Tahmini ve Bir Uygulama

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Rıdvan YÜKSEL

2016-03-01

Full Text Available Bu çalışmada altın fiyatlarını yapay sinir ağları ile öngörmek amacıyla, altın fiyatlarını etkileyebileceği düşünülen değişkenler olan Gümüş fiyatları, Brent Petrol fiyatları, ABD doları/ EUR paritesi, EuroNext100 endeksi, Amerika Dow Jones Endeksi, 13 Hafta vadeli ABD bonosu faiz oranı ve ABD TÜFE endeksi kullanılarak modeller kurulmuştur. Yapay sinir ağları ile kurulan modellerden elde edilen tahmin sonuçları, gerçek değerler ile R2, RMSE, MAE ve MAPE (% gibi performans kriterleri hesaplanarak karşılaştırılmıştır. Elde edilen bulgular yapay sinir ağlarının altın fiyatlarının tahmininde başarı ile kullanılabileceğini göstermektedir. Yapılan duyarlılık analizinin sonuçları değerlendirildiğinde altın fiyatlarını etkileyen faktörlerin başında gümüş ve petrol fiyatlarının geldiği tespit edilmiştir.

Effect of chlorpyrifos and enrofloxacin on selected enzymes in rats.

Science.gov (United States)

Barski, D; Spodniewska, A

2018-03-01

This study examined the effect of chlorpyrifos and/or enrofloxacin on the activity of acetylcholinesterase (AChE) in the blood and brain, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. The experiment was conducted on Wistar strain rats. Chlorpyrifos was administered with a stomach tube at a dose of 0.04 LD50 for 28 days and enrofloxacin at a dose of 5 mg/kg bw for 5 consecutive days. The experiment found that enrofloxacin changed the activity of the enzymes under study only to a small extent. At the dose applied in the experiment, chlorpyrifos decreased the activity of AChE significantly, both in blood and in the brain, and increased the activity of ALT and AST in rat serum. The administration of chlorpyrifos in combination with enrofloxacin changed the activity of the enzymes under study only slightly. A weaker, but longer, inhibition of AChE activity in both blood and the brain was observed in this group compared to the animals exposed only to chlorpyrifos. However, although enrofloxacin, like chlorpyrifos, increases the activity of ALT and AST in serum, their combined administration did not increase the hepatotoxic effect. Copyright© by the Polish Academy of Sciences.

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats.

Science.gov (United States)

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use.

Changes in serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease

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OU Qiang

2016-12-01

Full Text Available ObjectiveTo investigate the changes in the serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease (NAFLD. MethodsA total of 68 NAFLD patients who were admitted to The Eighth People′s Hospital of Shanghai from July 2014 to April 2016 were enrolled as NAFLD group, and 70 healthy persons who underwent physical examination were enrolled as healthy control group. Among the 68 patients in the NAFLD group, 24 had NAFLD alone and 44 were complicated by abnormal alanine aminotransferase (ALT level. The levels of aspartate aminotransferase (AST, ALT, total cholesterol (TC, triglyceride (TG, and serum markers of iron metabolism ［serum iron (SI, serum ferritin (SF, and serum hepcidin (HEPC］ were measured for all patients, and the correlations between abnormal ALT level and serum markers of iron metabolism were analyzed. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Pearson correlation coefficient was used to investigate the correlation between two variables. ResultsThe NAFLD group had significantly higher body mass index and serum levels of ALT, AST, TC, and TG than the healthy control group (t=9.8, 8.6, 8.5, 9.2, and 2.7, all P＜0.05. Compared with the healthy control group, the NAFLD group had significantly higher levels of SI (21.7±7.1 μmol/L vs 187±6.9 μmol/L, t=2.3, P=0.02 and SF (340.2±257.6 μg/L vs 119.1±81.2 μg/L, t=6.7, P＜0.01 and a significantly lower level of HEPC (12.2±5.3 μg/L vs 22.2±6.5 μg/L, t=9.9, P＜0.01. Compared with those with NAFLD alone, the patients complicated by abnormal ALT level had significantly higher serum levels of ALT (89±58 U/L vs 26±8 U/L, t=7.1, P＜0.01, SI (23.4±6.2 μmol/L vs 19.6±7.9 μmol/L, t=2.2, P=0.03, and SF (406.2±290.0 μg/L vs 219.4±112.0 μg/L, t=3.7, P＜0.01, as well as a significantly

Relationship between serum concetrations of type III procollagen, hyluronic acid and histopathological findings in the liver of HCV-positive blood donors Relação entre concentrações séricas de procolágeno tipo III, ácido hialurônico com achados histopatológicos do fígado em doadores de sangue anti-HCV positivos

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Vera Regina Rodrigues Camacho

2007-06-01

Full Text Available BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic liver disease. Among fibrosis markers, type III procollagen (PIIIP and hyaluronic acid have been studied in these patients. AIM: To evaluate the association between these serum markers with histological findings. METHODS: A prospective cross-sectional study was carried out with HCV-positive blood donors. The studied population included men and women whose age ranged from 18 to 60 years, with elevated liver function tests [ALT levels > 1.5 times the normal value and alterations of two or more of the following: any changes in the levels of ALT, aspartate aminotransferase, conjugated bilirrubin, gammaglobulin, gammaglutamyltranspeptidase, albumin, platelet count; alkaline phosphatase levels >1.5 times the normal value, or prothrombin time below 70% and above 60%]. Fourty-nine patients were submitted to liver biopsy, blood analysis of PIIIP, hyaluronic acid, besides liver function tests. RESULTS: Liver function tests were not associated with tissular fibrosis, as assessed by ALT (>1.5 times above normal, fibrosis risk=18.8%; RACIONAL: Marcadores sorológicos têm sido propostos para monitorar fibrose hepática em doença crônica do fígado. Dentre os marcadores de fibrose, ácido hialurônico e procolágeno tipo III têm sido estudados nestes pacientes. OBJETIVO: Avaliar a associação de marcadores séricos de fibrose com achados histológicos. MÉTODOS: Foi realizado estudo transversal prospectivo em doadores de sangue anti-HCV positivos. A população estudada incluiu homens e mulheres com idade entre 18-60 anos com provas de função hepática alteradas (níveis de alanina aminotransferase >1.5 vezes do normal e alterações de dois ou mais dos seguintes: qualquer alteração nos níveis de alanina aminotransferase, aspartato aminotransferase, bilirrubina conjugada, gamaglobulina, gamaglutamiltranspeptidase, albumina, plaquetas, níveis de fosfatase

The effect of aqueous extract of Carica papaya leaves on liver ...

African Journals Online (AJOL)

The effects of crude leaf extract of Carica papaya (Linn) on aspartate aminostransferase (AST), alanine aminotransferase (ALT), total white blood cells (WBC), lymphocytes, neutrophils, thrombocytes and on body weight of normal albino rats were investigated. Albino rats weighing between 74 g and 90.5 g, of both sexes ...

Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

Science.gov (United States)

Tweed, Conor Duncan; Wills, Genevieve Helen; Crook, Angela M; Dawson, Rodney; Diacon, Andreas H; Louw, Cheryl E; McHugh, Timothy D; Mendel, Carl; Meredith, Sarah; Mohapi, Lerato; Murphy, Michael E; Murray, Stephen; Murthy, Sara; Nunn, Andrew J; Phillips, Patrick P J; Singh, Kasha; Spigelman, M; Gillespie, S H

2018-03-28

Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment. Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements. A total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin > 2 × ULN. DILI was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard tuberculosis therapy, 41 experienced clinically significant enzyme elevations (peak ALT ≥ 3 × ULN). On standard therapy, 21.1% of patients aged >55 years developed a peak ALT/aspartate aminotransferase (AST) ≥ 3 × ULN (p = 0.01) and 15% of HIV-positive patients experienced a peak ALT/AST ≥ 3 × ULN compared to 9% of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in isoniazid-containing regimens vs no-isoniazid regimens (p tuberculosis patients on standard treatment. Older patients on standard therapy, HIV-positive patients, Asian patients and those receiving isoniazid were at higher risk of elevated enzyme levels. Monitoring hepatic enzymes during the first 2 months of standard therapy detected approximately 75% of patients with a peak enzyme elevation ≥3 × ULN, suggesting this should be a standard of care. These

A Retrospective Review of Thiazolidinediones with Development of a Troglitazone Conversion Protocol

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Cameron Lindsey

2003-01-01

Full Text Available The objective of this paper was (1 to assess compliance with the National Veterans Affairs Guidelines for the use of troglitazone and rosiglitazone and (2 to develop and implement a conversion protocol that allows effective management of patients receiving troglitazone. A retrospective chart review was conducted to assess adherence to guidelines for all patients receiving troglitazone and rosiglitazone at the medical center. Appropriateness of therapy through indication evaluation, safety through alanine aminotransferase (ALT monitoring compliance, and efficacy through hemoglobin A1c (HbA1c changes were used to assess adherence. According to National Veterans Affairs (VA Guidelines, 68% of troglitazone and 63% of rosiglitazone patients had an appropriate indication for the use of these agents. Baseline ALT levels were obtained in 40% of troglitazone and 71% of rosiglitazone patients. Full compliance with continual ALT monitoring was seen in 6 and 54% of patients, respectively. Goal HbA1c was achieved in 57 and 29% of patients, respectively. Of the 33 patients receiving troglitazone, 19 were converted to rosiglitazone therapy; 11 were maintained on current regimens without troglitazone, and 3 were lost to follow up. Adherence to guidelines needs to be reinforced, in particular, compliance with ALT monitoring. However, there were no reported cases of hepatotoxicity in the patients reviewed. Many patients did not achieve a HbA1c

Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease.

Science.gov (United States)

Hossain, Noreen; Afendy, Arian; Stepanova, Maria; Nader, Fatema; Srishord, Manirath; Rafiq, Nila; Goodman, Zachary; Younossi, Zobair

2009-11-01

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We investigated factors associated with advanced fibrosis in NAFLD. The study included 432 patients with histologically proven NAFLD (26.8% with nonalcoholic steatohepatitis [NASH] and 17.4% with moderate-to severe fibrosis). NASH was defined as steatosis, lobular inflammation, and ballooning degeneration with or without Mallory-Denk bodies and/or fibrosis. Fibrosis was classified into 2 groups: those with no or minimal fibrosis and those with moderate-to-severe fibrosis. Groups were compared using Mann-Whitney and chi-square method analyses. A model was constructed using a stepwise bidirectional method; its predictive power was measured using a 10-fold cross-validation technique. Patients with NASH were more likely to be male (P < .0001); have lower hip-to-waist ratios (P = .03); were less likely to be African American (P = .06); have higher levels of alanine aminotransferase (ALT; P < .0001), aspartate aminotransferase (AST; P < .0001), and serum triglycerides (P = .0154), but lower levels of high-density lipoprotein cholesterol (P < .0001). Patients with moderate-to-severe fibrosis were older (P = .0245); more likely to be male (P = .0189), Caucasian (P = .0382), have diabetes mellitus (P = .0238), and hypertension (P = .0375); and have a lower hip-to-waist ratio (P = .0077) but higher serum AST (P < .0001) and ALT (P < .0001) levels. The multivariate analysis model to predict moderate-to-severe fibrosis included male sex, Caucasian ethnicity, diabetes mellitus, and increased AST and ALT levels (model P value < .0001). In patients with NAFLD, diabetes mellitus and aminotransferase levels are independent predictors of moderate-to-severe fibrosis. They can be used to identify NAFLD patients at risk for advanced fibrosis.

Diagnosis of hepatitis C virus in Brazilian blood donors using a reverse transcriptase nested polymerase chain reaction: comparison with enzyme immunoassay and recombinant protein immunoblot assay Diagnóstico da hepatite por vírus C em doadores de sangue brasileiros, usando a reação de transcrição reversa e a reação em cadeia da polimerase "nested": comparação com os ensaios imunoenzimáticos e imunoblot recombinante

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Neiva S. L. GONÇALES

2000-10-01

Full Text Available Screening blood donations for anti-HCV antibodies and alanine aminotransferase (ALT serum levels generally prevents the transmission of hepatitis C virus (HCV by transfusion. The aim of the present study was to evaluate the efficiency of the enzyme immunoassay (EIA screening policy in identifying potentially infectious blood donors capable to transmit hepatitis C through blood transfusion. We have used a reverse transcriptase (RT-nested polymerase chain reaction (PCR to investigate the presence of HCV-RNA in blood donors. The prevalence of HCV-RNA positive individuals was compared with the recombinant immunoblot assay (RIBA-2 results in order to assess the usefulness of both tests as confirmatory assays. Both tests results were also compared with the EIA-2 OD/C ratio (optical densities of the samples divided by the cut off value. ALT results were expressed as the ALT quotient (qALT, calculated dividing the ALT value of the samples by the maximum normal value (53UI/l for the method. Donors (n=178 were divided into five groups according to their EIA anti-HCV status and qALT: group A (EIA > or = 3, ALT or = 3, ALT>1, group C (11 and group E (EIA or = 3 and detectable HCV-RNA by RT-nested PCR. We have also noted that blood donors with RIBA-2 indeterminate presented a high degree of detectable HCV-RNA using RT-nested PCR (75%, especially when the c22.3 band was detected.Na prevenção da transmissão de Hepatite por Vírus C (HCV em transfusões de hemocomponentes, utiliza-se rotineiramente, como testes de triagem de doadores de sangue, ensaios que detectam anticorpos anti-HCV e dosagens da enzima alanina-aminotransferase (ALT. O presente estudo tem como objetivo principal avaliar a eficiência do ensaio imunoenzimático de segunda geração (EIA-2 como teste de triagem, na identificação de doadores de sangue potencialmente infectados, e portanto, capazes de transmitir hepatite C pelos hemocomponentes. Nós utilizamos o ensaio de transcri

Acute liver failure in a term neonate after repeated paracetamol administration

OpenAIRE

Bucaretchi, Fabio; Fernandes, Carla Borrasca; Branco, Maira Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araujo; Porta, Gilda

2014-01-01

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL)...

Effect of a high monounsaturated vs high polyunsaturated fat hypocaloric diets in nonalcoholic fatty liver disease.

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Aller, R; de Luis, D A; Izaola, O; de la Fuente, B; Bachiller, R

2014-01-01

Hyperaminotransferasemia is an important problem in obese patients. We decide to examine the changes in hyperaminotransferasemia after weight reduction in obese patients with and without NAFLD secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets. A population of 306 obese patients was randomly allocated to two groups: Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). Patients were classified as group I (obese subjects; n=262) when serum ALT activity was normal or group II (NAFLD patients; n=44) when serum ALT activity was (≥ 43 UI/L). In NAFLD group with diet M, BMI, weight, fat mass, waist circumference, systolic blood pressure, total cholesterol, LDL cholesterol), insulin and HOMA-R decreased. In NAFLD group with diet P, BMI, weight, fat mass, waist circumference, systolic blood pressure, total cholesterol, LDL cholesterol), insulin and HOMA-R decreased, too. In NAFLD group, alanine aminotransferase [(diet M) -20.3±19.2 UI/L vs. (diet P) -14.2±20.1 UI/L], aspartate aminotransferase [(diet M) -11.3±12.2 UI/L vs. (diet P) -11.1±10.1 UI/L], and gammaglutamyl transferase [(diet M) -18.1±12.2 UI/L vs. (diet P) -10.9±20.1 UI/L] improved with both diets. We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hypertransaminasemia and insulin resistance in NAFLD patients.

