[Alanine aminotransferase (ALAT, GPT): a reevaluation of exclusion limits for blood donors].

PubMed

Grunenberg, R; Banik, N; Krüger, J

1995-06-01

The screening policy of alanine aminotransferase (ALT) testing in blood donors was reassessed. The cutoff value for ALT levels according to German guidelines has always been controversial. In this study the activity and distribution of ALT in a blood donor population were reevaluated and new exclusion levels were defined. 5,706 blood donors were tested for ALT activities with the Reflotron system at 37 degrees C. Donors with ALT levels > 51 IU/l were deferred, a detailed physical examination and additional serologic and biochemical testing were done. ALT values of blood donors were transformed in logarithmic values in order to get a Gaussian distribution. The mean transformed value +/- SD was calculated with 1.24 +/- 0.14 for females and with 1.35 +/- 0.16 for males, corresponding to mean values of ALT activity of 17.6 and 22.5 IU/l, respectively. Exclusion levels of > 33.4 IU/l for female and > 46.7 IU/l for male blood donors (geometric mean +2.0 SD) predict a loss of donations of 2.8 and 2.7%, respectively, cutoff values of > 39.1 or > 56.1 IU/l (geometric mean +2.5 SD) a loss of 1.8 and 1.4%, respectively. The most likely causes of elevated ALT levels in 166 of our donors included daily alcohol use (82), infections with/without antibiotic medication (29), therapy with hepatotoxic drugs (8), strenuous exercises (5), bodybuilding complemented by anabolic steroids (2), acute infections with HCV (1), HBV (1) and CMV (1), alcohol/drug abuse and detection of HCV antibodies (1). ALT screening is still considered a useful indicator of risk donors despite its nonspecificity and limited predictive value. The selection of the appropriate cutoff value has always been disputed. The present exclusion level of > 45 IU/l (25 degrees C), analogous to > 81.8 IU/l (37 degrees C), does not even take into account such a variable as sex. The cutoff value above 4.5 SD of the geometric mean for females and above 3.5 SD for males seems to be of limited medical and practical value.

Primary human immunodeficiency virus infection presenting as elevated aminotransferases.

PubMed

Chen, Yi-Jan; Tsai, Hung-Chin; Cheng, Ming-Fang; Lee, Susan Shin-Jung; Chen, Yao-Shen

2010-06-01

Primary human immunodeficiency virus type 1 (HIV-1) infection is often under-diagnosed because of its nonspecific presentations. Elevated aminotransferase levels is one of its clinical manifestations, but is infrequently reported in the literature. The objective of this study was to investigate cases of elevated aminotransferases as a manifestation of primary HIV-1 infection. A retrospective chart review from October 1990 to May 2009 of HIV-1 infected patients in a registered database at a tertiary hospital was conducted to identify patients diagnosed with primary HIV-1 infection. An elevated aminotransferase level was broadly defined as above-normal values of alanine or aspartate aminotransferases. Acute hepatitis markers were determined using stored serum samples. Twenty-three of the 827 (2.8%) patients were identified as having a primary HIV-1 infection. All were male, with a median age of 26 years (range, 19-77 years), and the majority were men who had sex with men (19/23, 82.6%). The most common clinical manifestations were fever (95.7%), elevated aminotransferases (65.2%), fatigue (47.8%), and pharyngitis (47.8%). The median CD4 lymphocyte count was 374/μL (range, 109-674/μL) and the median log HIV viral load was 5.0 (range, 4.3-5.9). For the 15 patients with abnormal liver function tests, the median aspartate aminotransferase level was 112 U/L (range, 62-969 U/L) and the median alanine aminotransferase level was 146 U/L (range, 42-1,110 U/L). Elevated aminotransferases may be an initial manifestation of primary HIV infection and is more common than expected. Primary HIV-1 infection should be one of the differential diagnoses considered in young men presenting with unexplained, new-onset liver function impairment. Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.

Paralogous ALT1 and ALT2 Retention and Diversification Have Generated Catalytically Active and Inactive Aminotransferases in Saccharomyces cerevisiae

PubMed Central

Peñalosa-Ruiz, Georgina; Aranda, Cristina; Ongay-Larios, Laura; Colon, Maritrini; Quezada, Hector; Gonzalez, Alicia

2012-01-01

Background Gene duplication and the subsequent divergence of paralogous pairs play a central role in the evolution of novel gene functions. S. cerevisiae possesses two paralogous genes (ALT1/ALT2) which presumably encode alanine aminotransferases. It has been previously shown that Alt1 encodes an alanine aminotransferase, involved in alanine metabolism; however the physiological role of Alt2 is not known. Here we investigate whether ALT2 encodes an active alanine aminotransferase. Principal Findings Our results show that although ALT1 and ALT2 encode 65% identical proteins, only Alt1 displays alanine aminotransferase activity; in contrast ALT2 encodes a catalytically inert protein. ALT1 and ALT2 expression is modulated by Nrg1 and by the intracellular alanine pool. ALT1 is alanine-induced showing a regulatory profile of a gene encoding an enzyme involved in amino acid catabolism, in agreement with the fact that Alt1 is the sole pathway for alanine catabolism present in S. cerevisiae. Conversely, ALT2 expression is alanine-repressed, indicating a role in alanine biosynthesis, although the encoded-protein has no alanine aminotransferase enzymatic activity. In the ancestral-like yeast L. kluyveri, the alanine aminotransferase activity was higher in the presence of alanine than in the presence of ammonium, suggesting that as for ALT1, LkALT1 expression could be alanine-induced. ALT2 retention poses the questions of whether the encoded protein plays a particular function, and if this function was present in the ancestral gene. It could be hypotesized that ALT2 diverged after duplication, through neo-functionalization or that ALT2 function was present in the ancestral gene, with a yet undiscovered function. Conclusions ALT1 and ALT2 divergence has resulted in delegation of alanine aminotransferase activity to Alt1. These genes display opposed regulatory profiles: ALT1 is alanine-induced, while ALT2 is alanine repressed. Both genes are negatively regulated by the Nrg1

Factors associated with elevated serum alanine aminotransferase in patients with type 1 diabetes mellitus.

PubMed

Hatanaka, S A; Silva, N O; Colombo, B S; Correa, C G; Alcaire, B P; Coral, M H; Schiavon, L L; Narciso-Schiavon, J L

2015-09-01

Metabolic syndrome and type 2 diabetes are associated with insulin resistance and hepatic steatosis, which are common causes of alanine aminotransferase (ALT) elevation. This study aims to identify variables associated with altered ALT in type 1 diabetic (DM1) subjects. A cross-sectional study conducted in the outpatient endocrinology clinic of a university hospital. Patients with DM1 were seen between December 2012 and September 2013; clinical variables were collected from medical records. Fifty-six patients were included aged 27 ± 10.1 years; 60.7% were men. The study subjects exhibited an average ALT of 36.7 ± 10.3 U/L (median = 35 U/L) and their average Body Mass Index (BMI) was 23.8 ± 3.8 kg/m2. When comparing individuals with elevated ALT > 35 U/L (N. = 27) with those ALT ≤ 35 U/L (N. = 29), we found that individuals with ALT values > 35 U/L showed a higher proportion of men (77.8% vs. 44.8%, P = 0.012) and a higher mean age (30.2 ± 12.3 vs. 24.6 ± 6.9 years, P = 0.046). When new ALT reference values were applied (19 U/L for women and 30 U/L for men), five individuals had normal ALT values. Individuals with elevated ALT had higher BMI (24.3 vs. 20.9; P = 0.036), fasting glucose (194.8 ± 101.2 vs. 123.6 ± 42.0 mg/dL; P = 0.013) and higher HbA1c (9.9 ± 2.8 vs. 7.8 ± 0.7%; P < 0.001) levels. In Pearson correlation analysis, ALT values ​correlated with HbA1c (r = 0.285; P = 0.033). In patients with DM1, elevated ALT values ​​are associated with BMI, fasting glucose and HbA1c.

Transient elastographic evaluation in adult subjects without overt liver disease: influence of alanine aminotransferase levels.

PubMed

Kumar, Manoj; Sharma, Praveen; Garg, Hitendra; Kumar, Ramesh; Bhatia, Vikram; Sarin, Shiv K

2011-08-01

  Studies on normal values of liver stiffness (LS) in subjects at "low risk" for liver disease are scant. The aim of the present study was to assess liver stiffness values in the subjects without overt liver disease with normal alanine aminotransferases (ALT) and to determine potential factors, which may influence these values with special reference to newly suggested updated upper limits of normal for ALT.   Liver stiffness measurements were performed in 445 subjects without overt liver disease (mean age, 41.1±13.6; male, 73.5%) and normal liver enzymes.   Mean LS value was 5.10±1.19kPa. LS values were higher in men than in women (5.18±1.67 vs 4.86±1.24kPa, respectively, P=0.008); in subjects with higher body mass index (BMI) category (Normal, overweight and obese subjects; 4.10±0.75, 5.08±0.66, and 6.05±1.28kPa, respectively; P<0.001); in subjects with metabolic syndrome than in those without (5.63±1.37 vs 5.01±1.14kPa, P=0.001); and in subjects with ALT levels more than updated limits of normal compared to subjects with ALT levels less than updated limits of normal (5.68±1.21 vs 4.77±1.05kPa, P<0.001). On multiple linear regression, BMI and ALT was found to be significant predictor of LS.   Liver stiffness values in subjects without overt liver disease with normal ALT are influenced by BMI and ALT levels. Subjects with ALT levels less than updated limits of normal have lower LS values as compared to those with higher levels. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Analysis of alanine aminotransferase in various organs of soybean (Glycine max) and in dependence of different nitrogen fertilisers during hypoxic stress.

PubMed

Rocha, Marcio; Sodek, Ladaslav; Licausi, Francesco; Hameed, Muhammad Waqar; Dornelas, Marcelo Carnier; van Dongen, Joost T

2010-10-01

Alanine aminotransferase (AlaAT) catalyses the reversible conversion of pyruvate and glutamate into alanine and oxoglutarate. In soybean, two subclasses were identified, each represented by two highly similar members. To investigate the role of AlaAT during hypoxic stress in soybean, changes in transcript level of both subclasses were analysed together with the enzyme activity and alanine content of the tissue. Moreover, the dependency of AlaAT activity and gene expression was investigated in relation to the source of nitrogen supplied to the plants. Using semi-quantitative PCR, GmAlaAT genes were determined to be highest expressed in roots and nodules. Under normal growth conditions, enzyme activity of AlaAT was detected in all organs tested, with lowest activity in the roots. Upon waterlogging-induced hypoxia, AlaAT activity increased strongly. Concomitantly, alanine accumulated. During re-oxygenation, AlaAT activity remained high, but the transcript level and the alanine content decreased. Our results show a role for AlaAT in the catabolism of alanine during the initial period of re-oxygenation following hypoxia. GmAlaAT also responded to nitrogen availability in the solution during waterlogging. Ammonium as nitrogen source induced both gene expression and enzyme activity of AlaAT more than when nitrate was supplied in the nutrient solution. The work presented here indicates that AlaAT might not only be important during hypoxia, but also during the recovery phase after waterlogging, when oxygen is available to the tissue again.

Cardiorespiratory Fitness, Waist Circumference and Alanine Aminotransferase in Youth

PubMed Central

Trilk, Jennifer L.; Ortaglia, Andrew; Blair, Steven N.; Bottai, Matteo; Church, Timothy S.; Pate, Russell R.

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is considered the liver component of the metabolic syndrome and is strongly associated with cardiometabolic diseases. In adults, cardiorespiratory fitness (CRF) is inversely associated with alanine aminotransferase (ALT), a blood biomarker for NAFLD. However, information regarding these associations is scarce for youth. Purpose To examine associations between CRF, waist circumference (WC) and ALT in youth. Methods Data were obtained from youth (n=2844, 12-19 years) in the National Health and Nutrition Examination Survey (NHANES) 2001-2004. CRF was dichotomized into youth FITNESSGRAM® categories of “low” and “adequate” CRF. Logistic and quantile regression were used for a comprehensive analysis of associations, and variables with previously-reported associations with ALT were a priori included in the models. Results Results from logistic regression suggested that youth with low CRF had 1.5 times the odds of having an ALT>30 than youth with adequate CRF, although the association was not statistically significant (P=0.09). However, quantile regression demonstrated that youth with low CRF had statistically significantly higher ALT (+1.04, +1.05, and +2.57 U/L) at the upper end of the ALT distribution (80th, 85th, and 90th percentiles, respectively) than youth with adequate CRF. For every 1-cm increase in WC, the odds of having an ALT>30 increased by 1.06 (P<0.001), and the strength of this association increased across the ALT distribution. Conclusions Future studies should examine whether interventions to improve CRF can decrease hepatic fat and liver enzyme concentrations in youth with ALT ≥80th percentile or in youth diagnosed with NAFLD. PMID:23190589

d-Alanine Oxidase from Escherichia coli: Localization and Induction by l-Alanine

PubMed Central

Raunio, R. P.; Jenkins, W. T.

1973-01-01

Dialyzed membranes of Escherichia coli prepared by an ethylenediaminetetraacetic acid-lysozyme method catalyze the oxidation of both l-alanine and d-alanine. The specific activities for the oxidations of both d-alanine and l-alanine are increased fivefold when the cells are grown in the presence of either l-alanine or dl-alanine, but are increased only slightly when grown in the presence of d-alanine. In the dl-alanine-induced system, the specific activities for the oxidations of some other d-amino acids are also raised. dl-alanine also induces two other alanine catabolizing enzymes, alanine dehydrogenase and alanine-glutamate aminotransferase which are found in the “soluble” fraction of lysozyme-treated cells. The oxidations of both l-alanine and d-alanine were associated with the membranes of induced cells. After the membranes were disintegrated by sonic treatment, both l-alanine and d-alanine oxidation catalysts sedimented in a sucrose density gradient together with d-lactate and l-lactate dehydrogenases, apparently as a single multienzyme complex. PMID:4146872

Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients.

PubMed

Chin, Kazuo; Nakamura, Takaya; Takahashi, Kenichi; Sumi, Kensuke; Ogawa, Yoshihiro; Masuzaki, Hiroaki; Muro, Shigeo; Hattori, Noboru; Matsumoto, Hisako; Niimi, Akio; Chiba, Tsutomu; Nakao, Kazuwa; Mishima, Michiaki; Ohi, Motoharu; Nakamura, Takashi

2003-04-01

Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients. We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment. Aminotransferase levels were abnormal in 35% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 +/- 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment. Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea. Copyright 2003 by Excerpta Medica Inc.

FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4), and their combinations in the assessment of liver fibrosis in patients with hepatitis B.

PubMed

Ding, Deping; Li, Hongbing; Liu, Ping; Chen, Lingli; Kang, Jian; Zhang, Yinhua; Ma, Deqiang; Chen, Yue; Luo, Jie; Meng, Zhongji

2015-01-01

The aim of this study was to assess the effects of FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4) and their combinations on liver fibrosis in patients with hepatitis B. 406 hospitalized patients with chronic hepatitis B (CHB) and cirrhosis in our hospital were analyzed retrospectively and collected patients clinical indicators, including liver stiffness (LS), AAR, APRI and FIB-4, and then compared the differences of these indicators between CHB group and hepatitis B with cirrhosis group. Receiver operating curve (ROC) was used to evaluate the differentiating capacity of these indicators on CHB and liver cirrhosis. Four indicators related to liver cirrhosis had a statistical significance between two groups (P < 0.01); the under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of CHB and liver cirrhosis were 0.866, 0.772, 0.632 and 0.885, respectively. The under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of liver cirrhosis at compensatory stage and de-compensatory stage were 0.627, 0.666, 0.795 and 0.820, respectively. LS, AAR, APRI and FIB-4 were good indicators as clinical diagnosis and differential diagnosis on hepatitis B related cirrhosis.

A novel C-S lyase from the latex-producing plant Taraxacum brevicorniculatum displays alanine aminotransferase and l-cystine lyase activity.

PubMed

Munt, Oliver; Prüfer, Dirk; Schulze Gronover, Christian

2013-01-01

We isolated a novel pyridoxal-5-phosphate-dependent l-cystine lyase from the dandelion Taraxacum brevicorniculatum. Real time qPCR analysis showed that C-S lyase from Taraxacum brevicorniculatum (TbCSL) mRNA is expressed in all plant tissues, although at relatively low levels in the latex and pedicel. The 1251 bp TbCSL cDNA encodes a protein with a calculated molecular mass of 46,127 kDa. It is homologous to tyrosine and alanine aminotransferases (AlaATs) as well as to an Arabidopsis thaliana carbon-sulfur lyase (C-S lyase) (SUR1), which has a role in glucosinolate metabolism. TbCSL displayed in vitrol-cystine lyase and AlaAT activities of 4 and 19nkatmg(-1) protein, respectively. However, we detected no in vitro tyrosine aminotransferase (TyrAT) activity and RNAi knockdown of the enzyme had no effect on phenotype, showing that TbCSL substrates might be channeled into redundant pathways. TbCSL is in vivo localized in the cytosol and functions as a C-S lyase or an aminotransferase in planta, but the purified enzyme converts at least two substrates specifically, and can thus be utilized for further in vitro applications. Copyright © 2012 Elsevier GmbH. All rights reserved.

Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph

PubMed Central

2012-01-01

Background Our previous studies suggest silkworms can be used as model animals instead of mammals in pharmacologic studies to develop novel therapeutic medicines. We examined the usefulness of the silkworm larvae Bombyx mori as an animal model for evaluating tissue injury induced by various cytotoxic drugs. Drugs that induce hepatotoxic effects in mammals were injected into the silkworm hemocoel, and alanine aminotransferase (ALT) activity was measured in the hemolymph 1 day later. Results Injection of CCl4 into the hemocoel led to an increase in ALT activity. The increase in ALT activity was attenuated by pretreatment with N-acetyl-L-cysteine. Injection of benzoic acid derivatives, ferric sulfate, sodium valproate, tetracycline, amiodarone hydrochloride, methyldopa, ketoconazole, pemoline (Betanamin), N-nitroso-fenfluramine, and D-galactosamine also increased ALT activity. Conclusions These findings indicate that silkworms are useful for evaluating the effects of chemicals that induce tissue injury in mammals. PMID:23137391

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

PubMed Central

Yokoyama, Miyuki; Otaki, Yoichiro; Takahashi, Hiroki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Shibata, Yoko; Daimon, Makoto; Kayama, Takamasa; Kubota, Isao

2016-01-01

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. PMID:27872510

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

PubMed

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.

Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus.

PubMed

Shlomai, Amir; Kariv, Revital; Leshno, Moshe; Beth-or, Anat; Sheinberg, Bracha; Halpern, Zamir

2010-10-01

Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ∼55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either 'normal' or 'healthy', with the later reflecting much lower values, above which an individual is at increased risk for DM. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Protein retention and liver aminotransferase activities in Atlantic salmon fed diets containing different energy sources

USGS Publications Warehouse

Fynn-Aikins, K.; Hughes, S.G.; Vandenberg, G.W.

1995-01-01

Atlantic salmon (Salmo salar) fingerlings (14.4 g) were fed diets containing either glucose, dextrin, raw corn starch and lipid, or a high protein U.S. Fish and Wildlife Service open-formula diet (ASD2-30) for 12 weeks. Significant differences in weight gain and feed: gain ratio were not observed among salmon fed the diets containing glucose, dextrin or ASD2-30. Diets containing dextrin and glucose supported greater protein retention and reduction in alanine aminotransferase activity than the other diets. Activity of aspartate aminotransferase was not affected by the dietary treatment. Protein retention correlated highly with alanine aminotransferase activity.

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.

PubMed

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 < 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. 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.

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

PubMed

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.

Association between alanine aminotransferase and intracerebral hemorrhage in East Asian populations.

PubMed

Kim, Hyeon Chang; Oh, Sun Min; Pan, Wen-Harn; Ueshima, Hirotsugu; Gu, Dongfeng; Chuang, Shao-Yuan; Fujiyoshi, Akira; Li, Ying; Zhao, Liancheng; Suh, Il

2013-01-01

Intracerebral hemorrhage (ICH) and chronic liver disease are relatively common in East Asian countries. However, the relationship between the two diseases is unclear. Thus, we investigated the association between serum alanine aminotransferase (ALT) levels and ICH risk in East Asian populations. The East Asian Network for Stroke Prevention enrolled 279,982 participants with ALT measurements from four cohort studies in Korea, Taiwan, Japan and mainland China. Among them, 1,324 ICH events and 493 ICH deaths were observed. Cox's proportional hazard regression analysis was performed in each cohort to estimate the hazard ratio (HR) after adjusting for age, blood pressure, diabetes, total cholesterol, smoking and alcohol intake. Combined HRs were then estimated using pooled analyses with fixed-effects models. The multivariate-adjusted pooled HRs (with 95% confidence interval, CI) for ICH incidence per 10 IU/l increments of ALT were 1.04 (1.03-1.04) in men and 1.01 (0.98-1.04) in women. Corresponding HRs for ICH mortality were 1.04 (1.02-1.05) in men and 1.04 (1.00-1.08) in women. The pooled HRs for ICH incidence in participants with ALT levels greater than or equal to 50 IU/l compared to those with levels less than 20 IU/l were 1.74 (1.41-2.16) in men and 1.60 (1.06-2.40) in women. The corresponding HRs for ICH mortality were 1.72 (1.21-2.44) in men and 1.63 (0.79-3.36) in women. An elevated ALT level was independently and significantly associated with an increased risk of ICH in East Asian men, but the association was less prominent in women. © 2013 S. Karger AG, Basel.

Modifiable clinical and lifestyle factors are associated with elevated alanine aminotransferase levels in newly diagnosed type 2 diabetes patients: results from the nationwide DD2 study.

PubMed

Mor, Anil; Svensson, Elisabeth; Rungby, Jørgen; Ulrichsen, Sinna Pilgaard; Berencsi, Klara; Nielsen, Jens Steen; Stidsen, Jacob Volmer; Friborg, Søren; Brandslund, Ivan; Christiansen, Jens Sandahl; Beck-Nielsen, Henning; Sørensen, Henrik Toft; Thomsen, Reimar Wernich

2014-11-01

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. 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 and >50 IU/L for men) and calculated prevalence ratios associated with clinical and lifestyle factors using Poisson regression. We examined the association with other biomarkers by linear regression. The median value of ALT was 24 IU/L (interquartile range: 18-32 IU/L) in women and 30 IU/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 <40 years old at diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14/>21 drinks per week for women/men) (aPR: 1.60, 95% CI: 1.03-2.50), and in those with no regular physical activity (aPR: 1.42, 95% CI: 1.04-1.93). Obesity and metabolic syndrome per se showed no association with elevated ALT when adjusted for other markers, whereas we found positive associations of ALT with increased C-peptide (β = 0.14, 95% CI: 0.06-0.21) and fasting blood glucose (β = 0.07, 95% CI: 0.03-0.11). Among newly diagnosed T2DM patients, several modifiable clinical and lifestyle factors are independent markers of elevated ALT levels. Copyright © 2014 John Wiley & Sons, Ltd.

Allele-specific Characterization of Alanine: Glyoxylate Aminotransferase Variants Associated with Primary Hyperoxaluria

PubMed Central

Lage, Melissa D.; Pittman, Adrianne M. C.; Roncador, Alessandro; Cellini, Barbara; Tucker, Chandra L.

2014-01-01

Primary Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type) and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele. PMID:24718375

Structure of GroEL in Complex with an Early Folding Intermediate of Alanine Glyoxylate Aminotransferase*

PubMed Central

Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Álvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

2010-01-01

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism. PMID:20056599

Structure of GroEL in complex with an early folding intermediate of alanine glyoxylate aminotransferase.

PubMed

Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Alvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

2010-02-26

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism.

Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38).

PubMed

Deetman, Petronella E; Alkhalaf, Alaa; Landman, Gijs W D; Groenier, Klaas H; Kootstra-Ros, Jenny E; Navis, Gerjan; Bilo, Henk J G; Kleefstra, Nanne; Bakker, Stephan J L

2015-08-01

Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine the associations of log2 -transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality. In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to noncardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P = 0.003). In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

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

PubMed

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

Plasma chemistry references values in psittaciformes.

PubMed

Lumeij, J T; Overduin, L M

1990-04-01

Reference values for 17 plasma chemical variables in African greys. Amazons, cockatoos and macaws were established for use in avian clinical practice. The inner limits are given for the percentiles P(2.5) and P(97.5) with a probability of 90%. The following variables were studied: urea, creatinine, uric acid, urea/uric acid ratio, osmolality, sodium, potassium, calcium, glucose, aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, lactate dehydrogenase, creatine kinase, bile acids, total protein, albumin/globulin ratio. Differences between methods used and values found in this study and those reported previously are discussed.

Utility of the FIB-4 Index for hepatocarcinogenesis in hepatitis C virus carriers with normal alanine aminotransferase levels.

PubMed

Ito, T; Kumada, T; Toyoda, H; Tada, T; Kiriyama, S; Tanikawa, M; Hisanaga, Y; Kanamori, A; Kitabatake, S

2015-10-01

The FIB-4 index is a simple formula using age, aspartate aminotransferase, alanine aminotransferase (ALT) and platelet count to evaluate liver fibrosis. We investigated the ability of the FIB-4 index for hepatocarcinogenesis in hepatitis C virus (HCV) carriers with normal ALT levels. A total of 516 patients with ALT levels persistently at or below 40 IU/L during an observation period of over 3 years were included. Factors associated with the development of HCC were determined. Hepatocellular carcinoma (HCC) developed in 60 of 516 patients (11.6%). The incidence rate of HCC at 5 and 10 years was 2.6% and 17.6%, respectively. When patients were categorized according to the FIB-4 index as ≤ 2.0 (n = 226), >2.0 and ≤ 4.0 (n = 169), and > 4.0 (n = 121), the cumulative incidence of HCC at 5 years was 0.5%, 1.3% and 8.0%, respectively, and 2.8%, 25.6% and 37.1% at 10 years, respectively. Patients with FIB-4 index >4.0 were at the highest risk (P < 0.001). Factors that were significantly associated with HCC in the multivariate analysis were FIB-4 index >2.0 (hazard ratio (HR), 7.690), FIB-4 index >4.0 (HR, 8.991), α-fetoprotein (AFP) >5 ng/mL (HR, 2.742), AFP >10 ng/mL (HR, 4.915) and total bilirubin >1.2 mg/dL (HR, 2.142). A scoring system for hepatocarcinogenesis that combines the FIB-4 index and AFP predicted patient outcomes with excellent discriminative ability. The FIB-4 index is strongly associated with the risk of HCC in HCV carriers with normal ALT levels. © 2015 John Wiley & Sons Ltd.

Peroxisomal Alanine: Glyoxylate Aminotransferase AGT1 Is Indispensable for Appressorium Function of the Rice Blast Pathogen, Magnaporthe oryzae

PubMed Central

Bhadauria, Vijai; Banniza, Sabine; Vandenberg, Albert; Selvaraj, Gopalan; Wei, Yangdou

2012-01-01

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 peroxisomes

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

PubMed

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.

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

PubMed

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 < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT. Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

PubMed Central

Liu, Chi-Ming; Tung, Tao-Hsin; Liu, Jorn-Hon; Chen, Victor Tze-Kai; Lin, Ching-Heng; Hsu, Chung-Te; Chou, Pesus

2005-01-01

AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study. PMID:15786537

The Association of Alanine Aminotransferase in Early Pregnancy with Gestational Diabetes.

PubMed

Yarrington, Christina D; Cantonwine, David E; Seely, Ellen W; McElrath, Thomas F; Zera, Chloe A

2016-06-01

Elevated alanine amino transferase, attributed to nonalcoholic fatty liver, is associated with later development of type 2 diabetes mellitus. We sought to determine whether maternal ALT values are associated with subsequent development of gestational diabetes. We performed a nested case-control study utilizing prospectively banked serum samples collected in early gestation. We excluded women with known diabetes, liver disease, or alcohol use. We included 83 cases of gestational diabetes mellitus (GDM) and 247 controls matched for prepregnancy body-mass index (BMI) and compared ALT values. We then performed a conditional logistic regression to model the adjusted odds of GDM in women with ALT ≥19 U/L, stratified by prepregnancy BMI. The median (interquartile range) ALT in cases was 15 (12, 19) IU/L compared to 13 (11, 18) IU/L in controls (P = 0.07). Among women with a prepregnancy BMI <30 kg/m(2), ALT ≥19 U/L was associated with a fourfold increased odds of GDM (adjusted odds ratio [aOR] 4.56 [1.45, 14.27]), while there was no such association among obese women (aOR 0.36 [0.11, 1.20]). Similarly, each unit increase in log-transformed ALT was associated with a threefold increased odds of GDM in nonobese (aOR 3.15 [1.04,9.54]), but not obese (aOR 3.15 [0.30,3.15]) women. The association of high normal ALT and later GDM in nonobese women may reflect the role of hepatic insulin resistance and visceral obesity.

Elevated alanine aminotransferase (ALT) in the deceased donor: impact on early post-transplant liver allograft function.

PubMed

Mangus, Richard S; Fridell, Jonathan A; Kubal, Chandrashekhar A; Davis, Jason P; Tector, A Joseph

2015-02-01

Serum alanine aminotransferase (ALT) levels are frequently elevated with liver injury and such elevations are common in deceased organ donors. The impact of this injury on early liver allograft function has not been well described. This study analyses the immediate function and 1-year graft and patient survival for liver allografts stratified by peak serum ALT levels in the deceased donor. The on-site organ procurement records for 1348 consecutive deceased liver donors were reviewed (2001–2011). Serum ALT was categorized into three study groups: normal/mild elevation, 0–499 μ/L; moderate elevation, 500–999 μ/L (>10× upper limit of normal) and severe elevation, ≥1000 μ/L (>20× upper limit of normal). Outcomes included early graft function and graft loss, and 1-year graft and patient survival. Distribution of subjects included: normal/mild, 1259 (93%); moderate, 34 (3%) and severe, 55 (4%). Risk of 30-day graft loss for the three study groups was: 72 (6%), 3 (9%) and 3 (6%) (P = 0.74). Graft and patient survival at 1 year for the three groups was: normal/mild, 1031 (87%), 1048 (88%); moderate, 31 (91%), 31 (91%) and severe, 43 (88%), 44 (90%) (P = 0.71, 0.79). Cox proportional hazards modelling of survival while controlling for donor age and recipient model for end-stage liver disease score (MELD) demonstrates no statistically significant difference among the three study groups. This study demonstrates clinical equivalence in early graft function and 1-year graft and patient survival for donor livers with varying peak levels of serum ALT. These donor allografts may, therefore, be utilized successfully.

A Novel Mutation of Human Liver Alanine:Glyoxylate Aminotransferase Causes Primary Hyperoxaluria Type 1: Immunohistochemical Quantification and Subcellular Distribution

PubMed Central

Kawai, Chikage; Minatogawa, Yohsuke; Akiyoshi, Hidetaka; Hirose, Shinichi; Suehiro, Tsunatoshi; Tone, Shigenobu

2012-01-01

A novel alanine:glyoxylate aminotransferase (AGT) mutation involved in primary hyperoxaluria type 1 (PH1) was studied in Japanese patients. Two mutations in exon 7, c.751T>A and c.752G>A, lead to a W251K amino acid substitution. Proband 1 (patient 1) was homozygous for the W251K mutation allele (DDBJ Accession No. AB292648), and AGT-specific activity in the patient’s liver was very low. To reveal the cause of the low enzymatic activity, the intracellular localization of AGT (W251K) was studied using immunohistochemistry and immunoelectron microscopy. The latter analysis showed that patient 2 had only one-fifth of the normal AGT expression per catalase, suggesting impairment of AGT (W251K) dependent transport into peroxisomes. Peroxisomal transport of human AGT is believed to be dependent on the presence of the type 1 peroxisomal targeting sequence. The C-terminal tripeptide of AGT, KKL is necessary for peroxisomal targeting. In cultured cells, EGFP-AGT (W251K) localized both in the peroxisome and cytosol. These results were consistent with the data obtained from liver analysis of patient 2. The subcellular distribution of AGT (W251K) and the results from a random mutagenesis study suggest that KKL is necessary for peroxisomal targeting of human AGT, but additional signal other than KKL may be necessary. PMID:22685354

Suppression of Hepatocellular Carcinoma by Inhibition of Overexpressed Ornithine Aminotransferase.

PubMed

Zigmond, Ehud; Ben Ya'acov, Ami; Lee, Hyunbeom; Lichtenstein, Yoav; Shalev, Zvi; Smith, Yoav; Zolotarov, Lidya; Ziv, Ehud; Kalman, Rony; Le, Hoang V; Lu, Hejun; Silverman, Richard B; Ilan, Yaron

2015-08-13

Hepatocellular carcinoma is the second leading cause of cancer death worldwide. DNA microarray analysis identified the ornithine aminotransferase (OAT) gene as a prominent gene overexpressed in hepatocellular carcinoma (HCC) from Psammomys obesus. In vitro studies demonstrated inactivation of OAT by gabaculine (1), a neurotoxic natural product, which suppressed in vitro proliferation of two HCC cell lines. Alpha-fetoprotein (AFP) secretion, a biomarker for HCC, was suppressed by gabaculine in both cell lines, but not significantly. Because of the active site similarity between GABA aminotransferase (GABA-AT) and OAT, a library of 24 GABA-AT inhibitors was screened to identify a more selective inhibitor of OAT. (1S,3S)-3-Amino-4-(hexafluoropropan-2-ylidene)cyclopentane-1-carboxylic acid (2) was found to be an inactivator of OAT that only weakly inhibits GABA-AT, l-aspartate aminotransferase, and l-alanine aminotransferase. In vitro administration of 2 significantly suppressed AFP secretion in both Hep3B and HepG2 HCC cells; in vivo, 2 significantly suppressed AFP serum levels and tumor growth in HCC-harboring mice, even at 0.1 mg/kg. Overexpression of the OAT gene in HCC and the ability to block the growth of HCC by OAT inhibitors support the role of OAT as a potential therapeutic target to inhibit HCC growth. This is the first demonstration of suppression of HCC by an OAT inactivator.

Partial trypsin digestion as an indicator of mis-folding of mutant alanine:glyoxylate aminotransferase and chaperone effects of specific ligands. Study of a spectrum of missense mutants.

PubMed

Coulter-Mackie, M B; Lian, Q

2008-07-01

Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme whose deficiency results in primary hyperoxaluria type 1 (PH1). More than 75 PH1 mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have previously demonstrated that many such mutants expressed by transcription/translation are subject to generalized degradation by the proteasome and a specific limited trimming by an endogenous ATP-independent protease activity. Here, we report the results of partial digestion using trypsin as a mimic for the endogenous non-proteasomal protease and the use of N-terminal protein sequencing to determine the sensitive site. Partial trypsin digestion also provided an indicator of proper folding of the mutant enzyme. For selected mutations the sensitivity to trypsin could be ameliorated by addition of pyridoxal phosphate or aminooxy acetic acid as specific pharmacological chaperones.

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

PubMed Central

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< 0.001). Multivariate analysis showed that an AFP ratio > 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

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study.

PubMed

Gómez-Sámano, Miguel Angel; Cuevas-Ramos, Daniel; Mehta, Roopa; Brau-Figueroa, Hasan; Meza-Arana, Clara Elena; Gulias-Herrero, Alfonso

2012-09-04

The association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp. However, there is no information about the association of ALT with the Hepatic Insulin Resistance Index (HIRI). The aim of this study was to evaluate the association between serum ALT levels and HIRI in subjects with differing degrees of impaired glucose metabolism. This cross-sectional study included subjects that had an indication for testing for type 2 diabetes mellitus (T2DM) with an oral glucose tolerance test (OGTT). Clinical and biochemical evaluations were carried out including serum ALT level quantification. HIRI was calculated for each participant. Correlation analyses and lineal regression models were used to evaluate the association between ALT levels and HIRI. A total of 324 subjects (37.6% male) were included. The mean age was 40.4 ± 14.3 years and the mean body mass index (BMI) was 32.0 ± 7.3 kg/m2. Individuals were divided into 1 of 5 groups: without metabolic abnormalities (n = 113, 34.8%); with the metabolic syndrome (MetS, n = 179, 55.2%), impaired fasting glucose (IFG, n = 85, 26.2%); impaired glucose tolerance (IGT, n = 91, 28.0%), and T2DM (n = 23, 7.0%). The ALT (p < 0.001) and HOMA2-IR (p < 0.001) values progressively increased with HIRI quartiles, while ISI-Matsuda (p < 0.001) progressively decreased. After adjustment for sex, age, and BMI, we identified a significant correlation between HIRI and ALT in persons with the MetS (r = 0.22, p = 0.003), IFG (r = 0.33, p < 0.001), IGT (r = 0.37, p < 0.001), and T2DM (r = 0.72, p < 0.001). Lineal regression analysis adjusting for age, HDL-C, TG and waist circumference (WC) showed an independent association between ALT and HIRI in subjects with the MetS (beta = 0.07, p = 0.01), IFG (beta = 0.10, p = 0.02), IGT (beta = 0.09, p = 0

A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1.

PubMed

Purdue, P E; Lumb, M J; Allsop, J; Minatogawa, Y; Danpure, C J

1992-05-01

We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW-approved symbol for the gene--AGXT) cDNA from the liver of a primary hyperoxaluria type 1 (PH1) patient who had normal levels of hepatic peroxisomal immunoreactive AGT protein, but no AGT catalytic activity. This revealed the presence of a single point mutation (G----A at cDNA nucleotide 367), which is predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT protein. This mutation is located in exon 2 of the AGT gene and leads to the loss of an AvaI restriction site. Exon 2-specific PCR followed by AvaI digestion showed that this patient was homozygous for this mutation. In addition, three other PH1 patients, one related to and two unrelated to, but with enzymological phenotype similar to that of the first patient, were also shown to be homozygous for the mutation. However, one other phenotypically similar PH1 patient was shown to lack this mutation. The mechanism by which the glycine-to-glutamate substitution at residue 82 causes loss of catalytic activity remains to be resolved. However, the protein sequence in this region is highly conserved between different mammals, and the substitution at residue 82 is predicted to cause significant local structural alterations.

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

PubMed

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.

Hematologic and biochemistry values for black-faced spoonbills (Platalea minor) with and recovering from botulism.

PubMed

Chou, Shih-Jen; Shieh, Yao-Ching; Yu, Chang-You

2008-07-01

Type C1 botulism outbreaks in Black-faced Spoonbills (Platalea minor) occurred in Taiwan from 2002 to 2003, and hematologic and biochemistry parameters from botulism-paralyzed birds and recovered birds were compared. Values for creatinine and uric acid were higher (P<0.0025) in birds with botulism than in recovered birds. Lower white blood cell counts (P<0.005) and values for alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and triglycerides (P<0.025) were observed in recovered birds. Based on these observations, we suggest that hematologic and biochemistry analyses should be performed to assess the health condition of birds recovering from botulism.

Crystal structure of the S187F variant of human liver alanine: Aminotransferase associated with primary hyperoxaluria type I and its functional implications

PubMed Central

Oppici, Elisa; Fodor, Krisztian; Paiardini, Alessandro; Williams, Chris; Voltattorni, Carla Borri; Wilmanns, Matthias; Cellini, Barbara

2013-01-01

The substitution of Ser187, a residue located far from the active site of human liver peroxisomal alanine:glyoxylate aminotransferase (AGT), by Phe gives rise to a variant associated with primary hyperoxaluria type I. Unexpectedly, previous studies revealed that the recombinant form of S187F exhibits a remarkable loss of catalytic activity, an increased pyridoxal 5′-phosphate (PLP) binding affinity and a different coenzyme binding mode compared with normal AGT. To shed light on the structural elements responsible for these defects, we solved the crystal structure of the variant to a resolution of 2.9 Å. Although the overall conformation of the variant is similar to that of normal AGT, we noticed: (i) a displacement of the PLP-binding Lys209 and Val185, located on the re and si side of PLP, respectively, and (ii) slight conformational changes of other active site residues, in particular Trp108, the base stacking residue with the pyridine cofactor moiety. This active site perturbation results in a mispositioning of the AGT-pyridoxamine 5′-phosphate (PMP) complex and of the external aldimine, as predicted by molecular modeling studies. Taken together, both predicted and observed movements caused by the S187F mutation are consistent with the following functional properties of the variant: (i) a 300- to 500-fold decrease in both the rate constant of L-alanine half-transamination and the kcat of the overall transamination, (ii) a different PMP binding mode and affinity, and (iii) a different microenvironment of the external aldimine. Proposals for the treatment of patients bearing S187F mutation are discussed on the basis of these results. Proteins 2013; 81:1457–1465. © 2013 Wiley Periodicals, Inc. PMID:23589421

Hematologic and plasma chemistry values in captive psittacine birds.

PubMed

Polo, F J; Peinado, V I; Viscor, G; Palomeque, J

1998-01-01

Reference values for some hematologic parameters in 19 species and plasma chemical values in 11 species of Psittacine birds, including cockatoos, parrots, amazons, macaws, conures, and lories, were established for use in veterinary medicine. The following parameters were studied: hematocrit, hemoglobin concentration, erythrocyte number, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte dimensions, leukocyte number and differential leukocyte count, glucose, urea, uric acid, cholesterol, triglycerides, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, gamma glutamyl transpeptidase, total plasma protein, albumin, globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total phosphorus, chloride, and osmolality. Hematologically, the Psittacine is a very homogeneous avian group, with small differences between species. They are, however, different from other groups of birds.