Andrographolide Ameliorates Liver Fibrosis in Mice: Involvement of TLR4/NF-κB and TGF-β1/Smad2 Signaling Pathways

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Liteng Lin

2018-01-01

Full Text Available Liver fibrosis is characterized by activated hepatic stellate cells (HSC and extracellular matrix accumulation. Blocking the activation of HSC and the inflammation response are two major effective therapeutic strategies for liver fibrosis. In addition to the long history of using andrographolide (Andro for inflammatory disorders, we aimed at elucidating the pharmacological effects and potential mechanism of Andro on liver fibrosis. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4 and the mice were intraperitoneally injected with Andro for 6 weeks. HSC cell line (LX-2 and primary HSC were also treated with Andro in vitro. Treatment of CCl4-induced mice with Andro decreased the levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST, Sirius red staining as well as the expression of α smooth muscle actin (α-SMA and transforming growth factor- (TGF- β1. Furthermore, the expression of Toll-like receptor (TLR4 and NF-κB p50 was also inhibited by Andro. Additionally, in vitro data confirmed that Andro treatment not only attenuated the expression of profibrotic and proinflammatory factors but also blocked the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways. These results demonstrate that Andro prevents liver inflammation and fibrosis, which is in correlation with the inhibition of the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways, highlighting Andro as a potential therapeutic strategy for liver fibrosis.

Antihepatocarcinoma Effect of Portulaca oleracea L. in Mice by PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB Pathway

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Guoyin, Zheng; Hao, Peng; Min, Li; Wei, Gu; Zhe, Chen

2017-01-01

The purpose of the present study was to evaluate the pharmacological effects of Portulaca oleracea L. (Purslane) (PL) on N-nitrosodiethylamine- (NDEA-) induced hepatocellular carcinomas (HCC) and explore its potential mechanism. Mice were randomly assigned to four groups: control group, NDEA group, NDEA + Purslane (100 mg/kg) group, and NDEA + Purslane (200 mg/kg) group. The animal of each group was given NDEA (100 ppm) in drinking water. 1 h later, Purslane dissolved in PBS was intragastrically administered for continuous seven days. The results showed that Purslane reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and serum. Purslane also reduced the contents of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and methane dicarboxylic aldehyde (MDA) and restored the activity of superoxygen dehydrogenises (SOD) in serum. Purslane could obviously attenuate the hepatic pathological alteration. Furthermore, treatment with Purslane effectively inhibited the phosphorylations of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), nuclear factor-kappa B (NF-κB), and inhibitor of NF-κBα (IκBα) and upregulated the expressions of NF-E2-related factor 2 (Nrf2) and heme oxygenase- (HO-) 1. In conclusion, our research suggested that Purslane exhibited protective effects on NDEA-induced hepatocellular carcinomas by anti-inflammatory and antioxidative properties via the PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB pathway. PMID:28659990

Gamma-glutamyltransferase, aspartate aminotransferase and alkaline phosphatase as markers of alcohol consumption in out-patient alcoholics

DEFF Research Database (Denmark)

Gluud, C; Andersen, I; Dietrichson, O

1981-01-01

and alkaline phosphatase in 18% and 7%. Neither the activity of gamma-glutamyltransferase, aspartate aminotransferase nor alkaline phosphatase showed any significant (P greater than 0.05) correlation with the history of alcohol consumption. The activities of gamma-glutamyltransferase and aspartate...

Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats

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Kuznietsova, H. M.; Lynchak, O. V.; Dziubenko, N. V.; Osetskyi, V. L.; Ogloblya, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Ritter, U.; Scharff, P.

2018-03-01

Sclerosing cholangitis is the liver disease of uncertain etiology, extremely unfavorable prognosis and lack of effective medication therapy. Therefore, the effect of water-soluble biocompatible C60 fullerenes (C60FAS) on the liver functional state on rat acute-cholangitis model was aimed to be discovered. Acute cholangitis was simulated by single α-naphthyl isothiocyanate (ANIT, 100 mg/kg) per os administration; C60FAS (0.5 mg/kg) was administered either per os or intraperitoneally in 24 and 48 h after ANIT ingestion, and in 72 h the animals were sacrificed. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), the total and direct bilirubin, creatinine and urea in the blood serum were determined, and the liver morphological state was assessed. In animals experienced ANIT-induced acute cholangitis, the total and direct bilirubin, creatinine, ALT, AST, ALP and LDH 1.5-4-fold increase were observed, indicating cytolysis of hepatocytes, cholestasis, and renal dysfunction. The features of periductal fibrosis, biliary epithelium atrophy, and portal-portal linking septa formation were detected, confirming the sclerosing cholangitis development. C60FAS promoted to the normalization of direct and total bilirubin levels, the ALT activity and diminution of fibrotic features. In addition, C60FAS intraperitoneal administration also normalized the ALP activity, indicating the attenuation of disease symptoms. However, the AST activity and creatinine level remained unchanged, and the LDH activity even increased, manifesting the partial persistence of cholestasis and renal dysfunction. Thus, the therapeutic application of C60FAS promotes a partial protection of liver against cholangitis.

Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.

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Wong, Anselm; Sivilotti, Marco L A; Gunja, Naren; McNulty, Richard; Graudins, Andis

2018-03-01

Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.

Influence of sex and developmental stage on acute hepatotoxic and inflammatory responses to liver procarcinogens in the mouse

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Hanna, Daniel; Riedmaier, Ariane Emami; Sugamori, Kim S.; Grant, Denis M.

2016-01-01

The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development. We also recently observed that female but not male mice exposed postnatally to ABP had slightly increased expression of the antioxidant defense genes Nqo1 and Ggt1, which are regulated by the oxidative stress response protein nuclear factor erythroid 2-related factor 2 (NRF2), while expression of Hmox1 was increased in both sexes. The goal of the present study was therefore to compare selected acute hepatotoxic, inflammatory and oxidative stress defense responses to ABP, DEN, or the prototype hepatotoxicant carbon tetrachloride (CCl 4 ), in male and female mice exposed to these chemicals either postnatally or as adults. Exposure of adult mice to ABP, DEN or CCl 4 produced a 2-fold greater acute elevation in serum levels of the hepatotoxicity biomarker alanine aminotransferase (ALT) in males than in females, while levels of the inflammatory biomarker interleukin-6 (IL-6) showed no sex difference. However, treatment of immature mice with either ABP or DEN using standard tumor-inducing postnatal exposure protocols produced no increase in serum ALT or IL-6 levels in either males or females, while CCl 4 produced a 40-fold ALT elevation but with no sex difference. Basal expression of the NRF2-responsive gene Nqo1 was higher in adult females than in males, but there was no sex difference in basal expression of Ggt1 or Hmox1. Sexually immature animals showed no sex difference in basal

Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus.

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Monteiro, Diana Amaral; Selistre-de-Araújo, Heloisa Sobreiro; Tavares, Driele; Fernandes, Marisa Narciso; Kalinin, Ana Lúcia; Rantin, Francisco Tadeu

2017-09-28

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg -1 , via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus , seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms.

[DEVELOPMENT OF FUNCTIONAL AND MORPHOLOGICAL CHANGES OF A PANCREAS DEPENDING ON THE DURATION OF OBSTRUCTIVE CHOLESTASIS].

Science.gov (United States)

Belyaev, A N; Kostin, S V; Belyaev, S A

2015-01-01

To study the severity and timing of the development of functional (reversible) and morphological (irreversible) disturbances in the pancreas, depending on the duration of obstructive cholestasis. Obstructive jaundice in the experiment 18 dogs modeled by applying the loop stranglehold on the common bile duct, followed by observation for 30 days. We measured total bilirubin and fractions aspartate aminotransferase activity (AST) and alanine aminotransferase (ALT), the contents alpha-amylase, pancreatic lipase, glucose, histological examination of the pancreas (magnification of 100 times and 400). On day 3 the common bile duct obstruction bilirubin increased from 7.1 to 286.8 μmol/l, ALT--from 0.17 to 4.18 μmol*h/l, alpha-amylase from 89 to 186 U/L and lipase--to 68 to 179 U/L. Then there was a slight decrease in the parameters studied with repeated their increase to 15 hours. Morphological changes in the first three days were characterized by reversible (swelling), impaired organ that 14-16 days passed in organic (irreversible) changes. Dynamics of fluctuations in the level of liver enzymes in the pancreas and obstructive cholestasis correlates with morphological abnormalities in the pancreas and fit into the concept of general biological organism's reaction to injury.

Protective Effect of Cymbopogon citratus Essential Oil in Experimental Model of Acetaminophen-Induced Liver Injury.

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Uchida, Nancy Sayuri; Silva-Filho, Saulo Euclides; Aguiar, Rafael Pazinatto; Wiirzler, Luiz Alexandre Marques; Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Silva-Comar, Francielli Maria de Souza; Becker, Tânia Cristina Alexandrino; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

2017-01-01

To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO. The livers were used to determine myeloperoxidase (MPO) activity, nitric oxide (NO) production and histological analysis. The effect of LGO on leukocyte migration was evaluated in vitro. Anti-oxidant activity was performed by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. LGO pretreatment decreased significantly the levels of ALT, AST and ALP compared with APAP group. MPO activity and NO production were decreased. The histopathological analysis showed an improved of hepatic lesions in mice after LGO pretreatment. LGO inhibited neutrophil migration and exhibited anti-oxidant activity. Our results suggest that LGO has protective activity against liver toxicity induced by paracetamol.

Cryoablation of Hepatocellular Carcinoma with High-Risk for Percutaneous Ablation: Safety and Efficacy

Energy Technology Data Exchange (ETDEWEB)

Kim, Gyoung Min; Won, Jong Yun, E-mail: jywon@yuhs.ac; Kim, Man Deuk; Park, Sung Il; Lee, Do Yun; Shin, Wonseon; Shin, Minwoo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Hospital (Korea, Republic of); Han, Kwang-Hyub; Kim, Do Young; Kim, Seung Up [Yonsei University College of Medicine, Department of Internal Medicine, Institute of Gastroenterology (Korea, Republic of)

2016-10-15

PurposeThe aim of this study was to evaluate the safety and effectiveness of cryoablation in the treatment of subcapsular hepatocellular carcinoma (HCC) adjacent to various organs.Materials and MethodsTwenty-eight patients with subcapsular HCC were treated with cryoablation in our institution. The degree of peri-procedural pain was measured using the visual analog scale (VAS). Technical success, local tumor progression, and overall disease progression rates were calculated. Procedure-related complications were identified by reviewing electronic medical records. Biochemical data, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels before and after the procedure were collected.ResultsSubcapsular HCC tumors were located near the gallbladder, colon, stomach, kidney, diaphragm, or abdominal wall. The technical success rate of cryoablation was 96.4 % (27/28). Local recurrence- and progression-free survival rates were 96 and 84 % at 6 months, and 82 and 43 % at 1 year, respectively. All patients survived during the follow-up period. The VAS pain score ranged from 0 to 3 (mean, 1.57). A major complication occurred in one patient (3.6 %) and minor complications occurred at a rate of 17.9 %. Transient elevations of serum AST, ALT, and bilirubin levels were observed.ConclusionCryoablation is a safe and an effective procedure for the treatment of subcapsular HCC adjacent to various major organs.

Cryoablation of Hepatocellular Carcinoma with High-Risk for Percutaneous Ablation: Safety and Efficacy

International Nuclear Information System (INIS)

Kim, Gyoung Min; Won, Jong Yun; Kim, Man Deuk; Park, Sung Il; Lee, Do Yun; Shin, Wonseon; Shin, Minwoo; Han, Kwang-Hyub; Kim, Do Young; Kim, Seung Up

2016-01-01

PurposeThe aim of this study was to evaluate the safety and effectiveness of cryoablation in the treatment of subcapsular hepatocellular carcinoma (HCC) adjacent to various organs.Materials and MethodsTwenty-eight patients with subcapsular HCC were treated with cryoablation in our institution. The degree of peri-procedural pain was measured using the visual analog scale (VAS). Technical success, local tumor progression, and overall disease progression rates were calculated. Procedure-related complications were identified by reviewing electronic medical records. Biochemical data, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels before and after the procedure were collected.ResultsSubcapsular HCC tumors were located near the gallbladder, colon, stomach, kidney, diaphragm, or abdominal wall. The technical success rate of cryoablation was 96.4 % (27/28). Local recurrence- and progression-free survival rates were 96 and 84 % at 6 months, and 82 and 43 % at 1 year, respectively. All patients survived during the follow-up period. The VAS pain score ranged from 0 to 3 (mean, 1.57). A major complication occurred in one patient (3.6 %) and minor complications occurred at a rate of 17.9 %. Transient elevations of serum AST, ALT, and bilirubin levels were observed.ConclusionCryoablation is a safe and an effective procedure for the treatment of subcapsular HCC adjacent to various major organs.

Hemihepatic versus total hepatic inflow occlusion during hepatectomy: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Hai-Qing; Yang, Jia-Yin; Yan, Lu-Nan

2011-07-14

To evaluate the clinical outcomes of patients undergoing hepatectomy with hemihepatic vascular occlusion (HHO) compared with total hepatic inflow occlusion (THO). Randomized controlled trials (RCTs) comparing hemihepatic vascular occlusion and total hepatic inflow occlusion were included by a systematic literature search. Two authors independently assessed the trials for inclusion and extracted the data. A meta-analysis was conducted to estimate blood loss, transfusion requirement, and liver injury based on the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Either the fixed effects model or random effects model was used. Four RCTs including 338 patients met the predefined inclusion criteria. A total of 167 patients were treated with THO and 171 with HHO. Meta-analysis of AST levels on postoperative day 1 indicated higher levels in the THO group with weighted mean difference (WMD) 342.27; 95% confidence intervals (CI) 217.28-467.26; P = 0.00 001; I(2) = 16%. Meta-analysis showed no significant difference between THO group and HHO group on blood loss, transfusion requirement, mortality, morbidity, operating time, ischemic duration, hospital stay, ALT levels on postoperative day 1, 3 and 7 and AST levels on postoperative day 3 and 7. Hemihepatic vascular occlusion does not offer satisfying benefit to the patients undergoing hepatic resection. However, they have less liver injury after liver resections.

Hepatoprotective properties of aqueous leaf extract of Persea Americana, Mill (Lauraceae) 'avocado' against CCL4-induced damage in rats.

Science.gov (United States)

Brai, Bartholomew I C; Adisa, Rahmat A; Odetola, Adebimpe A

2014-01-01

Natural products from plants have received considerable attention in recent years due to their diverse pharmacological properties, including antioxidants and hepatoprotective activities. The protective effects of aqueous extract of Persea americana (AEPA) against carbon tetrachloride (CCl4)-induced hepatotoxicity in male albino rats was investigated. Liver damage was induced in rats by administering a 1:1 (v/v) mixture of CCl4 and olive oil [3 ml/kg, subcutaneously (sc)] after pre-treatment for 7 days with AEPA. Hepatoprotective effects of AEPA was evaluated by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects of AEPA on biomarkers of oxidative damage (lipid peroxidation) and antioxidant enzymes namely, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were measured in liver post mitochondrial fraction. AEPA and Reducdyn® showed significant (p<0.05) hepatoprotective activity by decreasing the activities of ALT, AST, ALP and reducing the levels of TBL. The activities of antioxidant enzymes, levels of malondialdehyde and protein carbonyls were also decreased dose-dependently in the AEPA-treated rats. Pre-treatment with AEPA also decreased the serum levels of glutathione significantly. These data revealed that AEPA possesses significant hepatoprotective effects against CCl4-induced toxicity attributable to its constituent phytochemicals. The mechanism of hepatoprotection seems to be through modulation of antioxidant enzyme system.