Primary hyperoxaluria type 1: diagnostic relevance of mutations and polymorphisms in the alanine:glyoxylate aminotransferase gene (AGXT).

PubMed

Tarn, A C; von Schnakenburg, C; Rumsby, G

1997-09-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The disease shows considerable phenotypic, enzymatic and genetic heterogeneity. To date, 7 polymorphisms and 11 point mutations have been described in the gene encoding AGT. We report on the prevalence of these polymorphisms and mutations in 79 patients with PH1 with the aim of assessing their diagnostic relevance. A strong association of the C154T, intron 1 insertion and C386T polymorphisms is confirmed and this linkage extends to include the type 1 variant of a polymorphic tandem repeat in intron 4. Only 64 of 158 (40%) PH1 alleles have one of the defined mutations, with the G630A mutation accounting for 39 of these and T853C for 14. Overall only 20 (25%) of the patients studied had the genetic basis of their disease fully explained: 7 were homozygous for the G630A mutation, 5 were homozygous for the T853C mutation, 1 was homozygous for the C819T mutation, and 7 had two different mutations identified and were presumed to be compound heterozygotes. Only the two more frequent G630A and T853C mutations are of general diagnostic relevance for mutation screening. It seems likely that there are a significant number of other mutations, perhaps family-specific, still to be described. There was no apparent difference in the types of mutations in patients presenting in the first year of life (36%), suggesting that other factors, such as periods of dehydration or urinary tract infections, might contribute more to the clinical manifestation than genotype.

Role of aminotransferases in glutamate metabolism of human erythrocytes.

PubMed

Ellinger, James J; Lewis, Ian A; Markley, John L

2011-04-01

Human erythrocytes require a continual supply of glutamate to support glutathione synthesis, but are unable to transport this amino acid across their cell membrane. Consequently, erythrocytes rely on de novo glutamate biosynthesis from α-ketoglutarate and glutamine to maintain intracellular levels of glutamate. Erythrocytic glutamate biosynthesis is catalyzed by three enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamine aminohydrolase (GA). Although the presence of these enzymes in RBCs has been well documented, the relative contributions of each pathway have not been established. Understanding the relative contributions of each biosynthetic pathway is critical for designing effective therapies for sickle cell disease, hemolytic anemia, pulmonary hypertension, and other glutathione-related disorders. In this study, we use multidimensional (1)H-(13)C nuclear magnetic resonance (NMR) spectroscopy and multiple reaction mode mass spectrometry (MRM-MS) to measure the kinetics of de novo glutamate biosynthesis via AST, ALT, and GA in intact cells and RBC lysates. We show that up to 89% of the erythrocyte glutamate pool can be derived from ALT and that ALT-derived glutamate is subsequently used for glutathione synthesis.

Consequences of missense mutations for dimerization and turnover of alanine:glyoxylate aminotransferase: study of a spectrum of mutations.

PubMed

Coulter-Mackie, M B; Lian, Q

2006-12-01

Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme, deficiency of which results in primary hyperoxaluria type 1 (PH1). More than 65 PH1-related mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have generated a spectrum of 15 missense changes including the most common PH1 mutation, G170R, and expressed them on the appropriate background of the major or minor allele, in an Escherichia coli overexpression system and in a rabbit reticulocyte transcription/translation system. We have investigated their effects on enzyme activity, dimerization, aggregation, and turnover. The effect of pyridoxal phosphate (PLP) on dimerization and stability was also investigated. Although all 15 mutant AGTs were expressed as intact proteins in E. coli, only three: G41R and G41V on the major allele, and the common mutation G170R, resulted in significant amounts of enzymatic activity. Dimerization failure was a frequent observation (13/15) except for G41V and D183N. Dimerization was poor with S187F but was substantially improved with PLP. Proteasome-mediated protein degradation was observed for all the mutations except G41R on the major allele, G41V, D183N, G170R, and S218L. Increases in the stability of the mutant enzymes in the presence of PLP were small; however, G41R on the minor allele showed a direct relationship between its half life and the concentration of PLP. The minor allele AGT product and many of the mutants were subject to a limited non-proteasomal proteolytic cleavage when ATP was depleted.

A contribution for the definition of serum chemistry values in captive adults Antillean manatees (Trichechus manatus manatus Linnaeus, 1758).

PubMed

Silva, F M O; Vergara-Parente, J E; Gomes, J K N; Teixeira, M N; Lima, R P

2007-04-01

Serum chemistry analyses represents a fundamental tool for the diagnosis and understanding of diseases in marine mammals. Although several studies are being conducted within the field of clinical pathology, haematological and serum chemistry data for Antillean manatees are deficient. The purpose of this study was to determine serum chemistry values for captive Antillean manatees within the CMA/Ibama facility in Brazil. Serum samples were obtained from five captive adult Antillean manatees fed with seagrass and analysed for aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, urea, creatinine, glucose, triglycerides, cholesterol, total protein, albumin, globulin, phosphate, chloride, calcium and uric acid. Blood chemistry parameters were determined using a semi-automatic analyzer. Maximum, minimum, mean and standard deviations were calculated for each serum chemistry parameter. Differences on the values of males and females were verified using an unpaired Student's t-test. All the parameters analysed were similar between sexes, with exception of AP, which was higher in females (191.43 +/- 31.86 U/l). Alanine aminotransferase and uric acid values for Trichechus manatus manatus are reported for the first time in this paper. This study is the first to report serum chemistry parameter values for long-term captive male and female Antillean manatees. Therefore, the lower values of albumin, phosphate, chloride, cholesterol and triglycerides obtained here highlight the importance of clinical pathology during health monitoring of captive marine mammals.

Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea.

PubMed

Norman, Daniel; Bardwell, Wayne A; Arosemena, Farah; Nelesen, Richard; Mills, Paul J; Loredo, Jose S; Lavine, Joel E; Dimsdale, Joel E

2008-01-01

Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). Retrospective case series. 109 adult patients with OSA at a university hospital general clinical research center. Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = -0.31 to -0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome.

Alanine transaminase level in a healthy population in Morocco.

PubMed

Laouina, A; Abouyoub, A; Soulaymani, A; Alami, R

2012-03-01

A little is known about the prevalence of elevated alanine transaminase in a Moroccan healthy population. Our aim was to search for the upper limit of normal alanine transaminase in the blood donors and then to apply the upper limit of normal alanine found in the population so as to assess the prevalence of subjects with abnormal transaminase level. We then, investigated for factors associated with increased level of transaminase in our population. This study was carried out on 14071 blood donors, (74.1% of men and 25.9% female) aged between 18 to 60 years, randomly chosen. Serum transaminase activity was measured using on IEMS Reader, Labsystems. Hepatitis B and C were performed by ELISA. The upper limit of normal transaminase found were 64 for men and 52 for women. Consequently, 2.08% blood donors had an abnormal level of transaminase. Follow up results revealed that drug was the first cause of elevated transaminase in our cohort followed by diet and alcohol consumption. One seroconversion for hepatitis C was identified. In conclusion, this study showed that even though there is an evident lack of efficiency in using alanine aminotransferase testing qualifying blood donors in our country, preventing viral potential transmission through transfusions was possible.

Comparison of blood chemistry values for samples collected from juvenile chinook salmon by three methods

USGS Publications Warehouse

Congleton, J.L.; LaVoie, W.J.

2001-01-01

Thirteen blood chemistry indices were compared for samples collected by three commonly used methods: caudal transection, heart puncture, and caudal vessel puncture. Apparent biases in blood chemistry values for samples obtained by caudal transection were consistent with dilution with tissue fluids: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), triglyceride, and K+ were increased and Na+ and Cl- were decreased relative to values for samples obtained by caudal vessel puncture. Some enzyme activities (ALT, AST, LDH) and K+ concentrations were also greater in samples taken by heart puncture than in samples taken by caudal vessel puncture. Of the methods tested, caudal vessel puncture had the least effect on blood chemistry values and should be preferred for blood chemistry studies on juvenile salmonids.

Elevated alanine aminotransferase is associated with metabolic syndrome but not consistently associated with impaired fasting glucose or type 2 diabetes mellitus.

PubMed

Yueh, Chen-Yu; Chen, Jung-Hsiang; Lee, Li-Wen; Lu, Cheng-Wei; Parekh, Bhavin; Chi, Ching-Chi

2011-10-01

Abnormally elevated alanine aminotransferase (ALT) of nonspecific causes is a common outpatient problem. Without considering ethnicity, several studies had suggested that it was associated with insulin resistance (IR). To investigate whether nonspecific elevated ALT in Taiwanese population could reflect a likely underlying IR and was associated with impaired fasting glucose or type 2 diabetes mellitus (IFG/T2DM). The health examination profiles of 1313 Taiwanese were investigated cross-sectionally. The prevalence and odds ratios (ORs) for IFG/T2DM and metabolic abnormalities in relation to elevated ALT were analyzed. Subjects with metabolic syndrome (MS) all had IFG/T2DM. The elevated ALT significantly correlated with MS and IFG/T2DM (i.e., 19.9-29.2% vs. 7.8% for MS, and 27.0-31.5% vs. 16.1% for IFG/T2DM). However, after excluding MS and adjustment for age and sex, the elevated ALT alone was not consistently associated with IFG/T2DM (36 < ALT ≤ 80 IU/L with OR 0.97, 95% CI 0.58-1.61; 80 < ALT ≤ 120 IU/L with OR 0.55, 95% CI 0.13-2.37; none with ALT > 120 had IFG). In a cross-sectional analysis of Taiwanese industrial employees, elevated ALT associated with MS, but in subjects who did not meet MS criteria, elevated ALT by itself did not associate with IFG/T2DM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.

PubMed

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.

Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy

PubMed Central

Liu, Lingyun; Wang, Wei; Zhang, Yi; Long, Jianting; Zhang, Zhaohui; Li, Qiao; Chen, Bin; Li, Shaoqiang; Hua, Yunpeng; Shen, Shunli; Peng, Baogang

2018-01-01

Purpose Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. Materials and Methods Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. Results The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. Conclusion Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy. PMID:28602056

Serum Aminotransferase Levels are Associated with Markers of Hypoxia in Patients with Obstructive Sleep Apnea

PubMed Central

Norman, Daniel; Bardwell, Wayne A.; Arosemena, Farah; Nelesen, Richard; Mills, Paul J.; Loredo, Jose S.; Lavine, Joel E.; Dimsdale, Joel E.

2008-01-01

Study Objectives: Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). Design: Retrospective case series. Patients and Setting: 109 adult patients with OSA at a university hospital general clinical research center. Measurements and Results: Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = −0.31 to −0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. Conclusions: In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome. Citation: Norman D; Bardwell WA; Arosemena F; Nelesen R; Mills PJ; Loredo JS; Lavine JE; Dimsdale JE. Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea. SLEEP 2008;31(1):-121-126. PMID:18220085

Association of serum gamma-glutamyltransferase and alanine aminotransferase activities with risk of type 2 diabetes mellitus independent of fatty liver.

PubMed

Kim, Chul-Hee; Park, Joong-Yeol; Lee, Ki-Up; Kim, Jin-Ho; Kim, Hong-Kyu

2009-01-01

Although elevated serum concentrations of gamma-glutamyltrans- ferase (GGT) or alanine aminotransferase (ALT) have been associated with type 2 diabetes mellitus, it is unclear whether each is an independent predictor of type 2 diabetes or merely a surrogate marker for fatty liver or hepatic injury. We assessed clinical and laboratory findings in 3556 non-diabetic subjects (2217 men, 1339 women; age, 45.7 +/- 8.1 (range 20-79) years) without fatty liver or clinically significant hepatic dysfunction who underwent voluntary medical check-ups at a 5-year interval. The odds ratio of developing type 2 diabetes increased significantly with increasing GGT and ALT levels at baseline. In multiple logistic regression models adjusted for age, sex, alcohol consumption, smoking, body mass index (BMI), triglycerides, high-density lipoprotein (HDL)-cholesterol, fasting glucose, and ALT, the highest quartile of GGT remained significantly associated with type 2 diabetes. Compared with the first GGT quartile, the odds ratios of the second, third, and fourth GGT quartiles were 0.64 (95% CI, 0.25-1.65), 1.12 (0.45-2.78), and 3.07 (1.21-7.76), respectively. The adjusted odds ratios for the second, third, and fourth ALT quartiles in the same logistic regression model were 2.40 (0.83-6.94), 2.85 (1.03-7.90), and 4.31 (1.56-11.88), respectively. The risk of type 2 diabetes was additive with respect to GGT and ALT quartiles. Increased serum GGT and ALT levels are independent, additive risk factors for the development of type 2 diabetes mellitus in subjects without fatty liver or hepatic dysfunction. Copyright 2009 John Wiley & Sons, Ltd.

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

PubMed

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

2013-04-01

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.

[Relationship of visceral adiposity index with serum aminotransferase and nonalcoholic fatty liver disease in patients with sleep apnea].

PubMed

Qi, Jiachao; Lin, Qichang; Lin, Xin; Chen, Xiao

2015-11-10

To evaluate the relationship of visceral adiposity index (VAI) with serum aminotransferase levels and incidence of nonalcoholic fatty liver disease (NAFLD) in patients with sleep apnea (SA). Between January 2011 and December 2014, participants who were referred from Fujian Provincial Sleep-disordered Breathing (SDB) Clinic Center with repeated snoring or a clinical suspicion of SDB were recruited. All individuals underwent polysomnography (PSG) testing and an abdominal ultrasonography scan during this period. They were classified into four groups by apnea-hypopnea index (AHI), non-SA group, mild, moderate and severe group (AHI<5/h, 5-<15/h, 15-<30/h, ≥30/h, respectively). The differences in SA-related parameters, serum aminotransferase and VAI were tested, and the correlations of VAI with indices of PSG and serum aminotransferase were analyzed using Spearman coefficient. Receiver operating characteristic (ROC) curve was conducted to obtain a cut-off value of VAI for predicting NAFLD. Afterwards, logistic regression was performed to analyze VAI's predictive ability regarding incidence of NAFLD in SDB patients. A total of 152 participants including 110 males and 42 females were analyzed, with mean age (51.1±11.3) years. There were 20 subjects in non-SA group, 31 in mild, 39 in moderate and 62 in severe group, with 92 NAFLD patients and 60 controls. No differences in sex, age, alkaline phosphatase were observed among groups according to AHI. However, body mass index, waist circumference, AHI, lowest oxygen saturation, oxygen desaturation index(ODI), VAI, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase (GGT) and incidence of NAFLD were significantly different among groups. Significant positive relations were observed between VAI and AHI (β=0.222, P=0.006), ODI (β=0.216, P=0.008), ALT (β=0.237, P=0.003), GGT (β=0.238, P=0.003). As shown in ROC curve, the cut-off point of VAI for predicting NAFLD was 1.59 in all individuals

Functional Characterization of Alanine Racemase from Schizosaccharomyces pombe: a Eucaryotic Counterpart to Bacterial Alanine Racemase

PubMed Central

Uo, Takuma; Yoshimura, Tohru; Tanaka, Naotaka; Takegawa, Kaoru; Esaki, Nobuyoshi

2001-01-01

Schizosaccharomyces pombe has an open reading frame, which we named alr1+, encoding a putative protein similar to bacterial alanine racemase. We cloned the alr1+ gene in Escherichia coli and purified the gene product (Alr1p), with an Mr of 41,590, to homogeneity. Alr1p contains pyridoxal 5′-phosphate as a coenzyme and catalyzes the racemization of alanine with apparent Km and Vmax values as follows: for l-alanine, 5.0 mM and 670 μmol/min/mg, respectively, and for d-alanine, 2.4 mM and 350 μmol/min/mg, respectively. The enzyme is almost specific to alanine, but l-serine and l-2-aminobutyrate are racemized slowly at rates 3.7 and 0.37% of that of l-alanine, respectively. S. pombe uses d-alanine as a sole nitrogen source, but deletion of the alr1+ gene resulted in retarded growth on the same medium. This indicates that S. pombe has catabolic pathways for both enantiomers of alanine and that the pathway for l-alanine coupled with racemization plays a major role in the catabolism of d-alanine. Saccharomyces cerevisiae differs markedly from S. pombe: S. cerevisiae uses l-alanine but not d-alanine as a sole nitrogen source. Moreover, d-alanine is toxic to S. cerevisiae. However, heterologous expression of the alr1+ gene enabled S. cerevisiae to grow efficiently on d-alanine as a sole nitrogen source. The recombinant yeast was relieved from the toxicity of d-alanine. PMID:11244061

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

PubMed

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.

Association between continuous positive airway pressure and serum aminotransferases in patients with obstructive sleep apnea.

PubMed

Chen, Li-Da; Zhang, Liang-Ji; Lin, Xue-Jun; Qi, Jia-Chao; Li, Hao; Wu, Zhi; Xu, Qiao-Zhen; Huang, Ya-Ping; Lin, Li

2018-02-01

Obstructive sleep apnea (OSA) has been suggested to be a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). Studies on the association between continuous positive airway pressure (CPAP) and NAFLD in OSA patients are limited and controversial. The aim of this study was to assess the relationship between OSA and NAFLD and the effect of CPAP therapy on serum aminotransferase levels in OSA patients. A total of 160 consecutive patients who underwent standard polysomnography were enrolled. Blood samples were obtained in the morning after sleep for biological profile measurements. Non-invasive ultrasound techniques were used to assess liver steatosis and fibrosis. Within the OSA group, serum aminotransferases were detected before and after CPAP treatment. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, and liver steatosis score increased significantly with an increase in OSA severity. Stepwise multiple regression with liver steatosis score, ALT, AST as dependent variable, respectively, apnea-hypopnea index (β = 0.447, p = 0.020; β = 0.266, p = 0.001; β = 0.351, p = 0.020, respectively) significantly predicted the liver steatosis score, ALT, AST after adjustment for confounders. After 3 months of CPAP treatment, there was a significant decrease in both ALT (54.20 ± 24.34 vs. 46.52 ± 24.95, p = 0.000) and AST (31.82 ± 8.91 vs. 29.00 ± 8.34, p = 0.039). OSA severity was independently associated with liver steatosis and elevation of serum aminotransferases. 3 months of CPAP therapy were associated with a statistically significant improvement on liver injury in OSA patients.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sayer, Christopher; Isupov, Michail N.; Westlake, Aaron

2013-04-01

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 showmore » 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.« less

Statin-related aminotransferase elevation according to baseline aminotransferases level in real practice in Korea.

PubMed

Kim, H-S; Lee, S H; Kim, H; Lee, S-H; Cho, J H; Lee, H; Yim, H W; Kim, S-H; Choi, I-Y; Yoon, K-H; Kim, J H

2016-06-01

Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated. Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. The progression rate to abnormal AST/ALT values [>×3 the upper normal limit (UNL)] was significantly higher (2·4-16% vs. 0·3-1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables. © 2016 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd.

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

PubMed Central

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

2013-01-01

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. PMID:23519665

Experimental and computational thermochemical study of α-alanine (DL) and β-alanine.

PubMed

da Silva, Manuel A V Ribeiro; da Silva, Maria das Dores M C Ribeiro; Santos, Ana Filipa L O M; Roux, Maria Victoria; Foces-Foces, Concepción; Notario, Rafael; Guzmán-Mejía, Ramón; Juaristi, Eusebio

2010-12-16

This paper reports an experimental and theoretical study of the gas phase standard (p° = 0.1 MPa) molar enthalpies of formation, at T = 298.15 K, of α-alanine (DL) and β-alanine. The standard (p° = 0.1 MPa) molar enthalpies of formation of crystalline α-alanine (DL) and β-alanine were calculated from the standard molar energies of combustion, in oxygen, to yield CO2(g), N2(g), and H2O(l), measured by static-bomb combustion calorimetry at T = 298.15 K. The vapor pressures of both amino acids were measured as function of temperature by the Knudsen effusion mass-loss technique. The standard molar enthalpies of sublimation at T = 298.15 K was derived from the Clausius−Clapeyron equation. The experimental values were used to calculate the standard (p° = 0.1 MPa) enthalpy of formation of α-alanine (DL) and β-alanine in the gaseous phase, Δ(f)H(m)°(g), as −426.3 ± 2.9 and −421.2 ± 1.9 kJ·mol(−1), respectively. Standard ab initio molecular orbital calculations at the G3 level were performed. Enthalpies of formation, using atomization reactions, were calculated and compared with experimental data. Detailed inspections of the molecular and electronic structures of the compounds studied were carried out.

Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

PubMed Central

Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

1999-01-01

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine aminotransferase gene expression and enzymatic activity in the rat liver

PubMed Central

2011-01-01

Background Traditional assessment of drug-induced hepatotoxicity includes morphological examination of the liver and evaluation of liver enzyme activity in serum. The objective of the study was to determine the origin of drug-related elevation in serum alanine aminotransferase (ALT) activity in the absence of morphologic changes in the liver by utilizing molecular and immunohistochemical techniques. Methods Sixteen female Sprague-Dawley rats were divided into 2 groups (control and treated, n = 4 per group) and treated rats were dosed orally twice daily (400 mg/kg/day) for 7 days with a VEGFR-2 compound (AG28262), which in a previous study caused ALT elevation without morphological changes. Serum of both treated and control animals were evaluated on day 3 of treatment and at day 8. Three separate liver lobes (caudate, right medial, and left lateral) were examined for determination of ALT tissue activity, ALT gene expression and morphological changes. Results ALT activity was significantly (p < 0.01) elevated on day 3 and further increased on day 8. Histologic changes or increase in TUNEL and caspase3 positive cells were not observed in the liver lobes examined. ALT gene expression in the caudate lobe was significantly up-regulated by 63%. ALT expression in the left lateral lobe was not significantly affected. Statistically significant increased liver ALT enzymatic activity occurred in the caudate (96%) and right medial (41%) lobes but not in the left lateral lobe. Conclusions AG28262, a VEFG-r2 inhibitor, causes an increase in serum ALT, due in part to both gene up-regulation. Differences between liver lobes may be attributable to differential distribution of blood from portal circulation. Incorporation of molecular data, such as gene and protein expression, and sampling multiple liver lobes may shed mechanistic insight to the evaluation of hepatotoxicity. PMID:21846403

Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine aminotransferase gene expression and enzymatic activity in the rat liver.

PubMed

Fuentealba, Carmen; Bera, Monali; Jessen, Bart; Sace, Fred; Stevens, Greg J; Trajkovic, Dusko; Yang, Amy H; Evering, Winston

2011-08-17

Traditional assessment of drug-induced hepatotoxicity includes morphological examination of the liver and evaluation of liver enzyme activity in serum. The objective of the study was to determine the origin of drug-related elevation in serum alanine aminotransferase (ALT) activity in the absence of morphologic changes in the liver by utilizing molecular and immunohistochemical techniques. Sixteen female Sprague-Dawley rats were divided into 2 groups (control and treated, n = 4 per group) and treated rats were dosed orally twice daily (400 mg/kg/day) for 7 days with a VEGFR-2 compound (AG28262), which in a previous study caused ALT elevation without morphological changes. Serum of both treated and control animals were evaluated on day 3 of treatment and at day 8. Three separate liver lobes (caudate, right medial, and left lateral) were examined for determination of ALT tissue activity, ALT gene expression and morphological changes. ALT activity was significantly (p < 0.01) elevated on day 3 and further increased on day 8. Histologic changes or increase in TUNEL and caspase3 positive cells were not observed in the liver lobes examined. ALT gene expression in the caudate lobe was significantly up-regulated by 63%. ALT expression in the left lateral lobe was not significantly affected. Statistically significant increased liver ALT enzymatic activity occurred in the caudate (96%) and right medial (41%) lobes but not in the left lateral lobe. AG28262, a VEFG-r2 inhibitor, causes an increase in serum ALT, due in part to both gene up-regulation. Differences between liver lobes may be attributable to differential distribution of blood from portal circulation. Incorporation of molecular data, such as gene and protein expression, and sampling multiple liver lobes may shed mechanistic insight to the evaluation of hepatotoxicity.

Baseline hematology and clinical chemistry results from captive-raised trumpeter swans

USGS Publications Warehouse

Olsen, Glenn H.; Rininger, D.L.; Ets, M.K.; Sladen, William J. L.; Rees, Eileen C.; Earnst, Susan L.; Coulson, John C.

2002-01-01

Results from hematology and clinical chemistry tests are presented for healthy captive-raised Trumpeter Swans (Cygnus buccinator) to help establish baseline data. Blood samples were obtained from 14 cygnets between the ages of three to four and seven to eight months that were the subjects of a study to teach migration routes to swans. Males and females differed significantly in asparatate aminotransferase, alanine aminotransferase and total protein. Age categories differed significantly in hematocrit, white blood cell counts, alkaline phosphatase, aspar-rate aminotransferase, glucose, cholesterol and uric acid. There were no significant differences among age categories in values of alanine aminotransferase, calcium, triglycerides and total protein.

Reference values for 27 clinical chemistry tests in 70-year-old males and females.

PubMed

Carlsson, Lena; Lind, Lars; Larsson, Anders

2010-01-01

Reference values are usually defined based on blood samples from healthy men or nonpregnant women in the age range of 20-50 years. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference values are important for correct clinical decisions. To validate NORIP (Nordic Reference Interval Project) reference values in a 70-year-old population. We studied 27 frequently used laboratory tests. The 2.5th and 97.5th percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. Reference values are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, creatine kinase, C-reactive protein, glucose, gamma-glutamyltransferase, HDL-cholesterol, iron, lactate dehydrogenase, LDL-cholesterol, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, urate and urea. Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% CI of a Scandinavian population (NORIP). 2009 S. Karger AG, Basel.

Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.

PubMed

Jacobson, Ira M; Washington, Mary K; Buti, Maria; Thompson, Alexander; Afdhal, Nezam; Flisiak, Robert; Akarca, Ulus Salih; Tchernev, Konstantin G; Flaherty, John F; Aguilar Schall, Raul; Myers, Robert P; Subramanian, G Mani; McHutchison, John G; Younossi, Zobair; Marcellin, Patrick; Patel, Keyur

2017-07-01

Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate. We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level. Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P = .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P = .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P = .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level. HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. Clinical

Blood Chemistry Reference Values for Free-Ranging Asiatic Black Bears ( Ursus thibetanus) by Season, Age, and Sex.

PubMed

Yang, Jeong-Jin; Jeong, Dong-Hyuk; Lim, Yoon-Kyu

2018-04-19

Physiological characteristics, such as blood chemistry values, are valuable for evaluating the health of the animals. To our knowledge, these values have never been reported for the free-ranging Asiatic black bear ( Ursus thibetanus; ABB). Thus, 28 blood chemistry values from 50 free-ranging ABBs captured in Jirisan National Park, Republic of Korea, from 2005 to 2016 were evaluated. The aim of this study was to establish blood chemistry reference values for the free-ranging ABBs during both the hibernating and nonhibernating seasons. During hibernation, mean values of creatinine (CRE), total cholesterol, total protein (TP), albumin (ALB), triglycerides, and Mg were significantly higher than those during nonhibernation; however, mean values of blood urea nitrogen, urea nitrogen to creatinine (U/C) ratio, inorganic phosphorous (IP), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase (LDH), high-density lipoprotein cholesterol, and alkaline phosphatase (ALP) were significantly lower. Age differences (young vs. adult) were found in IP, LDH, TP, and ALB values during hibernation and in the U/C ratio, Ca, IP, ALP, creatine kinase myocardial band, CRE, total bilirubin, and uric acid values during nonhibernation. However, there were no sex differences (male vs. female).

Salivary lactate dehydrogenase and aminotransferases in diabetic patients

PubMed Central

Malicka, Barbara; Skoskiewicz-Malinowska, Katarzyna; Kaczmarek, Urszula

2016-01-01

Abstract Diabetes mellitus (DM) is a group of metabolic diseases resulting from impaired insulin secretion and/or action. DM is characterized by hyperglycemia that can lead to the dysfunction or damage of organs, including the salivary glands. The aim of this study was to compare the levels of salivary lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in diabetic patients. The study was approved by the Bioethics Committee of Wroclaw Medical University (Poland). The study comprised 90 adults of both sexes, aged 21 to 57 years. The patients were divided into 3 groups: type 1 diabetics (D1), type 2 diabetics (D2), and a healthy control group (C). Each group consisted of 30 age- and sex-matched subjects. Total protein (P, by Lowry method), LDH, AST, ALT (with Alpha Diagnostics kits), and salivary flow rate were measured in unstimulated mixed saliva. The level of glycosylated hemoglobin (HbA1c) was measured with DCA 2000 Reagent Kit. The obtained data were analyzed using the Mann–Whitney U test and the Spearman rank at a significance level of P < 0.05 with the use of STATISTICA 9.0 software. In comparison with C, D1 presented a significantly higher activity of LDH (P < 0.001), AST (P < 0.001), and ALT (P < 0.01), whereas D2 indicated higher levels of LDH (P < 0.001) and ALT (P < 0.05) compared with C. Comparing D1 to D2, approximately 3-fold higher activity of AST (P < 0.01) and approximately 4.5-fold higher activity of ALT (P < 0.01) was observed. Higher levels of salivary LDH, AST, and ALT in D1 compared with D2 and C confirm that salivary glands of D1 might be attributed to autoimmunological damage associated with the pathomechanism of DM. PMID:27893660

Salivary lactate dehydrogenase and aminotransferases in diabetic patients.

PubMed

Malicka, Barbara; Skoskiewicz-Malinowska, Katarzyna; Kaczmarek, Urszula

2016-11-01

Diabetes mellitus (DM) is a group of metabolic diseases resulting from impaired insulin secretion and/or action. DM is characterized by hyperglycemia that can lead to the dysfunction or damage of organs, including the salivary glands.The aim of this study was to compare the levels of salivary lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in diabetic patients.The study was approved by the Bioethics Committee of Wroclaw Medical University (Poland). The study comprised 90 adults of both sexes, aged 21 to 57 years. The patients were divided into 3 groups: type 1 diabetics (D1), type 2 diabetics (D2), and a healthy control group (C). Each group consisted of 30 age- and sex-matched subjects. Total protein (P, by Lowry method), LDH, AST, ALT (with Alpha Diagnostics kits), and salivary flow rate were measured in unstimulated mixed saliva. The level of glycosylated hemoglobin (HbA1c) was measured with DCA 2000 Reagent Kit. The obtained data were analyzed using the Mann-Whitney U test and the Spearman rank at a significance level of P < 0.05 with the use of STATISTICA 9.0 software.In comparison with C, D1 presented a significantly higher activity of LDH (P < 0.001), AST (P < 0.001), and ALT (P < 0.01), whereas D2 indicated higher levels of LDH (P < 0.001) and ALT (P < 0.05) compared with C. Comparing D1 to D2, approximately 3-fold higher activity of AST (P < 0.01) and approximately 4.5-fold higher activity of ALT (P < 0.01) was observed.Higher levels of salivary LDH, AST, and ALT in D1 compared with D2 and C confirm that salivary glands of D1 might be attributed to autoimmunological damage associated with the pathomechanism of DM.

Genetic predisposition to liver damage after halothane anesthesia in guinea pigs.

PubMed

Lunam, C A; Cousins, M J; Hall, P M

1986-11-01

Three 4-hr normoxic (21% oxygen) exposures to 1% halothane administered 3 days apart were associated with elevations in serum alanine aminotransferase (ALT) activity in four of 20 guinea pigs after the initial and third exposures. Serum alanine aminotransferase values were not measured after the second anesthetic. Susceptibility was defined as an ALT level greater than 300 IU/L after halothane. Nonsusceptible animals, that is, animals without significant increases in ALT values after halothane, remained nonsusceptible after reexposure. Serum alanine aminotransferase values after the first and third anesthesias were significantly correlated (rs = 0.86, P less than 0.001). Two exposures of another 30 guinea pigs at a 5-week interval resulted in high elevations of ALT in the same eight animals after both anesthetics. In contrast, after an initial exposure nonsusceptible animals remained nonsusceptible upon reexposure. Serum alanine aminotransferase levels after the first and second anesthetics were significantly correlated (rs = 0.85, P less than 0.001). The proportion of first generation (F1) males with elevated ALTs whose parents were susceptible to halothane hepatotoxicity (HH) was significantly higher than the proportion of males with elevated ALTs in a random group of 90 males (P less than 0.005). First generation males and females of nonsusceptible parents had ALTs within the normal range after halothane exposure. These studies suggest that in the guinea pig genetic predisposition is an important determinant of susceptibility to HH, although other contributing factors are not excluded.

Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.

PubMed

Santana, A; Salido, E; Torres, A; Shapiro, L J

2003-06-10

Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 --> Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 --> Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation.

Establishing a synthetic pathway for high-level production of 3-hydroxypropionic acid in Saccharomyces cerevisiae via β-alanine.

PubMed

Borodina, Irina; Kildegaard, Kanchana R; Jensen, Niels B; Blicher, Thomas H; Maury, Jérôme; Sherstyk, Svetlana; Schneider, Konstantin; Lamosa, Pedro; Herrgård, Markus J; Rosenstand, Inger; Öberg, Fredrik; Forster, Jochen; Nielsen, Jens

2015-01-01

Microbial fermentation of renewable feedstocks into plastic monomers can decrease our fossil dependence and reduce global CO2 emissions. 3-Hydroxypropionic acid (3HP) is a potential chemical building block for sustainable production of superabsorbent polymers and acrylic plastics. With the objective of developing Saccharomyces cerevisiae as an efficient cell factory for high-level production of 3HP, we identified the β-alanine biosynthetic route as the most economically attractive according to the metabolic modeling. We engineered and optimized a synthetic pathway for de novo biosynthesis of β-alanine and its subsequent conversion into 3HP using a novel β-alanine-pyruvate aminotransferase discovered in Bacillus cereus. The final strain produced 3HP at a titer of 13.7±0.3gL(-1) with a 0.14±0.0C-molC-mol(-1) yield on glucose in 80h in controlled fed-batch fermentation in mineral medium at pH 5, and this work therefore lays the basis for developing a process for biological 3HP production. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Coding variants in PNPLA3 and TM6SF2 are risk factors for hepatic steatosis and elevated serum alanine aminotransferases caused by a glucagon receptor antagonist

PubMed Central

Guzman, Cristina B.; Duvvuru, Suman; Akkari, Anthony; Bhatnagar, Pallav; Battioui, Chakib; Foster, Wendra; Zhang, Xiaotian Michelle; Shankar, Sudha S.; Deeg, Mark A.; Hardy, Thomas A.; Kazda, Christof M.

2018-01-01

LY2409021 is a glucagon receptor antagonist that was associated with hepatic steatosis and elevated aminotransferases in phase 2 diabetes studies. We investigated the relationship between selected genetic variants and hepatic steatosis and elevated alanine aminotransferases (ALTs) associated with LY2409021. Patients participated in a 6‐week placebo‐controlled trial (I1R‐MC‐GLDI [GLDI], n = 246) and a 52‐week placebo‐ and active comparator‐controlled trial (I1R‐MC‐GLDJ [GLDJ], n = 158). GLDJ had endpoints at 6 months, including measures of hepatic fat fraction (HFF) by magnetic resonance imaging. The five genes tested were patatin‐like phospholipase domain containing 3 (PNPLA3) (rs738409 and rs738491), transmembrane 6 superfamily member 2 (TM6SF2) (rs58542926), peroxisome proliferative activated receptor gamma coactivator 1 alpha (PPARGC1A) (rs4361373, rs3774921, rs2970849), adenylate cyclase 3 (ADCY3) (rs713586), and insulin‐like growth factor 1 (IGF‐1) (rs1520220). In GLDI, PNPLA3 I148M (P = 0.001) and TM6SF2 E167K (P = 0.001) were significantly associated with an increase in ALT at 6 weeks for LY2409021 but not for placebo. In GLDJ, PNPLA3 I148M showed the same effect (P = 0.007) on ALT at 6 months but the placebo or sitagliptin did not. In GLDJ, both PNPLA3 and TM6SF2 risk‐allele carriers showed increases in HFF that were numerically greater but not statistically significant. The carriers of PNPLA3 and/or TM6SF2 risk alleles showed significantly increased ALT (GLDI, +13.28 U/L in carriers versus +4.84 U/L in noncarriers, P = 4 × 10–5; GLDJ, +14.6 U/L in carriers versus +1.7 in noncarriers, P = 0.0018) and HFF (GLDJ, +5.35% in carriers versus 2.38% in noncarriers, P = 0.048). Elevation of transaminase and HFF were also noted in the noncarriers but at a significantly lower degree. Conclusion: The carriers of PNPLA3 and/or TM6SF2 variant alleles are at risk for hepatic steatosis and elevated ALT levels caused by LY2409021, a glucagon

Coding variants in PNPLA3 and TM6SF2 are risk factors for hepatic steatosis and elevated serum alanine aminotransferases caused by a glucagon receptor antagonist.

PubMed

Guzman, Cristina B; Duvvuru, Suman; Akkari, Anthony; Bhatnagar, Pallav; Battioui, Chakib; Foster, Wendra; Zhang, Xiaotian Michelle; Shankar, Sudha S; Deeg, Mark A; Chalasani, Naga; Hardy, Thomas A; Kazda, Christof M; Pillai, Sreekumar G

2018-05-01

LY2409021 is a glucagon receptor antagonist that was associated with hepatic steatosis and elevated aminotransferases in phase 2 diabetes studies. We investigated the relationship between selected genetic variants and hepatic steatosis and elevated alanine aminotransferases (ALTs) associated with LY2409021. Patients participated in a 6-week placebo-controlled trial (I1R-MC-GLDI [GLDI], n = 246) and a 52-week placebo- and active comparator-controlled trial (I1R-MC-GLDJ [GLDJ], n = 158). GLDJ had endpoints at 6 months, including measures of hepatic fat fraction (HFF) by magnetic resonance imaging. The five genes tested were patatin-like phospholipase domain containing 3 ( PNPLA3 ) (rs738409 and rs738491), transmembrane 6 superfamily member 2 ( TM6SF2 ) (rs58542926), peroxisome proliferative activated receptor gamma coactivator 1 alpha ( PPARGC1A ) (rs4361373, rs3774921, rs2970849), adenylate cyclase 3 ( ADCY3 ) ( rs713586), and insulin-like growth factor 1 ( IGF-1 ) (rs1520220). In GLDI, PNPLA3 I148M ( P = 0.001) and TM6SF2 E167K ( P = 0.001) were significantly associated with an increase in ALT at 6 weeks for LY2409021 but not for placebo. In GLDJ, PNPLA3 I148M showed the same effect ( P = 0.007) on ALT at 6 months but the placebo or sitagliptin did not. In GLDJ, both PNPLA3 and TM6SF2 risk-allele carriers showed increases in HFF that were numerically greater but not statistically significant. The carriers of PNPLA3 and/or TM6SF2 risk alleles showed significantly increased ALT (GLDI, +13.28 U/L in carriers versus +4.84 U/L in noncarriers, P = 4 × 10 -5 ; GLDJ, +14.6 U/L in carriers versus +1.7 in noncarriers, P = 0.0018) and HFF (GLDJ, +5.35% in carriers versus 2.38% in noncarriers, P = 0.048). Elevation of transaminase and HFF were also noted in the noncarriers but at a significantly lower degree. Conclusion: The carriers of PNPLA3 and/or TM6SF2 variant alleles are at risk for hepatic steatosis and elevated ALT levels caused by LY2409021, a glucagon receptor

Primary hyperoxaluria type 1 in the Canary Islands: A conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase

PubMed Central

Santana, A.; Salido, E.; Torres, A.; Shapiro, L. J.

2003-01-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 → Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 → Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation. PMID:12777626

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.

PubMed

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.

Alanine infusion during hypoglycaemia partly supports cognitive performance in healthy human subjects.

PubMed

Evans, M L; Hopkins, D; Macdonald, I A; Amiel, S A

2004-05-01

To investigate the potential for the non-glucose metabolic substrate alanine to support brain function during glucose deprivation in man. Seven healthy men were studied on two occasions using a hyperinsulinaemic glucose clamp to lower arterialized plasma glucose to 2.5 mmol/l, in the presence of either 2 mmol/kg/h alanine infusion or saline, measuring counter-regulatory hormonal responses, symptoms generated and cognitive function with a mini-battery of tests sensitive to hypoglycaemia. Alanine infusion elevated plasma alanine (peak value 1481 +/- 1260 vs. 138 +/- 32 micro mol/l, P = 0.02 alanine vs. saline) and lactate (peak value 3.09 +/- 0.14 vs. 2.05 +/- 0.12 mmol/l, P = 0.02). Cognitive function assessed by the Stroop word and colour subtests deteriorated less with alanine than saline (P < 0.01 for both). Other cognitive function tests deteriorated equally and counter-regulatory hormones rose equally during hypoglycaemia in both studies (P > 0.34) except for increased glucagon with alanine (peak 260 +/- 53 vs. 91 + 8 ng/l, P = 0.03). There was no significant effect of alanine on either autonomic or neuroglycopenic symptom scores. Some, but not all, aspects of cognitive performance may be supported by an alanine infusion during hypoglycaemia. It is not clear whether alanine supports brain function directly or via increased availability of lactate. These data contribute to the growing evidence that regional metabolic differences exist in the brain's ability to use non-glucose fuels during hypoglycaemia.

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

PubMed

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.

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

USGS Publications Warehouse

Harr, K.E.; Allison, K.; Bonde, R.K.; Murphy, D.; Harvey, J.W.

2008-01-01

Muscle injury is common in Florida manatees (Trichechus manatus latirostris). Plasma aspartate amino-transferase (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 ??mol 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

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

PubMed

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

Ornithine aminotransferase versus GABA aminotransferase: implications for the design of new anticancer drugs.

PubMed

Lee, Hyunbeom; Juncosa, Jose I; Silverman, Richard B

2015-03-01

Ornithine aminotransferase (OAT) and γ-aminobutyric acid aminotransferase (GABA-AT) are classified under the same evolutionary subgroup and share a large portion of structural, functional, and mechanistic features. Therefore, it is not surprising that many molecules that bind to GABA-AT also bind well to OAT. Unlike GABA-AT, OAT had not been viewed as a potential therapeutic target until recently; consequently, the number of therapeutically viable molecules that target OAT is very limited. In this review the two enzymes are compared with respect to their active-site structures, catalytic and inactivation mechanisms, and selective inhibitors. Insight is offered that could aid in the design and development of new selective inhibitors of OAT for the treatment of cancer. © 2014 Wiley Periodicals, Inc.

Four of the Most Common Mutations in Primary Hyperoxaluria Type 1 Unmask the Cryptic Mitochondrial Targeting Sequence of Alanine:glyoxylate Aminotransferase Encoded by the Polymorphic Minor Allele*

PubMed Central

Fargue, Sonia; Lewin, Jackie; Rumsby, Gill; Danpure, Christopher J.

2013-01-01

The gene encoding the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT, EC. 2.6.1.44) exists as two common polymorphic variants termed the “major” and “minor” alleles. The P11L amino acid replacement encoded by the minor allele creates a hidden N-terminal mitochondrial targeting sequence, the unmasking of which occurs in the hereditary calcium oxalate kidney stone disease primary hyperoxaluria type 1 (PH1). This unmasking is due to the additional presence of a common disease-specific G170R mutation, which is encoded by about one third of PH1 alleles. The P11L and G170R replacements interact synergistically to reroute AGT to the mitochondria where it cannot fulfill its metabolic role (i.e. glyoxylate detoxification) effectively. In the present study, we have reinvestigated the consequences of the interaction between P11L and G170R in stably transformed CHO cells and have studied for the first time whether a similar synergism exists between P11L and three other mutations that segregate with the minor allele (i.e. I244T, F152I, and G41R). Our investigations show that the latter three mutants are all able to unmask the cryptic P11L-generated mitochondrial targeting sequence and, as a result, all are mistargeted to the mitochondria. However, whereas the G170R, I244T, and F152I mutants are able to form dimers and are catalytically active, the G41R mutant aggregates and is inactive. These studies open up the possibility that all PH1 mutations, which segregate with the minor allele, might also lead to the peroxisome-to-mitochondrion mistargeting of AGT, a suggestion that has important implications for the development of treatment strategies for PH1. PMID:23229545

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

PubMed

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 <1, 1, and >=2 times/day, respectively. The proportions of individuals with elevated AST were 32.5%, 33.1%, and 26.7% in subjects who drank <1, 1, and >=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 <1 time/day (ALT: aOR=0.86, 95% CI=0.79-0.94; AST: aOR=0.83, 95% CI=0.76-0.91). In subgroup analysis, consumption of >=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.

Mechanism of d-Cycloserine Action: Transport Systems for d-Alanine, d-Cycloserine, l-Alanine, and Glycine1

PubMed Central

Wargel, Robert J.; Shadur, Craig A.; Neuhaus, Francis C.

1970-01-01

The accumulation of d-alanine, l-alanine, glycine, and d-cycloserine in Escherichia coli was found to be mediated by at least two transport systems. The systems for d-alanine and glycine are related, and are separate from that involved in the accumulation of l-alanine. d-Cycloserine appears to be primarily transported by the d-alanine-glycine system. The accumulation of d-alanine, glycine, and d-cycloserine was characterized by two line segments in the Lineweaver-Burk analysis, whereas the accumulation of l-alanine was characterized by a single line segment. d-Cycloserine was an effective inhibitor of glycine and d-alanine accumulation, and l-cycloserine was an effective inhibitor of l-alanine transport. The systems were further differentiated by effects of azide, enhancement under various growth conditions, and additional inhibitor studies. Since the primary access of d-cycloserine in E. coli is via the d-alanine-glycine system, glycine might be expected to be a better antagonist of d-cycloserine inhibition than l-alanine. Glycine and d-alanine at 10−5m antagonized the effect of d-cycloserine in E. coli, whereas this concentration of l-alanine had no effect. PMID:4919992

13C-methacetin-breath test compared to also noninvasive biochemical blood tests in predicting hepatic fibrosis and cirrhosis in chronic hepatitis C.

PubMed

Dinesen, L; Caspary, W F; Chapman, R W; Dietrich, C F; Sarrazin, C; Braden, B

2008-09-01

The (13)C-methacetin-breath test and also several noninvasive blood tests comprising routine laboratory parameters have been proposed to predict fibrosis and cirrhosis in chronic hepatitis C. The aim of the study was to compare the diagnostic accuracy between these tests referring to hepatic histology as gold standard. 96 patients with chronic hepatitis C virus infection underwent percutaneous liver biopsy and the (13)C-methacetin-breath test. The Fibroindex, the aspartate aminotransferase to platelet ratio index , and the aspartate aminotransferase to alanine aminotransferase ratio were used as parameters for the staging of fibrosis. The main endpoint was the area under the characteristic curves for the diagnosis of advanced fibrosis (F3-F4) and cirrhosis (F4) according to the Batts Ludwig criteria. ROC analysis revealed a cut-off <14.6 per thousand best with 92.6% sensitivity and 84.1% specificity for the (13)C-methacetin-breath test, for the Fibroindex >1.82 70.4% sensitivity and 91.3% specificity, for the aspartate aminotransferase to platelet ratio >1.0 a 66.7% sensitivity and 75.4% specificity, and for the aspartate aminotransferase to alanine aminotransferase ratio >1.0 63.0% sensitivity and 59.4% specificity in predicting liver cirrhosis. The areas under the curve for the breath test, the Fibroindex, aspartate aminotransferase to platelet ratio and the aspartate aminotransferase to alanine aminotransferase ratio were 0.958, 0.845, 0.799, and 0.688, respectively, when predicting cirrhosis. For identifying patients with advanced fibrosis, the areas under the curve were 0.827, 0.804, 0.779, and 0.561, respectively. Discordances between Fibroindex (21%), aspartate aminotransferase to platelet ratio (29%) or aspartate aminotransferase to alanine aminotransferase ratio (37.6%) and liver biopsy were significantly more frequent than between (13)C-breath test (11.6%) and liver biopsy (P<0.05). The (13)C-methacetin-breath test is more reliable in predicting advanced

BLOOD CHEMISTRY AND HEMATOLOGY VALUES IN HEALTHY AND REHABILITATED ROUGH-TOOTHED DOLPHINS ( STENO BREDANENSIS).

PubMed

Manire, Charles A; Reiber, C Melanie; Gaspar, Cécile; Rhinehart, Howard L; Byrd, Lynne; Sweeney, Jay; West, Kristi L

2018-01-01

Rehabilitation efforts for live stranded marine mammals are guided by diagnostic measures of blood chemistry and hematology parameters obtained from each individual undergoing treatment. Despite the widespread use of blood parameters, reference values are not available in the literature from healthy rough-toothed dolphins ( Steno bredanensis) with which to infer the health status of an animal. We examined serum or plasma chemistry and hematology data from 17 rough-toothed dolphins either housed at Dolphin Quest French Polynesia or during their rehabilitation at the Dolphin and Whale Hospital in Sarasota, Florida, US between 1994 and 2005. Blood parameters were compared among healthy animals, rehabilitation animals that were eventually released, and rehabilitation animals that died. This study indicated significant differences in many blood parameters for the poorly known rough-toothed dolphin that are likely to vary between healthy and sick animals. These included aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, bicarbonate, and globulins, which were greater in sick dolphins, and alkaline phosphatase and total protein which were greater in healthy individuals. Total white blood cell counts were lower in healthy animals as were the absolute numbers of neutrophils, monocytes, and eosinophils. Analysis of first blood sample levels for glucose, sodium, and erythrocyte sedimentation rate may have value for triage and prognostic evaluation.

Dose response of alanine detectors irradiated with carbon ion beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrmann, Rochus; Jaekel, Oliver; Palmans, Hugo

Purpose: The dose response of the alanine detector shows a dependence on particle energy and type when irradiated with ion beams. The purpose of this study is to investigate the response behavior of the alanine detector in clinical carbon ion beams and compare the results to model predictions. Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track structure based alanine response model developed by Hansen andmore » Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasimonoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.« less

Stratified aspartate aminotransferase-to-platelet ratio index accurately predicts survival in hepatocellular carcinoma patients undergoing curative liver resection.

PubMed

Yang, Hao-Jie; Jiang, Jing-Hang; Yang, Yu-Ting; Guo, Zhe; Li, Ji-Jia; Liu, Xuan-Han; Lu, Fei; Zeng, Feng-Hua; Ye, Jin-Song; Zhang, Ke-Lan; Chen, Neng-Zhi; Xiang, Bang-De; Li, Le-Qun

2017-03-01

The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.

Red cell aspartate aminotransferase saturation with oral pyridoxine intake.

PubMed

Oshiro, Marilena; Nonoyama, Kimiyo; Oliveira, Raimundo Antônio Gomes; Barretto, Orlando Cesar de Oliveira

2005-03-02

The coenzyme of aspartate aminotransferase is pyridoxal phosphate, generated from fresh vegetables containing pyridoxine. Vitamin B6-responsive sideroblastic anemia, myelofibrosis and Peyronies syndrome respond to high pyridoxine doses. The objective was to investigate the oral pyridoxine oral dose that would lead to maximized pyridoxal phosphate saturation of red cell aspartate aminotransferase. Controlled trial, in Hematology Division of Instituto Adolfo Lutz. Red cell aspartate aminotransferase activity was assayed (before and after) in normal volunteers who were given oral pyridoxine for 15-18 days (30 mg, 100 mg and 200 mg daily). In vitro study of blood from seven normal volunteers was also performed, with before and after assaying of aspartate aminotransferase activity. The in vivo study showed increasing aspartate aminotransferase saturation with increasing pyridoxine doses. 83% saturation was reached with 30 mg daily, 88% with 100 mg, and 93% with 200 mg after 20 days of oral supplementation. The in vitro study did not reach 100% saturation. Neither in vivo nor in vitro study demonstrated thorough aspartate aminotransferase saturation with its coenzyme pyridoxal phosphate in red cells, from increasing pyridoxine supplementation. However, the 200-mg dose could be employed safely in vitamin B6-responsive sideroblastic anemia, myelofibrosis and Peyronies syndrome treatment. Although maximum saturation in circulating red cells is not achieved, erythroblasts and other nucleated and cytoplasmic organelles containing cells certainly will reach thorough saturation, which possibly explains the results obtained in these diseases.

Cysteine-191 in aspartate aminotransferases appears to be conserved due to the lack of a neutral mutation pathway to the functional equivalent, alanine-191.

PubMed

Gloss, L M; Spencer, D E; Kirsch, J F

1996-02-01

It was previously suggested that the conserved Cys-191 of aspartate aminotransferases (AATases) is conserved, not because it is essential, but because it is frozen in the sequence, with no neutral corridor to traverse to the similar phenotype of Ala-191 (Gloss et al., Biochemistry 31:32-39, 1992). This hypothesis has now been tested by additional mutations. All possible one-base mutations from Cys were made at position 191. All of these variants display kinetic parameters (kcat and kcat/KM values) that differ from the wild-type enzyme by 30% or more. The non-conserved cysteines that are predominantly Ala in other AATase sequences (Cys-82, Cys-192, and Cys-401) were mutated to Ser to test the corollary that a neutral Cys->Ala corridor does exist for these positions. These Cys->Ser mutations yielded enzymes with wild-type-like kinetic parameters. The pKa values of the internal aldimines of the mutants, Cys-191->Ser, Phe, Tyr, and Trp are higher than that of wild type by 0.6-0.8 pH units. The stabilities to urea denaturation of the Cys-191 mutants are similar to that of wild type, while those of the non-conserved cysteines show greater variation. Examination of the three-dimensional environment of the five cysteines showed that the van der Waals contacts of Cys-191 are more conserved than are those of the non-conserved cysteines. These data provide further support for the above hypothesis.

Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

PubMed

Williams, Kathryn H; Sullivan, David R; Nicholson, Geoffrey C; George, Jacob; Jenkins, Alicia J; Januszewski, Andrzej S; Gebski, Val J; Manning, Patrick; Tan, Yong Mong; Donoghoe, Mark W; Ehnholm, Christian; Young, Simon; O'Brien, Richard; Buizen, Luke; Twigg, Stephen M; Keech, Anthony C

2016-05-01

Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years. Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-E-T-643: Pure Alanine Dosimeter for Verification Dosimetry in IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Karmi, Anan M.; Zraiqat, Fadi

Purpose: The objective of this study was evaluation of accuracy of pure alanine dosimeters measuring intensity-modulated radiation therapy (IMRT) dose distributions in a thorax phantom. Methods: Alanine dosimeters were prepared in the form of 110 mg pure L-α-alanine powder filled into clear tissue-equivalent polymethylmethacrylate (PMMA) plastic tubes with the dimensions 25 mm length, 3 mm inner diameter, and 1 mm wall thickness. A dose-response calibration curve was established for the alanine by placing the dosimeters at 1.5 cm depth in a 30×30×30 cm{sup 3} solid water phantom and then irradiating on a linac with 6 MV photon beam at 10×10more » cm{sup 2} field size to doses ranging from 1 to 5 Gy. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the absorbed dose in alanine. An IMRT treatment plan was designed for a commercial heterogeneous CIRS thorax phantom and the dose values were calculated at three different points located in tissue, lung, and bone equivalent materials. A set of dose measurements was carried out to compare measured and calculated dose values by placing the alanine dosimeters at those selected locations inside the thorax phantom and delivering the IMRT to the phantom. Results: The alanine dose measurements and the IMRT plan dose calculations were found to be in agreement within ±2%. Specifically, the deviations were −0.5%, 1.3%, and −1.7% for tissue, lung, and bone; respectively. The slightly large deviations observed for lung and bone may be attributed to tissue inhomogeneity, steep dose gradients in these regions, and uncontrollable changes in spectrometer conditions. Conclusion: The results described herein confirmed that pure alanine dosimeter was suitable for in-phantom dosimetry of IMRT beams because of its high sensitivity and acceptable accuracy. This makes the dosimeter a promising option for quality control of the therapeutic beams, complementing the commonly used ionization chambers, TLDs, and

Hematocrit and plasma chemistry values in adult collared scops owls (Otus lettia) and crested serpent eagles (Spilornis cheela hoya).

PubMed

Chan, Fang-Tse; Lin, Pei-I; Chang, Geng-Ruei; Wang, Hsien-Chi; Hsu, Tien-Huan

2012-07-01

In this study, we report hematocrit and plasma chemistry values for adult captive collared scops owls (Otus lettia) and crested serpent eagles (Spilornis cheela hoya). In particular, we address the gender-specific differences within these values. We measured hematocrit (HCT) and plasma chemistry values for uric acid (UA), plasma urea nitrogen (BUN), total protein (TP), albumin (ALB), glucose (GLU), cholesterol (CHO), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total bilirubin (TBIL), creatine (CRE), creatine phosphokinase (CPK), amylase (AMY), calcium (CA), ionic phosphorous (IP) and sodium (NA), potassium (K) and chloride ions (CL) in 37 adult captive collared scops owls and 39 adult captive crested serpent eagles. Significant differences between the sexes were found for UA, GLU and CPK in the collared scope owls. UA and GLU concentrations were significantly higher (P<0.01 and P<0.05) among males than females, while the CPK concentration was significantly lower (P<0.05) in males. There were no significant differences in of all of the measured parameters between male and female eagles. These finding suggested that HCT and plasma chemistry values of raptors vary individually according to species and sex. Our results provide the 1st available reference data for ranges of plasma values in adult captive collared scops owls and crested serpent eagles, making them a potentially useful complementary diagnostic tool for veterinary care of individuals for both species in captivity.

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with Primary Hyperoxaluria Type I☆

PubMed Central

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. PMID:22018727

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with primary hyperoxaluria type I.

PubMed

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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 <10,000 mg/L × IU/L developed hepatotoxicity (sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L × IU/L. When calculated within eight hours of ingestion, mild elevations of the multiplication product fell quickly on repeat testing in patients without ALI or hepatotoxicity. In modified-release 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

Physiological stress responses in big gamefish after capture: observations on plasma chemistry and blood factors.

PubMed

Wells, R M; McIntyre, R H; Morgan, A K; Davie, P S

1986-01-01

The plasma electrolytes, Na+, K+, Ca2+, Cl- and osmolarities had high values in capture-stressed big gamefish. Blood metabolites measured after stress showed glucose and lactate elevations. The activity of the plasma enzymes alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase and lactate dehydrogenase suggested tissue disruptions following severe capture stress. Haematocrit values and methaemoglobin were high in capture-stressed gamefish. The plasma chemistry of resting and capture-stressed snapper (Chrysophrys auratus) was studied for comparison. Specific differences in plasma biochemistry appeared to be the result of different strategies of fish behaviour during capture.

Insulin resistance and alanine amino transaminase (ALT) levels in first degree relatives of type 2 diabetes mellitus.

PubMed

Kuzhandai velu, V; Jyothirmayi, B; Kumar, J S

2011-01-01

Insulin resistance is established as an independent predictor of a range of disorders such as obesity, hypertension, dyslipidemia, type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. There is an association of hyperinsulinemia with hypertriglycerdemia, low level of HDL and high level of LDL. In nonalcoholic fatty liver disease, there is an elevation of ALT, raising the possibility that the prospective relationship between ALT and type 2 diabetes may reflect cross-sectional associations with insulin resistance or obesity. To find the significance of insulin resistance and alanine aminotransferase level in first degree relatives of type 2 diabetes mellitus. The study included 50 first degree relatives of type 2 diabetes (25 men and 25 women) aged 20-60 years and 30 control of similar age. All cases were taken from SRM Medical College Hospital and Research Centre, Chennai. All the cases were analyzed for HOMA(IR), QUICKI, IR ratio, fasting glucose, insulin (ELISA), lipid profile and alanine aminotransferase. Student's 't' test was applied for statistical analysis. The data show the significance of insulin resistance (HOMA(IR)) (2.76±1.46, 1.35±0.8, p<0.001) in the first degree relatives of type 2 diabetes mellitus when compared with controls respectively and increased level fasting plasma insulin (12.28±6.16, 6.12±3.04, p<0.001). In the lipid profile the total cholesterol and TAG are significant. No statistical significance was found in ALT (24.8±9.84, 20.08±11.02). Results of the study conclude that there is a high prevalence of insulin resistance in the first degree relatives of type 2 diabetes mellitus. ALT levels in the first degree relatives of type 2 diabetes mellitus had increased levels of insulin resistance, the pathogenesis suggesting increase in ALT levels as seen in insulin resistance condition. In our study, ALT was not statistically significant. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Re-evaluation of amino-oxyacetate as an inhibitor.

PubMed Central

Smith, S B; Briggs, S; Triebwasser, K C; Freedland, R A

1977-01-01

Data are provided which indicate that pyruvate and/or acetaldehyde can reverse the inhibition of alanine aminotransferase and aspartate aminotransferase by amino-oxyacetate. It was shown that acetaldehyde could reverse the inhibition of gluconeogenesis from alanine and that pyruvate could reverse the inhibition of urea synthesis by amino-oxyacetate. PMID:849292

21 CFR 172.540 - DL-Alanine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Agents and Related Substances § 172.540 DL-Alanine. DL-Alanine (a racemic mixture of D- and L-alanine; CAS Reg. No. 302-72-7) may be safely used as a flavor enhancer for sweeteners in pickling mixtures at a level not to exceed 1 percent of the pickling spice that is added to the pickling brine. [56 FR...

Effect of various alanine analogues on the L-alanine-adding enzyme from Escherichia coli.

PubMed

Liger, D; Blanot, D; van Heijenoort, J

1991-05-01

An extract from Escherichia coli containing the L-alanine-adding enzyme with a high specific activity was prepared. Several compounds structurally related to L-alanine were tested as inhibitors of this activity. Intact amino and carboxyl groups were necessary for an interaction with the enzyme. Certain halogenated (haloalanines) or unsaturated (L-vinylglycine, L-propargylglycine, 3-cyano-L-alanine) amino acids were good inhibitors. Radioactive glycine, serine and 1-aminoethylphosphonic acid were tested as substrates. Whereas glycine or L-serine gave rise to the formation of the corresponding nucleotide product, no synthesis of UDP-N-acetylmuramyl-L-1-aminoethylphosphonic acid could be detected.

Plasma chemistry in peregrine falcons (Falco peregrinus): Reference values and physiological variations of importance for interpretation.

PubMed

Lumeij, J T; Remple, J D; Remple, C J; Riddle, K E

1998-01-01

Reference values (inner limits of the percentiles P(2.5) and P(97.5) are given with a probability of 95%) for 21 plasma chemical variables were established in 79 peregrine falcons (Falco peregrinus). The following values were established: urea 0.8 to 3.9 mmol/l, creatinine 24 to 64 mumol/l, glucose 16.5 to 22.0 mmol/l, sodium 150 to 170 mmol/l, chloride 114 to 131 mmol/I, inorganic phosphorus 0.55 to 1.53 mmol/l, osmolal-ity 322 to 356 mOsmol/kg, alkaline phosphatase 31 to 121 IU/l, alanine aminotransferase 29 to 90 IU/l, aspartate aminotransferase 34 to 116 U/l, gamma glutamyl transferase 0 to 3 IU/l, lactate dehydrogenase 1008 to 2650 IU/l, creatine kinase 120 to 442 IU/l, cholinesterase 143 to 325 IU/1, glutamate dehydrogenase < 8 IU/l, total bile acids 5 to 69 mumol/l, uric acid 253 to 995 mumol/l, total protein 24 to 39 g/l, albumin 12.7 to 22.4 g/l. Reference values for the calculated albumin/globulin (A/G) ratio were 0.8 to 24. Based on previous studies, reference values for calcium were established using an adjustment formula using plasma total protein concentrations (before correction 1.86 to 2.49, after correction 1.97 to 2.46 mmol/l). Results of plasma potassium concentrations were erratic which was shown to be due to a time lag between sample collection and separation of plasma and cells.

Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis.

PubMed

Iida, Hiroya; Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Kon, Masanori

2018-01-27

To provide a simple surrogate marker predictive of liver cirrhosis (LC). Specimens from 302 patients who underwent resection for hepatocellular carcinoma between January 2006 and December 2012 were retrospectively analyzed. Based on pathologic findings, patients were divided into groups based on whether or not they had LC. Parameters associated with hepatic functional reserve were compared in these two groups using Mann-Whitney U -test for univariate analysis. Factors differing significantly in univariate analyses were entered into multivariate logistic regression analysis. There were significant differences between the LC group ( n = 100) and non-LC group ( n = 202) in prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, cholinesterase, type IV collagen, hyaluronic acid, indocyanine green retention rate at 15 min, maximal removal rate of technitium-99m diethylene triamine penta-acetic acid-galactosyl human serum albumin and ratio of mean platelet volume to platelet count (MPV/PLT). Multivariate analysis showed that prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin and hyaluronic acid, and MPV/PLT ratio were factors independently predictive of LC. The area under the curve value for MPV/PLT was 0.78, with a 0.8 cutoff value having a sensitivity of 65% and a specificity of 78%. The MPV/PLT ratio, which can be determined simply from the complete blood count, may be a simple surrogate marker predicting LC.

Hematology and serum biochemistry values of dusky-footed wood rat (Neotoma fuscipes).

PubMed

Weber, David K; Danielson, Kathleen; Wright, Stan; Foley, Janet E

2002-07-01

Serum chemistry values and complete blood counts were determined for 36 wild dusky-footed wood rats (Neotoma fuscipes) from Sonoma and western Yolo County, California (USA) in summer 1999 and spring 2001. All wood rats had adequate body condition and were hydrated. Many hematologic and biochemical values were comparable to those for house rat (Rattus rattus). There were differences between wood rats tested immediately after capture (those from Yolo County) and after a week of habituation in the laboratory (Sonoma County). Significant differences were noted in red blood cell counts, hemoglobin, hematocrit, neutrophil:lymphocyte ratio, glucose, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase values. The neutrophil:lymphocyte ratio may have been iatrogenically modified in the wood rats tested immediately after capture by stress-induced neutrophilia and lymphopenia. Eosinophilia may have been associated with parasites such as botflies in four individuals, and hyperglycemia in three individuals could have been associated with stress. The cause of elevated enzymes in the animals tested after laboratory habituation is unclear. The hematologic and biochemical values of these apparently healthy wood rats provide valuable baseline information for use in further medical studies performed with this species.

[Changes of serum aminotransferase in children with obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Zhenjiang; Duo, Likun

2013-08-01

Obstructive sleep apnea hypopnea syndrome (OSAHS) and non-alcoholic fatty liver disease (NAFLD) are both strongly associated with obesity. Whether OSAHS is an independent risk factor for liver injury or not is uncertain. To assess the hypothesis that OSAHS is associated with liver injury independent of obesity. One hundred and thirty children with OSAHS and 77 children with primary snoring(PS) were enrolled. Polysomnography was performed. Body mass index (BMI), liver function tests, serum lipids, fasting plasma glucose (FPG), and insulin (INS) were measured. Seventeen children of OSAHS had elevated serum aminotransferase levels,while only 2 children of non-OSAHS had elevated serum aminotransferase in healthy control group (chi2 = 5.18, P < 0.05; OR = 5.64 CI 1.27-24.97). Fifteen children of obese had elevated serum aminotransferase levels, while only 4 children had elevated serum aminotransferase in non-obese group (chi2 = 4.58, P < 0.05; (OR = 1.97 CI 1.06-3.67). Seventy cases of obese children, 15 cases of elevated aminotransferase levels (21.4%), namely fatty liver patients, of these children, 14 had OSAHS (93.3%). In contrast, OSAHS was present in only 67.3% of obese children without elevated aminotransferase. OSAHS may be a risk factor for liver injury independent of obesity; Increased liver enzyme levels are frequently found in obese snoring children, particularly among those with OSAHS.

β-Alanine supplementation and military performance.

PubMed

Hoffman, Jay R; Stout, Jeffrey R; Harris, Roger C; Moran, Daniel S

2015-12-01

During sustained high-intensity military training or simulated combat exercises, significant decreases in physical performance measures are often seen. The use of dietary supplements is becoming increasingly popular among military personnel, with more than half of the US soldiers deployed or garrisoned reported to using dietary supplements. β-Alanine is a popular supplement used primarily by strength and power athletes to enhance performance, as well as training aimed at improving muscle growth, strength and power. However, there is limited research examining the efficacy of β-alanine in soldiers conducting operationally relevant tasks. The gains brought about by β-alanine use by selected competitive athletes appears to be relevant also for certain physiological demands common to military personnel during part of their training program. Medical and health personnel within the military are expected to extrapolate and implement relevant knowledge and doctrine from research performed on other population groups. The evidence supporting the use of β-alanine in competitive and recreational athletic populations suggests that similar benefits would also be observed among tactical athletes. However, recent studies in military personnel have provided direct evidence supporting the use of β-alanine supplementation for enhancing combat-specific performance. This appears to be most relevant for high-intensity activities lasting 60-300 s. Further, limited evidence has recently been presented suggesting that β-alanine supplementation may enhance cognitive function and promote resiliency during highly stressful situations.

Plastidic aspartate aminotransferases and the biosynthesis of essential amino acids in plants.

PubMed

de la Torre, Fernando; Cañas, Rafael A; Pascual, M Belén; Avila, Concepción; Cánovas, Francisco M

2014-10-01

In the chloroplasts and in non-green plastids of plants, aspartate is the precursor for the biosynthesis of different amino acids and derived metabolites that play distinct and important roles in plant growth, reproduction, development or defence. Aspartate biosynthesis is mediated by the enzyme aspartate aminotransferase (EC 2.6.1.1), which catalyses the reversible transamination between glutamate and oxaloacetate to generate aspartate and 2-oxoglutarate. Plastids contain two aspartate aminotransferases: a eukaryotic-type and a prokaryotic-type bifunctional enzyme displaying aspartate and prephenate aminotransferase activities. A general overview of the biochemistry, regulation, functional significance, and phylogenetic origin of both enzymes is presented. The roles of these plastidic aminotransferases in the biosynthesis of essential amino acids are discussed. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Crystallization and preliminary crystallographic analysis of d-alanine-d-alanine ligase from Streptococcus mutans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Yong-Zhi; Sheng, Yu; Li, Lan-Fen

2007-09-01

A potential target for antibiotic drug design, d-alanine-d-alanine ligase from S. mutans, was expressed in E. coli, purified and crystallized. Diffraction data were collected to 2.4 Å resolution. d-Alanine-d-alanine ligase is encoded by the gene ddl (SMU-599) in Streptococcus mutans. This ligase plays a very important role in cell-wall biosynthesis and may be a potential target for drug design. To study the structure and function of this ligase, the gene ddl was amplified from S. mutans genomic DNA and cloned into the expression vector pET28a. The protein was expressed in soluble form in Escherichia coli strain BL21 (DE3). Homogeneous proteinmore » was obtained using a two-step procedure consisting of Ni{sup 2+}-chelating and size-exclusion chromatography. Purified protein was crystallized and the cube-shaped crystal diffracted to 2.4 Å. The crystal belongs to space group P3{sub 1}21 or P3{sub 2}21, with unit-cell parameters a = b = 79.50, c = 108.97 Å. There is one molecule per asymmetric unit.« less

Suspected fusariomycotoxicosis in sandhill cranes (Grus canadensis): clinical and pathological findings.

USGS Publications Warehouse

Roffe, Thomas J.; Stroud, Richard K.; Windingstad, Ronald M.

1989-01-01

In 1985 and 1986, large-scale natural die-offs of sandhill cranes in Texas were attributed to fusariomycotoxicosis. These birds demonstrated a progressive loss of motor control to the neck, wings, and legs. Based on necropsy and/or histopathology of 31 cranes, the most common lesions involved skeletal muscle and included hemorrhages, granulomatous myositis, thrombosis, and vascular degeneration. Serum chemistry results revealed that levels of creatinine kinase, aspartate aminotransferase, and alanine aminotransferase were above published normals. However, only alanine aminotransferase was higher in clinically affected cranes than in normal cranes collected from the same area.

Effects of dietary supplementation with vitamin C and vitamin E and their combination on growth performance, some biochemical parameters, and oxidative stress induced by copper toxicity in broilers.

PubMed

Cinar, Miyase; Yildirim, Ebru; Yigit, A Arzu; Yalcinkaya, Ilkay; Duru, Ozkan; Kisa, Uçler; Atmaca, Nurgul

2014-05-01

This study investigated effects of dietary supplementation with vitamin C, vitamin E on performance, biochemical parameters, and oxidative stress induced by copper toxicity in broilers. A total of 240, 1-day-old, broilers were assigned to eight groups with three replicates of 10 chicks each. The groups were fed on the following diets: control (basal diet), vitamin C (250 mg/kg diet), vitamin E (250 mg/kg diet), vitamin C + vitamin E (250 mg/kg + 250 mg/kg diet), and copper (300 mg/kg diet) alone or in combination with the corresponding vitamins. At the 6th week, the body weights of broilers were decreased in copper, copper + vitamin E, and copper + vitamin C + vitamin E groups compared to control. The feed conversion ratio was poor in copper group. Plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase activities, iron, copper concentrations, and erythrocyte malondialdehyde were increased; plasma vitamin A and C concentrations and erythrocyte superoxide dismutase were decreased in copper group compared to control. Glutathione peroxidase, vitamin C, and iron levels were increased; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and copper levels were decreased in copper + vitamin C group, while superoxide dismutase, glutathione peroxidase, and vitamin E concentrations were increased; aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were decreased in copper with vitamin E group compared to copper group. The vitamin C concentrations were increased; copper, uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and malondialdehyde were decreased in copper + vitamin C + vitamin E group compared to copper group. To conclude, copper caused oxidative stress in broilers. The combination of vitamin C and vitamin E addition might alleviate the harmful effects of copper as demonstrated by decreased lipid peroxidation and hepatic enzymes.

Alanine increases blood pressure during hypotension

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

1990-01-01

The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

A comparison of liver function after hepatectomy with inflow occlusion between sevoflurane and propofol anesthesia.

PubMed

Song, J C; Sun, Y M; Yang, L Q; Zhang, M Z; Lu, Z J; Yu, W F

2010-10-01

In this study, we compared liver function tests after hepatectomy with inflow occlusion as a function of propofol versus sevoflurane anesthesia. One hundred patients undergoing elective liver resection with inflow occlusion were randomized into a sevoflurane group or a propofol group. General anesthesia was induced with 3 μg/kg fentanyl, 0.2 mg/kg cisatracurium, and target-controlled infusion of propofol, set at a plasma target concentration of 4 to 6 μg/mL, or sevoflurane initially started at 8%. Anesthesia was maintained with target-controlled infusion of propofol (2-4 μg/mL) or sevoflurane (1.5%-2.5%). The primary end point was postoperative liver injury assessed by peak values of liver transaminases. Transaminase levels peaked between the first and the third postoperative day. Peak alanine aminotransferase was 504 and 571 U/L in the sevoflurane group and the propofol group, respectively. Peak aspartate aminotransferase was 435 U/L after sevoflurane and 581 U/L in the propofol group. There were no significant differences in peak alanine aminotransferase or peak aspartate aminotransferase between groups. Other liver function tests including bilirubin and alkaline phosphatase, and peak values of white blood cell counts and creatinine, were also not different between groups. Sevoflurane and propofol anesthetics resulted in similar patterns of liver function tests after hepatectomy with inflow occlusion. These data suggest that the 2 anesthetics are equivalent in this clinical context.

Comparative evaluation of different extracts of leaves of Psidium guajava Linn. for hepatoprotective activity.

PubMed

Roy, Chanchal K; Das, Amit Kumar

2010-01-01

The study was designed to evaluate the hepatoprotective activity of different extracts (petroleum ether, chloroform, ethyl acetate, methanol and aqueous) of P. guajava in acute experimental liver injury induced by carbon tetrachloride and paracetamol. The effects observed were compared with a known hepatoprotective agent, silymarin (100 mg/kg p.o.). In the acute liver damage induced by different hepatotoxins, P. guajava methanolic leaf extract (200 mg/kg, p.o.) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin in carbon tetrachloride and paracetamol induced hepatotoxicity. P. guajava ethyl acetate leaf extract (200 mg/kg, p.o.) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase and bilirubin in carbon tetrachloride induced hepatotoxicity whereas P. guajava aqueous leaf extract (200 mg/kg, p.o.) significantly reduced the elevated serum levels of alkaline phosphatase, alanine aminotransferase and bilirubin in carbon tetrachloride induced hepatotoxicity. P. guajava ethyl acetate and aqueous leaf extracts (200 mg/kg, p.o.) significantly reduced the elevated serum levels of aspartate aminotransferase in paracetamol induced hepatotoxicity. Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the methanolic extract of leaves of Psidium guajava plant possesses better hepatoprotective activity compared to other extracts.

The baseline serum value of α-amylase is a significant predictor of distance running performance.

PubMed

Lippi, Giuseppe; Salvagno, Gian Luca; Danese, Elisa; Tarperi, Cantor; La Torre, Antonio; Guidi, Gian Cesare; Schena, Federico

2015-02-01

This study was planned to investigate whether serum α-amylase concentration may be associated with running performance, physiological characteristics and other clinical chemistry analytes in a large sample of recreational athletes undergoing distance running. Forty-three amateur runners successfully concluded a 21.1 km half-marathon at 75%-85% of their maximal oxygen uptake (VO2max). Blood was drawn during warm up and 15 min after conclusion of the run. After correction for body weight change, significant post-run increases were observed for serum values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, creatine kinase (CK), iron, lactate dehydrogenase (LDH), triglycerides, urea and uric acid, whereas the values of body weight, glomerular filtration rate, total and low density lipoprotein-cholesterol were significantly decreased. The concentration of serum α-amylase was unchanged. In univariate analysis, significant associations with running performance were found for gender, VO2max, training regimen and pre-run serum values of α-amylase, CK, glucose, high density lipoprotein-cholesterol, LDH, urea and uric acid. In multivariate analysis, only VO2max (p=0.042) and baseline α-amylase (p=0.021) remained significant predictors of running performance. The combination of these two variables predicted 71% of variance in running performance. The baseline concentration of serum α-amylase was positively correlated with variation of serum glucose during the trial (r=0.345; p=0.025) and negatively with capillary blood lactate at the end of the run (r=-0.352; p=0.021). We showed that the baseline serum α-amylase concentration significantly and independently predicts distance running performance in recreational runners.

Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faraci, W.S.; Walsh, C.T.

1988-05-03

Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substratemore » PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Q Han; T Cai; D Tagle

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 KATsmore » 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.« less

Staphylococcus aureus MurC participates in L-alanine recognition via histidine 343, a conserved motif in the shallow hydrophobic pocket.

PubMed

Kurokawa, Kenji; Nishida, Satoshi; Ishibashi, Mihoko; Mizumura, Hikaru; Ueno, Kohji; Yutsudo, Takashi; Maki, Hideki; Murakami, Kazuhisa; Sekimizu, Kazuhisa

2008-03-01

UDP-N-acetylmuramic acid:L-alanine ligase that is encoded by the murC gene, is indispensable for bacterial peptidoglycan biosynthesis and an important target for the development of antibacterial agents. Structure of MurC ligase with substrates has been described, however, little validation via studying the effects of mutations on the structure of MurC has been performed. In this study, we carried out a functional in vitro and in vivo characterization of Staphylococcus aureus MurCH343Y protein that has a temperature-sensitive mutation of a conserved residue in the predicted shallow hydrophobic pocket that holds a short L-alanine side chain. Purified H343Y and wild-type MurC had K(m) values for L-alanine of 3.2 and 0.44 mM, respectively, whereas there was no significant difference in their K(m) values for ATP and UDP-N-acetylmuramic acid, suggesting the specific alteration of L-alanine recognition in MurCH343Y protein. In a synthetic medium that excluded L-alanine, S. aureus murCH343Y mutant cells showed an allele-specific slow growth phenotype that was suppressed by addition of L-alanine. These results suggest that His343 of S. aureus MurC is essential for high-affinity binding to L-alanine both in vitro and in vivo and provide experimental evidence supporting the structural information of MurC ligase.

Kinetic and crystallographic studies of Escherichia coli UDP-N-acetylmuramate:L-alanine ligase.

PubMed Central

Emanuele, J. J.; Jin, H.; Jacobson, B. L.; Chang, C. Y.; Einspahr, H. M.; Villafranca, J. J.

1996-01-01

Uridine diphosphate-N-acetylmuramate:L-alanine ligase (EC 6.3.2.8, UNAM:L-Ala ligase or MurC gene product) catalyzes the ATP-dependent ligation of the first amino acid to the sugar moiety of the peptidoglycan precursor. This is an essential step in cell wall biosynthesis for both gram-positive and gram-negative bacteria. Optimal assay conditions for initial velocity studies have been established. Steady-state assays were carried out to determine the effect of various parameters on enzyme activity. Factors studies included: cation specificity, ionic strength, buffer composition and pH. At 37 degrees C and pH 8.0, kcat was equal to 980 +/- 40 min-1, while K(m) values for ATP, UNAM, and L-alanine were, 130 +/- 10, 44 +/- 3, and 48 +/- 6 microM, respectively. Of the metals tested only Mn, Mg, and Co were able to support activity. Sodium chloride, potassium chloride, ammonium chloride, and ammonium sulfate had no effect on activity up to 75 mM levels. The enzyme, in appropriate buffer, was stable enough to be assayed over the pH range of 5.6 to 10.1. pH profiles of Vmax/K(m) for the three substrates and of Vmax were obtained. Crystallization experiments with the enzyme produced two crystal forms. One of these has been characterized by X-ray diffraction as monoclinic, space group C2, with cell dimensions a = 189.6, b = 92.1, c = 75.2 A, beta = 105 degrees, and two 54 kDa molecules per asymmetric unit. It was discovered that the enzyme will hydrolyze ATP in the absence of L-alanine. This L-alanine independent activity is dependent upon the concentrations of both ATP and UNAM; kcat for this activity is less than 4% of the biosynthetic activity measured in the presence of saturating levels of L-alanine. Numerous L-alanine analogs tested were shown to stimulate ATP hydrolysis. A number of these L-alanine analogs produced novel products as accessed by HPLC and mass spectral analysis. All of the L-alanine analogs tested as inhibitors were competitive versus L-alanine. PMID

Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study.

PubMed

Nannipieri, Monica; Gonzales, Clicerio; Baldi, Simona; Posadas, Rosalinda; Williams, Ken; Haffner, Steven M; Stern, Michael P; Ferrannini, Ele

2005-07-01

To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes. From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT). At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations. Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.

Fluorenone based fluorescent probe for selective "turn-on" detection of pyrophosphate and alanine

NASA Astrophysics Data System (ADS)

Daniel Thangadurai, T.; Nithya, I.; Manjubaashini, N.; Bhuvanesh, N.; Bharathi, G.; Nandhakumar, R.; Nataraj, D.