Evaluation of the toxic effect of star fruit on serum biochemical parameters in rats.

Science.gov (United States)

Khoo, Z Y; Teh, C C; Rao, N K; Chin, J H

2010-04-01

The objective of the present study was to evaluate the toxic effect of Averrhoa carambola (star fruit) juice at different storage conditions in Sprague Dawley (SD) rats. Twenty female rats weighing 180 +/- 20 g were randomly assigned into four groups with five rats per group (n = 5). First group served as the control group, fed with distilled water (vehicle). Second, third and fourth groups were orally treated with juice of A. carambola stored for 0, 1 and 3 h respectively for 14 days. Cage-side observations were done daily after each treatment. Body weight, food consumption and water intake were recorded on day-0, day-3, day-7 and day-14. All rats were fasted overnight prior to blood collection through cardiac puncture on day-15. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine in blood serum were measured. Data were analyzed using Dunnett's test. From the results obtained, there was no lethality found and LD(50) could not be determined. Increment of ALT levels (Pcarambola juice stored for 3 h. On the basis of these results, we can conclude that A. carambola juice stored for 0 hand 1 h are safe to be consumed. However, juice stored for 3 h exerts toxic effect on rat liver at hepatocellular level.

A Randomized Controlled Trial of the Effects of an Almond-enriched, Hypocaloric Diet on Liver Function Tests in Overweight/Obese Women.

Science.gov (United States)

Abazarfard, Zohreh; Eslamian, Ghazaleh; Salehi, Mousa; Keshavarzi, Sareh

2016-03-01

Gradual weight reduction has been shown to be associated with improvements in liver enzymes. However, some evidence demonstrated that liver enzymes may transiently increase immediately after a diet-induced weight loss. This study was designed to assess the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on liver function tests in the context of a three-month weight reduction program in overweight/obese women. This randomized controlled clinical trial was registered at Iranian Registry of Clinical Trials with ID number of IRCT2013062313751N1. Overweight and obese Iranian women [n = 108; age = 42.7 y, body mass index = 29.6 kg/m(2)] were randomly assigned to consume an AED or NFD. The carefully planned hypocaloric diets were identical for both groups except for the AED group who consumed 50 grams of almonds daily for three months. Anthropometric measurements and laboratory measurements including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) were assessed before and immediately after the intervention. Of 108 participants, 50 women in AED group and 50 women in NFD group completed the protocol of the study (response rate: 92.6 %). The AED led to a median weight loss of 3.79 kg (interquartile range: 4.4 kg). Significant decreases within AED and NFD were observed in ALT (-16.6 ± 16.3 and -11.7 ± 16.8, P < 0.001, respectively). Similar significant decreases were observed in AST (-13.6 ± 15.7 and -7.7 ± 16.1; P < 0.001, respectively). The decrease in GGT was also significant in both groups (-11.4 ± 21.6 and -6.2 ± 19.8; P < 0.001 respectively). ALT, AST and GGT decreased significantly in the AED group compared to the NFD group (P < 0.001). AED improved liver enzymes in obese women. However, mild, transient increases in ALT and AST values can be observed immediately after an NFD in women.

Empty virions in AAV8 vector preparations reduce transduction efficiency and may cause total viral particle dose-limiting side effects

Directory of Open Access Journals (Sweden)

Kai Gao

2014-01-01

Full Text Available Empty virions are inadvertent by-products of recombinant adeno-associated virus (rAAV packaging process, resulting in vector lots with mixtures of full and empty virions at variable ratios. Impact of empty virions on the efficiency and side effects of rAAV transduction has not been well characterized. Here, we generated partially and completely empty AAV8 virions, fully packaged rAAV8 lots, and mixtures of empty and fully packaged virions with variable ratios of empty virions. The aforementioned dosing formulations of rAAV8 expressing either cellular (EGFP (enhanced green fluorescent protein or nuclear-targeted (n LacZ or secreted (human α1-antitrypsin (hA1AT reporter genes were intravenously injected into two different mouse strains, followed by analyses of transgene expressions and serum alanine aminotransferase (ALT levels at different time points. We found that addition of empty particles to the fixed doses of rAAV8 preparations repressed liver transduction up to 64% (serum hA1AT and 44% (nLacZ in C57BL/6 mice, respectively. The similar trend in inhibiting EGFP expression together with concurrent elevations of serum ALT levels were observed in the BALB/c mice, indicating that empty particles may also exacerbate side effects of rAAV8 EGFP transduction. Our results suggest that removal of empty particles from rAAV preparations may improve efficacy and safety of AAV in clinical applications.

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

International Nuclear Information System (INIS)

Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J.

2014-01-01

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na + -K + -ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na + -K + -ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na + -K + -ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis

Enzimas de função hepática na aflatoxicose aguda experimental em frangos de corte Hepatic enzimes function in experimental acute enzimes aflatoxicosis in broilers

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Adriana Borsa

1998-12-01

Full Text Available Com o objetivo de avaliar a função hepática de aves experimentalmente intoxicadas por aflatoxina, com e sem uso de bentonita sódica, foram utilizados 40 (quarenta frangos de corte, machos, linhagem Ross, divididos em 4 (quatro grupos de 10 (dez. animais, sendo que cada grupo foi submetido a um tratamento: T1 - controle (ração sem aflatoxina ou bentonita, T2 - ração com 5ppm de aflatoxina, T3 - ração com 5ppm de aflatoxina e 0,5% de bentonita sódica e T4 - ração com 0,5% de bentonita sódica. Todos estes tratamentos foram aplicados do 1° ao 42 ° dia de vida das aves. Aos 21, 35 e 42 dias de idade, foram analisados os níveis séricos das enzimas aspartato aminotransferase (AST, alanina aminotransferase (ALT, lactato desidrogenase (LDH e gama glutamiltransferase (GGT, A análise da variância mostrou que houve interação entre os tratamentos e datas de colheita de material, para as seguintes variáveis: AST, LDH e GGT. Para estas, foi aplicado o teste de Tukey, comparando-se as médias de cada tratamento em cada data. Observou-se que as enzimas AST, ALT e GGT não apresentaram diferenças significativas entre tratamentos, porém, nos tratamentos l e 2, a AST apresentou um aumento linear (pThe aim ofthis study is to evaluate ïhe hepatic function of experimentally intoxicated broilers by aflatoxin with and without sodium bentonite. Forty Ross mole broilers, were used divided into 4 groups of 10 birds, and such groups have been submitted to the following treatments: T1- control (feed without aflatoxin or sodium bentonite, T2- feed containing 5ppm of aflatoxin, T3- feed containing 5ppm of aflatoxin and 0.5% of sodium bentonite and T4- feed containing 0.5% of sodium bentonite. Ali these treatments have been appiied from the l st to the 42nd day of lif e. On the days 21, 35 and 42, the serum leveis of the enzimes aspartate aminotransferase (AST, alanino aminotransferase (ALT, lactate dehydrogenase (LDH and gamma glutamiltransferase (GGT

Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in D-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M

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Yin, Xinru [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Gong, Xia [Department of Anatomy, Chongqing Medical University, Chongqing 400016 (China); Zhang, Li; Jiang, Rong [Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016 (China); Kuang, Ge [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Wang, Bin [Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chen, Xinyu [Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021 (China); Wan, Jingyuan, E-mail: jywan@cqmu.edu.cn [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China)

2017-04-01

Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100 mg/kg) 1 h before lipopolysaccharide (LPS)/D-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production. - Highlights: • Glycyrrhetinic acid protected from LPS/D-GalN-induced liver injury in mice. • Glycyrrhetinic acid inhibited LPS-induced TNF-α production in vivo and in vitro. • Glycyrrhetinic

Alanine aminotransferase variants conferring diverse NUE phenotypes in Arabidopsis thaliana.