2018-06-01

To sense biologically important entities with different size and dimensions, a fluorenone based fluorescent receptor was designed and synthesized. Probe 1 displayed a distinct fluorescence enhancement emission at 565 nm for pyrophosphate and 530 nm for alanine in polar solvent. The fluorescence titration experiments confirm 1:1 stoichiometric ratio with high-binding constant and very low limit of detection (LoD) values. Receptor 1 showed a highly selective and sensitive recognition to HP2O73 - and to alanine over other competitive anions and amino acids. In addition, the fluorescence lifetime measurement and reversible binding study results support the practical importance of 1.

Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia.

PubMed

Danpure, C J; Fryer, P; Jennings, P R; Allsop, J; Griffiths, S; Cunningham, A

1994-08-01

As part of a wider study on the molecular evolution of alanine:glyoxylate aminotransferase 1 (AGT1) intracellular compartmentalization, we have determined the subcellular distribution of immunoreactive AGT1, using postembedding protein A-gold immunoelectron microscopy, in the livers of various members of the classes Mammalia, Aves, and Amphibia. As far as organellar distribution is concerned, three categories could be distinguished. In members of the first category (type I), all, or nearly all, of the immunoreactive AGT1 was concentrated within the peroxisomes. In the second category (type II), AGT1 was found more evenly distributed in both peroxisomes and mitochondria. In the third category (type III), AGT1 was localized mainly within the mitochondria with much lower, but widely variable, amounts in the peroxisomes. Type I animals include the human, two great apes (gorilla, orangutan), two Old World monkeys (anubis baboon, Japanese macaque), a New World monkey (white-faced Saki monkey), a lago, morph (European rabbit), a bat (Seba's short-tailed fruit bat), two caviomorph rodents (guinea pig, orange-rumped agouti), and two Australian marsupials (koala, Bennett's wallaby). Type II animals include two New World monkeys (common marmoset, cotton-top tamarin), three prosimians (brown lemur, fat-tailed dwarf lemur, pygmy slow loris), five rodents (a hybrid crested porcupine, Colombian ground squirrel, laboratory rat, laboratory mouse, golden hamster), an American marsupial (grey short-tailed opossum), and a bird (raven). Type III animals include the large tree shrew, three insectivores (common Eurasian mole, European hedgehog, house shrew), four carnivores (domestic cat, ocelot, domestic dog, polecat ferret), and an amphibian (common frog). In addition to these categories, some animals (e.g. guinea pig, common frog) possessed significant amounts of cytosolic AGT1. Whereas the subcellular distribution of AGT1 in some orders (e.g. Insectivora and Carnivora) did not appear

Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus.

PubMed

Frank, Marlies; Finsterer, Josef

2012-01-01

To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation.

Identification and elucidation of in vivo function of two alanine racemases from Pseudomonas putida KT2440.

PubMed

Duque, Estrella; Daddaoua, Abdelali; Cordero, Baldo F; De la Torre, Jesús; Antonia Molina-Henares, Maria; Ramos, Juan-Luis

2017-10-01

The genome of Pseudomonas putida KT2440 contains two open reading frames (ORFs), PP_3722 and PP_5269, that encode proteins with a Pyridoxal phosphate binding motif and a high similarity to alanine racemases. Alanine racemases play a key role in the biosynthesis of D-alanine, a crucial amino acid in the peptidoglycan layer. For these ORFs, we generated single and double mutants and found that inactivation of PP_5269 resulted in D-alanine auxotrophy, while inactivation of PP_3722 did not. Furthermore, as expected, the PP_3722/PP_5269 double mutant was a strict auxotroph for D-alanine. These results indicate that PP_5269 is an alr allele and that it is the essential alanine racemase in P. putida. We observed that the PP_5269 mutant grew very slowly, while the double PP_5269/PP_3722 mutant did not grow at all. This suggests that PP_3722 may replace PP_5269 in vivo. In fact, when the ORF encoding PP_3772 was cloned into a wide host range expression vector, ORF PP_3722 successfully complemented P. putida PP_5269 mutants. We purified both proteins to homogeneity and while they exhibit similar K M values, the V max of PP_5269 is fourfold higher than that of PP_3722. Here, we propose that PP_5269 and PP_3722 encode functional alanine racemases and that these genes be named alr-1 and alr-2 respectively. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Performance effects of acute β-alanine induced paresthesia in competitive cyclists.

PubMed

Bellinger, Phillip M; Minahan, Clare L

2016-01-01

β-alanine is a common ingredient in supplements consumed by athletes. Indeed, athletes may believe that the β-alanine induced paresthesia, experienced shortly after ingestion, is associated with its ergogenic effect despite no scientific mechanism supporting this notion. The present study examined changes in cycling performance under conditions of β-alanine induced paresthesia. Eight competitive cyclists (VO2max = 61.8 ± 4.2 mL·kg·min(-1)) performed three practices, one baseline and four experimental trials. The experimental trials comprised a 1-km cycling time trial under four conditions with varying information (i.e., athlete informed β-alanine or placebo) and supplement content (athlete received β-alanine or placebo) delivered to the cyclist: informed β-alanine/received β-alanine, informed placebo/received β-alanine, informed β-alanine/received placebo and informed placebo/received placebo. Questionnaires were undertaken exploring the cyclists' experience of the effects of the experimental conditions. A possibly likely increase in mean power was associated with conditions in which β-alanine was administered (±95% CL: 2.2% ± 4.0%), but these results were inconclusive for performance enhancement (p = 0.32, effect size = 0.18, smallest worthwhile change = 56% beneficial). A possibly harmful effect was observed when cyclists were correctly informed that they had ingested a placebo (-1.0% ± 1.9%). Questionnaire data suggested that β-alanine ingestion resulted in evident sensory side effects and six cyclists reported placebo effects. Acute ingestion of β-alanine is not associated with improved 1-km TT performance in competitive cyclists. These findings are in contrast to the athlete's "belief" as cyclists reported improved energy and the ability to sustain a higher power output under conditions of β-alanine induced paresthesia.

Elevated tumour necrosis factor-alpha was associated with intima thickening in obese children.

PubMed

Bo, Luo; Yi-Can, Yang; Qing, Zhou; Xiao-Hui, Wu; Ke, Huang; Chao-Chun, Zou

2017-04-01

This study investigated the relationship between intima-media thickness (IMT) and immune parameters in obese children from five to 16 years of age. We enrolled 185 obese children with a mean age of 10.65 ± 2.10 years and 211 controls with a mean age of 10.32 ± 1.81 years. Glycometabolism, lipid metabolism, sex hormones, immune indices and carotid IMT were measured. Serum interleukin (IL)-6, IL-10, tumour necrosis factor (TNF)-alpha, white blood cells and common and internal carotid artery IMTs in the obese group were higher than those in the control group (p < 0.05, respectively). Bivariate correlation analysis showed that the common carotid arterial IMT was positively correlated with alanine aminotransferase, triglyceride, uric acid, apolipoprotein B, IL-6, IL-10, TNF-alpha, follicle-stimulating hormone and testosterone. Internal carotid artery IMT was positively correlated with alanine aminotransferase and follicle-stimulating hormone. Both common and internal carotid artery IMTs were inversely correlated with apolipoprotein A1 (p < 0.05, respectively). Stepwise multiple regression analysis showed that testosterone, alanine aminotransferase and TNF-alpha were the independent determinants of common carotid arterial IMT. Tumour necrosis factor-alpha, alanine aminotransferase and testosterone were associated with intima thickening in the early life in obese children and may increase later risks of premature atherogenicity and adult cardio-cerebrovascular diseases. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Serum aminotransferase changes with significant weight loss: sex and age effects.

PubMed

Suzuki, Ayako; Binks, Martin; Sha, Ronald; Wachholtz, Amy; Eisenson, Howard; Diehl, Anna Mae

2010-02-01

In obese subjects, the liver may be differentially affected by significant weight loss depending on as yet unknown factors. We explored clinical factors associated with serum alanine aminotransferase (ALT) changes during significant weight loss in a residential weight loss program. Clinical data from 362 adults who received a comprehensive weight loss intervention (ie, diets, physical fitness, and behavioral modification) in the program were analyzed. Serum ALT was used as a surrogate marker of liver injury. The ALT changes during the program were calculated to create study outcome categories (improvement, no change, or deterioration of ALT during significant weight loss). Variables of demography, lifestyle, and comorbidities at baseline, and total/rate of weight change during the program were explored for associations with the ALT change categories using multiple logistic regression models. Variation by sex was apparent among predictors of ALT deterioration; men with rapid weight loss and women with higher initial body mass index were more likely to experience ALT deterioration, whereas men with prior alcohol consumption were less likely to experience ALT deterioration even after adjusting for baseline ALT (Ps < .03). Variation by age was apparent among predictors of ALT improvement; younger patients with current smoking and older patients with rapid weight loss, diabetes or impaired fasting glucose, or sleep apnea or who followed a reduced-carbohydrate diet were less likely to experience ALT improvement (Ps < .05). A number of clinical factors influence ALT changes during weight loss in sex- and age-specific manners. The patterns that we detected may have pathophysiologic significance beyond the practical implications of our findings in clinical practice related to underlying changes in fat metabolism. Copyright 2010 Elsevier Inc. All rights reserved.

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

PubMed

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.

Toxicovigilance: new biochemical tool used in sulfonylurea herbicides toxicology studies.

PubMed

Belhadj-Tahar, Hafid; Adamczewski, Nicolas; Nassar, Bertrand; Coulais, Yvon

2003-06-01

In vitro toxic effects of sulfonylurea herbicides (thifensulfuron-methyl and metsulfuron-methyl) were evaluated according to a new protocol. Physiological conditions were reproduced in order to boost toxicovigilance. Sulfonylureas and their hydrolysis products were added to biological substrates such as urea, alanine, aspartic acid, alpha-ketoglutarate, oxaloacetate, pyruvate and then incubated with some specific enzymes. Addition of these sulfonylureas and their degradation products did not significantly change the enzymatic activity of the urease, aspartate-aminotransferase, glutamate dehydrogenase, malate dehydrogenase and lactate dehydrogenase. However, the acid hydrolysis products inhibited up to 95% of the activity of the alanine-aminotransferase at low concentrations (0.27 micromol L(-1)). Inhibition did not affect the mitochondrial aspartate-aminotransferase.

Defining the optimal cut-off values for liver enzymes in diagnosing blunt liver injury.

PubMed

Koyama, Tomohide; Hamada, Hirohisa; Nishida, Masamichi; Naess, Paal A; Gaarder, Christine; Sakamoto, Tetsuya

2016-01-25

Patients with blunt trauma to the liver have elevated levels of liver enzymes within a short time post injury, potentially useful in screening patients for computed tomography (CT). This study was performed to define the optimal cut-off values for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with blunt liver injury diagnosed with contrast enhanced multi detector-row CT (CE-MDCT). All patients admitted from May 2006 to July 2013 to Teikyo University Hospital Trauma and Critical Care Center, and who underwent abdominal CE-MDCT within 3 h after blunt trauma, were retrospectively enrolled. Using receiver operating characteristic (ROC) curve analysis, the optimal cut-off values for AST and ALT were defined, and sensitivity and specificity were calculated. Of a total of 676 blunt trauma patients 64 patients were diagnosed with liver injury (Group LI+) and 612 patients without liver injury (Group LI-). Group LI+ and LI- were comparable for age, Revised Trauma Score, and Probability of survival. The groups differed in Injury Severity Score [median 21 (interquartile range 9-33) vs. 17 (9-26) (p < 0.01)]. Group LI+ had higher AST than LI- [276 (48-503) vs. 44 (16-73); p < 0.001] and higher ALT [240 (92-388) vs. 32 (16-49); p < 0.001]. Using ROC curve analysis, the optimal cut-off values for AST and ALT were set at 109 U/l and 97 U/l, respectively. Based on these values, AST ≥ 109 U/l had a sensitivity of 81%, a specificity of 82%, a positive predictive value of 32%, and a negative predictive value of 98%. The corresponding values for ALT ≥ 97 U/l were 78, 88, 41 and 98%, respectively, and for the combination of AST ≥ 109 U/l and/or ALT ≥ 97 U/l were 84, 81, 32, 98%, respectively. We have identified AST ≥ 109 U/l and ALT ≥ 97 U/l as optimal cut-off values in predicting the presence of liver injury, potentially useful as a screening tool for CT scan in patients otherwise eligible for observation only or as a transfer

EPR/alanine dosimetry for two therapeutic proton beams

NASA Astrophysics Data System (ADS)

Marrale, Maurizio; Carlino, Antonio; Gallo, Salvatore; Longo, Anna; Panzeca, Salvatore; Bolsi, Alessandra; Hrbacek, Jan; Lomax, Tony

2016-02-01

In this work the analysis of the electron paramagnetic resonance (EPR) response of alanine pellets exposed to two different clinical proton beams employed for radiotherapy is performed. One beam is characterized by a passive delivery technique and is dedicated to the eyes treatment (OPTIS2 beam line). Alanine pellets were irradiated with a 70 MeV proton beam corresponding to 35 mm range in eye tissue. We investigated how collimators with different sizes and shape used to conform the dose to the planned target volume influence the delivered dose. For this purpose we performed measurements with varying the collimator size (Output Factor) and the results were compared with those obtained with other dosimetric techniques (such as Markus chamber and diode detector). This analysis showed that the dosimeter response is independent of collimator diameter if this is larger than or equal to 10 mm. The other beam is characterized by an active spot-scanning technique, the Gantry1 beam line (maximum energy 230 MeV), and is used to treat deep-seated tumors. The dose linearity of alanine response in the clinical dose range was tested and the alanine dose response at selected locations in depth was measured and compared with the TPS planned dose in a quasi-clinical scenario. The alanine response was found to be linear in the dose in the clinical explored range (from 10 to 70 Gy). Furthermore, a depth dose profile in a quasi-clinical scenario was measured and compared to the dose computed by the Treatment Planning System PSIPLAN. The comparison of calibrated proton alanine measurements and TPS dose shows a difference under 1% in the SOBP and a "quenching" effect up to 4% in the distal part of SOBP. The positive dosimetric characteristics of the alanine pellets confirm the feasibility to use these detectors for "in vivo" dosimetry in clinical proton beams.

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury

PubMed Central

2014-01-01

Introduction Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. Methods Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. Results Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 μmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 μmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 μmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 μmol/ l; p < 0.05, ANOVA, post hoc Dunn’s test). Plasma glutamate remained unchanged and cerebral glutamate was decreased without any signs of cerebral impairment. Urea and ammonia were significantly increased within normal limits without signs of organ dysfunction (urea: from 2.7 ± 1.6 to 5.5 ± 1.5 mmol/ l; ammonia: from 12 ± 6.3 to 26 ± 8.3 μmol/ l; p < 0.05, ANOVA, post hoc Dunn’s test). Conclusions High dose L-alanine-L-glutamine infusion (0

Impact of charged amino acid substitution in the transmembrane domain of L-alanine exporter, AlaE, of Escherichia coli on the L-alanine export.

PubMed

Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

2017-01-01

The Escherichia coli alaE gene encodes the L-alanine exporter, AlaE, that catalyzes active export of L-alanine using proton electrochemical potential. The transporter comprises only 149 amino acid residues and four predicted transmembrane domains (TMs), which contain three charged amino acid residues. The AlaE-deficient L-alanine non-metabolizing cells (ΔalaE cells) appeared hypersusceptible to L-alanyl-L-alanine showing a minimum inhibitory concentration (MIC) of 2.5 µg/ml for the dipeptide due to a toxic accumulation of L-alanine. To elucidate the mechanism by which AlaE exports L-alanine, we replaced charged amino acid residues in the TMs, glutamic acid-30 (TM-I), arginine-45 (TM-II), and aspartic acid-84 (TM-III) with their respective charge-conserved amino acid or a net neutral cysteine. The ΔalaE cells producing R45K or R45C appeared hypersusceptible to the dipeptide, indicating that arginine-45 is essential for AlaE activity. MIC of the dipeptide in the ΔalaE cells expressing E30D and E30C was 156 µg/ml and >10,000 µg/ml, respectively, thereby suggesting that a negative charge at this position is not essential. The ΔalaE cells expressing D84E or D84C showed an MIC >10,000 and 78 µg/ml, respectively, implying that a negative charge is required at this position. These results were generally consistent with that of the L-alanine accumulation experiments in intact cells. We therefore concluded that charged amino acid residues (R45 and D84) in the AlaE transmembrane domain play a pivotal role in L-alanine export. Replacement of three cysteine residues at C22, C28 (both in TM-I), and C135 (C-terminal region) with alanine showed only a marginal effect on L-alanine export.

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

PubMed

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.

The predictive value of noninvasive serum markers of liver fibrosis in patients with chronic hepatitis C.

PubMed

Gökcan, Hale; Kuzu, Ufuk Barış; Öztaş, Erkin; Saygılı, Fatih; Öztuna, Derya; Suna, Nuretdin; Tenlik, İlyas; Akdoğan, Meral; Kaçar, Sabite; Kılıç, Zeki Mesut Yalın; Kayaçetin, Ertuğrul

2016-03-01

This study aims to show the predictive value of noninvasive serum markers on the hepatic fibrosis level. This cross sectional study involves 120 patients with chronic hepatitis C. The noninvasive markers used were as follows: age-platelet index (AP index), cirrhosis discriminant score (CDS), aspartate aminotransferase (AST)-alanine aminotransferase (ALT) ratio (AAR), fibrosis-4 (FIB-4) index, AST-platelet ratio index (APRI), Goteborg University Cirrhosis Index (GUCI), FibroQ, King's score, platelet count. Concurrent liver biopsies were evaluated using the modified Ishak and Knodell scoring systems. In accordance with the Knodell scores, F3-F4 scores were defined as "severe fibrosis," and the modified Ishak scores stage of ≥3 (F3-F6) were defined as "clinically significant fibrosis." Receiver Operating Characteristic (ROC) curve analyses were carried out to compare the noninvasive markers with hepatic fibrosis level. Mean age of the patients was 51.7±11.6. A total of 10 patients (8.3%) with Knodell scores and 24 patients (20%) with modified Ishak scores were evaluated to have ≥F3 hepatic fibrosis. ROC analyses with the Knodell and modified Ishak scores were as follows: AP index=0.61-0.57, CDS=0.66-0.55, AAR=0.60-0.49, FIB-4=0.70-0.68, APRI=0.67-0.72, GUCI=0.66-0.72, FibroQ=0.64-0.54, King's score=0.68-0.54, platelet count=0.61-0.55. We found that APRI, FIB-4, King's score, and GUCI can be used to determination patients with mild fibrosis with a high negative predictive value and in the differentiation of severe/significant fibrosis from mild to moderate fibrosis.

Effects of cadmium on some haematological and biochemical characteristics of Oreochromis niloticus (Linnaeus, 1758) dietary supplemented with tomato paste and vitamin E.

PubMed

Mekkawy, Imam A A; Mahmoud, Usama M; Wassif, Ekbal T; Naguib, Mervat

2011-03-01

The present study investigates the potential protective effects of tomato paste (9 mg/kg-lycopene) in comparison with vitamin E (50 mg/kg) against the impacts of cadmium (Cd) toxicity (4.64 mg/l: ¼ of 96 h LC50) on fishes Cd exposed for 15 and 30 days. Cd impacts were evaluated in terms of biological, haematological and biochemical characteristics. Cd significantly induced free radicals in serum and liver. The activities of aspartate aminotransferase and alanine aminotransferase in serum were significantly increased due to Cd. Treatment with Cd caused a significant increase in Lipid peroxidation and DNA fragmentation in liver tissue and serum glucose and total lipid. On the other hand, Cd significantly led to decline in serum total protein, blood haemoglobin, red blood cell count, haematocrit value, mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. Dietary supplementation with vitamin E and/or tomato paste to Cd-exposed fish declined significantly the increased lipid peroxidation and DNA fragmentation in liver tissue and the increased aspartate aminotransferase, alanine aminotransferase, glucose and total lipid in serum to the normal condition. This supplementation also significantly increased the declined serum total protein, blood haemoglobin, red blood cell count, haematocrit value, mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration to the normal state. Cd impacts and tomato paste/or vitamin E supplementations did not reflected on the condition factor of the fish. These findings demonstrated the beneficial diet supplementation of tomato paste phytonutrients and vitamin E in counteracting the harmful effects of Cd on the characters investigated.

Relationship between analytic values and canine obesity.

PubMed

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 < 0.05) in obese dogs with respect to normal weight dogs. In conclusion, obesity in dogs is associated with higher serum lipid levels.

Structure of the Mycobacterium tuberculosis D-Alanine:D-Alanine Ligase, a Target of the Antituberculosis Drug D-Cycloserine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruning, John B.; Murillo, Ana C.; Chacon, Ofelia

D-Alanine:D-alanine ligase (EC 6.3.2.4; Ddl) catalyzes the ATP-driven ligation of two D-alanine (D-Ala) molecules to form the D-alanyl:D-alanine dipeptide. This molecule is a key building block in peptidoglycan biosynthesis, making Ddl an attractive target for drug development. D-Cycloserine (DCS), an analog of D-Ala and a prototype Ddl inhibitor, has shown promise for the treatment of tuberculosis. Here, we report the crystal structure of Mycobacterium tuberculosis Ddl at a resolution of 2.1 {angstrom}. This structure indicates that Ddl is a dimer and consists of three discrete domains; the ligand binding cavity is at the intersection of all three domains and conjoinedmore » by several loop regions. The M. tuberculosis apo Ddl structure shows a novel conformation that has not yet been observed in Ddl enzymes from other species. The nucleotide and D-alanine binding pockets are flexible, requiring significant structural rearrangement of the bordering regions for entry and binding of both ATP and D-Ala molecules. Solution affinity and kinetic studies showed that DCS interacts with Ddl in a manner similar to that observed for D-Ala. Each ligand binds to two binding sites that have significant differences in affinity, with the first binding site exhibiting high affinity. DCS inhibits the enzyme, with a 50% inhibitory concentration (IC{sub 50}) of 0.37 mM under standard assay conditions, implicating a preferential and weak inhibition at the second, lower-affinity binding site. Moreover, DCS binding is tighter at higher ATP concentrations. The crystal structure illustrates potential drugable sites that may result in the development of more-effective Ddl inhibitors.« less

Study of the overproduced uridine-diphosphate-N-acetylmuramate:L-alanine ligase from Escherichia coli.

PubMed

Liger, D; Masson, A; Blanot, D; van Heijenoort, J; Parquet, C

1996-01-01

The UDP-N-acetylmuramate:L-alanine ligase of Escherichia coli is responsible for the addition of the first amino acid of the peptide moiety in the assembly of the monomer unit of peptidoglycan. It catalyzes the formation of the amide bond between UDP-N-acetylmuramic acid (UDP-MurNAc) and L-alanine. The UDP-MurNAc-L-alanine ligase was overproduced 2000-fold in a strain harboring a recombinant plasmid (pAM1005) with the murC gene under the control of the inducible promoter trc. The murC gene product appears as a 50-kDa protein accounting for ca. 50% of total cell proteins. A two-step purification led to 1 g of a homogeneous protein from an 8-liter culture. The N-terminal sequence of the purified protein correlated with the nucleotide sequence of the gene. The stability of the enzymatic activity is strictly dependent on the presence of 2-mercaptoethanol. The K(m) values for substrates UDP-N-acetylmuramic acid, L-alanine, and ATP were estimated; 100, 20, and 450 microM, respectively. The specificity of the enzyme for its substrates was investigated with various analogues. Preliminary experiments attempting to elucidate the enzymatic mechanism were consistent with the formation of an acylphosphate intermediate.

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis.

PubMed

Liberato, Isabella Ramos de Oliveira; Lopes, Edmundo Pessoa de Almeida; Cavalcante, Maria Alina Gomes de Mattos; Pinto, Tiago Costa; Moura, Izolda Fernades; Loureiro Júnior, Luiz

2012-01-01

The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before

Meta-analysis of the relationship of mycotoxins with biochemical and hematological parameters in broilers.

PubMed

Andretta, I; Kipper, M; Lehnen, C R; Lovatto, P A

2012-02-01

A meta-analysis was carried out to study the association of mycotoxins with hematological and biochemical profiles in broilers. Ninety-eight articles published between 1980 and 2009 were used in the database, totaling 37,371 broilers. The information was selected from the Materials and Methods and Results sections in the selected articles and then tabulated in a database. Meta-analysis followed 3 sequential analyses: graphic, correlation, and variance-covariance. Mycotoxins reduced (P < 0.05) the hematocrit (-5%), hemoglobin (-15%), leukocytes (-25%), heterophils (-2%), lymphocytes (-2%), uric acid (-31%), creatine kinase (-27%), creatinine (-23%), triglycerides (-39%), albumin (-17%), globulin (-1%), total cholesterol (-14%), calcium (-5%), and inorganic phosphorus (-12%). Mycotoxins also altered (P < 0.05) the concentrations of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. A quadratic effect was observed on the relationship between the concentration of aflatoxin in diets and the serum concentration of alkaline phosphatase, γ-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase. The total protein concentration in blood was 18% lower (P < 0.05) in broilers challenged by aflatoxins compared with that of the unchallenged ones. The inclusion of antimycotoxin additives in diets with aflatoxins altered (P < 0.05) some variables (uric acid, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase) in relation to the group that received diets with the mycotoxin and without the additive. The meta-analysis performed in this study allowed us to address and quantify systematically the relationship of mycotoxins with alterations in hematologic and biochemical profiles in broilers.

Effect of oral contraceptive use on the erythrocytic glutathione reductase and aspartate aminotransferase activities in women with or without clinical signs of vitamin deficiency.

PubMed

Tovar, A; Bourges, H; Canto, T; Torres, N; Lopez-castro, B R

1985-07-01

The effect of the chronic use of combined oral contraceptives (OCs) on the "activity coefficients" (alpha = coenzyme-stimulated activity/basal activity) of erythrocytic glutathione reductase and aspartate aminotransferase was studied in 2 groups of 90 female volunteers each; 1 of the groups, from the state of Yucatan in southeast Mexico, presented clinical lesions of vitamin deficiency, while the other group, from Mexico City, did not have any clinical evidence of vitamin deficiency. One half of the women (45) in each group were chronic OC users and the other half were not. The results were analyzed comparing OC users with non-users in each location. For both glutathione reductase and aspartate aminotransferase, the Mexico City OC users had significantly higher (p 0.001) alpha values than nonusers, while in the Yucatan women, the alpha values were similarly high independent of OC use.

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

PubMed

Escalera-Fanjul, Ximena; Campero-Basaldua, Carlos; Colón, Maritrini; González, James; Márquez, Dariel; González, Alicia

2017-01-01

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, Sc Alt2 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 Lk Alt1 and Kl Alt1 independent alanine transaminase activity and additional unidentified alanine biosynthetic and catabolic pathway(s). Furthermore, phenotypic analysis of null mutants uncovered the fact that Kl Alt1 and Lk Alt1 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 Sc Alt2 conserves 64% identity with

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

PubMed Central

Escalera-Fanjul, Ximena; Campero-Basaldua, Carlos; Colón, Maritrini; González, James; Márquez, Dariel; González, Alicia

2017-01-01

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% identity with LkAlt1

Compound-specific nitrogen isotope analysis of D-alanine, L-alanine, and valine: application of diastereomer separation to delta15N and microbial peptidoglycan studies.

PubMed

Takano, Yoshinori; Chikaraishi, Yoshito; Ogawa, Nanako O; Kitazato, Hiroshi; Ohkouchi, Naohiko

2009-01-01

We have developed an analytical method to determine the compound-specific nitrogen isotope compositions of individual amino acid enantiomers using gas chromatography/combustion/isotope ratio mass spectrometry. A novel derivatization of amino acid diastereomers by optically active (R)-(-)-2-butanol or (S)-(+)-2-butanol offers two advantages for nitrogen isotope analysis. First, chromatographic chiral separation can be achieved without the use of chiral stationary-phase columns. Second, the elution order of these compounds on the chromatogram can be switched by a designated esterification reaction. We applied the method to the compound-specific nitrogen isotope analysis of D- and L-alanine in a peptidoglycan derived from the cell walls of cultured bacteria (Firmicutes and Actinobacteria; Enterococcus faecalis, Staphylococcus aureus, Staphylococcus staphylolyticus, Lactobacillus acidophilus, Bacillus subtilis, Micrococcus luteus, and Streptomyces sp.), natural whole bacterial cells (Bacillus subtilis var. natto), (pseudo)-peptidoglycan from archaea (Methanobacterium sp.), and cell wall from eukaryota (Saccharomyces cerevisiae). We observed statistically significant differences in nitrogen isotopic compositions; e.g., delta15N ( per thousand vs air) in Staphylococcus staphylolyticus for d-alanine (19.2 +/- 0.5 per thousand, n = 4) and L-alanine (21.3 +/- 0.8 per thousand, n = 4) and in Bacillus subtilis for D-alanine (6.2 +/- 0.2 per thousand, n = 3) and L-alanine (8.2 +/- 0.4 per thousand, n = 3). These results suggest that enzymatic reaction pathways, including the alanine racemase reaction, produce a nitrogen isotopic difference in amino acid enantiomers, resulting in 15N-depleted D-alanine. This method is expected to facilitate compound-specific nitrogen isotope studies of amino acid stereoisomers.

Cellular Transfection to Deliver Alanine-Glyoxylate Aminotransferase to Hepatocytes: A Rational Gene Therapy for Primary Hyperoxaluria-1 (PH-1)

PubMed Central

Koul, Sweaty; Johnson, Thomas; Pramanik, Saroj; Koul, Hari

2005-01-01

Background: Primary hyperoxaluria-type 1 (PH-1) is a rare autosomal recessive disorder of glyoxalate metabolism caused by deficiency in the liver-specific peroxisomal enzyme alanine-glyoxalate transaminase 1 (AGT) resulting in the increased oxidation of glyoxalate to oxalate. Accumulation of oxalate in the kidney and other soft tissues results in loss of renal function and significant morbidity. The present treatment options offer some relief in the short term, but they are not completely successful. In the present study, we tested the feasibility of corrective gene therapy for this metabolic disorder. Methods: A cDNA library was made from HepG2 cells. PCR primers were designed for the AGT sequence with modifications to preclude mistargeting during gene delivery. Amplified AGT cDNA was cloned as a fusion protein with green fluorescent protein (GFP) using the vector EGFP-C1 (Clontech) for monitoring subcellular distribution. Sequence and expression of the fusion protein was verified. Fusion protein vectors were transfected into hepatocytes by liposomal transfection. AGT expression and subcellular distribution was monitored by GFP fluorescence. Results: HepG2 cells express full-length mRNA coding for AGT as confirmed by insert size as well as sequence determination. Selective primers allowed us to generate a modified recombinant GFP-AGT fusion protein. Cellular transfections with Lipofectamine resulted in transfection efficiencies of 60–90%. The recombinant AGT did localize to peroxisomes as monitored by GFP fluorescence. Conclusions: The results demonstrate preliminary in vitro feasibility data for AGT transfection into the hepatocytes. To the best of our knowledge, this is the first study to attempt recombinant AGT gene therapy for treatment of primary hyperoxaluria-1. PMID:15849465

Role of beta-alanine supplementation on muscle carnosine and exercise performance.

PubMed

Artioli, Guilherme Giannini; Gualano, Bruno; Smith, Abbie; Stout, Jeffrey; Lancha, Antonio Herbert

2010-06-01

In this narrative review, we present and discuss the current knowledge available on carnosine and beta-alanine metabolism as well as the effects of beta-alanine supplementation on exercise performance. Intramuscular acidosis has been attributed to be one of the main causes of fatigue during intense exercise. Carnosine has been shown to play a significant role in muscle pH regulation. Carnosine is synthesized in skeletal muscle from the amino acids l-histidine and beta-alanine. The rate-limiting factor of carnosine synthesis is beta-alanine availability. Supplementation with beta-alanine has been shown to increase muscle carnosine content and therefore total muscle buffer capacity, with the potential to elicit improvements in physical performance during high-intensity exercise. Studies on beta-alanine supplementation and exercise performance have demonstrated improvements in performance during multiple bouts of high-intensity exercise and in single bouts of exercise lasting more than 60 s. Similarly, beta-alanine supplementation has been shown to delay the onset of neuromuscular fatigue. Although beta-alanine does not improve maximal strength or VO2max, some aspects of endurance performance, such as anaerobic threshold and time to exhaustion, can be enhanced. Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested. The symptoms, however, are transient and related to the increase in plasma concentration. They can be prevented by using controlled release capsules and smaller dosing strategies. No important side effect was related to the use of this amino acid so far. In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.

Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

NASA Technical Reports Server (NTRS)

Profy, A. T.; Usher, D. A.

1984-01-01

The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

In Quest of the Alanine R3 Radical: Multivariate EPR Spectral Analyses of X-Irradiated Alanine in the Solid State.

PubMed

Jåstad, Eirik O; Torheim, Turid; Villeneuve, Kathleen M; Kvaal, Knut; Hole, Eli O; Sagstuen, Einar; Malinen, Eirik; Futsaether, Cecilia M

2017-09-28

The amino acid l-α-alanine is the most commonly used material for solid-state electron paramagnetic resonance (EPR) dosimetry, due to the formation of highly stable radicals upon irradiation, with yields proportional to the radiation dose. Two major alanine radical components designated R1 and R2 have previously been uniquely characterized from EPR and electron-nuclear double resonance (ENDOR) studies as well as from quantum chemical calculations. There is also convincing experimental evidence of a third minor radical component R3, and a tentative radical structure has been suggested, even though no well-defined spectral signature has been observed experimentally. In the present study, temperature dependent EPR spectra of X-ray irradiated polycrystalline alanine were analyzed using five multivariate methods in further attempts to understand the composite nature of the alanine dosimeter EPR spectrum. Principal component analysis (PCA), maximum likelihood common factor analysis (MLCFA), independent component analysis (ICA), self-modeling mixture analysis (SMA), and multivariate curve resolution (MCR) were used to extract pure radical spectra and their fractional contributions from the experimental EPR spectra. All methods yielded spectral estimates resembling the established R1 spectrum. Furthermore, SMA and MCR consistently predicted both the established R2 spectrum and the shape of the R3 spectrum. The predicted shape of the R3 spectrum corresponded well with the proposed tentative spectrum derived from spectrum simulations. Thus, results from two independent multivariate data analysis techniques strongly support the previous evidence that three radicals are indeed present in irradiated alanine samples.

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

PubMed Central

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, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046–0.0143, P<0.001). Conclusions The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alanine, N-(2-carboxyethyl)-N-alkyl... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for the...

40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alanine, N-(2-carboxyethyl)-N-alkyl... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for the...

Atomic Layer Deposition of L-Alanine Polypeptide

DOE PAGES

Fu, Yaqin; Li, Binsong; Jiang, Ying-Bing; ...

2014-10-30

L-Alanine polypeptide thin films were synthesized via atomic layer deposition (ALD). Rather, instead of using an amino acid monomer as the precursor, an L-alanine amino acid derivatized with a protecting group was used to prevent self-polymerization, increase the vapor pressure, and allow linear cycle-by-cycle growth emblematic of ALD. Moreover, the successful deposition of a conformal polypeptide film has been confirmed by FTIR, TEM, and Mass Spectrometry, and the ALD process has been extended to polyvaline.

Changes in hepatic levels of tyrosine aminotransferase messenger RNA during induction by hydrocortisone. [Xenopus laevis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nickol, J.M.; Lee, K.L.; Kenney, F.T.

Messenger RNA specific for tyrosine aminotransferase was quantitated by microinjection into oocytes of Xenopus laevis. The heterologously translated enzyme was identified by specific immunoprecipitation and found to be identical with authentic aminotransferase by several criteria. The level of functional message present in rat liver increases during hydrocortisone induction, and this increase is directly proportional to the increased rate of synthesis of the enzyme. Kinetic analysis of the changes in tyrosine aminotransferase mRNA levels during induction and withdrawal indicates that the steroid does not affect the stability of the message, which has a half-life of approximately 1.2 h. Hydrocortisone, therefore, actsmore » to increase the rate of synthesis of the specific messenger by stimulating either its transcription or processing to functional mRNA.« less

Diagnostic Dilemma for Low Viremia with Significant Fibrosis; Is HBV DNA Threshold Level a Good Indicator for Predicting Liver Damage?

PubMed

Yenilmez, Ercan; Çetinkaya, Rıza Aytaç; Tural, Ersin

2018-05-04

The most important difficulties about management of hepatitis B are still determining the liver damage and the right time to start antiviral therapy. To reveal the role of hepatitis B virus DNA threshold level for prediction of liver fibrosis and inflammation in young-aged hepatitis B e antigen negative chronic hepatitis B patients. Diagnostic accuracy study. A total of 273 hepatitis B e antigen negative young chronic hepatitis B patients with any hepatitis B virus DNA levels between 2008 and 2016, who had liver biopsy after at least 6 months follow up period, enrolled in this retrospective study. We created two groups as case and control, cases with hepatitis B virus DNA levels below 2.000 IU/mL and controls with hepatitis B virus DNA levels over 2.000 IU/mL. Having histological activity index ≥4 or/and fibrosis scores ≥2 were defined as significant histological abnormality. Then, we analyzed the relationship between these groups. We showed that significant fibrosis may occur in one third of young chronic hepatitis B patients with low viremia (30.2%, n=42/139 in cases, %55.2, n=74/134 in controls). Among the 42 cases with low viremia and significant fibrosis, 21.4% had alanine aminotransferase level between 40-59 U/L, 42.8% had alanine aminotransferase level between 60-79 U/L, and 35.7% had alanine aminotransferase level over 80 U/L. There was weak correlation between hepatitis B virus DNA threshold level and fibrosis score (p=0.000, rho=0.253). The optimum serum hepatitis B virus DNA threshold level in our study for predicting significant fibrosis was 1293 IU/mL (p=0.00, AUC: 0.657±0.034). The optimum alanine aminotransferase threshold level for predicting significant histological activity index and fibrosis was 64.5 and 59.5 U/L, respectively. The sensitivity and the specificity of 1293 vs 2000 IU/mL hepatitis B virus DNA threshold with 60 U/L alanine aminotransferase threshold level for predicting F≥2 fibrosis score were similar (sensitivity: 0.43 and 0

Schisandra chinensis fruit modulates the gut microbiota composition in association with metabolic markers in obese women: a randomized, double-blind placebo-controlled study.

PubMed

Song, Mi-young; Wang, Jing-hua; Eom, Taewoong; Kim, Hojun

2015-08-01

Schisandra chinensis fruit (SCF) is known to have beneficial effects on metabolic diseases, including obesity, and to affect gut microbiota in in vivo studies. However, in human research, there have been a few studies in terms of its clinical roles in lipid metabolism and modulation of gut microbiota. A double-blind, placebo-controlled study with 28 obese women with SCF or placebo was conducted for 12 weeks. Anthropometry and blood and fecal sampling were performed before and after treatment. Analysis of the gut microbiota in feces was performed using denaturing gradient gel electrophoresis and quantitative polymerase chain reaction. Although the values did not differ significantly between the 2 groups, the SCF group tended to show a greater decrease in waist circumference, fat mass, fasting blood glucose, triglycerides, aspartate aminotransferase, and alanine aminotransferase than the placebo group. Clustering of the denaturing gradient gel electrophoresis fingerprints for total bacteria before and after treatment indicated more separate clustering in SCF group than placebo. In correlation analysis, Bacteroides and Bacteroidetes (both increased by SCF) showed significant negative correlation with fat mass, aspartate aminotransferase, and/or alanine aminotransferase, respectively. Ruminococcus (decreased by SCF) showed negative correlation with high-density lipoprotein cholesterol and fasting blood glucose. In conclusion, administration of SCF for 12 weeks resulted in modulation of the gut microbiota composition in Korean obese women, and significant correlations with some bacterial genera and metabolic parameters were noted. However, in general, SCF was not sufficient to induce significant changes in obesity-related parameters compared with placebo. Copyright © 2015 Elsevier Inc. All rights reserved.

How similar is the electronic structures of β-lactam and alanine?

NASA Astrophysics Data System (ADS)

Chatterjee, Subhojyoti; Ahmed, Marawan; Wang, Feng

2016-02-01

The C1s spectra of β-lactam i.e. 2-azetidinone (C3H5NO), a drug and L-alanine (C3H7NO2), an amino acid, exhibit striking similarities, which may be responsible for the competition between 2-azetidinone and the alanyl-alanine moiety in biochemistry. The present study is to reveal the degree of similarities and differences between their electronic structures of the two model molecular pairs. It is found that the similarities in C1s and inner valence binding energy spectra are due to their bonding connections but other properties such as ring structure (in 2-azetidinone) and chiral carbon (alanine) can be very different. Further, the inner valence region of ionization potential greater than 18 eV for 2-azetidinone and alanine is also significantly similar. Finally the strained lactam ring exhibits more chemical reactivity measured at all non-hydrogen atoms by Fukui functions with respect to alanine.

Hepatitis C virus-infected patients with a persistently normal alanine aminotransferase: do they exist and is this really a group with mild disease?