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McAllister, Chandra H; Good, Allen G

2015-01-01

Alanine aminotransferase (AlaAT, E.C. 2.6.1.2), is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes the reversible transfer of an amino group from alanine to 2-oxoglutarate to produce glutamate and pyruvate, or vice versa. It has been well documented in both greenhouse and field studies that tissue-specific over-expression of AlaAT from barley (Hordeum vulgare, HvAlaAT) results in a significant increase in plant NUE in both canola and rice. While the physical phenotypes associated with over-expression of HvAlaAT have been well characterized, the role this enzyme plays in vivo to create a more N efficient plant remains unknown. Furthermore, the importance of HvAlaAT, in contrast to other AlaAT enzyme homologues in creating this phenotype has not yet been explored. To address the role of AlaAT in NUE, AlaAT variants from diverse sources and different subcellular locations, were expressed in the wild-type Arabidopsis thaliana Col-0 background and alaat1;2 (alaat1-1;alaat2-1) knockout background in various N environments. The analysis and comparison of both the physical and physiological properties of AlaAT over-expressing transgenic plants demonstrated significant differences between plants expressing the different AlaAT enzymes under different external conditions. This analysis indicates that the over-expression of AlaAT variants other than HvAlaAT in crop plants could further increase the NUE phenotype(s) previously observed.

Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice.

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Zhang, Chen; Li, Juan; Hu, Chunlong; Wang, Jing; Zhang, Jianjun; Ren, Zhenzhen; Song, Xinling; Jia, Le

2017-09-07

The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH 2 , -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.

Relationship between analytic values and canine obesity.

Science.gov (United States)

Peña, C; Suárez, L; Bautista, I; Montoya, J A; Juste, M C

2008-06-01

The objective of this study was to assess the relationship between canine body condition and metabolic parameters like serum lipids, blood glucose and alanine aminotransferase (ALT) concentrations. We selected 127 dogs (42 males and 85 females) that were taken to our veterinary medicine service during routine visits. The mean age was 6.67 +/- 5.24 years. Body condition (BC) was measured by Laflamme scale and dogs were considered as obese when BC score was over 6. The following variables were collected: total cholesterol, high-density lipoprotein cholesterol, triglycerides, basal glucose and ALT. 66.1% of the dog cohort were obese. Total cholesterol and triglycerides were found to be higher (p obese dogs with respect to normal weight dogs. In conclusion, obesity in dogs is associated with higher serum lipid levels.

A low-pungency S3212 genotype of Capsicum frutescens caused by a mutation in the putative aminotransferase (p-AMT) gene.

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Park, Young-Jun; Nishikawa, Tomotaro; Minami, Mineo; Nemoto, Kazuhiro; Iwasaki, Tomohiro; Matsushima, Kenichi

2015-12-01

The purpose of this study was to identify the genetic mechanism underlying capsinoid biosynthesis in S3212, a low-pungency genotype of Capsicum frutescens. Screening of C. frutescens accessions for capsaicinoid and capsiate contents by high-performance liquid chromatography revealed that low-pungency S3212 contained high levels of capsiate but no capsaicin. Comparison of DNA coding sequences of pungent (T1 and Bird Eye) and low-pungency (S3212) genotypes uncovered a significant 12-bp deletion mutation in exon 7 of the p-AMT gene of S3212. In addition, p-AMT gene transcript levels in placental tissue were positively correlated with the degree of pungency. S3212, the low-pungency genotype, exhibited no significant p-AMT transcript levels, whereas T1, one of the pungent genotypes, displayed high transcript levels of this gene. We therefore conclude that the deletion mutation in the p-AMT gene is related to the loss of pungency in placental tissue and has given rise to the low-pungency S3212 C. frutescens genotype. C. frutescens S3212 represents a good natural source of capsinoids. Finally, our basic characterization of the uncovered p-AMT gene mutation should contribute to future studies of capsinoid biosynthesis in Capsicum.

Selective interaction between Chloroplast B ATPase and TGB1 retards severe symptoms caused by Alternanthera mosaic virus infection

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The multifunctional triple gene block protein 1 (TGB1) of the Potexvirus Alternanthera mosaic virus (AltMV) has been reported to have silencing suppressor, cell-to-cell movement, and helicase functions. Yeast two hybrid screening using an Arabidopsis thaliana cDNA library with TGB1 as bait, and co-p...

PsAAT3, an oomycete-specific aspartate aminotransferase, is required for full pathogenicity of the oomycete pathogen Phytophthora sojae.

Science.gov (United States)

Wang, Rongbo; Zhang, Meixiang; Liu, Hong; Xu, Jing; Yu, Jia; He, Feng; Zhang, Xiong; Dong, Suomeng; Dou, Daolong

2016-04-01

Pathogen nutrient acquisition and metabolism are critical for successful infection and colonization. However, the nutrient requirements and metabolic pathways related to pathogenesis in oomycete pathogens are unknown. In this study, we bioinformatically identified Phytophthora sojae aspartate aminotransferases (AATs), which are key enzymes that coordinate carbon and nitrogen metabolism. We demonstrated that P. sojae encodes more AATs than the analysed fungi. Some of the AATs contained additional prephenate dehydratase and/or prephenate dehydrogenase domains in their N-termini, which are unique to oomycetes. Silencing of PsAAT3, an infection-inducible expression gene, reduced P. sojae pathogenicity on soybean plants and affected the growth under N-starving condition, suggesting that PsAAT3 is involved in pathogen pathogenicity and nitrogen utilisation during infection. Our results suggest that P. sojae and other oomycete pathogens may have distinct amino acid metabolism pathways and that PsAAT3 is important for its full pathogenicity. Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115).

Science.gov (United States)

Lee, Hyunbeom; Doud, Emma H; Wu, Rui; Sanishvili, Ruslan; Juncosa, Jose I; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

2015-02-25

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.

Selection and Evaluation of Indexes Commonly Used to Determine Contamination with T-2 Toxin in Pacific White Shrimp Litopenaeus vannamei by the Grey Relational Method.

Science.gov (United States)

Lu, Pengli; Wang, Yaling; Dai, Zhe; Sun, Lijun; Xu, Defeng; Liu, Ying; Ye, Riying; Gooneratne, Ravi; Bi, Siyuan

2017-09-01

The objectives of the present study were to evaluate the effects of different concentrations of the mycotoxin T-2 toxin in feed on muscle performance in the Pacific white shrimp Litopenaeus vannamei, evaluate indexes of physiological variables that indicate T-2 toxin contamination in the shrimp using the grey relational method, and determine the dose-response relationships between T-2 toxin and the indexes. Of the 6 physical, 7 biochemical, and 17 nutritional indexes examined, the values of the grey relational coefficients were highest for the hepatopancreas: body weight ratio (HBR), alanine aminotransferase (ALT) activity, and serine (SER) content (0.83, 0.68, and 0.82, respectively). Therefore, the HBR, ALT activity, and SER content were selected as appropriate indexes for contamination of Pacific white shrimp muscle with T-2 toxin. Based on their dose-response relationship curves, mean effective doses of 1.45, 1.69, and 1.33 mg of T-2 toxin/kg of feed were obtained for the HBR, ALT activity, and SER content, respectively. These results offer technical reference points for the evaluation and control of T-2 toxin in shrimp feed. Received April 28, 2016; accepted April 9, 2017.