PubMed

Lawson, A

2010-01-01

Opinion varies on whether or not hepatitis C virus (HCV) infected patients with persistently normal aminotransferase (PNALT) levels represent a group with mild disease. To evaluate the risk of ALT flare and fibrosis progression in patients with PNALT followed up as part of the Trent HCV cohort. Treatment-naïve patients with an elevated ALT (n = 1140) or PNALT, the latter defined as either an ALT < or = 30 IU/L (n = 43) or an ALT < or = 40 IU/L (n = 87) on > or =2 occasions in the 6 months following diagnosis, and no ALT > 40 U/L were included. The likelihood of maintaining a PNALT < or = 30 IU/L was 42.2% and PNALT < or = 40 IU/L 41.7% at 3 years. The Ishak fibrosis score was > or =3 in 3.7%, 8.3% and 29.6% of patients with PNALT < or = 30 IU/L, PNALT < or = 40 IU/L and elevated ALT, respectively. Fibrosis progression between paired biopsies was similar for patients with PNALT < or = 30 IU/L (0.33 +/- 0.94 Ishak fibrosis points/year), PNALT < or = 40 IU/L (0.35 +/- 0.82) and elevated ALT (0.19 +/- 0.48). The majority of those defined as PNALT subsequently have an abnormal ALT. They have a similar risk of disease progression to other HCV infected patients and, therefore, warrant the same consideration with regard to treatment.

Role of L-alanine for redox self-sufficient amination of alcohols.

PubMed

Klatte, Stephanie; Wendisch, Volker F

2015-01-23

In white biotechnology biocatalysis represents a key technology for chemical functionalization of non-natural compounds. The plasmid-born overproduction of an alcohol dehydrogenase, an L-alanine-dependent transaminase and an alanine dehydrogenase allows for redox self-sufficient amination of alcohols in whole cell biotransformation. Here, conditions to optimize the whole cell biocatalyst presented in (Bioorg Med Chem 22:5578-5585, 2014), and the role of L-alanine for efficient amine functionalization of 1,10-decanediol to 1,10-diaminodecane were analyzed. The enzymes of the cascade for amine functionalization of alcohols were characterized in vitro to find optimal conditions for an efficient process. Transaminase from Chromobacterium violaceum, TaCv, showed three-fold higher catalytic efficiency than transaminase from Vibrio fluvialis, TaVf, and improved production at 37°C. At 42°C, TaCv was more active, which matched thermostable alcohol dehydrogenase and alanine dehydrogenase and improved the 1,10-diaminodecane production rate four-fold. To study the role of L-alanine in the whole cell biotransformation, the L-alanine concentration was varied and 1,10.diaminodecane formation tested with constant 10 mM 1,10- decanediol and 100 mM NH4Cl. Only 5.6% diamine product were observed without added L-alanine. L-alanine concentrations equimolar to that of the alcohol enabled for 94% product formation but higher L-alanine concentrations allowed for 100% product formation. L-alanine was consumed by the E. coli biocatalyst, presumably due to pyruvate catabolism since up to 16 mM acetate accumulated. Biotransformation employing E. coli strain YYC202/pTrc99a-ald-adh-ta Cv, which is unable to catabolize pyruvate, resulted in conversion with a selectivity of 42 mol-%. Biotransformation with E. coli strains only lacking pyruvate oxidase PoxB showed similar reduced amination of 1,10-decanediol indicating that oxidative decarboxylation of pyruvate to acetate by PoxB is primarily

Enzymatic determination of carbon-14 labeled L-alanine in biological samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serra, F.; Palou, A.; Pons, A.

A method for determination of L-alanine-specific radioactivity in biological samples is presented. This method is based on the specific enzymatic transformation of L-alanine to pyruvic acid hydrazone catalyzed by the enzyme L-alanine dehydrogenase, formation of the pyruvic acid 2,4-dinitrophenylhydrazone derivative, and quantitative trapping in Amberlite XAD-7 columns, followed by radioactivity counting of the lipophilic eluate. No interferences from other UC-labeled materials such as D-glucose, glycerol, L-lactate, L-serine, L-glutamate, L-phenylalanine, glycine, L-leucine, and L-arginine were observed. This inexpensive and high-speed method is applicable to the simultaneous determination of L-alanine-specific radioactivity for a large number of samples.

Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome.

PubMed

Setji, Tracy L; Holland, Nicole D; Sanders, Linda L; Pereira, Kathy C; Diehl, Anna Mae; Brown, Ann J

2006-05-01

Nonalcoholic fatty liver disease and polycystic ovary syndrome (PCOS) are both associated with insulin resistance. Thus, women with PCOS may have an increased prevalence of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH). The objective of the study was to determine the prevalence and characteristics of NASH and abnormal aminotransferase activity in women with PCOS. The study is a retrospective chart review. The setting is an academic endocrinology clinic. Patients were 200 women with PCOS, defined as irregular menses and hyperandrogenism. Biopsy-documented NASH and aminotransferase levels were the main outcome measures. Fifteen percent (29 of 200) had aspartate aminotransferase and/or alanine aminotransferase more than 60 U/liter. Women with aminotransferase elevations had lower high-density lipoprotein (HDL) (41 vs. 50 mg/dl, P = 0.006), higher triglycerides (174 vs. 129 mg/dl, P = 0.024), and higher fasting insulin (21 vs. 12 microIU/ml, P = 0.036) compared with women with normal aminotransferases. Six women (mean age 29 yr) with persistent aminotransferase elevations underwent liver biopsy. All six had NASH with fibrosis. Compared with the 194 of 200 PCOS women who did not undergo biopsy, women with biopsy-documented NASH had lower HDL (median 34 vs. 50 mg/dl, P < 0.001), and higher triglycerides (245 vs. 132 mg/dl, P = 0.025), fasting insulin (26 vs. 13 microIU/ml, P = 0.038), aspartate aminotransferase (144 vs. 22 U/liter, P < 0.001), and alanine aminotransferase (143 vs. 28 U/liter, P < 0.001). Abnormal aminotransferase activity is common in women with PCOS. Low HDL, high triglycerides, and high fasting insulin were associated with abnormal aminotransferase activity. Some women already had evidence of NASH with fibrosis. Further studies are needed to evaluate whether to screen PCOS women for liver disease at an earlier age than is currently recommended for the general population.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

PubMed

Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

2014-01-01

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Short article: A randomized-controlled study of sitagliptin for treating diabetes mellitus complicated by nonalcoholic fatty liver disease.

PubMed

Deng, Xiao-Long; Ma, Rui; Zhu, Hong-Xia; Zhu, Jun

2017-03-01

This study aimed to evaluate the efficacy and safety of sitagliptin for treating Chinese patients with type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). In total, 72 Chinese T2DM patients with NAFLD were divided randomly into two groups of 36 patients each group. All 72 patients were assigned to receive either sitagliptin or diet and exercise for 52 weeks between January 2013 and December 2015. The outcomes' measurements included serum levels of hemoglobin A1c, fasting plasma glucose, aspartate aminotransferase, and alanine aminotransferase. Seventy patients completed the study. Sitagliptin showed greater efficacy than the diet and exercise in decreasing the hemoglobin A1c and fasting plasma glucose levels at weeks 13, 26, 39, and 52. In addition, no significant changes in the average aspartate aminotransferase and alanine aminotransferase levels were found during the 52-week follow-up in both the sitagliptin and the control groups. The results of this study indicate that sitagliptin is an effective and safe treatment for patients with T2DM and NAFLD.

Effects of Monovalent Cations on the Sodium-Alanine Interaction in Rabbit Ileum

PubMed Central

Frizzell, Raymond A.; Schultz, Stanley G.

1970-01-01

H, K, Rb, and Li inhibit Na-dependent alanine influx across the brush border of rabbit ileum. Kinetic analysis indicates that H and K behave as competitive inhibitors of influx so that increasing the concentration of H or K in the mucosal solution is kinetically indistinguishable from decreasing the Na concentration. In addition the coupling between alanine and Na influxes is markedly reduced at pH 2.5. With the exception of H and Li, none of these monovalent cations significantly affects carrier-mediated alanine influx in the absence of Na indicating that their inhibitory effects are largely restricted to the Na-dependent fraction of influx. Increasing H concentration from 0.03 to 3 mM does not affect influx in the absence of Na but markedly inhibits influx in the presence of Na. Li significantly enhances alanine influx in the absence of Na. Ag, UO2, and La also inhibit the Na-dependent fraction of alanine influx. These findings suggest that anionic groups having a pKa of approximately 4 are involved in the interaction between Na and the alanine-carrier complex; present evidence implicates carboxylate groups however, phosphoryl residues cannot be ruled out. The previously proposed kinetic model for the Na-alanine interaction has been extended to accommodate these effects of H and other monovalent cations. The mechanistic and physiological implications of these findings are discussed. PMID:5507092

Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

PubMed Central

Caruso, John; Charles, Jessica; Unruh, Kayla; Giebel, Rachel; Learmonth, Lexis; Potter, William

2012-01-01

β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former’s merits as a buffer. Carnosine normally makes a small contribution to a cell’s total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that in turn improve a muscle’s ability to buffer protons. Numerous studies assessed the impact of oral β-alanine intake on muscle carnosine levels and exercise performance. β-alanine may best act as an ergogenic aid when metabolic acidosis is the primary factor for compromised exercise performance. Blood lactate kinetics, whereby the concentration of the metabolite is measured as it enters and leaves the vasculature over time, affords the best opportunity to assess the merits of β-alanine supplementation’s ergogenic effect. Optimal β-alanine dosages have not been determined for persons of different ages, genders and nutritional/health conditions. Doses as high as 6.4 g day−1, for ten weeks have been administered to healthy subjects. Paraesthesia is to date the only side effect from oral β-alanine ingestion. The severity and duration of paraesthesia episodes are dose-dependent. It may be unwise for persons with a history of paraesthesia to ingest β-alanine. As for any supplement, caution should be exercised with β-alanine supplementation. PMID:22852051

d-Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans.

PubMed

Qiu, W; Zheng, X; Wei, Y; Zhou, X; Zhang, K; Wang, S; Cheng, L; Li, Y; Ren, B; Xu, X; Li, Y; Li, M

2016-10-01

Part of the d-alanine (d-Ala) metabolic pathway in bacteria involves the conversion of l-alanine to d-Ala by alanine racemase and the formation of d-alanyl-d-alanine by d-alanine-d-alanine ligase, the product of which is involved in cell wall peptidoglycan synthesis. At present, drugs that target the metabolic pathway of d-Ala are already in clinical use - e.g. d-cycloserine (DCS) is used as an antibiotic against Mycobacterium tuberculosis. Streptococcus mutans is the main cariogenic bacterium in the oral cavity. Its d-Ala metabolism-associated enzymes alanine racemase and d-alanine-d-alanine ligase are encoded by the genes smu.1834 and smu.599, respectively, which may be potential targets for inhibitors. In this study, the addition of DCS blocked the d-Ala metabolic pathway in S. mutans, leading to bacterial cell wall defects, significant inhibition of bacterial growth and biofilm formation, and reductions in extracellular polysaccharide production and bacterial adhesion. However, the exogenous addition of d-Ala could reverse the inhibitory effect of DCS. Through the means of drug regulation, our study demonstrated, for the first time, the importance of d-Ala metabolism in the survival and biofilm formation of S. mutans. If the growth of S. mutans can be specifically inhibited by designing drugs that target d-Ala metabolism, then this may serve as a potential new treatment for dental caries. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early Liver and Kidney Dysfunction Associated with Occupational Exposure to Sub-Threshold Limit Value Levels of Benzene, Toluene, and Xylenes in Unleaded Petrol

PubMed Central

Neghab, Masoud; Hosseinzadeh, Kiamars; Hassanzadeh, Jafar

2015-01-01

Background Unleaded petrol contains significant amounts of monocyclic aromatic hydrocarbons such as benzene, toluene, and xylenes (BTX). Toxic responses following occupational exposure to unleaded petrol have been evaluated only in limited studies. The main purpose of this study was to ascertain whether (or not) exposure to unleaded petrol, under normal working conditions, is associated with any hepatotoxic or nephrotoxic response. Methods This was a cross-sectional study in which 200 employees of Shiraz petrol stations with current exposure to unleaded petrol, as well as 200 unexposed employees, were investigated. Atmospheric concentrations of BTX were measured using standard methods. Additionally, urine and fasting blood samples were taken from individuals for urinalysis and routine biochemical tests of kidney and liver function. Results The geometric means of airborne concentrations of BTX were found to be 0.8 mg m−3, 1.4 mg m−3, and 2.8 mg m−3, respectively. Additionally, means of direct bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea and plasma creatinine were significantly higher in exposed individuals than in unexposed employees. Conversely, serum albumin, total protein, and serum concentrations of calcium and sodium were significantly lower in petrol station workers than in their unexposed counterparts. Conclusion The average exposure of petrol station workers to BTX did not exceed the current threshold limit values (TLVs) for these chemicals. However, evidence of subtle, subclinical and prepathologic early liver and kidney dysfunction was evident in exposed individuals. PMID:26929843

Changes in alanine turnover rate due to nutritional and genetic obesity in the rat.

PubMed

Yebras, M; Salvadó, J; Arola, L; Remesar, X; Segués, T

1994-08-01

The changes in alanine turnover were determined in Zucker rats, which were either genetically obese (fa/fa) or rendered obese by dietary treatment (cafeteria fed). The whole body rate of alanine turnover was higher in genetically obese rats than in rats in which obesity was induced by diet (cafeteria). This is possibly due to variations in the rate of the amino acid incorporation into proteins, since the rate of whole body alanine degradation is the same for both groups. Thus, the different pattern followed by alanine turnover rate in these types of obese animals reflects the differences in the nitrogen economy of these animals, pointing to a higher alanine utilization in the genetically obese animals and a conservative management of alanine in the cafeteria-fed animals.

Substrate specificity of the aspartate:alanine antiporter (AspT) of Tetragenococcus halophilus in reconstituted liposomes.

PubMed

Sasahara, Ayako; Nanatani, Kei; Enomoto, Masaru; Kuwahara, Shigefumi; Abe, Keietsu

2011-08-19

The aspartate:alanine antiporter (AspT) of the lactic acid bacterium Tetragenococcus halophilus is a member of the aspartate:alanine exchanger (AAEx) transporter family. T. halophilus AspT catalyzes the electrogenic exchange of L-aspartate(1-) with L-alanine(0). Although physiological functions of AspT were well studied, L-aspartate(1-):L-alanine(0) antiport mechanisms are still unsolved. Here we report that the binding sites of L-aspartate and L-alanine are independently present in AspT by means of the kinetic studies. We purified His(6)-tagged T. halophilus AspT and characterized its kinetic properties when reconstituted in liposomes (K(m) = 0.35 ± 0.03 mm for L-aspartate, K(m) = 0.098 ± 0 mm for D-aspartate, K(m) = 26 ± 2 mm for L-alanine, K(m) = 3.3 ± 0.2 mm for D-alanine). Competitive inhibition by various amino acids of L-aspartate or L-alanine in self-exchange reactions revealed that L-cysteine selectively inhibited L-aspartate self-exchange but only weakly inhibited L-alanine self-exchange. Additionally, L-serine selectively inhibited L-alanine self-exchange but barely inhibited L-aspartate self-exchange. The aspartate analogs L-cysteine sulfinic acid, L-cysteic acid, and D-cysteic acid competitively and strongly inhibited L-aspartate self-exchange compared with L-alanine self-exchange. Taken together, these kinetic data suggest that the putative binding sites of L-aspartate and L-alanine are independently located in the substrate translocation pathway of AspT.

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

PubMed

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%, p<0.05). The skeletal muscle index was negatively correlated with most cardiometabolic risk factors, including fasting glucose and cholesterol levels. 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.

Biochemical properties and subcellular localization of tyrosine aminotransferases in Arabidopsis thaliana.

PubMed

Wang, Minmin; Toda, Kyoko; Maeda, Hiroshi A

2016-12-01

Plants produce various L-tyrosine (Tyr)-derived compounds that are of pharmaceutical or nutritional importance to humans. Tyr aminotransferase (TAT) catalyzes the reversible transamination between Tyr and 4-hydroxyphenylpyruvate (HPP), the initial step in the biosynthesis of many Tyr-derived plant natural products. Herein reported is the biochemical characterization and subcellular localization of TAT enzymes from the model plant Arabidopsis thaliana. Phylogenetic analysis showed that Arabidopsis has at least two homologous TAT genes, At5g53970 (AtTAT1) and At5g36160 (AtTAT2). Their recombinant enzymes showed distinct biochemical properties: AtTAT1 had the highest activity towards Tyr, while AtTAT2 exhibited a broad substrate specificity for both amino and keto acid substrates. Also, AtTAT1 favored the direction of Tyr deamination to HPP, whereas AtTAT2 preferred transamination of HPP to Tyr. Subcellular localization analysis using GFP-fusion proteins and confocal microscopy showed that AtTAT1, AtTAT2, and HPP dioxygenase (HPPD), which catalyzes the subsequent step of TAT, are localized in the cytosol, unlike plastid-localized Tyr and tocopherol biosynthetic enzymes. Furthermore, subcellular fractionation indicated that, while HPPD activity is restricted to the cytosol, TAT activity is detected in both cytosolic and plastidic fractions of Arabidopsis leaf tissue, suggesting that an unknown aminotransferase(s) having TAT activity is also present in the plastids. Biochemical and cellular analyses of Arabidopsis TATs provide a fundamental basis for future in vivo studies and metabolic engineering for enhanced production of Tyr-derived phytochemicals in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Effects of ß-alanine supplementation on athletic performance].

PubMed

Domínguez, Raúl; Hernández Lougedo, Juan; Maté-Muñoz, José Luis; Garnacho-Castaño, Manuel Vicente

2014-10-06

Carnosine, dipeptide formed by amino acids ß-alanine and L-histidine, has important physiological functions among which its antioxidant and related memory and learning. However, in connection with the exercise, the most important functions would be associated with muscle contractility, improving calcium sensitivity in muscle fibers, and the regulatory function of pH. Thus, it is proposed that carnosine is the major intracellular buffer, but could contribute to 7-10% in buffer or buffer capacity. Since carnosine synthesis seems to be limited by the availability of ß-alanine supplementation with this compound has been gaining increasing popularity among the athlete population. Therefore, the objective of this study literature review was to examine all those research works have shown the effect of ß-alanine supplementation on athletic performance. Moreover, it also has attempted to establish a specific dosage that maximizing the potential benefits, minimize paresthesia, the main side effect presented in response to supplementation. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

Calibration of helical tomotherapy machine using EPR/alanine dosimetry.

PubMed

Perichon, Nicolas; Garcia, Tristan; François, Pascal; Lourenço, Valérie; Lesven, Caroline; Bordy, Jean-Marc

2011-03-01

Current codes of practice for clinical reference dosimetry of high-energy photon beams in conventional radiotherapy recommend using a 10 x 10 cm2 square field, with the detector at a reference depth of 10 cm in water and 100 cm source to surface distance (SSD) (AAPM TG-51) or 100 cm source-to-axis distance (SAD) (IAEA TRS-398). However, the maximum field size of a helical tomotherapy (HT) machine is 40 x 5 cm2 defined at 85 cm SAD. These nonstandard conditions prevent a direct implementation of these protocols. The purpose of this study is twofold: To check the absorbed dose in water and dose rate calibration of a tomotherapy unit as well as the accuracy of the tomotherapy treatment planning system (TPS) calculations for a specific test case. Both topics are based on the use of electron paramagnetic resonance (EPR) using alanine as transfer dosimeter between the Laboratoire National Henri Becquerel (LNHB) 60Co-gamma-ray reference beam and the Institut Curie's HT beam. Irradiations performed in the LNHB reference 60Co-gamma-ray beam allowed setting up the calibration method, which was then implemented and tested at the LNHB 6 MV linac x-ray beam, resulting in a deviation of 1.6% (at a 1% standard uncertainty) relative to the reference value determined with the standard IAEA TRS-398 protocol. HT beam dose rate estimation shows a difference of 2% with the value stated by the manufacturer at a 2% standard uncertainty. A 4% deviation between measured dose and the calculation from the tomotherapy TPS was found. The latter was originated by an inadequate representation of the phantom CT-scan values and, consequently, mass densities within the phantom. This difference has been explained by the mass density values given by the CT-scan and used by the TPS which were not the true ones. Once corrected using Monte Carlo N-Particle simulations to validate the accuracy of this process, the difference between corrected TPS calculations and alanine measured dose values was then

Characteristics of an outpatient chronic hepatitis B virus infection cohort

PubMed Central

de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

2015-01-01

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

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

PubMed

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.

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

PubMed

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 <0.05) . There were no significantdifferences in the serum level and abnormal rate of AST between the subgroups with different 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 <0.05) . There were no significant differences in the serum level and abnormal rate of ALT between thesubgroups with different 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 was not correlated with the serum level of ALT ( r =-0.044, P >0.05) , and that the serum level of AST was positively correlated

The Effects of Direct Oxygen Supply During Static Cold Preservation of Rat Livers: An Experimental Study.

PubMed

Zumrutdal, Emin; Karateke, Faruk; Eser, Pınar Eylem; Turan, Umit; Ozyazici, Sefa; Sozutek, Alper; Gulkaya, Mustafa; Kunt, Mevlut

2016-12-01

We aimed to determine the biochemical and histopathologic effects of direct oxygen supply to the preservation fluid of static cold storage system with a simple method on rat livers. Sixteen rats were randomly divided into 2 groups: the control group, which contained Ringer's lactate as preservation fluid; and the oxygen group, which contained oxygen and Ringer's lactate for preservation. Each liver was placed in a bag containing 50 mL Ringer's lactate and placed in ice-filled storage containers. One hundred percent oxygen supplies were given via a simple, inexpensive system created in our laboratory, to the livers in oxygen group. We obtained samples for histopathologic evaluation in the 12th hour. In addition, 3 mL of preservation fluid was subjected to biochemical analysis at 0, sixth, and twelfth hours. Aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and pH levels were measured from the preservation fluid. In oxygen-supplemented group, the acceleration speed of increase in alanine aminotransferase and lactate dehydrogenase levels at sixth hour and lactate dehydrogenase, alanine aminotransferase, and lactate dehydrogenase levels at 12th hour were statistically significantly reduced. In histopathologic examination, all parameters except ballooning were statistically significantly better in the oxygen-supplemented group. This simple system for oxygenation of liver tissues during static cold storage was shown to be effective with good results in biochemical and histopathologic assessments. Because this is a simple, inexpensive, and easily available method, larger studies are warranted to evaluate its effects (especially in humans).

Comparison of biomedical evaluation for white-fronted brown lemurs (Eulemur fulvus albifrons) from four sites in Madagascar.

PubMed

Junge, Randall E; Dutton, Christopher J; Knightly, Felicia; Williams, Cathy V; Rasambainarivo, Fidisoa T; Louis, Edward E

2008-12-01

Health and nutritional assessments of wildlife are important management tools and can provide a means to evaluate ecosystem health. Such examinations were performed on 37 white-fronted brown lemurs (Eulemur fulvus albifrons) from four sites in Madagascar. Comparison of health parameters between sites revealed statistically significant differences in body weight, body temperature, respiratory rate, hematology parameters (white cell count, hematocrit, segmented neutrophil count, and lymphocyte count), serum chemistry parameters (aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, total protein, albumin, phosphorus, calcium, sodium, chloride, and creatinine phosphokinase), and nutrition parameters (copper, zinc, ferritin, retinol, tocopherol, and 25-hydroxycholecalciferol). Two of 10 lemurs tested were positive for toxoplasmosis; none of 10 were positive for Cryptosporidium or Giardia. Enteric bacteria and endo- and ectoparasites were typical. Statistically different values in hematology and chemistry values probably do not reflect clinically significant differences, whereas nutrition parameter differences are likely related to season, soil, and forage availability.

Possible health effects of liquefied petroleum gas on workers at filling and distribution stations of Gaza governorates.

PubMed

Sirdah, M M; Al Laham, N A; El Madhoun, R A

2013-03-01

Liquefied petroleum gas (LPG) is widely used in the Gaza Strip for domestic purposes, in agriculture and industry and, illegally, in cars. This study aimed to identify possible health effects on workers exposed to LPG in Gaza governorates. Data were collected by a questionnaire interview, and haematological and biochemical analyses of venous blood samples were made from 30 workers at filling and distribution stations and 30 apparently healthy controls. Statistically significant differences were found in all self-reported health-related complaints among LPG workers versus controls. LPG workers had significantly higher values of red blood cell counts, haemoglobin, haematocrit mean corpuscular haemoglobin and platelet counts. They also had significantly higher values of kidney function tests (urea, creatinine and uric acid) and liver function enzyme activities (aspartate aminotransferase and alanine aminotransferase). LPG workers at Gaza Strip petroleum stations are at higher risk for health-related symptoms and clinical abnormalities.

GMXPBSA 2.0: A GROMACS tool to perform MM/PBSA and computational alanine scanning

NASA Astrophysics Data System (ADS)

Paissoni, C.; Spiliotopoulos, D.; Musco, G.; Spitaleri, A.

2014-11-01

GMXPBSA 2.0 is a user-friendly suite of Bash/Perl scripts for streamlining MM/PBSA calculations on structural ensembles derived from GROMACS trajectories, to automatically calculate binding free energies for protein-protein or ligand-protein complexes. GMXPBSA 2.0 is flexible and can easily be customized to specific needs. Additionally, it performs computational alanine scanning (CAS) to study the effects of ligand and/or receptor alanine mutations on the free energy of binding. Calculations require only for protein-protein or protein-ligand MD simulations. GMXPBSA 2.0 performs different comparative analysis, including a posteriori generation of alanine mutants of the wild-type complex, calculation of the binding free energy values of the mutant complexes and comparison of the results with the wild-type system. Moreover, it compares the binding free energy of different complexes trajectories, allowing the study the effects of non-alanine mutations, post-translational modifications or unnatural amino acids on the binding free energy of the system under investigation. Finally, it can calculate and rank relative affinity to the same receptor utilizing MD simulations of proteins in complex with different ligands. In order to dissect the different MM/PBSA energy contributions, including molecular mechanic (MM), electrostatic contribution to solvation (PB) and nonpolar contribution to solvation (SA), the tool combines two freely available programs: the MD simulations software GROMACS and the Poisson-Boltzmann equation solver APBS. All the calculations can be performed in single or distributed automatic fashion on a cluster facility in order to increase the calculation by dividing frames across the available processors. The program is freely available under the GPL license.

[Predictive value of liver enzymes and alcohol consumption for risk of type 2 diabetes].

PubMed

Ma, Xiaokun; Wang, Qingzhu; Qin, Guijun; Zhao, Yanyan; Zhang, Yinghui; Ma, Xiaojun; Li, Zhizhen; Wang, Zhimin; Ren, Gaofei; Bi, Yufang; Wang, Weiqing; Ning, Guang

2015-01-01

To compare the predictive value of liver enzymes and alcohol consumption for determining risk of type 2 diabetes (T2DM). A cross-sectional study was conducted in Zhengzhou with a total of 2, 693 men.Participants' height, weight, and histories of smoking and drinking were recorded. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and blood glucose, as well as related metabolic indexes were detected. Moderate daily alcohol consumption (more than 35 g ethanol/week and less than 140 g ethanol/week) decreased the risk of type 2 diabetes (OR =0.376, 95% CI:0.306 -0.463, P less than 0.05) but increased risk for higher levels of GGT and ALT (OR GGT =3.012, 95% CI:2.357-3.849, Pless than 0.01; ORALT =1.473, 95% CI:1.043-2.081, Pless than 0.05). In joint analyses of alcohol consumption and liver enzymes, the group of nondrinkers/light drinkers (less than or equal to 35 g ethanol/week) in the fourth quartile of GGT levels had the highest risk for type 2 diabetes (OR =12.219, 95% CI:6.217-24.016, P less than 0.01). The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT (nondrinkers/light drinkers in the fourth quartile of ALT levels (OR =5.357, 95% CI:3.070-9.350, P less than 0.0 1). GGT, ALT and daily alcohol consumption were independently associated with risk of type 2 diabetes. Nondrinkers/light drinkers with the highest levels ofGGT orALT were at high risk of type 2 diabetes.

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.

PubMed

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.

Influence of Asymptomatic Pneumonia on the Response to Hemorrhage and Resuscitation in Swine

DTIC Science & Technology

2010-01-01

and complete blood count (Pentra-120 Hemato- logy Analyzer, ABX Diagnostics, Irvine, CA); 3) total plasma protein, glucose, creatinine , lactate...dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), amylase and lactate (Vitros Chemistry System...CK. Creatinine increased at 15 min in both groups and remained elevated throughout the study. Mean total protein, amylase and ALT decreased similarly

Thirteen Week Oral Toxicity Study of WR238605 with a Thirteen Week Recovery Period in Rats. Volume 2 of 3

DTIC Science & Technology

1993-06-18

Standards, Part 2. IFCC Method for Aspartate Aminotransferase, Amsterdam, Elsevier Scientific Publishing Company (1975) Alanine Aminotransferase (ALT...Activity 7b. ADDRESS (Orty, State, and ZIP Code) ATTN: SGRD-RMA-RCD Fort Detrick Frederick, M0 21702 9. PROCUREMENT INSTRUMENT IDENTIFICATION ...Study No. 097 and Study No. 098 ANALYSTS: THOMAS TOLHURST A. KARL LARSEN, JR. STUDY SITE: FORENSIC TOXICOLOGY LABORATORY COLLEGE OF PHARMACY

ESR/Alanine gamma-dosimetry in the 10-30 Gy range.

PubMed

Fainstein, C; Winkler, E; Saravi, M

2000-05-01

We report Alanine Dosimeter preparation, procedures for using the ESR/Dosimetry method, and the resulting calibration curve for gamma-irradiation in the range from 10-30 Gy. We use calibration curve to measure the irradiation dose in gamma-irradiation of human blood, as required in Blood Transfusion Therapy. The ESR/Alanine results are compared against those obtained using the thermoluminescent dosimetry (TLD) method.

A novel archaeal alanine dehydrogenase homologous to ornithine cyclodeaminase and mu-crystallin.

PubMed

Schröder, Imke; Vadas, Alexander; Johnson, Eric; Lim, Sierin; Monbouquette, Harold G

2004-11-01

A novel alanine dehydrogenase (AlaDH) showing no significant amino acid sequence homology with previously known bacterial AlaDHs was purified to homogeneity from the soluble fraction of the hyperthermophilic archaeon Archaeoglobus fulgidus. AlaDH catalyzed the reversible, NAD+-dependent deamination of L-alanine to pyruvate and NH4+. NADP(H) did not serve as a coenzyme. The enzyme is a homodimer of 35 kDa per subunit. The Km values for L-alanine, NAD+, pyruvate, NADH, and NH4+ were estimated at 0.71, 0.60, 0.16, 0.02, and 17.3 mM, respectively. The A. fulgidus enzyme exhibited its highest activity at about 82 degrees C (203 U/mg for reductive amination of pyruvate) yet still retained 30% of its maximum activity at 25 degrees C. The thermostability of A. fulgidus AlaDH was increased by more than 10-fold by 1.5 M KCl to a half-life of 55 h at 90 degrees C. At 25 degrees C in the presence of this salt solution, the enzyme was approximately 100% stable for more than 3 months. Closely related A. fulgidus AlaDH homologues were found in other archaea. On the basis of its amino acid sequence, A. fulgidus AlaDH is a member of the ornithine cyclodeaminase-mu-crystallin family of enzymes. Similar to the mu-crystallins, A. fulgidus AlaDH did not exhibit any ornithine cyclodeaminase activity. The recombinant human mu-crystallin was assayed for AlaDH activity, but no activity was detected. The novel A. fulgidus gene encoding AlaDH, AF1665, is designated ala.

[The effect of diet ratio of polyunsaturated fatty acids of omega-3 and omega-6 families on activity of aminotransferases and gamma-glutamyltransferase in rat blood serum].

PubMed

Ketsa, O V; Marchenko, M M

2014-01-01

The effect of diet fat compositions with various ratio of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) activities in blood serum of 45 white mongrel rats weighing 90-110 g (9 animals in group) has been investigated. Fat components in the semi-synthetic diet, compiled on the basis of AIN-93 diet, and sources of omega-6 and omega-3 PUFA were presented by sunflower oil, soybean oil and fish oil. It has been shown that four-week inclusion of linoleic acid (LA) and alpha-linolenic acid (alpha-LNA) in a ratio of 7:1 into the diet (soybean oil) as well as use of only omega-6 PUFA (sunflower oil) has lead to an increase in the activity of ALT and GGT in rat blood serum compared to control animals treated with the complex of linolenic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid through the mixture of sunflower oil and fish oil (9:1) with the ratio of omega-6 and omega-3 PUFA 7:1. Along with this, the AST:ALT ratio (de Ritis ratio) was lower (p < 0.05) as compared with the control group of rat, amounting respectively 0.92 +/- 0.08 and 0.79 +/- 0.12 vs 1.26 +/- 0.10. The use of high doses of omega-3 fatty acids (600 mg EPA and 400 mg DHA per kg of animal weight per day coming through fish oil) did not affect the activity of ALT and GGT, but increased AST serum activity (0.47 +/- 0.04 micromoles/min per mg protein) and the de Ritis ratio (2.53 +/- 0.23). The diet deprived with fat increased enzyme activity of ALT, AST and GGT in rat blood serum.

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

PubMed

Bin Sayeed, Muhammad Shahdaat; Mostofa, A G M; Ferdous, F M Touhidul Islam; Islam, Md Siddiqul

2013-09-01

A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.

Reference values for 34 frequently used laboratory tests in 80-year-old men and women.

PubMed

Helmersson-Karlqvist, Johanna; Ridefelt, Peter; Lind, Lars; Larsson, Anders

2016-10-01

Reference values are usually based on blood samples from healthy individuals in the age range 20-50 years. Most patients seeking health care are older than this reference population. Many reference intervals are age dependent and there is thus a need to have appropriate reference intervals also for elderly individuals. We analyzed a group of frequently used laboratory tests in an 80-year-old population (n=531, 266 females and 265 males). The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values. Reference values are reported for serum alanine transaminase (ALT), albumin, alkaline phosphatase, pancreatic amylase, apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, aspartate aminotransferase (AST), AST/ALT ratio, bilirubin, calcium, calprotectin, cholesterol, HDL-cholesterol, creatinine kinase (CK), creatinine, creatinine estimated GFR, C-reactive protein, cystatin C, cystatin C estimated GFR, gamma-glutamyltransferase (GGT), iron, iron saturation, lactate dehydrogenase (LDH), magnesium, phosphate, transferrin, triglycerides, urate, urea, zinc, hemoglobin, platelet count and white blood cell count. The upper reference limit for creatinine and urea was significantly increased while the lower limit for iron and albumin was decreased in this elderly population in comparison with the population in the Nordic Reference Interval Project (NORIP). Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% confidence interval of NORIP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels.

PubMed

Otsuka, Momoka; Uchida, Yuki; Kawaguchi, Takumi; Taniguchi, Eitaro; Kawaguchi, Atsushi; Kitani, Shingo; Itou, Minoru; Oriishi, Tetsuharu; Kakuma, Tatsuyuki; Tanaka, Suiko; Yagi, Minoru; Sata, Michio

2012-10-01

  Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV-PNALT) remains unclear. The decision-tree algorithm is a data-mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV-PNALT using a decision-tree algorithm.   Twenty-seven HCV-PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision-tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC).   In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV-PNALT. The decision-tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV-PNALT. On the other hand, 11.5% of the subjects were HCV-PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV-PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40-83.67, P = 0.0005). Fivefold cross-validation of the decision-tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656-0.8238, P = 0.0067).   The decision-tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV-PNALT. © 2012 The Japan Society of Hepatology.

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PubMed

Bonekamp, David; Bonekamp, Susanne; Ou, Hsin-You; Torbenson, Michael S; Corona-Villalobos, Celia Pamela; Mezey, Esteban; Kamel, Ihab R

2014-11-01

Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC. © 2013 Wiley Periodicals, Inc.

Two Week Oral Dose Range-Finding Toxicity Study of WR269410 in Rats

DTIC Science & Technology

1993-07-09

Part 2. IFCC Method for Aspartate Aminotransferase, Amsterdam, Elsevier Scientific Publishing Company (1975) Alanine Aminotransferase (ALT/GPT... IDENTIFICATION NUMBER DAMD17-92-C-2001 [8c ADDRESS (City, State, and ZIP Code) Fort Detrick Frederick, MD 21702-5009 10. SOURCE OF FUNDING NUMBERS...STATEMENT 3 SIGNATURE PAGE 4 TABLE OF CONTENTS 5 1. SUMMARY 7 2. INTRODUCTION 7 3. MATERIALS AND METHODS 7 3.1 Test

End-to-end tests using alanine dosimetry in scanned proton beams

NASA Astrophysics Data System (ADS)

Carlino, A.; Gouldstone, C.; Kragl, G.; Traneus, E.; Marrale, M.; Vatnitsky, S.; Stock, M.; Palmans, H.

2018-03-01

This paper describes end-to-end test procedures as the last fundamental step of medical commissioning before starting clinical operation of the MedAustron synchrotron-based pencil beam scanning (PBS) therapy facility with protons. One in-house homogeneous phantom and two anthropomorphic heterogeneous (head and pelvis) phantoms were used for end-to-end tests at MedAustron. The phantoms were equipped with alanine detectors, radiochromic films and ionization chambers. The correction for the ‘quenching’ effect of alanine pellets was implemented in the Monte Carlo platform of the evaluation version of RayStation TPS. During the end-to-end tests, the phantoms were transferred through the workflow like real patients to simulate the entire clinical workflow: immobilization, imaging, treatment planning and dose delivery. Different clinical scenarios of increasing complexity were simulated: delivery of a single beam, two oblique beams without and with range shifter. In addition to the dose comparison in the plastic phantoms the dose obtained from alanine pellet readings was compared with the dose determined with the Farmer ionization chamber in water. A consistent systematic deviation of about 2% was found between alanine dosimetry and the ionization chamber dosimetry in water and plastic materials. Acceptable agreement of planned and delivered doses was observed together with consistent and reproducible results of the end-to-end testing performed with different dosimetric techniques (alanine detectors, ionization chambers and EBT3 radiochromic films). The results confirmed the adequate implementation and integration of the new PBS technology at MedAustron. This work demonstrates that alanine pellets are suitable detectors for end-to-end tests in proton beam therapy and the developed procedures with customized anthropomorphic phantoms can be used to support implementation of PBS technology in clinical practice.

Impact of the ovarian cycle and pregnancy on plasma chemistry values in ewes

PubMed Central

Zywicki, Micaela E.; Blohowiak, Sharon E.; Magness, Ronald R.; Segar, Jeffrey L.; Kling, Pamela J.

2018-01-01

Normative data for plasma chemistry values in pregnant and non-pregnant reproductive age ewes are scant. Availability of data would aid monitoring of ewe health for both research and veterinary medicine. We determined specific plasma chemistry 95% confidence reference intervals (RIs) in non-pregnant and pregnant ewes. Mixed Western-breed ewes were grouped based on phase of ovarian cycle: luteal (n = 15), follicular (n = 17), or late-gestation pregnant (n = 102). Plasma samples were collected for analysis on a commercial biochemical analyzer. For RIs, chemistry panels for the 3 groups of ewes included nutrients and metabolites (glucose, triglycerides, cholesterol, urea, creatinine, total protein, albumin, and bilirubin), enzymes (lactate dehydrogenase, aspartate transaminase, gamma-glutamyl transferase, alanine aminotransferase, and alkaline phosphatase [ALP]), and micronutrients (calcium, phosphorus, iron, sodium, potassium, and chloride). Sample chemistry values for glucose and total protein in pregnant ewes were lower than in follicular ewes; cholesterol was lower in pregnant and luteal ewes than in follicular ewes. In addition, total bilirubin in pregnant ewes differed from that in luteal ewes, and that in follicular ewes also differed from luteal ewes. ALP in pregnant ewes was higher than other groups; phosphorus in pregnant ewes was lower than in luteal ewes. Iron was higher in pregnant ewes than in luteal ewes, with iron in luteal ewes lower than in follicular ewes. These data provide clinical RIs comparing pregnant and non-pregnant ewes for use in monitoring ewe health in both human research and veterinary medicine. PMID:29291683

Impact of the ovarian cycle and pregnancy on plasma chemistry values in ewes.

PubMed

Zywicki, Micaela E; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2018-03-01

Normative data for plasma chemistry values in pregnant and non-pregnant reproductive age ewes are scant. Availability of data would aid monitoring of ewe health for both research and veterinary medicine. We determined specific plasma chemistry 95% confidence reference intervals (RIs) in non-pregnant and pregnant ewes. Mixed Western-breed ewes were grouped based on phase of ovarian cycle: luteal ( n = 15), follicular ( n = 17), or late-gestation pregnant ( n = 102). Plasma samples were collected for analysis on a commercial biochemical analyzer. For RIs, chemistry panels for the 3 groups of ewes included nutrients and metabolites (glucose, triglycerides, cholesterol, urea, creatinine, total protein, albumin, and bilirubin), enzymes (lactate dehydrogenase, aspartate transaminase, gamma-glutamyl transferase, alanine aminotransferase, and alkaline phosphatase [ALP]), and micronutrients (calcium, phosphorus, iron, sodium, potassium, and chloride). Sample chemistry values for glucose and total protein in pregnant ewes were lower than in follicular ewes; cholesterol was lower in pregnant and luteal ewes than in follicular ewes. In addition, total bilirubin in pregnant ewes differed from that in luteal ewes, and that in follicular ewes also differed from luteal ewes. ALP in pregnant ewes was higher than other groups; phosphorus in pregnant ewes was lower than in luteal ewes. Iron was higher in pregnant ewes than in luteal ewes, with iron in luteal ewes lower than in follicular ewes. These data provide clinical RIs comparing pregnant and non-pregnant ewes for use in monitoring ewe health in both human research and veterinary medicine.