Clinical and laboratory findings in patients with dengue associated with hepatopathy

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Delso do Nascimento

2011-12-01

Full Text Available INTRODUCTION: Hepatic disorders caused by dengue infection may progress to severe manifestations, including mortality and morbidity. Cytokines are involved in it, such as the migration inhibitory factor of macrophages (MIF, tumor necrosis factor (TNF, natural killer cells (NK, B lymphocytes, and macrophages. METHODS: This study was carried out from January to April 2007 at a public hospital from the Federal University of Mato Grosso do Sul, Campo Grande, Brazil. Sixty-eight patients were studied concerning hepatic alterations, with 56 reported having classic dengue, 6 with hemorrhagic dengue grade I, and 6 with hemorrhagic dengue grade II. RESULTS: Among the 56 with classic dengue, 83.3% had aspartate aminotransferase (AST alterations, and 69.6% had altered alanine aminotransferase (ALT. For those with hemorrhagic dengue grade I, 100% had AST alterations, and 83.3% had altered ALT. All the patients with hemorrhagic dengue grade II had AST and ALT alterations. AST variations reached 22.0 and 907.0, with an average value of 164.6. For ALT, we found variations between 25.0 and 867.0, with an average value of 166.07. There had been statistical significance between dengue clinical shapes and hepatic function markers. CONCLUSIONS: We conclude that the infection was predominant in adults, females, and in those with low income and education. The liver enzymes were of larger amount in hemorrhagic dengue, but there was weak statistical evidence of the clinical manifestations and transaminases. Major signs and clinical symptoms were fever, headache, myalgia, arthralgia, weakness, severe pain behind the eyes, and rashes.

Preparation of a Sepia Melanin and Poly(ethylene-alt-maleic Anhydride Hybrid Material as an Adsorbent for Water Purification

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Guido Panzarasa

2018-01-01

Full Text Available Meeting the increasing demand of clean water requires the development of novel efficient adsorbent materials for the removal of organic pollutants. In this context the use of natural, renewable sources is of special relevance and sepia melanin, thanks to its ability to bind a variety of organic and inorganic species, has already attracted interest for water purification. Here we describe the synthesis of a material obtained by the combination of sepia melanin and poly(ethylene-alt-maleic anhydride (P(E-alt-MA. Compared to sepia melanin, the resulting hybrid displays a high and fast adsorption efficiency towards methylene blue (a common industrial dye for a wide pH range (from pH 2 to 12 and under high ionic strength conditions. It is easily recovered after use and can be reused up to three times. Given the wide availability of sepia melanin and P(E-alt-MA, the synthesis of our hybrid is simple and affordable, making it suitable for industrial water purification purposes.

Falencia hepatica aguda en neonato a termino despues de la ingestion de dosis repetidas de paracetamol

OpenAIRE

Bucaretchi, Fabio; Fernandes, Carla Borrasca; Branco, Maira Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araujo; Porta, Gilda

2014-01-01

Objective:Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate.Case description:A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after r...

SERUM ACTIVITIES OF ASPARTATE AMINOTRANSFERASE, CREATINE KINASE AND LACTATE DEHYDROGENASE IN HORSES WITH COLIC ATIVIDADE SÉRICA DAS ENZIMAS ASPARTATO AMINOTRANSFERASE, CREATINA QUINASE E LACTATO DESIDROGENASE EM EQÜINOS COM CÓLICA

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Aureo Evangelista Santana

2008-12-01

Full Text Available Seventy equines distributed in two experimental groups were used, G1 (20 healthy equines, and G2 (50 equines with colic. Blood samples were obtained by jugular vein puncture in ten different moments. The variables aspartate aminotransferase (AST, creatine kinase (CK, and lactate dehydrogenase (LDH were determined by spectrophotometric assay using specific reagents. The average values presented by the animals of the G2 for variables CK, AST, and LDH were higher (P<0.05 than the values presented by the animals of the G1 in all the evaluation moments. The results showed for G2 animals suggest the existence of acute muscle injury. The muscle injuries in equines with colic were attributed to the tissue hypoperfusion, and the muscular damage.

KEY WORDS: Acute abdomen, horses, muscles enzyme. De setenta eqüinos, distribuídos em dois grupos experimentais – G1 (vinte eqüinos hígidos e G2 (cinqüenta eqüinos com cólica –, colheram-se amostras de sangue em dez diferentes momentos, mediante punção da jugular, para a determinação da atividade sérica das enzimas aspartato aminotransferase (AST, creatina quinase (CK e lactato desidrogenase (LDH. Os valores médios apresentados pelos animais do G2, para as variáveis CK, AST e LDH, foram superiores (P<0,05 aos valores médios apresentados pelos animais do G1 em todos os momentos de avaliação. Os resultados apresentados pelos animais com cólica (G2 sugerem a existência de lesão muscular aguda, porém com tendência a cura, e foram atribuídos a hipoperfusão tecidual e a traumas musculares. A análise seriada das enzimas CK, AST e LDH auxilia tanto no diagnóstico de lesões musculares em eqüinos com cólica como no acompanhamento da evolução do processo de cura.

PALAVRAS-CHAVES: Abdômen agudo, cavalos, enzimas musculares.

Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: results from the ANRS CO13 HEPAVIH cohort study.

Science.gov (United States)

Carrieri, M Patrizia; Lions, Caroline; Sogni, Philippe; Winnock, Maria; Roux, Perrine; Mora, Marion; Bonnard, Philippe; Salmon, Dominique; Dabis, François; Spire, Bruno

2014-01-01

We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Frequency of hepatitis C viral RNA in anti-hepatitis C virus non-reactive blood donors with normal alanine aminotransferase

International Nuclear Information System (INIS)

Ali, N.; Moinuddin, A.; Ahmed, S.A.

2010-01-01

To determine the frequency of HCV RNA in an anti-HCV non-reactive blood donor population with normal ALT, and its cost effectiveness. Study Design: An observational study. Place and Duration of Study: Baqai Institute of Haematology, Baqai Medical University, Karachi, and Combined Military Hospital, Malir Cantt, Karachi, from May 2006 to April 2008. Methodology: After initial interview and mini-medical examination, demographic data of blood donors was recorded, and anti-HCV, HBsAg and HIV were screened by third generation ELISA. Those reactive to anti-HCV, HbsAg and/or HIV were excluded. Four hundred consecutive donors with ALT within the reference range of 15-41 units/L were included in study. HCV RNA RT-PCR was performed on 5 sample mini-pools using Bio-Rad Real time PCR equipment. Results: All 400 donors were male, with mean age 27 years SD + 6.2. ALT of blood donors varied between 15-41 U/L with mean of 31.5+6.4 U/L, HCV RNA was detected in 2/400 (0.5%) blood donors. Screening one blood bag for HCV RNA costs Rs 4,000.00 equivalent to 50 US dollars, while screening through 5 sample mini-pools was Rs. 800.00 equivalent to approximately 10 US dollars. Conclusion: HCV RNA frequency was 0.5% (2/400) in the studied anti-HCV non-reactive normal ALT blood donors. Screening through mini-pools is more cost-effective. (author)

"Almha La Vengadora": Protagonista del indigenismo de neovanguardia alteño

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Maria Irina Soto-Mejia

2016-03-01

Este artículo discute la obra de Crispín Portugal (1976-2007, un escritor alteño, en el contexto de la lucha contra la pobreza y el racismo que enfrentan a las ciudades de El Alto y La Paz, y del movimiento en contra del mercado  que comenzó en Argentina produciendo libros con tapas de cartón compradas a los cartoneros. Portugal y otros escritores indígenas iniciaron un proyecto editorial llamado Yerba Mala Cartonera, que cuenta con su propio blog, para diseminar la literatura boliviana que no cuenta con otros medios de difusión. A través de la revisión de un cuento de Portugal (Almha La Vengadora que describe a una chola luchadora de El Alto cuyo nombre en el cuadrilátero es “la vengadora”, este trabajo plantea la configuración de un indigenismo alteño de neovanguardia equiparable al vanguardismo de Gamaliel Churata.  Con este propósito, presta especial atención a El Alto –la ciudad indígena más grande de Latinoamérica- situándolo como escenario clave para el desarrollo de una neovanguardia que se alimenta del neoliberalismo fallido para configurar una propuesta de modernidad que recupera el pasado indígena aymara para inventar otras formas de futuro.