Comparison between meloxicam and carprofen for postoperative analgesia after feline ovariohysterectomy.

PubMed

Slingsby, L S; Waterman-Pearson, A E

2002-07-01

Eighty female cats presented for ovariohysterectomy were randomly allocated to one of two treatment groups in this assessor-blinded trial. After pre-anaesthetic assessment, the cats were premedicated with acepromazine (0.1 mg/kg). Anaesthesia was induced with thiopentone and maintained with halothane in oxygen. Forty cats received carprofen (4 mg/kg subcutaneously) and 40 received meloxicam (0.3 mg/kg subcutaneously) after anaesthetic induction. Following routine flank ovariohysterectomy the cats were assessed using visual analogue scale scores for pain and sedation over a 20-hour study period. Blood samples were taken before sedation and at 20 hours for serum biochemistry (urea, creatinine, alanine aminotransferase and aspartate aminotransferase). There were no significant differences between the groups for pain and sedation scores. Serum biochemistry values were similar between the groups, with some differences within groups between the pre-sedation and 20-hour values. One cat in the carprofen group and two cats in the meloxicam group required rescue analgesia with intramuscular morphine (0.2 mg/kg).

Eukaryotic beta-alanine synthases are functionally related but have a high degree of structural diversity.

PubMed Central

Gojković, Z; Sandrini, M P; Piskur, J

2001-01-01

beta-Alanine synthase (EC 3.5.1.6), which catalyzes the final step of pyrimidine catabolism, has only been characterized in mammals. A Saccharomyces kluyveri pyd3 mutant that is unable to grow on N-carbamyl-beta-alanine as the sole nitrogen source and exhibits diminished beta-alanine synthase activity was used to clone analogous genes from different eukaryotes. Putative PYD3 sequences from the yeast S. kluyveri, the slime mold Dictyostelium discoideum, and the fruit fly Drosophila melanogaster complemented the pyd3 defect. When the S. kluyveri PYD3 gene was expressed in S. cerevisiae, which has no pyrimidine catabolic pathway, it enabled growth on N-carbamyl-beta-alanine as the sole nitrogen source. The D. discoideum and D. melanogaster PYD3 gene products are similar to mammalian beta-alanine synthases. In contrast, the S. kluyveri protein is quite different from these and more similar to bacterial N-carbamyl amidohydrolases. All three beta-alanine synthases are to some degree related to various aspartate transcarbamylases, which catalyze the second step of the de novo pyrimidine biosynthetic pathway. PYD3 expression in yeast seems to be inducible by dihydrouracil and N-carbamyl-beta-alanine, but not by uracil. This work establishes S. kluyveri as a model organism for studying pyrimidine degradation and beta-alanine production in eukaryotes. PMID:11454750

Establishing pediatric reference intervals for 13 biochemical analytes derived from normal subjects in a pediatric endocrinology clinic in Korea.

PubMed

Cho, Sun-Mi; Lee, Sang-Guk; Kim, Ho Seong; Kim, Jeong-Ho

2014-12-01

Defining pediatric reference intervals is one of the most difficult tasks for laboratory physicians. The continuously changing physiology of growing children makes their laboratory values moving targets. In addition, ethnic and behavioral differences might also cause variations. The aim of this study was to establish age- and sex-specific partitioned reference intervals for 13 serum biochemical analytes in Korean children. A total of 2474 patients, girls aged 2-14 years and boys aged 2-16 years, who underwent a short stature workup but were diagnosed as normal at the Pediatric Endocrinology Clinic of Severance Hospital (Seoul, Korea) between September 2010 and June 2012 were included in this study. The levels of serum calcium, inorganic phosphorus, blood urea nitrogen, creatinine, uric acid, glucose, total cholesterol, total protein, albumin, alkaline phosphatase, aspartic aminotransferase, alanine aminotransferase, and total bilirubin were measured using a Hitachi 7600 analyzer (Hitachi High-Technologies Corporation, Tokyo, Japan). Reference intervals were partitioned according to sex or age subgroups using the Harris and Boyd method. Most analytes except calcium and albumin required partitioning either by sex or age. Age-specific partitioned reference intervals for alkaline phosphatase, creatinine, and total bilirubin were established for both males and females after being partitioned by sex. Additional age-specific partitioning of aspartic aminotransferase in females and total protein and uric acid in males was also required. Inorganic phosphorus, total cholesterol, alanine aminotransferase, blood urea nitrogen, and glucose were partitioned only by sex. This study provided updated age- and sex-specific pediatric reference intervals for 13 basic serum chemistry analytes from a sufficient number of healthy children by using a modern analytical chemistry platform. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights

A new machine-learning method to prognosticate paraquat poisoned patients by combining coagulation, liver, and kidney indices.

PubMed

Hu, Lufeng; Li, Huaizhong; Cai, Zhennao; Lin, Feiyan; Hong, Guangliang; Chen, Huiling; Lu, Zhongqiu

2017-01-01

The prognosis of paraquat (PQ) poisoning is highly correlated to plasma PQ concentration, which has been identified as the most important index in PQ poisoning. This study investigated the predictive value of coagulation, liver, and kidney indices in prognosticating PQ-poisoning patients, when aligned with plasma PQ concentrations. Coagulation, liver, and kidney indices were first analyzed by variance analysis, receiver operating characteristic curves, and Fisher discriminant analysis. Then, a new, intelligent, machine learning-based system was established to effectively provide prognostic analysis of PQ-poisoning patients based on a combination of the aforementioned indices. In the proposed system, an enhanced extreme learning machine wrapped with a grey wolf-optimization strategy was developed to predict the risk status from a pool of 103 patients (56 males and 47 females); of these, 52 subjects were deceased and 51 alive. The proposed method was rigorously evaluated against this real-life dataset, in terms of accuracy, Matthews correlation coefficients, sensitivity, and specificity. Additionally, the feature selection was investigated to identify correlating factors for risk status. The results demonstrated that there were significant differences in the coagulation, liver, and kidney indices between deceased and surviving subjects (p<0.05). Aspartate aminotransferase, prothrombin time, prothrombin activity, total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, urea nitrogen, and creatinine were the most highly correlated indices in PQ poisoning and showed statistical significance (p<0.05) in predicting PQ-poisoning prognoses. According to the feature selection, the most important correlated indices were found to be associated with aspartate aminotransferase, the aspartate aminotransferase to alanine ratio, creatinine, prothrombin time, and prothrombin activity. The method proposed here showed excellent results that were better than

Experimental determination of the carboxylate oxygen electric-field-gradient and chemical shielding tensors in L-alanine and L-phenylalanine

NASA Astrophysics Data System (ADS)

Yamada, Kazuhiko; Asanuma, Miwako; Honda, Hisashi; Nemoto, Takahiro; Yamazaki, Toshio; Hirota, Hiroshi

2007-10-01

We report a solid-state 17O NMR study of the 17O electric-field-gradient (EFG) and chemical shielding (CS) tensors for each carboxylate group in polycrystalline L-alanine and L-phenylalanine. The magic angle spinning (MAS) and stationary 17O NMR spectra of these compounds were obtained at 9.4, 14.1, and 16.4 T. Analyzes of these 17O NMR spectra yielded reliable experimental NMR parameters including 17O CS tensor components, 17O quadrupole coupling parameters, and the relative orientations between the 17O CS and EFG tensors. The extensive quantum chemical calculations at both the restricted Hartree-Fock and density-functional theories were carried out with various basis sets to evaluate the quality of quantum chemical calculations for the 17O NMR tensors in L-alanine. For 17O CS tensors, the calculations at the B3LYP/D95 ∗∗ level could reasonably reproduce 17O CS tensors, but they still showed some discrepancies in the δ11 components by approximately 36 ppm. For 17O EFG calculations, it was advantageous to use calibrated Q value to give acceptable CQ values. The calculated results also demonstrated that not only complete intermolecular hydrogen-bonding networks to target oxygen in L-alanine, but also intermolecular interactions around the NH3+ group were significant to reproduce the 17O NMR tensors.

Tryptophan metabolism via transamination. In vitro aminotransferase assay using dinitrophenylhydrazine method.

PubMed

Drsata, Jaroslav

2003-01-01

Transamination of tryptophan belongs to minor pathways of amino acid metabolism. The present paper describes conditions for application of dinitrophenylhydrazine method, originally prepared for alanine aminortansferase and aspartate aminotransferase assay, to the measurement of tryptophan transamination catalysed by any of the enzymes mentioned above. The method was tested using purified pig heart AST. While the free enzyme showed a characteristic absorption profile with the maxima at 360 and 430 nm, the course of transamination of tryptophan was confirmed by the measurement of UV-VIS spectral changes of the coenzyme in the active site of the enzyme in the presence of the amino acid substrate only, when tryptophan caused a shift of the peak from 360 nm to 330 nm due to a change of the pyridoxal form to the pyridoxamine form (= the first step of ping-pong transaminating reaction). A general limitation of dinitrophenylhydrazine method is the interference of hydrazones formed from the coenzyme pyridoxal-5'-phosphate and from the oxo- substrate 2-oxoglutarate, showing the absorption maxima at 492 nm and 388 nm, respectively with the hydrazones formed by the oxo- products (pyruvate and/or oxaloacetate in the case of ALT/AST, the absorption maxima at 443 nm in our measurements). In the case of tryptophan transamination, indolepyruvate as the oxo- product of a catalysed reaction forms dinitrophenylhydrazone, which has, besides a maximum at 435 nm, a distinct peak at 542 nm, convenient for the product concentration measurement. This is favourable for resolution from other (interfering) hydrazones. Suitable conditions for tryptophan transamination in tissue and enzyme preparations were found. Reaching optimal conditions for tryptophan transamination measurements in vitro is generally limited by low solubility of the amino acid in water solutions: With AST preparation, the velocity of catalysed reaction at 5-50 x 10(-3) M tryptophan concentration was of 1st order to the

Lack of Effect of Sodium Benzoate at Reported Clinical Therapeutic Concentration on d-Alanine Metabolism in Dogs.

PubMed

Popiolek, Michael; Tierney, Brendan; Steyn, Stefanus J; DeVivo, Michael

2018-06-19

Cognitive decline and psychosis have been hypothesized to be mediated by N-methyl-d-aspartate receptor (NMDAR) hypofunction. Consistent with this hypothesis, chronic treatment with d-alanine, a coagonist at the glycine site of the NMDAR, leads to an improvement of positive and cognitive symptoms in schizophrenic patients. d-alanine is oxidized by d-amino acid oxidase (DAAO); thus, an inhibitor of DAAO would be expected to enhance d-alanine levels and likewise lead to desirable clinical outcomes. Sodium benzoate, on the basis of d-amino acid inhibition, was observed to display beneficial clinical effects in schizophrenic and Alzheimer's patients. However, in the clinical pilot studies using sodium benzoate, d-amino acids were not quantified to verify that sodium benzoate's efficacy was mediated through DAAO inhibition. In this study, d-alanine content was monitored in cerebral spinal fluid (CSF) of dogs treated with daily injections of d-alanine (30 mg/kg) alone and in combination with sodium benzoate (30 mg/kg) for seven consecutive days. We reasoned that the cerebral spinal fluid d-alanine quantity is reflective of the brain d-alanine levels and it would increase as a consequence of DAAO inhibition with sodium benzoate. We found that d-alanine treatment lead to maximal concentration of 7.51 μM CSF d-alanine level; however, coadministration of sodium benzoate and d-alanine did not change CSF d-alanine level beyond that of d-alanine treatment alone. As a consequence, we conclude that clinical efficacy associated with chronic administration of sodium benzoate in schizophrenic and Alzheimer's patients is likely not mediated through inhibition of DAAO.

Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two South Indian families with primary hyperoxaluria type 1 causing later onset end-stage kidney disease

PubMed Central

Dutta, A. K.; Paulose, B. K.; Danda, S.; Alexander, S.; Tamilarasi, V.; Omprakash, S.

2016-01-01

Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase deficiency. Here, we describe two unrelated patients who were diagnosed to have primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation was detected in both the patients and the parents were found to be heterozygous carriers. Our patients developed end-stage renal disease at 23 years and 35 years of age. However, in the largest series published from OxalEurope cohort, the median age of end-stage renal disease for null mutations carriers was 9.9 years, which is much earlier than our cases. Our patients had slower progressions as compared to three unrelated patients from North India and Pakistan, who had homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further, patients need to be studied to find out if c.445_452delGTGCTGCT mutation represents a founder mutation in Southern India. PMID:27512303

Single-Dose Absorption and Pharmacokinetics of WR 6026. Phase 1

DTIC Science & Technology

1988-08-01

glucose, uric acid , calcium, phosphate, 8 total protein, albumin, direct and total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase...Fitted Equation 42 Table 8 Elimination Rate Constant and Plasma Half-Life of WK 6026 43 Table 9 Pharmacokinetic Data for Individual Subjects 44 Table 10...failure rate of antimony compounds and the toxicity of other effective drugs, there is a clear need for development of alternative drugs. WR 6026 (8-(6

l-Alanine Auxotrophy of Lactobacillus johnsonii as Demonstrated by Physiological, Genomic, and Gene Complementation Approaches

PubMed Central

van der Kaaij, Hengameh; Desiere, Frank; Mollet, Beat; Germond, Jacques-Edouard

2004-01-01

Using a chemically defined medium without l-alanine, Lactobacillus johnsonii was demonstrated to be strictly auxotrophic for that amino acid. A comparative genetic analysis showed that all known genes involved in l-alanine biosynthesis are absent from the genome of L. johnsonii. This auxotrophy was complemented by heterologous expression of the Bacillus subtilis l-alanine dehydrogenase. PMID:15006820

Metabolic biomarkers for non-alcoholic fatty liver disease induced by high-fat diet: In vivo magnetic resonance spectroscopy of hyperpolarized [1-{sup 13}C] pyruvate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, Chung-Man; Oh, Chang-Hyun; Ahn, Kyu-Youn

Hyperpolarized {sup 13}C magnetic resonance spectroscopy (MRS) to assess hepatic metabolism in non-alcoholic fatty liver disease (NAFLD) has not been reported. This study searched for cellular metabolism-based biomarkers for NAFLD induced by a high-fat diet (HFD) in rats. Also, correlations of the biomarkers with enzyme levels and histopathology were identified during a 6-week follow-up. Six rats were fed a control diet (CD) and seven rats were fed the HFD for 6 weeks. Hyperpolarized {sup 13}C dynamic MRS was performed on rat liver following an injection of hyperpolarized [1-{sup 13}C] pyruvate. Compared with CD-fed rats, HFD-fed rats showed significant increases inmore » the levels of serum alanine aminotransferase and low-density lipoprotein cholesterol at weeks 4 and 6 of follow-up. After the 6-week HFD, the ratios of [1-{sup 13}C] alanine/pyruvate and [1-{sup 13}C] lactate/pyruvate were significantly increased, as were the levels of alanine aminotransferase and lactate dehydrogenase, which are potentially associated with hepatosteatosis. The results implicate [1-{sup 13}C] alanine and [1-{sup 13}C] lactate as potentially useful noninvasive biomarkers of hepatosteatosis occurring in NAFLD. - Highlights: • Hyperpolarized {sup 13}C-alanine and lactate are noninvasive biomarkers on hepatosteatosis. • During the course of HFD feeding, {sup 13}C-alanine and lactate were increased in HFD-rats. • Hyperpolarized {sup 13}C dynamic MRS will be helpful to monitor the progression of NAFLD.« less

"Normal" liver stiffness values differ between men and women: a prospective study for healthy living liver and kidney donors in a native Korean population.

PubMed

Kim, Beom Kyung; Kim, Seung Up; Choi, Gi Hong; Han, Woong Kyu; Park, Mi Sung; Kim, Eun Hye; Park, Jun Yong; Kim, Do Young; Choi, Jin Sub; Yang, Seung Choul; Choi, Eun Hee; Song, Kijun; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon

2012-04-01

Liver stiffness (LS) measurement can distinguish individuals with potential liver disease (LD) from the general population. However, if LS is sex-sensitive, prevalence of LD may be incorrectly estimated when the same reference LS value is applied irrespective of sex. Here, we evaluated whether normal ranges of LS differ between healthy men and women. LS was measured in a cohort of healthy living liver and kidney donors, none of whom suffered from diabetes mellitus, hypertension, hepatitis B or C virus infection, heart or liver dysfunction, or metabolic syndrome. Patients with abnormal laboratory findings related to potential LD (platelet count < 150 × 10(3) /µL; aspartate aminotransferase > 40 IU/L; alanine aminotransferase [ALT] > 40 IU/L; albumin < 3.3 g/dL; total bilirubin > 1.2 mg/dL; gamma-glutamyl transpeptidase > 54 IU/L; alkaline phosphatase > 115 IU/L) were excluded. Among 242 patients analyzed, the mean age was 34.1 for men (n = 121) and 40.5 years for women (n = 121) (P < 0.001). Men had a higher mean LS value than women (5.2 ± 1.2 vs 4.8 ± 1.1 kPa/P < 0.001). Multivariate-linear regression analysis identified sex as the only independent factor for LS values (β = 0.361/P = 0.021). Using the 5th-95th percentiles, we determined normal LS ranges of 3.7-7.0 kPa in men and 3.3-6.8 kPa in women. In subgroups with ALT < 30 IU/L (subgroup-1, n = 216) and ALT < 20 IU/L (subgroup-2, n = 163), men had significantly higher LS values than women (5.2 ± 1.3 vs 4.7 ± 1.1 kPa/P = 0.003 and 5.1 ± 1.2 vs 4.7 ± 1.1 kPa/P = 0.030, respectively), demonstrating an independent sex effect (β = 0.483/P = 0.003 and β = 0.389/P = 0.030, respectively). An independent sex effect on LS values was confirmed. Thus, sex-specific references should be used for effective screening based on LS measurements. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Determination of the carbon, hydrogen and nitrogen contents of alanine and their uncertainties using the certified reference material L-alanine (NMIJ CRM 6011-a).

PubMed

Itoh, Nobuyasu; Sato, Ayako; Yamazaki, Taichi; Numata, Masahiko; Takatsu, Akiko

2013-01-01

The carbon, hydrogen, and nitrogen (CHN) contents of alanine and their uncertainties were estimated using a CHN analyzer and the certified reference material (CRM) L-alanine. The CHN contents and their uncertainties, as measured using the single-point calibration method, were 40.36 ± 0.20% for C, 7.86 ± 0.13% for H, and 15.66 ± 0.09% for N; the results obtained using the bracket calibration method were also comparable. The method described in this study is reasonable, convenient, and meets the general requirement of having uncertainties ≤ 0.4%.

The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis.

PubMed

Rangboo, Vajiheh; Noroozi, Mostafa; Zavoshy, Roza; Rezadoost, Seyed Amirmansoor; Mohammadpoorasl, Asghar

2016-01-01

Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1.

The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis

PubMed Central

Rangboo, Vajiheh; Noroozi, Mostafa; Zavoshy, Roza; Rezadoost, Seyed Amirmansoor; Mohammadpoorasl, Asghar

2016-01-01

Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1. PMID:27293900

Antioxidative Role of Hatikana (Leea macrophylla Roxb.) Partially Improves the Hepatic Damage Induced by CCl4 in Wistar Albino Rats

PubMed Central

Akhter, Samina; Rahman, Md. Atiar; Aklima, Jannatul; Hasan, Md. Rakibul; Hasan Chowdhury, J. M. Kamirul

2015-01-01

This research investigated the protective role of Leea macrophylla extract on CCl4-induced acute liver injury in rats. Different fractions of Leea macrophylla (Roxb.) crude extract were subjected to analysis for antioxidative effects. Rats were randomly divided into four groups as normal control, hepatic control, and reference control (silymarin) group and treatment group. Evaluations were made for the effects of the fractions on serum enzymes and biochemical parameters of CCl4-induced albino rat. Histopathological screening was also performed to evaluate the changes of liver tissue before and after treatment. Different fractions of Leea macrophylla showed very potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, FeCl3 reducing effect, superoxide scavenging effect, and iron chelating effect. Carbon tetrachloride induction increased the level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and other biochemical parameters such as lipid profiles, total protein, and CK-MB. In contrast, treatment of Leea macrophylla reduced the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities as well as biochemical parameters activities. L. macrophylla partially restored the lipid profiles, total protein, and CK-MB. Histopathology showed the treated liver towards restoration. Results evidenced that L. macrophylla can be prospective source of hepatic management in liver injury. PMID:26221590

Effect of Polysaccharide from Cordyceps militaris (Ascomycetes) on Physical Fatigue Induced by Forced Swimming.

PubMed

Xu, Yan-Feng

2016-01-01

Cordyceps militaris is the one of the most important medicinal mushrooms, widely used in East Asian countries. Polysaccharide is considered to be the principal active component in C. militaris and has a wide range of biological and pharmacological properties. This study was undertaken to investigate the effect of polysaccharide from C. militaris (PCM) on physical fatigue induced in animals through a forced swimming test. The mice were divided into 4 groups receiving 28 days' treatment with drinking water (exercise control) or low-, medium-, and high-dose PCM (40, 80, and 160 mg/kg/day, respectively). After 28 days, the mice were subjected to the forced swimming test; the exhaustive swimming time was measured and fatigue-related biochemical parameters, including serum lactic acid, urea nitrogen, creatine kinase, alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, glutathi- one peroxidase, catalase, malondialdehyde, liver glycogen, and muscle glycogen, were analyzed. The results showed that PCM could significantly prolong the exhaustive swimming time of mice; decrease concentrations of serum lactic acid, urea nitrogen, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde; and increase liver and muscle glycogen contents and the concentrations of serum superoxide dismutase, glutathione per- oxidase, and catalase. The data suggest that PCM has an antifatigue effect, and it might become a new functional food or medicine for fatigue resistance.

Hepatoprotective Effect of Cuscuta campestris Yunck. Whole Plant on Carbon Tetrachloride Induced Chronic Liver Injury in Mice.

PubMed

Peng, Wen-Huang; Chen, Yi-Wen; Lee, Meng-Shiou; Chang, Wen-Te; Tsai, Jen-Chieh; Lin, Ying-Chih; Lin, Ming-Kuem

2016-12-07

Cuscuta seeds and whole plant have been used to nourish the liver and kidney. This study was aimed to investigate the hepatoprotective activity of the ethanol extract of Cuscuta campestris Yunck. whole plant (CC EtOH ). The hepatoprotective effect of CC EtOH (20, 100 and 500 mg/kg) was evaluated on carbon tetrachloride (CCl₄)-induced chronic liver injury. Serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol were measured and the fibrosis was histologically examined. CC EtOH exhibited a significant inhibition of the increase of serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol. Histological analyses showed that fibrosis of liver induced by CCl₄ were significantly reduced by CC EtOH . In addition, 20, 100 and 500 mg/kg of the extract decreased the level of malondialdehyde (MDA) and enhanced the activities of anti-oxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. We demonstrate that the hepatoprotective mechanisms of CC EtOH were likely to be associated to the decrease in MDA level by increasing the activities of antioxidant enzymes such as SOD, GPx and GRd. In addition, our findings provide evidence that C. campestris Yunck. whole plant possesses a hepatoprotective activity to ameliorate chronic liver injury.

Hepatoprotective Effect of Cuscuta campestris Yunck. Whole Plant on Carbon Tetrachloride Induced Chronic Liver Injury in Mice

PubMed Central

Peng, Wen-Huang; Chen, Yi-Wen; Lee, Meng-Shiou; Chang, Wen-Te; Tsai, Jen-Chieh; Lin, Ying-Chih; Lin, Ming-Kuem

2016-01-01

Cuscuta seeds and whole plant have been used to nourish the liver and kidney. This study was aimed to investigate the hepatoprotective activity of the ethanol extract of Cuscuta campestris Yunck. whole plant (CCEtOH). The hepatoprotective effect of CCEtOH (20, 100 and 500 mg/kg) was evaluated on carbon tetrachloride (CCl4)-induced chronic liver injury. Serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol were measured and the fibrosis was histologically examined. CCEtOH exhibited a significant inhibition of the increase of serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol. Histological analyses showed that fibrosis of liver induced by CCl4 were significantly reduced by CCEtOH. In addition, 20, 100 and 500 mg/kg of the extract decreased the level of malondialdehyde (MDA) and enhanced the activities of anti-oxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. We demonstrate that the hepatoprotective mechanisms of CCEtOH were likely to be associated to the decrease in MDA level by increasing the activities of antioxidant enzymes such as SOD, GPx and GRd. In addition, our findings provide evidence that C. campestris Yunck. whole plant possesses a hepatoprotective activity to ameliorate chronic liver injury. PMID:27941627

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C. Part 9: reference procedure for the measurement of catalytic concentration of alkaline phosphatase International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Scientific Division, Committee on Reference Systems of Enzymes (C-RSE) (1)).

PubMed

Schumann, Gerhard; Klauke, Rainer; Canalias, Francesca; Bossert-Reuther, Steffen; Franck, Paul F H; Gella, F-Javier; Jørgensen, Poul J; Kang, Dongchon; Lessinger, Jean-Marc; Panteghini, Mauro; Ceriotti, Ferruccio

2011-09-01

Abstract This paper is the ninth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C and the certification of reference preparations. Other parts deal with: Part 1. The concept of reference procedures for the measurement of catalytic activity concentrations of enzymes; Part 2. Reference procedure for the measurement of catalytic concentration of creatine kinase; Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase; Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase; Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase; Part 6. Reference procedure for the measurement of catalytic concentration of γ-glutamyltransferase; Part 7. Certification of four reference materials for the determination of enzymatic activity of γ-glutamyltransferase, lactate dehydrogenase, alanine aminotransferase and creatine kinase at 37 °C; Part 8. Reference procedure for the measurement of catalytic concentration of α-amylase. The procedure described here is derived from the previously described 30 °C IFCC reference method. Differences are tabulated and commented on in Appendix 1.

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

PubMed

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

Four Weeks of β-alanine Supplementation Improves High-Intensity Game Activities in Water Polo.

PubMed

Brisola, Gabriel Motta Pinheiro; de Souza Malta, Elvis; Santiago, Paulo Roberto Pereira; Vieira, Luiz Henrique Palucci; Zagatto, Alessandro Moura

2018-04-13

The present study aimed to investigate whether four weeks of β-alanine supplementation improves total distance covered, distance covered and time spent in different speed zones, and sprint numbers during a simulated water polo game. The study design was double-blind, parallel and placebo controlled. Eleven male water polo players participated in the study, divided randomly into two homogeneous groups (placebo and β-alanine groups). The participants performed a simulated water polo game before and after the supplementation period (4 weeks). Participants received 4.8g∙day -1 of dextrose or β-alanine on the first ten days and 6.4g∙day -1 on the final 18 days. Only the β-alanine group presented a significant improvement in total sprint numbers compared to the pre-supplementation moment (PRE=7.8±5.2a.u.; POST=20.2±7.8a.u.; p=.002). Furthermore, β-alanine supplementation presented a likely beneficial effect on improving total distance covered (83%) and total time spent (81%) in zone 4 of speed (i.e., speed≥1.8m∙s -1 ). There was no significant interaction effect (group×time) for any variable. To conclude, four weeks of β-alanine supplementation can slightly improve sprint numbers and had a likely beneficial effect on improving distance covered and time spent in zone 4 of speed in a water polo simulated game.

Implementation of alanine/EPR as transfer dosimetry system in a radiotherapy audit programme in Belgium.

PubMed

Schaeken, B; Cuypers, R; Lelie, S; Schroeyers, W; Schreurs, S; Janssens, H; Verellen, D

2011-04-01

A measurement procedure based on alanine/electron paramagnetic resonance (EPR) dosimetry was implemented successfully providing simple, stable, and accurate dose-to-water (D(w)) measurements. The correspondence between alanine and ionization chamber measurements in reference conditions was excellent. Alanine/EMR dosimetry might be a valuable alternative to thermoluminescent (TLD) and ionization chamber based measuring procedures in radiotherapy audits. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia.

PubMed

Stein, Evan A; Bays, Harold; O'Brien, Dennis; Pedicano, Jim; Piper, Edward; Spezzi, Andrea

2011-05-10

Lapaquistat acetate is a squalene synthase inhibitor investigated for the treatment of hypercholesterolemia. This report summarizes the phase 2 and 3 results from the lapaquistat clinical program, which was halted at an advanced stage as a result of potential hepatic safety issues. Efficacy and safety data were pooled from 12 studies (n=6151). These were 6- to 96-week randomized, double-blind, parallel, placebo- or active-controlled trials with lapaquistat monotherapy or coadministration with other lipid-altering drugs in dyslipidemic patients, including a large (n=2121) 96-week safety study. All studies included lapaquistat 100 mg daily; 5 included 50 mg; and 1 included 25 mg. The main outcome measures were the percent change in low-density lipoprotein cholesterol, secondary lipid/metabolic parameters, and overall safety. Lapaquistat 100 mg significantly decreased low-density lipoprotein cholesterol by 21.6% in monotherapy and by 18.0% in combination with a statin. It also reduced other cardiovascular risk markers, such as C-reactive protein. Total adverse events were higher for lapaquistat than placebo, although individual events were generally similar. At 100 mg, there was an increase in alanine aminotransferase value ≥3 times the upper limit of normal on ≥2 consecutive visits (2.0% versus 0.3% for placebo in the pooled efficacy studies; 2.7% versus 0.7% for low-dose atorvastatin in the long-term study). Two patients receiving lapaquistat 100 mg met the Hy Law criteria of alanine aminotransferase elevation plus increased total bilirubin. Squalene synthase inhibition with lapaquistat acetate, alone or in combination with statins, effectively lowered low-density lipoprotein cholesterol in a dose-dependent manner. Elevations in alanine aminotransferase, combined with a rare increase in bilirubin, presented potential hepatic safety issues, resulting in termination of development. The lapaquistat experience illustrates the current challenges in lipid

dbAMEPNI: a database of alanine mutagenic effects for protein–nucleic acid interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ling; Xiong, Yi; Gao, Hongyun

Protein–nucleic acid interactions play essential roles in various biological activities such as gene regulation, transcription, DNA repair and DNA packaging. Understanding the effects of amino acid substitutions on protein–nucleic acid binding affinities can help elucidate the molecular mechanism of protein–nucleic acid recognition. Until now, no comprehensive and updated database of quantitative binding data on alanine mutagenic effects for protein–nucleic acid interactions is publicly accessible. Thus, we developed a new database of Alanine Mutagenic Effects for Protein-Nucleic Acid Interactions (dbAMEPNI). dbAMEPNI is a manually curated, literature-derived database, comprising over 577 alanine mutagenic data with experimentally determined binding affinities for protein–nucleic acidmore » complexes. Here, it contains several important parameters, such as dissociation constant (Kd), Gibbs free energy change (ΔΔG), experimental conditions and structural parameters of mutant residues. In addition, the database provides an extended dataset of 282 single alanine mutations with only qualitative data (or descriptive effects) of thermodynamic information.« less

Different β-alanine dimeric forms in trifluoromethanesulfonic acid salts. XRD and vibrational studies.

PubMed

Wołoszyn, Łukasz; Ilczyszyn, Maria M

2018-03-15

Two new crystalline salts: β-alaninium trifluoromethanesulfonate (β-AlaOTf) and bis(β-alanine) trifluoromethanesulfonate (β-2AlaOTf) were obtained. The former one contains diprotonated β-alanine dimer, the latter one monoprotonated β-alanine dimer. Both compounds were studied by single crystal XRD, vibrational (IR and Raman) spectroscopy and calorimetric method. The quantum-mechanical calculations (DFT/B3LYP/6-311++G(2d,2p)) for the diprotonated dimer were carried out. The β-AlaOTf salt crystallizes in the P1¯ space group of triclinic system (Z=2), the β-2AlaOTf in the P2 1 /m space group of monoclinic system (Z=2). The vibrational data for the studied compounds are discussed in relation to their crystal structure, and provide insight into the character of hydrogen bonds and β-alanine protonation. The studied crystals do not exhibit phase transitions in the solid state. Copyright © 2017 Elsevier B.V. All rights reserved.

dbAMEPNI: a database of alanine mutagenic effects for protein–nucleic acid interactions

DOE PAGES

Liu, Ling; Xiong, Yi; Gao, Hongyun; ...

2018-04-02

Protein–nucleic acid interactions play essential roles in various biological activities such as gene regulation, transcription, DNA repair and DNA packaging. Understanding the effects of amino acid substitutions on protein–nucleic acid binding affinities can help elucidate the molecular mechanism of protein–nucleic acid recognition. Until now, no comprehensive and updated database of quantitative binding data on alanine mutagenic effects for protein–nucleic acid interactions is publicly accessible. Thus, we developed a new database of Alanine Mutagenic Effects for Protein-Nucleic Acid Interactions (dbAMEPNI). dbAMEPNI is a manually curated, literature-derived database, comprising over 577 alanine mutagenic data with experimentally determined binding affinities for protein–nucleic acidmore » complexes. Here, it contains several important parameters, such as dissociation constant (Kd), Gibbs free energy change (ΔΔG), experimental conditions and structural parameters of mutant residues. In addition, the database provides an extended dataset of 282 single alanine mutations with only qualitative data (or descriptive effects) of thermodynamic information.« less

Prognostic value of high sensitivity C-reaction protein in non-insulin dependent diabetes mellitus patients with non-alcoholic fatty liver disease.

PubMed

Bi, Yiliang; Min, Min; Shen, Wei; Deng, Pei; Du, Qiupeng; Dong, Mingjie; Liu, Yan

2015-01-01

High sensitivity C-reaction protein (hsCRP) has been used as a significant predictive factor of cardiovascular events in patients with non-insulin dependent diabetes mellitus (NIDDM). However, existing reports in regards to the significance of hsCRP in predicting the progression of hepatic complications in NIDDM patients are too sparse to deliver clear results. This study is aimed at investigating the prognostic value of hsCRP in NIDDM patients with non-alcoholic fatty liver disease (NAFLD). 1128 NIDDM patients with a definite diagnosis of NAFLD were enrolled and followed for one year. The baseline body mass index (BMI), waist-hip circumference ratio (WHR), serum aspartate aminotransferase (AST), presence of hypertension, alanine aminotransferase (ALT), serum hsCRP, total cholesterol (Tch), fasting blood glucose (FBG), triglycerine (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hepatitis B surface antigen (HBsAg) were recorded to analyze the significance of hsCRP in predicting the short-term progression from NAFLD to non-alcoholic steatohepatitis (NASH). One year after baseline, 32% of the NAFLD patients suffered progression to NASH and the percentages of NASH were respectively 8.2%, 12.5%, 33.8% and 72.6% in 4 groups with quartered baseline serum level of hsCRP; there was significant difference among the 4 groups in percentage of NASH (P<0.001). With sex, age, WHR, BMI, hypertension, TG, TCH, HDL-C, LDL-C, FBG and HBsAg included, the calibrated regression model gave the OR values of 1.000, 1.669, 6.635 and 32.131 in in 4 quartered baseline serum levels of hsCRP. High serum level of hsCRP is an independent risk factor of short-term progression to NASH in patients with NIDDM and NAFLD. Those NIDDM patients with NAFLD that present with high serum level of hsCRP should be subjected to regular monitoring, lifestyle intervention and medication.

Hydrogen Cyanide Related Deaths and Detection in the Blood

DTIC Science & Technology

2012-01-01

elevations in creatinine , glucose, and bilirubin have been reported, as have decrease alanine aminotransferase, and unpredictable results for... creatine phosphokinase, phosphate, and lactate dehydrogenase [4]. Urinalyses are often uninterruptable [3]. Thus, we are concerned that deceased patients

Metabolism of 7-ethyoxycoumarin by Isolated Perfused Rainbow Trout Livers

EPA Science Inventory

Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption, vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase leakage, and metabolic clearanc...

Antimicrobial activity of antihypertensive food-derived peptides and selected alanine analogues.

PubMed

McClean, Stephen; Beggs, Louise B; Welch, Robert W

2014-03-01

This study evaluated four food-derived peptides with known antihypertensive activities for antimicrobial activity against pathogenic microorganisms, and assessed structure-function relationships using alanine analogues. The peptides (EVSLNSGYY, barley; PGTAVFK, soybean; TTMPLW, α-casein; VHLPP, α-zein) and the six alanine substitution peptides of PGTAVFK were synthesised, characterised and evaluated for antimicrobial activity using the bacteria, Escherichia coli, Staphylococcus aureus, and Micrococcus luteus and the yeast, Candida albicans. The peptides TTMPLW and PGTAVFK inhibited growth of all four microorganisms tested, with activities of a similar order of magnitude to ampicillin and ethanol controls. EVSLNSGYY inhibited the growth of the bacteria, but VHLPP showed no antimicrobial activity. The alanine analogue, PGAAVFK showed the highest overall antimicrobial activity and PGTAVFA showed no activity; overall, the activities of the analogues were consistent with their structures. Some peptides with antihypertensive activity also show antimicrobial activity, suggesting that food-derived peptides may exert beneficial effects via a number of mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria.

PubMed

Peng, Bo; Su, Yu-Bin; Li, Hui; Han, Yi; Guo, Chang; Tian, Yao-Mei; Peng, Xuan-Xian

2015-02-03

Multidrug-resistant bacteria are an increasingly serious threat to human and animal health. However, novel drugs that can manage infections by multidrug-resistant bacteria have proved elusive. Here we show that glucose and alanine abundances are greatly suppressed in kanamycin-resistant Edwardsiella tarda by GC-MS-based metabolomics. Exogenous alanine or glucose restores susceptibility of multidrug-resistant E. tarda to killing by kanamycin, demonstrating an approach to killing multidrug-resistant bacteria. The mechanism underlying this approach is that exogenous glucose or alanine promotes the TCA cycle by substrate activation, which in turn increases production of NADH and proton motive force and stimulates uptake of antibiotic. Similar results are obtained with other Gram-negative bacteria (Vibrio parahaemolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacterium (Staphylococcus aureus), and the results are also reproduced in a mouse model for urinary tract infection. This study establishes a functional metabolomics-based strategy to manage infection by antibiotic-resistant bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

Over-production, purification and properties of the uridine-diphosphate-N-acetylmuramate:L-alanine ligase from Escherichia coli.

PubMed

Liger, D; Masson, A; Blanot, D; van Heijenoort, J; Parquet, C

1995-05-15

The UDP-N-acetylmuramate:L-alanine ligase of Escherichia coli was over-produced in strains harbouring recombinant plasmids bearing the murC gene under the control of the lac or trc promoter. Plasmid pAM1005, in which the promoter and ribosome-binding site region of murC were removed and in which the gene was directly under the control of promoter trc, led to a 2000-fold amplification of the L-alanine-adding activity after induction by isopropyl-thio-beta-D-galactopyranoside. The murC gene product was visualized as a 50-kDa protein accounting for approximately 50% of the cell protein. A two-step purification led to 1 g of a homogeneous protein from an 18-1 culture. The N-terminal sequence of the purified protein correlated with the nucleotide sequence of the murC gene. The presence of 2-mercaptoethanol and glycerol was essential for the stability of the enzyme. The Km values for UDP-N-acetylmuramic acid, L-alanine and ATP/Mg2+ were estimated at 100, 20 and 450 microM, respectively. Under the optimal in vitro conditions a turnover number of 928 min-1 was calculated and a copy number/cell of 600 could be roughly estimated. The specificity of the enzyme for its substrates was investigated with various analogues. The enzyme also catalysed the reverse reaction.

Comparison of the UDP-N-Acetylmuramate:l-Alanine Ligase Enzymes from Mycobacterium tuberculosis and Mycobacterium leprae

PubMed Central

Mahapatra, Sebabrata; Crick, Dean C.; Brennan, Patrick J.

2000-01-01

In the peptidoglycan of Mycobacterium leprae, l-alanine of the side chain is replaced by glycine. When expressed in Escherichia coli, MurC (UDP-N-acetyl-muramate:l-alanine ligase) of M. leprae showed Km and Vmax for l-alanine and glycine similar to those of Mycobacterium tuberculosis MurC, suggesting that another explanation should be sought for the presence of glycine. PMID:11073931

Enzyme activities in plasma, kidney, liver, and muscle of five avian species

USGS Publications Warehouse

Franson, J.C.; Murray, H.C.; Bunck, C.

1985-01-01

Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) were determined in plasma, kidney, liver, and muscle from five species of captive birds. Few differences occurred in plasma activities between sexes but considerable differences occurred between species. All five enzymes were detected in each of the tissues sampled. Relative enzyme activities in liver, kidney, and muscle were similar for each species. CPK activity was much higher in muscle than in liver or kidney and, of the five enzymes studied, may be the best indicator of muscle damage. Most of the other enzymes were more evenly distributed among the three tissues, and no organ-specific enzyme could be identified for liver or kidney. Because of interspecific variations in plasma enzyme activities, it is important to establish baseline values for each species to ensure accurate interpretation of results.

Muscle Carnosine Concentration with the Co-Ingestion of Carbohydrate with β-alanine in Male Rats.