Clinical and laboratory findings in patients with dengue associated with hepatopathy Achados clínicos e laboratoriais em pacientes com dengue associada à hepatopatia

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Delso do Nascimento

2011-12-01

Full Text Available INTRODUCTION: Hepatic disorders caused by dengue infection may progress to severe manifestations, including mortality and morbidity. Cytokines are involved in it, such as the migration inhibitory factor of macrophages (MIF, tumor necrosis factor (TNF, natural killer cells (NK, B lymphocytes, and macrophages. METHODS: This study was carried out from January to April 2007 at a public hospital from the Federal University of Mato Grosso do Sul, Campo Grande, Brazil. Sixty-eight patients were studied concerning hepatic alterations, with 56 reported having classic dengue, 6 with hemorrhagic dengue grade I, and 6 with hemorrhagic dengue grade II. RESULTS: Among the 56 with classic dengue, 83.3% had aspartate aminotransferase (AST alterations, and 69.6% had altered alanine aminotransferase (ALT. For those with hemorrhagic dengue grade I, 100% had AST alterations, and 83.3% had altered ALT. All the patients with hemorrhagic dengue grade II had AST and ALT alterations. AST variations reached 22.0 and 907.0, with an average value of 164.6. For ALT, we found variations between 25.0 and 867.0, with an average value of 166.07. There had been statistical significance between dengue clinical shapes and hepatic function markers. CONCLUSIONS: We conclude that the infection was predominant in adults, females, and in those with low income and education. The liver enzymes were of larger amount in hemorrhagic dengue, but there was weak statistical evidence of the clinical manifestations and transaminases. Major signs and clinical symptoms were fever, headache, myalgia, arthralgia, weakness, severe pain behind the eyes, and rashes.INTRODUÇÃO: Afecções hepáticas causadas pela infecção da dengue podem evoluir para quadro grave, incluindo mortalidade e morbidade. O mecanismo de lesão do fígado está relacionado com a exacerbação da resposta imune. As citocinas estão envolvidas nele como fator inibidor da migração de macrófagos (MIF, fator de necrose

Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and -nonresponsive forms of gyrate atrophy

International Nuclear Information System (INIS)

Ramesh, V.; McClatchey, A.I.; Ramesh, N.; Benoit, L.A.; Berson, E.L.; Shih, V.E.; Gusella, J.F.

1988-01-01

Gyrate atrophy (GA), a recessive eye disease involving progressive loss of vision due to chorioretinal degeneration, is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase with consequent hyperornithinemia. Genetic heterogeneity of GA has been suggested by the demonstration that administration of pyridoxine to increase the level of pyridoxal phosphate, a cofactor of OATase, reduces hyperornithinemia in a subset of patients. The authors have cloned and sequences cDNAs for OATase from two GA patients, one responsive and one nonresponsive to pyridoxine treatment. The respective cDNAs contained different single missense mutations, which were sufficient to eliminate OATase activity when each cDNA was tested in a eukaryotic expression system. However, like the enzyme in fibroblasts from the pyridoxine-responsive patient, OATase encoded by the corresponding cDNA from this individual showed a significant increase in activity when assayed in the presence of an increased pyridoxal phosphate concentration. These data firmly establish that both pyridoxine responsive and nonresponsive forms of GA result from mutations in the OATase structural gene. Moreover, they provide a molecular characterization of the primary lesion in a pyridoxine-responsive genetic disorder

Experimental data suggesting that inflammation mediated rat liver mitochondrial dysfunction results from secondary hypoxia rather than from direct effects of inflammatory mediators

Directory of Open Access Journals (Sweden)

Adelheid eWeidinger

2013-06-01

Full Text Available Systemic inflammatory response (SIR comprises direct effects of inflammatory mediators (IM and indirect effects, such as secondary circulatory failure which results in tissue hypoxia (HOX. These two key components, SIR and HOX, cause multiple organ failure (MOF. Since HOX and IM occur and interact simultaneously in vivo, it is difficult to clarify their individual pathological impact. To eliminate this interaction, precision cut liver slices (PCLS were used in this study aiming to dissect the effects of HOX and IM on mitochondrial function, integrity of cellular membrane and the expression of genes associated with inflammation. HOX was induced by incubating PCLS or rat liver mitochondria at pO2<1% followed by reoxygenation (HOX/ROX model. Inflammatory injury was stimulated by incubating PCLS with IM (IM model. We found upregulation of inducible nitric oxide synthase (iNOS expression only in the IM model, while heme oxygenase 1 (HO-1 expression was upregulated only in the HOX/ROX model. Elevated expression of interleukin 6 (IL-6 was found in both models reflecting converging pathways regulating the expression of this gene. Both models caused damage to hepatocytes resulting in the release of alanine aminotransferase (ALT. The leakage of aspartate aminotransferase (AST was observed only during the hypoxic phase in the HOX/ROX model. The reoxygenation phase of HOX, but not IM, drastically impaired mitochondrial electron supply via complex I and II. Additional experiments performed with isolated mitochondria showed that free iron, released during HOX, is likely a key prerequisite of mitochondrial dysfunction induced during the reoxygenation phase. Our data suggests that mitochondrial dysfunction, previously observed in in vivo SIR-models is the result of secondary circulatory failure inducing HOX rather than the result of a direct interaction of IM with liver cells.

Ambient Ionization Mass Spectrometry Measurement of Aminotransferase Activity

Science.gov (United States)

Yan, Xin; Li, Xin; Zhang, Chengsen; Xu, Yang; Cooks, R. Graham

2017-06-01

A change in enzyme activity has been used as a clinical biomarker for diagnosis and is useful in evaluating patient prognosis. Current laboratory measurements of enzyme activity involve multi-step derivatization of the reaction products followed by quantitative analysis of these derivatives. This study simplified the reaction systems by using only the target enzymatic reaction and directly detecting its product. A protocol using paper spray mass spectrometry for identifying and quantifying the reaction product has been developed. Evaluation of the activity of aspartate aminotransferase (AST) was chosen as a proof-of-principle. The volume of sample needed is greatly reduced compared with the traditional method. Paper spray has a desalting effect that avoids sprayer clogging problems seen when examining serum samples by nanoESI. This very simple method does not require sample pretreatment and additional derivatization reactions, yet it gives high quality kinetic data, excellent limits of detection (60 ppb from serum), and coefficients of variation <10% in quantitation. [Figure not available: see fulltext.

Gene expression profiles in adenosine-treated human mast cells

African Journals Online (AJOL)

ajl yemi

2011-10-26

Oct 26, 2011 ... assignment (Ewing and Green, 1998a; Ewing et al., 1998b). The trace files were trimmed with trim-alt 0.05 (P-score>20). In addition, vector trimming was conducted with cross-match software. Each gene expression pattern was analyzed by clustering. (30 bp or more 94% homology) and assembly.