PubMed

Naderi, Alireza; Sadeghi, Mehdi; Sarshin, Amir; Imanipour, Vahid; Nazeri, Seyed Ali; Farkhayi, Fatemeh; Willems, Mark E T

2017-07-04

Muscle carnosine is an intracellular buffer. The intake of β-alanine, combined with carbohydrate and protein, enhanced carnosine loading in human muscle. The aim of the present study was to examine if muscle carnosine loading was enhanced by β-alanine intake and co-ingestion of glucose in male rats. Thirty-six male rats were divided into three groups and supplemented for four weeks: β-alanine (βA group, 1.8% β-alanine in drinking water), β-alanine and glucose (βAGL group, 1.8% β-alanine and 5% glucose in drinking water), and control (C group, drinking water). During the supplementation period, rats were exercised (20 m·min -1 , 10 min·day -1 , 4 days·week -1 for 4 weeks). Muscle carnosine concentration was quantified in soleus (n = 12) and rectus femoris (n = 6) muscles using high-performance liquid chromatography. In soleus muscle, carnosine concentration was 2.24 ± 1.10, 6.12 ± 1.08, and 6.93 ± 2.56 mmol/kg dw for control, βA, and βAGL, respectively. In rectus femoris, carnosine concentration was 2.26 ± 1.31, 7.90 ± 1.66, and 8.59 ± 2.33 mmol/kg dw for control, βA, and βAGL respectively. In each muscle, βA and βAGL resulted in similar carnosine increases compared to the control. In conclusion, β-alanine intake for four weeks, either alone or with glucose co-ingestion, equally increased muscle carnosine content. It appears that the potential insulin response to fluid glucose intake does not affect muscle carnosine loading in male rats.

Hydrogen bonds in crystalline D-alanine: diffraction and spectroscopic evidence for differences between enantiomers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belo, Ezequiel A.; Pereira, Jose E. M.; Freire, Paulo T. C.

Enantiomeric amino acids have specific physiological functions in complex biological systems. Systematic studies focusing on the solid-state properties of D-amino acids are, however, still limited. To shed light on this field, structural and spectroscopic studies of D-alanine using neutron powder diffraction, polarized Raman scattering and ab initio calculations of harmonic vibrational frequencies were carried out. Clear changes in the number of vibrational modes are observed as a function of temperature, which can be directly connected to variations of the N—D bond lengths. These results reveal dissimilarities in the structural properties of D-alanine compared with L-alanine.

Hydrogen bonds in crystalline D-alanine: diffraction and spectroscopic evidence for differences between enantiomers

DOE PAGES

Belo, Ezequiel A.; Pereira, Jose E. M.; Freire, Paulo T. C.; ...

2018-01-01

Enantiomeric amino acids have specific physiological functions in complex biological systems. Systematic studies focusing on the solid-state properties of D-amino acids are, however, still limited. To shed light on this field, structural and spectroscopic studies of D-alanine using neutron powder diffraction, polarized Raman scattering and ab initio calculations of harmonic vibrational frequencies were carried out. Clear changes in the number of vibrational modes are observed as a function of temperature, which can be directly connected to variations of the N—D bond lengths. These results reveal dissimilarities in the structural properties of D-alanine compared with L-alanine.

Serum biochemistry of captive and free-ranging gray wolves (Canis lupus)

USGS Publications Warehouse

Constable, Peter; Hinchcliff, Ken; Demma, Nick; Callahan, Margaret; Dale, B.W.; Fox, Kevin; Adams, Layne G.; Wack, Ray; Kramer, Lynn

1998-01-01

Normal serum biochemistry values are frequently obtained from studies of captive sedentary (zoo) or free-ranging (wild) animals. It is frequently assumed that values from these two populations are directly referable to each other. We tested this assumption using 20 captive gray wolves (Canis lupus) in Minnesota, USA, and 11 free-ranging gray wolves in Alaska, USA. Free-ranging wolves had significantly (P<0.05) lower sodium, chloride, and creatine concentrations and significantly higher potassium and blood urea nitrogen (BUN) concentrations; BUN to creatine ratios; and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities relative to captive wolves. Corticosteroid-induced alkaline phosphatase activity (a marker of stress in domestic dogs) was detected in 3 of 11 free-ranging wolves and in 0 of 20 captive wolves (P = 0.037). This study provides clear evidence that serum biochemical differences can exist between captive and free-ranging populations of one species. Accordingly, evaluation of the health status of an animal should incorporate an understanding of the potential confounding effect that nutrition, activity level, and environmental stress could have on the factor(s) being measured.

[Clinical value of serum presepsin (SCD14-ST) concentration measurement in patients with pesticide poisoning].

PubMed

Gao, X; Zhu, B Y; Wang, W Z; He, J Q; Han, D L; Liu, Y J; Meng, H; Xiao, Q M; Liu, X T; Han, Y Y

2016-05-20

To investigate the value of serum presepsin concentration measurement in the clinical diagnosis and treatment of patients with pesticide poisoning patients. A total of 160 patients with pesticide poisoning were enrolled as study subjects and divided into moderate organophosphate pesticide poisoning group (40 patients) , severe organophosphate pesticide poisoning group (40 patients) , abamectin pesticide poisoning group (40 patients) , and paraquat poisoning group (40 patients). A total of 20 healthy volunteers were enrolled as the control group. All the patients with poisoning received conventional treatment of pesticide poisoning immediately after admission, and serum presepsin concentration was measured on days 1 (within 24 hours after poisoning) , 3, and 7 of admission, and biochemical and radiological parameters related to the patient's condition were also examined. The patients with a Presepsin concentration of >800 pg/ml on day 1 of admission were randomly divided into conventional treatment group and ulinastatin treatment group, and the treatment outcome was compared between the two groups. Compared with the healthy control group, the groups with pesticide poisoning showed significant increases in serum Presepsin concentrations, with the highest degree of increase on day 1 (P <0.05). The serum Presepsin concentration was positively correlated with alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase MB, lactate dehydrogenase, serum creatinine, blood urea nitrogen, interleukin-18, and white blood cell count, but negatively correlated with cholinesterase. In the conventional treatment group and ulinastatin treatment group, the overall response rate was 68% and 78.8%, respectively, with a significant difference between the two groups (P<0.05). In 40 patients with paraquat poisoning, 32 experienced an increase in serum presepsin concentration, and among these 32 patients, 27 (83%) experienced exudation on lung CT. Serum

Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mutans.

PubMed

Wei, Yuan; Qiu, Wei; Zhou, Xue-Dong; Zheng, Xin; Zhang, Ke-Ke; Wang, Shi-Da; Li, Yu-Qing; Cheng, Lei; Li, Ji-Yao; Xu, Xin; Li, Ming-Yun

2016-12-16

D-alanine (D-Ala) is an essential amino acid that has a key role in bacterial cell wall synthesis. Alanine racemase (Alr) is a unique enzyme that interconverts L-alanine and D-alanine in most bacteria, making this enzyme a potential target for antimicrobial drug development. Streptococcus mutans is a major causative factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Alr in S. mutans. We constructed alr mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that alr deletion was lethal to S. mutans. A minimal supplement of D-Ala (150 μg·mL -1 ) was required for the optimal growth of the alr mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the alr mutant strain. We also determined the compromised competitiveness of the alr mutant strain relative to the wild-type S. mutans against other oral streptococci (S. sanguinis or S. gordonii), demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of alr to the growth and competitiveness of S. mutans, Alr may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.

Photochemical redox reactions of copper(II)-alanine complexes in aqueous solutions.

PubMed

Lin, Chen-Jui; Hsu, Chao-Sheng; Wang, Po-Yen; Lin, Yi-Liang; Lo, Yu-Shiu; Wu, Chien-Hou

2014-05-19

The photochemical redox reactions of Cu(II)/alanine complexes have been studied in deaerated solutions over an extensive range of pH, Cu(II) concentration, and alanine concentration. Under irradiation, the ligand-to-metal charge transfer results in the reduction of Cu(II) to Cu(I) and the concomitant oxidation of alanine, which produces ammonia and acetaldehyde. Molar absorptivities and quantum yields of photoproducts for Cu(II)/alanine complexes at 313 nm are characterized mainly with the equilibrium Cu(II) speciation where the presence of simultaneously existing Cu(II) species is taken into account. By applying regression analysis, individual Cu(I) quantum yields are determined to be 0.094 ± 0.014 for the 1:1 complex (CuL) and 0.064 ± 0.012 for the 1:2 complex (CuL2). Individual quantum yields of ammonia are 0.055 ± 0.007 for CuL and 0.036 ± 0.005 for CuL2. Individual quantum yields of acetaldehyde are 0.030 ± 0.007 for CuL and 0.024 ± 0.007 for CuL2. CuL always has larger quantum yields than CuL2, which can be attributed to the Cu(II) stabilizing effect of the second ligand. For both CuL and CuL2, the individual quantum yields of Cu(I), ammonia, and acetaldehyde are in the ratio of 1.8:1:0.7. A reaction mechanism for the formation of the observed photoproducts is proposed.

Interference of ascorbic acid with chemical analytes.

PubMed

Meng, Qing H; Irwin, William C; Fesser, Jennifer; Massey, K Lorne

2005-11-01

Ascorbic acid can interfere with methodologies involving redox reactions, while comprehensive studies on main chemistry analysers have not been reported. We therefore attempted to determine the interference of ascorbic acid with analytes on the Beckman Synchron LX20. Various concentrations of ascorbic acid were added to serum, and the serum analytes were measured on the LX20. With a serum ascorbic acid concentration of 12.0 mmol/L, the values for sodium, potassium, calcium and creatinine increased by 43%, 58%, 103% and 26%, respectively (P<0.01). With a serum ascorbic acid concentration of 12.0 mmol/L, the values for chloride, total bilirubin and uric acid decreased by 33%, 62% and 83%, respectively (P<0.01), and were undetectable for total cholesterol, triglyceride, ammonia and lactate. There was no definite influence of ascorbic acid on analytical values for total CO(2), urea, glucose, phosphate, total protein, albumin, amylase, creatine kinase, creatine kinase-MB, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total iron, unbound iron-binding capacity or magnesium. Ascorbic acid causes a false increase in sodium, potassium, calcium and creatinine results and a false decrease in chloride, total bilirubin, uric acid, total cholesterol, triglyceride, ammonia and lactate results.

Optimization of an Isolated Perfused Rainbow Trout Liver Model: Clearance Studies with 7-Ethoxycoumarin

EPA Science Inventory

Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption (VO2), vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase (ALT) leakage, and meta...

Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs.

PubMed

Yu, Hong; Bao, En-Dong; Zhao, Ru-Qian; Lv, Qiong-Xia

2007-11-01

To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs. 24 pigs (mean weight, 20 +/- 1 kg). Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA. No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs. Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.

Measurement of Creatine kinase and Aspartate aminotransferase in saliva of dogs: a pilot study.

PubMed

Tvarijonaviciute, Asta; Barranco, Tomas; Rubio, Monica; Carrillo, Jose Maria; Martinez-Subiela, Silvia; Tecles, Fernando; Carrillo, Juana Dolores; Cerón, José J

2017-06-09

Muscle enzymes in saliva have been reported to be possible markers of heart and muscle damage in humans. The aim of this study was to assess if Creatine kinase (CK) and Aspartate aminotransferase (AST) activities could be measured in canine saliva, and to evaluate their possible changes in situations of muscle damage. The spectrophotometric assays for CK and AST measurement in saliva of dogs showed intra- and inter-assay imprecision lower than 1 and 16% and coefficients of correlation close to 1 in linearity under dilution tests. Healthy dogs showed activities in saliva of CK between 27 and 121 U/L and AST between 46 and 144 U/L, whereas in saliva of dogs with muscle damage CK ranged between 132 and 3862 U/L and AST between 154 and 4340 U/L. Positive moderate correlations were found between saliva and serum activities of the two enzymes (CK, r = 0.579; P = 0.001; AST, r = 0.674; P = 0.001). CK and AST activities can be measured in canine saliva with commercially available spectrophotometric assays. In addition these enzymes show higher values in saliva of dogs with muscle damage and their values are moderately correlated with those of serum.

Effect of Inhaling Cymbopogon martinii Essential Oil and Geraniol on Serum Biochemistry Parameters and Oxidative Stress in Rats.

PubMed

Andrade, Bruna Fernanda Murbach Teles; Braga, Camila Pereira; Dos Santos, Klinsmann Carolo; Barbosa, Lidiane Nunes; Rall, Vera Lúcia Mores; Sforcin, José Maurício; Fernandes, Ana Angélica Henrique; Fernandes Júnior, Ary

2014-01-01

The effects of the inhalation of Cymbopogon martinii essential oil (EO) and geraniol on Wistar rats were evaluated for biochemical parameters and hepatic oxidative stress. Wistar rats were divided into three groups (n = 8): G1 was control group, treated with saline solution; G2 received geraniol; and G3 received C. martinii EO by inhalation during 30 days. No significant differences were observed in glycemia and triacylglycerol levels; G2 and G3 decreased (P < 0.05) total cholesterol level. There were no differences in serum protein, urea, aspartate aminotransferase activity, and total hepatic protein. Creatinine levels increased in G2 but decreased in G3. Alanine aminotransferase activity and lipid hydroperoxide were higher in G2 than in G3. Catalase and superoxide dismutase activities were higher in G3. C. martinii EO and geraniol increased glutathione peroxidase. Oxidative stress caused by geraniol may have triggered some degree of hepatic toxicity, as verified by the increase in serum creatinine and alanine aminotransferase. Therefore, the beneficial effects of EO on oxidative stress can prevent the toxicity in the liver. This proves possible interactions between geraniol and numerous chemical compounds present in C. martinii EO.

Hepatocellular integrity after parenteral nutrition: comparison of a fish-oil-containing lipid emulsion with an olive-soybean oil-based lipid emulsion.

PubMed

Piper, Swen N; Schade, Ingo; Beschmann, Ralf B; Maleck, Wolfgang H; Boldt, Joachim; Röhm, Kerstin D

2009-12-01

Parenteral nutrition including lipids might be associated with liver disease. The cause leading to parenteral nutrition-related liver dysfunction remains largely unknown but is likely to be multifactorial. The study was performed to assess the effects of a lipid emulsion based on soybean oil, medium-chain triglycerides, olive and fish oil (SMOFlipid20%) compared with a lipid emulsion based on olive and soybean oil on hepatic integrity. In a prospective, randomized, double-blinded trial, 44 postoperative patients with an indication for parenteral nutrition were allocated to one of two regimens: group A (n = 22) received SMOFlipid, group B (n = 22) a lipid emulsion based on olive and soybean oil for 5 days. Aspartate aminotransferase, alanin-aminotransferase, and serum alpha-glutathion S-transferase were measured before the start of parenteral nutrition (d0), at day 2 (d2), and day 5 (d5) after the start of parenteral nutrition. The significance level was defined at a P value of less than 0.05. There was no significant difference at d0, but at d2 and d5, significantly lower aspartate aminotransferase (d2: group A: 27 +/- 13 vs. group B: 47 +/- 36 U l(-1); d5: A: 31 +/- 14 vs. B: 56 +/- 45 U l(-1)), alanin-aminotransferase (d2: A: 20 +/- 12 vs. B: 42 +/- 39 U l(-1); d5: A: 26 +/- 15 vs. B: 49 +/- 44 U l(-1)), and alpha-glutathion S-transferase levels (d2: A: 5 +/- 6 vs. B: 17 +/- 21 U l(-1); d5: A: 6 +/- 7 vs. B: 24 +/- 27 microg l(-1)) were found in soybean oil, medium-chain triglycerides, olive and fish oil group compared with the control group. Hepatic integrity was well retained with the administration of SMOFlipid whereas in patients receiving a lipid emulsion based on olive and soybean oil liver enzymes were elevated indicating a lower liver tolerability.

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

PubMed

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.

Evaluation of alanine as a reference dosimeter for therapy level dose comparisons in megavoltage electron beams

NASA Astrophysics Data System (ADS)

McEwen, Malcolm; Sharpe, Peter; Vörös, Sándor

2015-04-01

When comparing absorbed dose standards from different laboratories (e.g. National Measurement Institutes, NMIs, for Key or Supplementary comparisons) it is rarely possible to carry out a direct comparison of primary standard instruments, and therefore some form of transfer detector is required. Historically, air-filled, unsealed ionization chambers have been used because of the long history of using these instruments, very good stability over many years, and ease of transport. However, the use of ion chambers for therapy-level comparisons is not without its problems. Findings from recent investigations suggest that ion chambers are prone to non-random variations, they are not completely robust to standard courier practices, and failure at any step in a comparison can render all measurements potentially useless. An alternative approach is to identify a transfer system that is insensitive to some of these concerns—effectively a dosimeter that is inexpensive, simple to use, robust, but with sufficient precision and of a size relevant to the disseminated quantity in question. The alanine dosimetry system has been successfully used in a number of situations as an audit dosimeter and therefore the purpose of this investigation was to determine whether alanine could also be used as the transfer detector for dosimetric comparisons, which require a lower value for the measurement uncertainty. A measurement protocol was developed for comparing primary standards of absorbed dose to water in high-energy electron beams using alanine pellets irradiated in a water-equivalent plastic phantom. A trial comparison has been carried out between three NMIs and has indicated that alanine is a suitable alternative to ion chambers, with the system used achieving a precision of 0.1%. Although the focus of the evaluation was on the performance of the dosimeter, the comparison results are encouraging, showing agreement at the level of the combined uncertainties (~0.6%). Based on this

Amino Acid Isotopic Trophic Enrichment in Mesozooplankton: Is Alanine a Better Predictor of Protistan Grazer Steps?

NASA Astrophysics Data System (ADS)

Decima, M.; Landry, M. R.; Bradley, C. J.; Fogel, M. L.

2016-02-01

Food-web studies within marine environments are increasingly reliant upon results from compound-specific isotope analysis of amino acids (CSIA-AA). The approach is advantageous because it allows consumer trophic positions to be estimated without sampling the dynamic primary producers. The baseline signal in the source AA phenylalanine is preserved, and a constant enrichment in glutamic acid at each trophic step is assumed, regardless of consumer type or diet. However, a number of recent studies challenge the assumption of universal and invariant isotopic fractionation of glutamic acid for all trophic levels, as well as its specific applicability to the main grazers in the ocean: the protistan microzooplankton. We present results from both laboratory and field studies that further explore this issue. Experiments include six 2-stage chemostats, using two different microzooplankton-phytoplankton pairs and one copepod-phytoplankton pair, and one 3-stage experiment using a copepod-microzooplankton-phytoplankton chain. We confirm previous observations of negligible fractionation of glutamic acid in protistan consumers when nutrients are limiting. In contrast, a consistent trophic enrichment effect was observed for alanine, with increasing δ15N values by trophic level for both metazoan and protistan consumers. A re-analysis of published CSIA-AA data of zooplankton species show that an index using alanine and phenylalanine gives trophic level estimates closer to expected given current understanding of the linkages within microbial food webs. Our results examine the details of isotopic fractionation of alanine within defined food chains and generally support its potential use as a trophic level indicator that includes the protistan contribution to mesozooplankton diet.

Novel alanines bearing a heteroaromatic side chain: synthesis and studies on fluorescent chemosensing of metal cations with biological relevance.

PubMed

Ferreira, Rosa Cristina M; Raposo, Maria Manuela M; Costa, Susana P G

2018-06-01

A family of novel thienylbenzoxazol-5-yl-L-alanines, consisting of an alanine core bearing a benzoxazole at the side chain with a thiophene ring at position 2, substituted with different (hetero)aryl substituents, was synthesised to study the tuning of the photophysical and chemosensory properties of the resulting compounds. These novel heterocyclic alanines 3a-f and a series of structurally related bis-thienylbenzoxazolyl-alanines 3g-j were evaluated for the first time in the recognition of selected metal cations with environmental, medicinal and analytical interest such as Co 2+ , Cu 2+ , Zn 2+ and Ni 2+ , in acetonitrile solution, with the heterocycles at the side chain acting simultaneously as the coordinating and reporting units, via fluorescence changes. This behaviour can be explained by the involvement of the electron donor heteroatoms in the recognition event, through complexation of the metal cations. The spectrofluorimetric titrations showed that thienylbenzoxazolyl-alanines 3a-j and 4a,b were non-selective fluorimetric chemosensors for the above-mentioned cations, with the best results being obtained for the interaction of Cu 2+ with bis-alanine 3j and deprotected alanines 4a,b. The encouraging photophysical and metal ion sensing properties of these thienylbenzoxazolyl-alanines suggest that they can be used to obtain bioinspired fluorescent reporters for metal ion such as peptides/proteins with chemosensory/probing ability.

Self-Assembly, Supramolecular Organization, and Phase Behavior of L-Alanine Alkyl Esters (n = 9-18) and Characterization of Equimolar L-Alanine Lauryl Ester/Lauryl Sulfate Catanionic Complex.

PubMed

Sivaramakrishna, D; Swamy, Musti J

2015-09-08

A homologous series of l-alanine alkyl ester hydrochlorides (AEs) bearing 9-18 C atoms in the alkyl chain have been synthesized and characterized with respect to self-assembly, supramolecular structure, and phase transitions. The CMCs of AEs bearing 11-18 C atoms were found to range between 0.1 and 10 mM. Differential scanning calorimetric (DSC) studies showed that the transition temperatures (Tt), enthalpies (ΔHt) and entropies (ΔSt) of AEs in the dry state exhibit odd-even alternation, with the odd-chain-length compounds having higher Tt values, but the even-chain-length homologues showing higher values of ΔHt and ΔSt. In DSC measurements on hydrated samples, carried out at pH 5.0 and pH 10.0 (where they exist in cationic and neutral forms, respectively), compounds with 13-18 C atoms in the alkyl chain showed sharp gel-to-liquid crystalline phase transitions, and odd-even alternation was not seen in the thermodynamic parameters. The molecular structure, packing properties, and intermolecular interactions of AEs with 9 and 10 C atoms in the alkyl chain were determined by single crystal X-ray diffraction, which showed that the alkyl chains are packed in a tilted interdigitated bilayer format. d-Spacings obtained from powder X-ray diffraction studies exhibited a linear dependence on the alkyl chain length, suggesting that the other AEs also adopt an interdigitated bilayer structure. Turbidimetric, fluorescence spectroscopic, and isothermal titration calorimetric (ITC) studies established that in aqueous dispersions l-alanine lauryl ester hydrochloride (ALE·HCl) and sodium dodecyl sulfate (SDS) form an equimolar complex. Transmission electron microscopic and DSC studies indicate that the complex exists as unilamellar liposomes, which exhibit a sharp phase transition at ∼39 °C. The aggregates were disrupted at high pH, suggesting that the catanionic complex would be useful to develop a base-labile drug delivery system. ITC studies indicated that ALE·HCl forms

[Effects of ß-alanine supplementation on wingate tests in university female footballers].

PubMed

Rodríguez Rodríguez, Fernando; Delgado Ormeño, Alex; Rivera Lobos, Patricio; Tapia Aranda, Víctor; Cristi-Montero, Carlos

2014-11-01

Football is a sport that develops actions intermittent high-intensity exercise using the anaerobic pathway, for that reason, the muscle fatigue would produce primarily by increasing acidosis. Carnosine, which is formed from L-histidine, ß-alanine, has proven to produce an effect "buffer" of acidosis. To determine the effect of ß-alanine supplementation, on three successive Wingate tests and compare the average power, maximum power and lactate blood in selected female college soccer. We evaluated 10 football players who were three Wingate, 5 min rest between each sprint, determining the average power, maximum and lactate at the end of each test, then consumed 2,4 gr/day of ß-alanine for 30 days and repeated the tests. The control group (n=8) performed the same tests, but without consuming the supplement. Monark cycle ergometer was used (Ergomedic 874E) and to measure lactate the Lactate Pro 2. The group with supplementation significantly improved mean power difference from the control group. The maximum power improved only in the first sprint unlike the control group and Lactate did not differ. The evidence shows that the ß-alanine improves performance on tests of more than 30 second long, but in our study improves average power and peak power even when performing consecutive sprint, being able to emulate the reality of the football game. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

AlaScan: A Graphical User Interface for Alanine Scanning Free-Energy Calculations.

PubMed

Ramadoss, Vijayaraj; Dehez, François; Chipot, Christophe

2016-06-27

Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of amino-acid replacement in protein-ligand and protein-protein complexes, or probe the thermostability of individual proteins. Because human effort represents a significant cost that precludes the routine use of this form of free-energy calculations, minimizing manual intervention constitutes a stringent prerequisite for any such systematic computation. With this objective in mind, we propose a new plug-in, referred to as AlaScan, developed within the popular visualization program VMD to automate the major steps in alanine-scanning calculations, employing free-energy perturbation as implemented in the widely used molecular dynamics code NAMD. The AlaScan plug-in can be utilized upstream, to prepare input files for selected alanine mutations. It can also be utilized downstream to perform the analysis of different alanine-scanning calculations and to report the free-energy estimates in a user-friendly graphical user interface, allowing favorable mutations to be identified at a glance. The plug-in also assists the end-user in assessing the reliability of the calculation through rapid visual inspection.

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

PubMed

Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

2015-11-01

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase

Synthesis and characterization of poly(L-alanine)-block-poly(ethylene glycol) monomethyl ether as amphiphilic biodegradable co-polymers.

PubMed

Zhang, Guolin; Ma, Jianbiao; Li, Yanhong; Wang, Yinong

2003-01-01

Di-block co-polymers of poly(L-alanine) with poly(ethylene glycol) monomethyl ether (MPEG) were synthesized as amphiphilic biodegradable co-polymers. The ring-opening polymerization of N-carboxy-L-alanine anhydride (NCA) in dichloromethane was initiated by amino-terminated poly(ethylene glycol) monomethyl ether (MPEG-NH2, M(n) = 2000) to afford poly(L-alanine)-block-MPEG. The weight ratio of two blocks in the co-polymers could be altered by adjusting the feeding ratio of NCA to MPEG-NH2. Their chemical structures were characterized on the basis of infrared spectrometry and nuclear magnetic resonance. According to circular dichroism measurement, the poly(L-alanine) chain on the co-polymers in an aqueous medium had a alpha-helix conformation. Two melting points from MPEG block and poly(L-alanine), respectively, could be observed in differential scanning calorimetry curves of the co-polymers, suggesting that a micro-domain phase separation appeared in their bulky states. The co-polymers could take up some water and the capacity was dependent on the ratio of poly(L-alanine) block to MPEG. Such co-polymers might be useful in drug-delivery systems and other biomedical applications.

GMXPBSA 2.1: A GROMACS tool to perform MM/PBSA and computational alanine scanning

NASA Astrophysics Data System (ADS)

Paissoni, C.; Spiliotopoulos, D.; Musco, G.; Spitaleri, A.

2015-01-01

GMXPBSA 2.1 is a user-friendly suite of Bash/Perl scripts for streamlining MM/PBSA calculations on structural ensembles derived from GROMACS trajectories, to automatically calculate binding free energies for protein-protein or ligand-protein complexes [R.T. Bradshaw et al., Protein Eng. Des. Sel. 24 (2011) 197-207]. GMXPBSA 2.1 is flexible and can easily be customized to specific needs and it is an improvement of the previous GMXPBSA 2.0 [C. Paissoni et al., Comput. Phys. Commun. (2014), 185, 2920-2929]. Additionally, it performs computational alanine scanning (CAS) to study the effects of ligand and/or receptor alanine mutations on the free energy of binding. Calculations require only for protein-protein or protein-ligand MD simulations. GMXPBSA 2.1 performs different comparative analyses, including a posteriori generation of alanine mutants of the wild-type complex, calculation of the binding free energy values of the mutant complexes and comparison of the results with the wild-type system. Moreover, it compares the binding free energy of different complex trajectories, allowing the study of the effects of non-alanine mutations, post-translational modifications or unnatural amino acids on the binding free energy of the system under investigation. Finally, it can calculate and rank relative affinity to the same receptor utilizing MD simulations of proteins in complex with different ligands. In order to dissect the different MM/PBSA energy contributions, including molecular mechanic (MM), electrostatic contribution to solvation (PB) and nonpolar contribution to solvation (SA), the tool combines two freely available programs: the MD simulations software GROMACS [S. Pronk et al., Bioinformatics 29 (2013) 845-854] and the Poisson-Boltzmann equation solver APBS [N.A. Baker et al., Proc. Natl. Acad. Sci. U.S.A 98 (2001) 10037-10041]. All the calculations can be performed in single or distributed automatic fashion on a cluster facility in order to increase the

Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate

NASA Astrophysics Data System (ADS)

Barb, A. W.; Hekmatyar, S. K.; Glushka, J. N.; Prestegard, J. H.

2013-03-01

Hyperpolarized metabolites offer a tremendous sensitivity advantage (>104 fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, 13C-enriched analog of pyruvic acid, 13C3D3-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct 13C observation and indirect observation through methyl protons introduced by ALT-catalyzed H-D exchange. Exchange on injecting hyperpolarized 13C3D3-pyruvate into ALT dissolved in buffered 1H2O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5 s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized 13C3-pyruvate and products in imaging applications are discussed.

Prevalence of abnormal plasma liver enzymes in older people with Type 2 diabetes.

PubMed

Morling, J R; Strachan, M W J; Hayes, P C; Butcher, I; Frier, B M; Reynolds, R M; Price, J F

2012-04-01

To determine the prevalence and distribution of abnormal plasma liver enzymes in a representative sample of older adults with Type 2 diabetes. Plasma concentrations of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were measured in a randomly selected, population-based cohort of 1066 men and women aged 60-75 years with Type 2 diabetes (the Edinburgh Type 2 Diabetes Study). Overall, 29.1% (95% CI 26.1-31.8) of patients had one or more plasma liver enzymes above the upper limit of the normal reference range. Only 10.1% of these patients had a prior history of liver disease and a further 12.4% reported alcohol intake above recommended limits. Alanine aminotransferase was the most commonly raised liver enzyme (23.1% of patients). The prevalence of abnormal liver enzymes was significantly higher in men (odds ratio 1.40, 95% CI 1.07-1.83), in the youngest 5-year age band (odds ratio 2.02, 95% CI 1.44-2.84), in patients with diabetes duration < 5 years (odds ratio 1.38, 95% CI 1.01-1.90), plasma HbA(1c) ≥ 58 mmol/mol (7.5%) (odds ratio 1.43, 95% CI 1.09-1.88), obese BMI (odds ratio 2.84, 95% CI 1.59-3.06) and secondary care management for their diabetes (odds ratio 1.40, 95% CI 1.05-1.87). However, all these factors combined accounted for only 7.6% of the variation in liver enzyme abnormality. The prevalence of elevated liver enzymes in people with Type 2 diabetes is high, with only modest variation between clinically defined patient groups. Further research is required to determine the prognostic value of raised, routinely measured liver enzymes to inform decisions on appropriate follow-up investigations. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens. PMID:19043818

Effects of Urtica dioica on hepatic ischemia-reperfusion injury in rats.

PubMed

Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

2010-01-01

To evaluate the effects of Urtica dioica on hepatic ischemia-reperfusion injury. Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. Urtica dioica has a protective effect on the liver in hepatic ischemia-reperfusion-injured rats.

Effects of Urtica dioica on hepatic ischemia‐reperfusion injury in rats

PubMed Central

Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

2010-01-01

OBJECTIVES: To evaluate the effects of Urtica dioica on hepatic ischemia‐reperfusion injury. METHODS: Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. CONCLUSIONS: Urtica dioica has a protective effect on the liver in hepatic ischemia‐reperfusion‐injured rats. PMID:21340227

Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study.

PubMed

Ogihara, Takeshi; Mita, Tomoya; Osonoi, Yusuke; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Gosho, Masahiko; Kanazawa, Akio; Watada, Hirotaka

2017-01-01

While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal-metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. UMIN000010932.

The crystal structure of the D-alanine-D-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding.

PubMed

Huynh, Kim-Hung; Hong, Myoung-ki; Lee, Clarice; Tran, Huyen-Thi; Lee, Sang Hee; Ahn, Yeh-Jin; Cha, Sun-Shin; Kang, Lin-Woo

2015-11-01

Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity.

PubMed

Toyama, Yoshiro; Tanizawa, Kiminobu; Kubo, Takeshi; Chihara, Yuichi; Harada, Yuka; Murase, Kimihiko; Azuma, Masanori; Hamada, Satoshi; Hitomi, Takefumi; Handa, Tomohiro; Oga, Toru; Chiba, Tsutomu; Mishima, Michiaki; Chin, Kazuo

2015-01-01

Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m2 or visceral fat area ≥100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R2 = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent. Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity

PubMed Central

Toyama, Yoshiro; Tanizawa, Kiminobu; Kubo, Takeshi; Chihara, Yuichi; Harada, Yuka; Murase, Kimihiko; Azuma, Masanori; Hamada, Satoshi; Hitomi, Takefumi; Handa, Tomohiro; Oga, Toru; Chiba, Tsutomu; Mishima, Michiaki; Chin, Kazuo

2015-01-01

Rationale Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. Objectives To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. Methods Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. Results Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m2 or visceral fat area ≥100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R2 = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent. Conclusions Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver

Two Site-Directed Mutations are Required for the Conversion of a Sugar Dehydratase into an Aminotransferase¶

PubMed Central

Cook, Paul D.; Kubiak, Rachel L.; Toomey, Daniel P.; Holden, Hazel M.

2009-01-01

l-colitose and d-perosamine are unusual sugars found in the O-antigens of some Gram-negative bacteria such as Escherichia coli, Vibrio cholerae, and Salmonella enterica, among others. The biosynthetic pathways for these two sugars begin with the formation of GDP-mannose from d-mannose-1-phosphate and GTP followed by the subsequent dehydration and oxidation of GDP-mannose to yield GDP-4-keto-6-deoxymannose. Following the production of GDP-4-keto-6-deoxymannose, the two pathways diverge. In the case of GDP-perosamine biosynthesis, the next step involves an amination reaction at the C-4′ position of the sugar, whereas in GDP-colitose production, the 3′-hydroxyl group is removed. The enzymes catalyzing these reactions are GDP-perosamine synthase and GDP-4-keto-6-deoxymannose-3-dehydratase (ColD), respectively. Both of these enzymes are pyridoxal-5′-phosphate (PLP)-dependent and their three-dimensional structures place them into the well-characterized aspartate aminotransferase superfamily. A comparison of the active site architecture of ColD from Escherichia coli (Strain 5a, type O55:H7) to that of GDP-perosamine synthase from Caulobacter crescentus CB15, suggested that only two mutations would be required to convert ColD into an aminotransferase. Here we present a combined structural and functional analysis of the ColD S187N/H188K mutant protein that, indeed, has been converted from a dehydratase into an aminotransferase. PMID:19402712

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

PubMed

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.

beta-Alanine elevates dopamine levels in the rat nucleus accumbens: antagonism by strychnine.

PubMed

Ericson, Mia; Clarke, Rhona B C; Chau, PeiPei; Adermark, Louise; Söderpalm, Bo

2010-04-01

Glycine receptors (GlyRs) in the nucleus accumbens (nAc) have recently been suggested to be involved in the reinforcing and dopamine-elevating properties of ethanol via a neuronal circuitry involving the VTA. Apart from ethanol, both glycine and taurine have the ability to modulate dopamine output via GlyRs in the same brain region. In the present study, we wanted to explore whether yet another endogenous ligand for the GlyR, beta-alanine, had similar effects. To this end, we monitored dopamine in the nAc by means of in vivo microdialysis and found that local perfusion of beta-alanine increased dopamine output. In line with previous observations investigating ethanol, glycine and taurine, the competitive GlyR antagonist strychnine completely blocked the dopamine elevation. The present results suggest that beta-alanine has the ability to modulate dopamine levels in the nAc via strychnine-sensitive GlyRs, and are consistent with previous studies suggesting the importance of this receptor for modulating dopamine output.

Ambient Ionization Mass Spectrometry Measurement of Aminotransferase Activity

NASA Astrophysics Data System (ADS)

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.

Beta-Alanine Supplementation Improves Throwing Velocities in Repeated Sprint Ability and 200-m Swimming Performance in Young Water Polo Players.

PubMed

Claus, Gabriel Machado; Redkva, Paulo Eduardo; Brisola, Gabriel Mota Pinheiro; Malta, Elvis Sousa; de Araujo Bonetti de Poli, Rodrigo; Miyagi, Willian Eiji; Zagatto, Alessandro Moura

2017-05-01

The purpose of this study was to investigate the effects of beta-alanine supplementation on specific tests for water polo. Fifteen young water polo players (16 ± 2 years) underwent a 200-m swimming performance, repeated-sprint ability test (RSA) with free throw (shooting), and 30-s maximal tethered eggbeater kicks. Participants were randomly allocated into two groups (placebo × beta-alanine) and supplemented with 6.4g∙day -1 of beta-alanine or a placebo for six weeks. The mean and total RSA times, the magnitude based inference analysis showed a likely beneficial effect for beta-alanine supplementation (both). The ball velocity measured in the throwing performance after each sprint in the RSA presented a very like beneficial inference in the beta-alanine group for mean (96.4%) and percentage decrement of ball velocity (92.5%, likely beneficial). Furthermore, the percentage change for mean ball velocity was different between groups (beta-alanine=+2.5% and placebo=-3.5%; p = .034). In the 30-s maximal tethered eggbeater kicks the placebo group presented decreased peak force, mean force, and fatigue index, while the beta-alanine group maintained performance in mean force (44.1%, possibly beneficial), only presenting decreases in peak force. The 200-m swimming performance showed a possibly beneficial effect (68.7%). Six weeks of beta-alanine supplementation was effective for improving ball velocity shooting in the RSA, maintaining performance in the 30-s test, and providing possibly beneficial effects in the 200-m swimming performance.

Hematological and plasma biochemical reference ranges of Alaskan seabirds: Their ecological significance and clinical importance

USGS Publications Warehouse

Newman, S.H.; Piatt, John F.; White, J.

1997-01-01

Blood was analyzed from 151 pelagic marine birds to establish reference ranges for hematological and plasma biochemical parameters from healthy, wild populations of Pacific seabirds. Of the 13 species examined, 9 were from the Family Alcidae (N = 122 individuals) and the remainder (N = 29) from the Families Phalacrocoracidae, Laridae, and Procellariidae. Three of 8 hematological parameters (total white blood cell count, lymphocyte count and eosinophil count) differed significantly among species, as did 9 of 13 plasma biochemical parameters (alkaline phosphatase, aspartate aminotransferase, creatine kinase, cholesterol, glucose, lactate dehydrogenase, total bilirubin, total protein and field total protein). There were no differences among species for packed cell volume, buffy coat, cell counts of heterophils, monocytes and basophils, or for concentrations of alanine aminotransferase, triglycerides, uric acid and calcium. Plasma calcium concentration, triglyceride levels and field total protein varied significantly between sexes, with females having higher mean concentrations of all 3 parameters. However, no significant relationships between measures of breeding condition (brood patch size, subcutaneous and mesenteric fat deposits, or ovarian follicle size and ovary weight) and calcium or alkaline phosphatase concentrations in female birds could be identified. Alanine aminotransferase and uric acid were the only analytes which did not differ significantly between species or sexes.

Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/AIDS-coinfected patients under tuberculosis treatment.

PubMed

Ngouleun, Williams; Biapa Nya, Prosper Cabral; Pieme, Anatole Constant; Telefo, Phelix Bruno

2016-12-01

Tuberculosis (TB) is a worldwide public health problem. It is a contagious and grave disease caused by Mycobacterium tuberculosis. Current drugs such as isoniazid, pyrazinamide, and rifampicin used for the treatment of tuberculosis are potentially hepatotoxic and can lead to drug hepatitis. In order to improve the follow-up of TB patients in Cameroon, we carried out a study which aimed to evaluate the hepatotoxicity risk factors associated with anti-TB drugs. The studies were performed on 75 participants who had visited the Loum District Hospital located in the littoral region of Cameroon for their routine consultation. Participants have been selected based on pre-established criteria of inclusion and exclusion. Prior to the informed consent signature, patients were given compelling information about the objective and the result output of the study. They were questioned about antioxidant food and alcohol consumption as well as some clinical signs of hepatotoxicity such as fever, nausea, vomiting, and tiredness. The collected blood was tested for the determination of biochemical markers (transaminases and C-reactive protein) using standard spectrophotometric methods. Biochemical analysis of samples showed a significant increase (p<.05) of aspartate aminotransferase and alanine aminotransferase values in TB patients coinfected with human immunodeficiency virus/AIDS (33.28±16.58UI/L and 30.84±17.17UI/L, respectively) compared with the respective values of the controls (16.35±5.31UI/L and 16.45±4.83UI/L). Taking individually, the liver injury patient percentage of TB patients was significant compared to TBC when considering alanine aminotransferase and aspartate aminotransferase parameters. When considering risk factors, antioxidant food consumption significantly reduced the liver injury patient percentage for the above parameters, whereas an opposite situation was observed with alcohol consumption between TB-coinfection and TB patients. Regarding the C

Effects of Different Levels of Intra-Abdominal Pressure on the Postoperative Hepatic Function of Patients Undergoing Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis.

PubMed

Cheng, Zheng-Jun; Wang, Yun-Bing; Chen, Long; Gong, Jian-Ping; Zhang, Wei

2018-04-18

The aim of this meta-analysis is to compare the differences in postoperative markers of the hepatic function under different intra-abdominal pressures in laparoscopic cholecystectomy (LC). Several databases were searched for control studies, and then the weighted data were pooled with random-effect models. A total of 11 studies involving 865 patients were included. The meta-analysis reveals that the level of the aspartate aminotransferase and alanine transaminase of the low-pressure group has a lower postoperative increase than the moderate-pressure group (P<0.001). The level of the aspartate aminotransferase and alanine transaminase of the moderate-pressure group has a lower postoperative increase than the high-pressure group (P<0.001). Totally, the effect of lower pressure LC on postoperative hepatic functions is less significant than that of the higher one. Potential subgroup analysis does not modify these results. The recommended pressure in LC is suggested to be lower so as to result in a better surgical safety, especially for special populations.

Attenuation of intestinal ischemia-reperfusion-injury by β-alanine: a potentially glycine-receptor mediated effect.

PubMed

Brencher, Lisa; Verhaegh, Rabea; Kirsch, Michael

2017-05-01

Acute mesenteric ischemia is often caused by embolization of the mesenteric arterial circulation. Coherent intestinal injury due to ischemia and following reperfusion get visible on macroscopic and histologic level. In previous studies, application of glycine caused an ameliorated intestinal damage after ischemia-reperfusion in rats. Because we speculated that glycine acted here as a signal molecule, we investigated whether the glycine-receptor agonist β-alanine evokes the same beneficial effect in intestinal ischemia-reperfusion. β-alanine (10, 30, and 100 mg/kg) was administered intravenously. Ischemia/reperfusion of the small intestine was initiated by occluding and reopening the superior mesenteric artery in rats. After 90 min of ischemia and 120 min of reperfusion, the intestine was analyzed with regard to macroscopic and histologic tissue damage, the activity of the saccharase, and accumulation of macrophages. In addition, systemic parameters and metabolic ones (e.g., acid-base balance, electrolytes, and blood glucose) were measured at certain points in time. All three dosages of β-alanine did not change systemic parameters but prevent from hyponatremia during the period of reperfusion. Most importantly, application of 100-mg β-alanine clearly diminished intestinal tissue damage, getting visible on macroscopic and histologic level. In addition, I/R-mediated decrease of saccharase activity and accumulation of macrophages in the small intestine were ameliorated. The present study demonstrated that β-alanine was a potent agent to ameliorate I/R-induced injury of the small intestine. Due to its diminishing effect on the accumulation of macrophages, β-alanine is strongly expected to mediate its beneficial effect via glycine receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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.

Genetic Mapping of a Mutant Defective in d, l-Alanine Racemase in Bacillus subtilis 168

PubMed Central

Dul, Michael J.; Young, Frank E.

1973-01-01

Genetic analysis of a d-alanine requiring mutant (dal) of Bacillus subtilis reveals that the gene that codes for d,l-alanine racemase is linked to purB. The order of genes in this region of the chromosome is purB, pig, tsi, dal. Thus there are at least two clusters of genes that regulate cell wall biosynthesis in B. subtilis. PMID:4199510

Serum enzymes levels and influencing factors in three indigenous Ethiopian goat breeds.

PubMed

Tibbo, M; Jibril, Y; Woldemeskel, M; Dawo, F; Aragaw, K; Rege, J E O

2008-12-01

Serum enzymes were studied in 163 apparently healthy goats from three indigenous goat breeds of Ethiopia. The effect of breed, age, sex and season on alanine aminotransferase (ALT) / glutamic pyruvic transaminase (GPT), aspartate aminotransferase (AST) / glutamic oxalacetic transaminases (GOT), alkaline phosphatase (ALP) and acid phosphatase (AcP) levels was assessed. The mean serum enzymes levels of the indigenous Arsi-Bale, Central Highland and Long-eared Somali goat breeds ranged from 14.0-20.2 iu L(-1) for ALT/GPT, from 43.2-49.3 iu L(-1) for AST/GOT, from 83.7-98.8 iu L(-1) for ALP, and from 2.99-4.23 iu L(-1) for AcP, were within the normal range for goats elsewhere. Breed had significant influence on AST/GOT values. Sex had significant effect on ALT/GPT for Arsi-Bale goats with higher values in males than females. Age was significant on all serum enzymes studied in the Arsi-Bale goats and on ALP in the Central Highland goats. Season had significant influence on all serum enzymes except for ALT/GPT in the Arsi-Bale goats. The serum enzyme levels of these indigenous goat breeds can be used as normal reference values for Ethiopian goat breeds adapted to similar agro-ecology and production system.

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

PubMed

Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

1984-01-01

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

β-alanine Supplementation Fails to Increase Peak Aerobic Power or Ventilatory Threshold in Aerobically Trained Males.

PubMed

Greer, Beau Kjerulf; Katalinas, Matthew E; Shaholli, Danielle M; Gallo, Paul M

2016-01-01

The purpose of the present study was to determine the effect of 30 days of β-alanine supplementation on peak aerobic power and ventilatory threshold (VT) in aerobically fit males. Fourteen males (28.8 ± 9.8 yrs) were assigned to either a β-alanine (SUPP) or placebo (PLAC) group; groups were matched for VT as it was the primary outcome measure. β-alanine supplementation consisted of 3 g/day for 7 days, and 6 g/day for the remaining 23 days. Before and after the supplementation period, subjects performed a continuous, graded cycle ergometry test to determine VO2 peak and VT. Metabolic data were analyzed using a 2 × 2 ANOVA with repeated measures. Thirty days of β-alanine supplementation (SUPP) did not increase VO2 peak (4.05 ± 0.6 vs. 4.14 ± 0.6 L/min) as compared to the placebo (PLAC) group (3.88 ± 0.2 vs. 3.97 ± 0.2 L/min) (p > .05). VT did not significantly improve in either the SUPP (3.21 ± 0.5 vs. 3.33 ± 0.5 L/min) or PLAC (3.19 ± 0.1 vs. 3.20 ± 0.1 L/min) group (p > .05). In conclusion, 30 days of β-alanine supplementation had no effect on VO2 peak or VT in aerobically trained athletes.

Effects of Escherichia coli challenge and transport stress on hematology and serum chemistry values of three genetic lines of turkeys.

PubMed

Huff, G R; Huff, W E; Rath, N C; Anthony, N B; Nestor, K E

2008-11-01

Three lines of turkeys were compared for response to an Escherichia coli challenge followed by transport stress (transport). The turkey lines were a slow-growing line selected for increased egg production (egg line), a fast-growing line selected for increased 16-wk BW (F line), and a commercial line (Comm line). Birds were challenged at 14 wk of age with an air sac injection of 5,000 to 10,000 cfu of E. coli. At 8 d postchallenge, birds were subjected to a transport stress procedure that included 12 h of holding time in a transport vehicle. The following morning all birds (n = 10 to 19 birds/line) were bled. Whole blood was analyzed using the Cell-Dyn 3500 blood analysis system (Abbott Diagnostics), and serum chemistry was measured using the Express Plus analyzer (Ciba-Corning Diagnostics Corp.). Transport significantly decreased the levels of hematocrit, hemoglobin, mean cell volume, mean corpuscular hemoglobin, glucose, triglycerides, cholesterol, phosphorus, iron, albumin, and alkaline phosphatase (AP) and increased the levels of uric acid, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Line differences were variable, but the levels of both iron and AP were least in the fastest-growing Comm line birds and greatest in the slowest-growing egg-line birds with intermediate values in the F line. Iron and AP were also the only parameters influenced by sex, with males having greater levels of both compared with females. The creatine kinase levels were more than 6-fold greater in transported Comm line birds, and iron levels of transported Comm males were 3-fold less than controls. Previously, the growth rate of these lines was positively correlated with increased heterophil to lymphocyte ratios and susceptibility to colibacillosis. The differences seen in the Comm line for these commonly measured blood parameters suggest that they may be useful for profiling flocks to determine their response to transport stress and feed

The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmitz, T., E-mail: schmito@uni-mainz.de; Bassler, N.; Blaickner, M.

Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particlemore » spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields

The catalytic effect of L- and D-histidine on alanine and lysine peptide formation.

PubMed

Fitz, Daniel; Jakschitz, Thomas; Rode, Bernd M

2008-12-01

A starting phase of chemical evolution on our ancient Earth around 4 billion years ago was the formation of amino acids and their combination to peptides and proteins. The salt-induced peptide formation (SIPF) reaction has been shown to be appropriate for this condensation reaction under moderate and plausible primitive Earth conditions, forming short peptides from amino acids in aqueous solution containing sodium chloride and Cu(II) ions. In this paper we report results about the formation of dialanine and dilysine from their monomers in this reaction. The catalytic influence of l- and d-histidine dramatically increases dialanine yields when starting from lower alanine concentrations, but also dilysine formation is markedly boosted by these catalysts. Attention is paid to measurable preferences for one enantiomeric form of alanine and lysine in the SIPF reaction. Alanine, especially, shows stereospecific behaviour, mostly in favour of the l-form.

β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis.

PubMed

Saunders, Bryan; Elliott-Sale, Kirsty; Artioli, Guilherme G; Swinton, Paul A; Dolan, Eimear; Roschel, Hamilton; Sale, Craig; Gualano, Bruno

2017-04-01

To conduct a systematic review and meta-analysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance. This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data. 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('β-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine'). Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses. 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI -0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)). β-alanine had a

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

PubMed

Hui, C-K; Zhang, H-Y; Shek, T; Yao, H; Yueng, Y-H; Leung, K-W; Lai, S-T; Lai, J-Y; Leung, N; Lau, G K

2007-06-01

Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

A New Octadecenoic Acid Derivative from Caesalpinia gilliesii Flowers with Potent Hepatoprotective Activity

PubMed Central

Osman, Samir M.; El-Haddad, Alaadin E.; El-Raey, Mohamed A.; Abd El-Khalik, Soad M.; Koheil, Mahmoud A.; Wink, Michael

2016-01-01

Background: Caesalpinia gilliesii Hook is an ornamental shrub with showy yellow flowers. It was used in folk medicine due to its contents of different classes of secondary metabolites. In our previous study, dichloromethane extract of C. gilliesii flowers showed a good antioxidant activity. Aim of the Study: Isolation and identification of bioactive hepatoprotective compounds from C. gilliesii flowers dichloromethane fraction. Materials and Methods: The hepatoprotective activity of dichloromethane fraction and isolated compounds were studied in CCl4-intoxicated rat liver slices by measuring liver injury markers (alanine aminotransferase, aspartate aminotransferase and glutathione [GSH]). All compounds were structurally elucidated on the basis of electron ionization-mass spectrometry, one- and two-dimensional nuclear magnetic resonance. Results: A new 12,13,16-trihydroxy-14(Z)-octadecenoic acid was identified in addition to the known β-sitosterol-3-O-butyl, daucosterol, isorhamnetin, isorhamnetin-3-O-rhamnoside, luteolin-7,4’-dimethyl ether, genistein-5-methyl ether, luteolin-7-O-rhamnoside, isovanillic acid, and p-methoxybenzoic acid. Dichloromethane fraction and isorhamnetin were able to significantly protect the liver against intoxication. Moreover, the dichloromethane fraction and the isolated phytosterols induced GSH above the normal level. Conclusion: The hepatoprotective activity of C. gilliesii may be attributed to its high content of phytosterols and phenolic compounds. SUMMARY Bioactive Hepatoprotective phytosterols and phenolics from chloroform extract of Caesalpinia gilliesii Abbreviations used: ALT: Alanine Aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione; SC50: Scavenging Capacity 50 (SC 50); COSY: Correlation spectroscopy; NMR: Nuclear Magnetic Resonance; CC: Column chromatography; EI-MS: Electron-impact mass spectrometry; HSQC: Heteronuclear single-quantum correlation. PMID:27563221

Verification of chemistry reference ranges using a simple method in sub-Saharan Africa

PubMed Central

Taylor, Douglas; Mandala, Justin; Nanda, Kavita; Van Campenhout, Christel; Agingu, Walter; Madurai, Lorna; Barsch, Eva-Maria; Deese, Jennifer; Van Damme, Lut; Crucitti, Tania

2016-01-01

Background Chemistry safety assessments are interpreted by using chemistry reference ranges (CRRs). Verification of CRRs is time consuming and often requires a statistical background. Objectives We report on an easy and cost-saving method to verify CRRs. Methods Using a former method introduced by Sigma Diagnostics, three study sites in sub-Saharan Africa, Bondo, Kenya, and Pretoria and Bloemfontein, South Africa, verified the CRRs for hepatic and renal biochemistry assays performed during a clinical trial of HIV antiretroviral pre-exposure prophylaxis. The aspartate aminotransferase/alanine aminotransferase, creatinine and phosphorus results from 10 clinically-healthy participants at the screening visit were used. In the event the CRRs did not pass the verification, new CRRs had to be calculated based on 40 clinically-healthy participants. Results Within a few weeks, the study sites accomplished verification of the CRRs without additional costs. The aspartate aminotransferase reference ranges for the Bondo, Kenya site and the alanine aminotransferase reference ranges for the Pretoria, South Africa site required adjustment. The phosphorus CRR passed verification and the creatinine CRR required adjustment at every site. The newly-established CRR intervals were narrower than the CRRs used previously at these study sites due to decreases in the upper limits of the reference ranges. As a result, more toxicities were detected. Conclusion To ensure the safety of clinical trial participants, verification of CRRs should be standard practice in clinical trials conducted in settings where the CRR has not been validated for the local population. This verification method is simple, inexpensive, and can be performed by any medical laboratory. PMID:28879112

Verification of chemistry reference ranges using a simple method in sub-Saharan Africa.

PubMed

De Baetselier, Irith; Taylor, Douglas; Mandala, Justin; Nanda, Kavita; Van Campenhout, Christel; Agingu, Walter; Madurai, Lorna; Barsch, Eva-Maria; Deese, Jennifer; Van Damme, Lut; Crucitti, Tania

2016-01-01

Chemistry safety assessments are interpreted by using chemistry reference ranges (CRRs). Verification of CRRs is time consuming and often requires a statistical background. We report on an easy and cost-saving method to verify CRRs. Using a former method introduced by Sigma Diagnostics, three study sites in sub-Saharan Africa, Bondo, Kenya, and Pretoria and Bloemfontein, South Africa, verified the CRRs for hepatic and renal biochemistry assays performed during a clinical trial of HIV antiretroviral pre-exposure prophylaxis. The aspartate aminotransferase/alanine aminotransferase, creatinine and phosphorus results from 10 clinically-healthy participants at the screening visit were used. In the event the CRRs did not pass the verification, new CRRs had to be calculated based on 40 clinically-healthy participants. Within a few weeks, the study sites accomplished verification of the CRRs without additional costs. The aspartate aminotransferase reference ranges for the Bondo, Kenya site and the alanine aminotransferase reference ranges for the Pretoria, South Africa site required adjustment. The phosphorus CRR passed verification and the creatinine CRR required adjustment at every site. The newly-established CRR intervals were narrower than the CRRs used previously at these study sites due to decreases in the upper limits of the reference ranges. As a result, more toxicities were detected. To ensure the safety of clinical trial participants, verification of CRRs should be standard practice in clinical trials conducted in settings where the CRR has not been validated for the local population. This verification method is simple, inexpensive, and can be performed by any medical laboratory.

Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study

PubMed Central

Ogihara, Takeshi; Osonoi, Yusuke; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Gosho, Masahiko; Kanazawa, Akio; Watada, Hirotaka

2017-01-01

Introduction While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal—metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. Participants and methods The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Results Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. Conclusions The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. Trial registration UMIN000010932 PMID:28273173

Clinicopathologic, gross necropsy, and histologic findings after intramuscular injection of carprofen in a pigeon (Columba livia) model.

PubMed

Zollinger, Tawina J; Hoover, John P; Payton, Mark E; Schiller, Chris A

2011-09-01

To evaluate the pathologic effects of carprofen in a pigeon model (Columba livia), 52 young adult pigeons were used in a randomized control study design. Sixteen pigeons were randomly assigned to 1 of 3 treatment groups and received carprofen by intramuscular injection at dosages of either 2, 5, or 10 mg/kg once daily for 7 days. Four pigeons served as saline-injected controls. Four pigeons from each group and 1 control pigeon were randomly selected on days 2, 4, 6, and 8 to obtain blood samples and then were euthanatized and submitted for necropsy. Histologic lesions in pectoral muscle, liver, kidney, and digestive tract tissue samples were ranked in severity as 0, normal/not present; 1, minimal; 2, mild; 3, mild to moderate; 4, moderate; 5, moderate to marked; and 6, marked pathologic changes. Two-way analysis of variance (day x dose) and pairwise t tests revealed significant (P < or = .05) mild decreases in total protein and glucose concentrations and marked increases in aspartate aminotransferase and alanine aminotransferase enzyme activities after carprofen treatments. Gross lesions in carprofen-treated pigeons were pale injection sites (23/48 [47.9%]), mottled yellow livers (9/48 [18.8%]), and congestion of small intestines (7/48 [14.6%]). Liver, kidney, and muscle injection sites had significantly increased (P < or = .05) severity of histologic lesions. In pigeons, intramuscular administration of carprofen is associated with increased aspartate aminotransferase and alanine aminotransferase enzyme concentrations, gross lesions in muscle injection sites and liver, and histologic lesions in liver and muscle.

The effects of beta alanine plus creatine administration on performance during repeated bouts of supramaximal exercise in sedentary men.

PubMed

Okudan, N; Belviranli, M; Pepe, H; Gökbel, H

2015-11-01

The aim of this study was to investigate the effects of beta alanine and/or creatine supplementation on performance during repeated bouts of supramaximal exercise in sedentary men. Forty-four untrained healthy men (aged 20-22 years, weight: 68-72 kg, height: 174-178 cm) participated in the present study. After performing the Wingate Test (WAnT) for three times in the baseline exercise session, the subjects were assigned to one of four treatment groups randomly: 1) placebo (P; 10 g maltodextrose); 2) creatine (Cr; 5 g creatine plus 5 g maltodextrose); 3) beta-alanine (β-ALA; 1,6 g beta alanine plus 8,4 g maltodextrose); and 4) beta-alanine plus creatine (β-ALA+Cr; 1,6 g beta alanine plus 5 g creatine plus 3,4 g maltodextrose). Participants were given the supplements orally twice a day for 22 consecutive days, then four times a day for the following 6 days. After 28 days, the second exercise session was applied during which peak power (PP) and mean power (MP) were measured and fatigue index (FI) was calculated. PP and MP decreased and FI increased in all groups during exercise before and after the treatment. During the postsupplementation session PP2 and PP3 increased in creatine supplemented group (from 642.7±148.6 to 825.1±205.2 in PP2 and from 522.9±117.5 to 683.0±148.0 in PP3, respectively). However, MP increased in β-ALA+Cr during the postsupplementation compared to presupplementation in all exercise sessions (from 586.2±55.4 to 620.6±49.6 in MP1, from 418.1±37.2 to 478.3±30.3 in MP2 and from 362.0±41.3 to 399.1±3 in MP3, respectively). FI did not change with beta alanine and beta alanine plus creatine supplementation during the postsupplementation exercise session. Beta-alanine and beta alanine plus creatine supplementations have strong performance enhancing effect by increasing mean power and delaying fatigue Index during the repeated WAnT.

Serine and alanine racemase activities of VanT: a protein necessary for vancomycin resistance in Enterococcus gallinarum BM4174.

PubMed

Arias, C A; Weisner, J; Blackburn, J M; Reynolds, P E

2000-07-01

Vancomycin resistance in Enterococcus gallinarum results from the production of UDP-MurNAc-pentapeptide[D-Ser]. VanT, a membrane-bound serine racemase, is one of three proteins essential for this resistance. To investigate the selectivity of racemization of L-Ser or L-Ala by VanT, a strain of Escherichia coli TKL-10 that requires D-Ala for growth at 42 degrees C was used as host for transformation experiments using plasmids containing the full-length vanT from Ent. gallinarum or the alanine racemase gene (alr) of Bacillus stearothermophilus: both plasmids were able to complement E. coli TKL-10 at 42 degrees C. No alanine or serine racemase activities were detected in the host strain E. coli TKL-10 grown at 30, 34 or 37 degrees C. Serine and alanine racemase activities were found almost exclusively (96%) in the membrane fraction of E. coli TKL-10/pCA4(vanT): the alanine racemase activity of VanT was 14% of the serine racemase activity in both E. coli TKL-10/pCA4(vanT) and E. coli XL-1 Blue/pCA4(vanT). Alanine racemase activity was present mainly (95%) in the cytoplasmic fraction of E. coli TKL-10/pJW40(alr), with a trace (1.6%) of serine racemase activity. Additionally, DNA encoding the soluble domain of VanT was cloned and expressed in E. coli M15 as a His-tagged polypeptide and purified: this polypeptide also exhibited both serine and alanine racemase activities; the latter was approximately 18% of the serine racemase activity, similar to that of the full-length, membrane-bound enzyme. N-terminal sequencing of the purified His-tagged polypeptide revealed a single amino acid sequence, indicating that the formation of heterodimers between subunits of His-tagged C-VanT and endogenous alanine racemases from E. coli was unlikely. The authors conclude that the membrane-bound serine racemase VanT also has alanine racemase activity but is able to racemize serine more efficiently than alanine, and that the cytoplasmic domain is responsible for the racemase activity.

Seasonal hematology and serum chemistry of wild beluga whales (Delphinapterus leucas) in Bristol Bay, Alaska, USA.

PubMed

Norman, Stephanie A; Goertz, Caroline E C; Burek, Kathy A; Quakenbush, Lori T; Cornick, Leslie A; Romano, Tracy A; Spoon, Tracey; Miller, Woutrina; Beckett, Laurel A; Hobbs, Roderick C

2012-01-01

We collected blood from 18 beluga whales (Delphinapterus leucas), live-captured in Bristol Bay, Alaska, USA, in May and September 2008, to establish baseline hematologic and serum chemistry values and to determine whether there were significant differences in hematologic values by sex, season, size/age, or time during the capture period. Whole blood was collected within an average of 19 min (range=11-30 min) after the net was set for capture, and for eight animals, blood collection was repeated in a later season after between 80-100 min; all blood was processed within 12 hr. Mean hematocrit, chloride, creatinine, total protein, albumin, and alkaline phosphatase were significantly lower in May than they were in September, whereas mean corpuscular hemoglobin concentration, monocytes, phosphorous, magnesium, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltranspeptidase, and creatinine kinase were significantly higher. Mean total protein, white blood cell count, neutrophils, and lymphocytes were significantly higher early in the capture period than they were later. No significant differences in blood analyte values were noted between males and females. Using overall body length as a proxy for age, larger (older) belugas had lower white blood cell, lymphocyte, and eosinophil counts as well as lower sodium, potassium, and calcium levels but higher creatinine levels than smaller belugas. These data provide values for hematology and serum chemistry for comparisons with other wild belugas.

Thermal Condensation of Glycine and Alanine on Metal Ferrite Surface: Primitive Peptide Bond Formation Scenario.

PubMed

Iqubal, Md Asif; Sharma, Rachana; Jheeta, Sohan; Kamaluddin

2017-03-27

The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe₂O₄), cobalt ferrite (CoFe₂O₄), copper ferrite (CuFe₂O₄), zinc ferrite (ZnFe₂O₄), and manganese ferrite (MnFe₂O₄) nanoparticles surfaces, in the temperature range from 50-120 °C for 1-35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe₂O₄ produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe₂O₄ was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C.

Titration of Alanine Monitored by NMR Spectroscopy: A Biochemistry Laboratory Experiment

ERIC Educational Resources Information Center

Waller, Francis J.; And Others

1977-01-01

The experiment described here involves simultaneous monitoring of pH and NMR chemical shifts during an aqueous titration of alpha- and beta-alanine. This experiment is designed for use in an undergraduate biochemistry course. (MR)

Ammonia assimilation and synthesis of alanine, aspartate, and glutamate in Methanosarcina barkeri and Methanobacterium thermoautotrophicum.

PubMed Central

Kenealy, W R; Thompson, T E; Schubert, K R; Zeikus, J G

1982-01-01

The mechanism of ammonia assimilation in Methanosarcina barkeri and Methanobacterium thermoautotrophicum was documented by analysis of enzyme activities, 13NH3 incorporation studies, and comparison of growth and enzyme activity levels in continuous culture. Glutamate accounted for 65 and 52% of the total amino acids in the soluble pools of M. barkeri and M. thermoautotrophicum. Both organisms contained significant activities of glutamine synthetase, glutamate synthase, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase. Hydrogen-reduced deazaflavin-factor 420 or flavin mononucleotide but not NAD, NADP, or ferredoxin was used as the electron donor for glutamate synthase in M. barkeri. Glutamate dehydrogenase activity was not detected in either organism, but alanine dehydrogenase activity was present in M. thermoautotrophicum. The in vivo activity of the glutamine synthetase was verified in M. thermoautotrophicum by analysis of 13NH3 incorporation into glutamine, glutamate, and alanine. Alanine dehydrogenase and glutamine synthetase activity varied in response to [NH4+] when M. thermoautotrophicum was cultured in a chemostat with cysteine as the sulfur source. Alanine dehydrogenase activity and growth yield (grams of cells/mole of methane) were highest when the organism was cultured with excess ammonia, whereas growth yield was lower and glutamine synthetase was maximal when ammonia was limiting. PMID:6122678

Crystal Structure-Based Selective Targeting of the Pyridoxal 5′-Phosphate Dependent Enzyme Kynurenine Aminotransferase II for Cognitive Enhancement†

PubMed Central

Rossi, Franca; Valentina, Casazza; Garavaglia, Silvia; Sathyasaikumar, Korrapati V.; Schwarcz, Robert; Kojima, Shin-ichi; Okuwaki, Keisuke; Ono, Shin-ichiro; Kajii, Yasushi; Rizzi, Menico

2014-01-01

Fluctuations in the brain levels of the neuromodulator kynurenic acid may control cognitive processes and play a causative role in several catastrophic brain diseases. Elimination of the pyridoxal 5′-phosphate dependent enzyme kynurenine aminotransferase II reduces cerebral kynurenic acid synthesis and has procognitive effects. The present description of the crystal structure of human kynurenine aminotransferase II in complex with its potent and specific primary amine-bearing fluoroquinolone inhibitor (S)-(−)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid (BFF-122) should facilitate the structure-based development of cognition-enhancing drugs. From a medicinal chemistry perspective our results demonstrate that the issue of inhibitor specificity for highly conserved PLP-dependent enzymes could be successfully addressed. PMID:20684605

Enzyme activities in plasma, liver, and kidney of black ducks and mallards

USGS Publications Warehouse

Franson, J. Christian

1982-01-01

Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were measured in plasma, liver, and kidney, and gamma-glutamyl transferase (GGT) was measured in liver and kidney of black ducks (Anas rubripes). Activities of ALT, AST, GGT, and ornithine carbamyl transferase (OCT) were assayed in plasma, liver, and kidney of game-farm mallards (Anas platyrhynchos). Appreciable OCT and AST activity occurred in both liver and kidney. Activities of ALT, CPK, ALP and GGT were higher in kidney, while LDH was higher in liver, GGT was detected in plasma from one of four mallards.

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

PubMed Central

Hwang, Tsong-Long; Shen, Hsin-I; Liu, Fu-Chao; Tsai, Hsin-I; Wu, Yang-Chang; Chang, Fang-Rong; Yu, Huang-Ping

2014-01-01

Neutrophil activation is associated with the development of organ injury after trauma–hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma–hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma–hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma–hemorrhagic shock-induced organ injury in rats. PMID:25360589

A Blend of Extracts from Houttuynia cordata, Nelumbo nucifera, and Camellia sinensis Protects Against Ethanol-Induced Liver Damage in C57BL/6 Mice.

PubMed

You, Yanghee; Lee, Hyunmi; Yoon, Ho-Geun; Park, Jeongjin; Kim, Ok-Kyung; Kim, Kyungmi; Lee, Min-Jae; Lee, Yoo-Hyun; Lee, Jeongmin; Jun, Woojin

2018-02-01

The protective activity of a mixture of aqueous and ethanolic extracts from Houttuynia cordata Thunb, Nelumbo nucifera G. leaves, and Camellia sinensis seed (HNC) was evaluated in C57BL/6 mice. Pretreatment with HNC prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase caused by ethanol-induced hepatic damage. The HNC-treated mice showed significantly lower triglyceride levels, reduced CYP2E1 activity, and increased antioxidant enzyme activities and lipogenic mRNA levels. These results suggest that HNC might be a candidate agent for liver protection against ethanol-induced oxidative damage, through enhancement of antioxidant and antilipogenic activity.

[Effect of space flight on the Kosmos-1129 biosatellite on enzyme activity of the rat liver].

PubMed

Nemeth, S; Tigranian, R A

1983-01-01

After the 18.5 day Cosmos-1129 flight the activity of 7 glucocorticoid-stimulated enzymes of the rat liver was measured. Immediately postflight the activity of tyrosine aminotransferase, tryptophan pyrolase and serine dehydrogenase increased. These enzymes rapidly (within several hours) react to increased glucocorticoids. The activity of aspartate and alanine aminotransferases also increased. These enzymes require many days of a continuous effect of glucocorticoids. The glycogen concentration in the rat liver also grew. At R + 6 the activity of tryptophan pyrolase and serine dehydrogenase decreased and that of the other enzymes returned to normal. The immobilization stress applied postflight led to an increased activity of tyrosine aminotransferase and tryptophan pyrolase. This study gives evidence that after space flight rats are in an acute stress state, evidently, produced by the biosatellite recovery.

Rotational isomers of N-(β-phenylpropionyl)alanine ethyl dithioester: a Raman spectroscopic and MO study

NASA Astrophysics Data System (ADS)

Fausto, R.; Teixeira-Dias, J. J. C.; Tonge, P. J.; Carey, P. R.

1994-07-01

Raman spectra of N-(β-phenylpropionyl)alanine ethyl dithioester (C 6H 5CH 2CH 2C(O)NHCH(CH 3)C(S)SC 2H 5) in CCl 4 and CH 3CN solutions were measured as a function of temperature and the enthalpy differences (Δ H) between rotational isomers differing by internal rotation around the NHCH(CH 3) and CH(CH 3)C(S) bonds (forms A, B and C 5) were evaluated from relative band intensities. The spectroscopic results are consistent with a greater thermodynamical stability of the B-type conformer, where the N and S (thiol) atoms are in close contact. In addition, a comparison of the measured Δ H(A-B) for the present molecules with previously reported values for a series of similar glycine-based ethyl dithioesters shows that the presence of the extra CH 3 group at the α-carbon atom leads to a stabilization of the B-type conformer relative to the A-type form in the alanine-based dithioester. Semiempirical AM1 molecular orbital calculations were also performed on the title molecule and on its glycine analogue, N(β-phenylpropionyl)glycine ethyl dithioester. In general terms, the results of these calculations agree with the experimental findings, thus providing good theoretical support for the experimental data.

SU-E-T-608: Perturbation Corrections for Alanine Dosimeters in Different Phantom Materials in High-Energy Photon Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voigts-Rhetz, P von; Czarnecki, D; Anton, M

Purpose: Alanine dosimeters are often used for in-vivo dosimetry purposes in radiation therapy. In a Monte Carlo study the influence of 20 different surrounding/phantom materials for alanine dosimeters was investigated. The investigations were performed in high-energy photon beams, covering the whole range from {sup 60}Co up to 25 MV-X. The aim of the study is the introduction of a perturbation correction k{sub env} for alanine dosimeters accounting for the environmental material. Methods: The influence of different surrounding materials on the response of alanine dosimeters was investigated with Monte Carlo simulations using the EGSnrc code. The photon source was adapted withmore » BEAMnrc to a {sup 60}Co unit and an Elekta (E{sub nom}=6, 10, 25 MV-X) linear accelerator. Different tissue-equivalent materials ranging from cortical bone to lung were investigated. In addition to available phantom materials, some material compositions were taken and scaled to different electron densities. The depth of the alanine detectors within the different phantom materials corresponds to 5 cm depth in water, i.e. the depth is scaled according to the electron density (n{sub e}/n{sub e,w}) of the corresponding phantom material. The dose was scored within the detector volume once for an alanine/paraffin mixture and once for a liquid water voxel. The relative response, the ratio of the absorbed dose to alanine to the absorbed dose to water, was calculated and compared to the corresponding ratio under reference conditions. Results: For each beam quality the relative response r and the correction factor for the environment kenv was calculated. k{sub env}=0.9991+0.0049 *((n{sub e}/n{sub e,w})−0.7659){sup 3} Conclusion: A perturbation correction factor k{sub env} accounting for the phantom environment has been introduced. The response of the alanine dosimeter can be considered independent of the surrounding material for relative electron densities (n{sub e}/n{sub e,w}) between 1 and

β-N-Methylamino-L-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling.

PubMed

Engskog, Mikael K R; Ersson, Lisa; Haglöf, Jakob; Arvidsson, Torbjörn; Pettersson, Curt; Brittebo, Eva

2017-05-01

β-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC-MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

Quantitative Analysis of Solid-State Homonuclear Correlation Spectra of Antiparallel β-Sheet Alanine Tetramers.

PubMed

Naito, Akira; Okushita, Keiko; Nishimura, Katsuyuki; Boutis, Gregory S; Aoki, Akihiro; Asakura, Tetsuo

2018-03-15

Poly-l-alanine (PLA) sequences are a key element in the structure of the crystalline domains of spider dragline silks, wild silkworm silks, antifreeze proteins, and amyloids. To date, no atomic-level structures of antiparallel (AP)-PLA longer than Ala 4 have been reported using the single-crystal X-ray diffraction analysis. In this work, dipolar-assisted rotational resonance solid-state NMR spectra were observed to determine the effective internuclear distances of 13 C uniformly labeled alanine tetramer with antiparallel (AP) β-sheet structure whose atomic coordinates are determined from the X-ray crystallographic analysis. Initial build-up rates, R j, k , were obtained from the build-up curves of the cross peaks by considering the internuclear distances arising in the master equation. Subsequently, experimentally obtained effective internuclear distances, r eff j, k (obs), were compared with the calculated r eff j, k (calc) values obtained from the X-ray crystallographic data. Fairly good correlation between r eff j, k (obs) and r eff j, k (calc) was obtained in the range of 1.0-6.0 Å, with the standard deviation of 0.244 Å, without considering the zero-quantum line-shape functions. It was further noted that the internuclear distances of intermolecular contributions provide details relating to the molecular packing in solid-state samples. Thus, the present data agree well with AP-β-sheet packing but do not agree with P-β-sheet packing.

Understanding the antimicrobial properties/activity of an 11-residue Lys homopeptide by alanine and proline scan.

PubMed

Carvajal-Rondanelli, P; Aróstica, M; Álvarez, C A; Ojeda, C; Albericio, F; Aguilar, L F; Marshall, S H; Guzmán, F

2018-05-01

Previous work demonstrated that lysine homopeptides adopt a polyproline II (PPII) structure. Lysine homopeptides with odd number of residues, especially with 11 residues (K11), were capable of inhibiting the growth of a broader spectrum of bacteria than those with an even number. Confocal studies also determined that K11 was able to localize exclusively in the bacterial membrane, leading to cell death. In this work, the mechanism of action of this peptide was further analyzed focused on examining the structural changes in bacterial membrane induced by K11, and in K11 itself when interacting with bacterial membrane lipids. Moreover, alanine and proline scans were performed for K11 to identify relevant positions in structure conformation and antibacterial activity. To do so, circular dichroism spectroscopy (CD) was conducted in saline phosphate buffer (PBS) and in lipidic vesicles, using large unilamellar vesicles (LUV), composed of 2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) or bacterial membrane lipid. Antimicrobial activity of K11 and their analogs was evaluated in Gram-positive and Gram-negative bacterial strains. The scanning electron microscopy (SEM) micrographs of Staphylococcus aureus ATCC 25923 exposed to the Lys homopeptide at MIC concentration showed blisters and bubbles formed on the bacterial surface, suggesting that K11 exerts its action by destabilizing the bacterial membrane. CD analysis revealed a remarkably enhanced PPII structure of K11 when replacing some of its central residues by proline in PBS. However, when such peptide analogs were confronted with either DMPG-LUV or membrane lipid extract-LUV, the tendency to form PPII structure was severely weakened. On the contrary, K11 peptide showed a remarkably enhanced PPII structure in the presence of DMPG-LUV. Antibacterial tests revealed that K11 was able to inhibit all tested bacteria with an MIC value of 5 µM, while proline and alanine analogs have a reduced activity on Listeria

Effect of Harm Anchors in Visual Displays of Test Results on Patient Perceptions of Urgency About Near-Normal Values: Experimental Study.

PubMed

Zikmund-Fisher, Brian J; Scherer, Aaron M; Witteman, Holly O; Solomon, Jacob B; Exe, Nicole L; Fagerlin, Angela

2018-03-26

Patient-facing displays of laboratory test results typically provide patients with one reference point (the "standard range"). To test the effect of including an additional harm anchor reference point in visual displays of laboratory test results, which indicates how far outside of the standard range values would need to be in order to suggest substantial patient risk. Using a demographically diverse, online sample, we compared the reactions of 1618 adults in the United States who viewed visual line displays that included both standard range and harm anchor reference points ("Many doctors are not concerned until here") to displays that included either (1) only a standard range, (2) standard range plus evaluative categories (eg, "borderline high"), or (3) a color gradient showing degree of deviation from the standard range. Providing the harm anchor reference point significantly reduced perceived urgency of close-to-normal alanine aminotransferase and creatinine results (P values <.001) but not generally for platelet count results. Notably, display type did not significantly alter perceptions of more extreme results in potentially harmful ranges. Harm anchors also substantially reduced the number of participants who wanted to contact their doctor urgently or go to the hospital about these test results. Presenting patients with evaluative cues regarding when test results become clinically concerning can reduce the perceived urgency of out-of-range results that do not require immediate clinical action. ©Brian J Zikmund-Fisher, Aaron M Scherer, Holly O Witteman, Jacob B Solomon, Nicole L Exe, Angela Fagerlin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.03.2018.

Role of insulin resistance and adipocytokines on serum alanine aminotransferase in obese patients with type 2 diabetes mellitus.

PubMed

de Luis, D A; Aller, R; Izaola, O; Gonzalez Sagrado, M; Conde, R; de la Fuente, B

2013-01-01

The aim of our study was to study the association of insulin resistance expressed by HOMA and adipokines in obese type 2 diabetic patients with or without hyper-transaminasemia. A population of 72 obese patients with type 2 diabetes mellitus was analyzed. HOMA-IR was calculated as indicator of insulin-resistance. Adipocytokines blood levels were measured. Patients were classified as group I (n=37) when serum ALT activity was normal or group II (NAFLD patients: n=35) when serum ALT activity was greater than the median value of the group (≥ 28 UI/L). In NAFLD group, BMI, weight, fat mass, waist to hip ratio, waist circumference, triglycerides, HOMA and insulin levels were higher than control group. In the logistic regression analysis with a dependent variable (ALT) and the statistical univariant variables as independent variables, the HOMA-IR remained in the model, with an Odd's ratio of 1.21 (CI:95%: 1.11-1.35) to have a high ALT level with each 1 unit of HOMA-IR adjusted by age, sex, weight, and dietary intake. Some metabolic parameters are associated with elevated ALT in female obese patients. However, adjusted by other variables, only insulin resistance remained associated.

β-alanine supplementation improves tactical performance but not cognitive function in combat soldiers

PubMed Central

2014-01-01

Background There are no known studies that have examined β-alanine supplementation in military personnel. Considering the physiological and potential neurological effects that have been reported during sustained military operations, it appears that β-alanine supplementation may have a potential benefit in maintaining physical and cognitive performance during high-intensity military activity under stressful conditions. The purpose of this study was to examine the effect of 28 days of β-alanine ingestion in military personnel while fatigued on physical and cognitive performance. Methods Twenty soldiers (20.1 ± 0.9 years) from an elite combat unit were randomly assigned to either a β-alanine (BA) or placebo (PL) group. Soldiers were involved in advanced military training, including combat skill development, navigational training, self-defense/hand-to-hand combat and conditioning. All participants performed a 4-km run, 5-countermovement jumps using a linear position transducer, 120-m sprint, a 10-shot shooting protocol with assault rifle, including overcoming a misfire, and a 2-min serial subtraction test to assess cognitive function before (Pre) and after (Post) 28 days of supplementation. Results The training routine resulted in significant increases in 4-km run time for both groups, but no between group differences were seen (p = 0.597). Peak jump power at Post was greater for BA than PL (p = 0.034), while mean jump power for BA at Post was 10.2% greater (p = 0.139) than PL. BA had a significantly greater (p = 0.012) number of shots on target at Post (8.2 ± 1.0) than PL (6.5 ± 2.1), and their target engagement speed at Post was also significantly faster (p = 0.039). No difference in serial subtraction performance was seen between the groups (p = 0.844). Conclusion Results of this study indicate that 4-weeks of β-alanine ingestion in young, healthy soldiers did not impact cognitive performance, but did enhance power

Fragment Screening of Human Kynurenine Aminotransferase-II.

PubMed

Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, W Bret

2018-03-01

Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors. Surface plasmon resonance (SPR) was used to screen a fragment library containing 1000 compounds, of which 41 hits were identified. These hits were further evaluated with SPR, and 18 were selected for inhibition studies. From these hits, two fragments, F6037-0164 and F0037-7280, were pursued and determined to have an IC 50 of 524.5 (± 25.6) μM and 115.2 (± 4.5) μM, respectively. This strategy shows the viability of using FBDD in gleaning knowledge about KAT-II inhibition and generating leads for the production of KAT-II inhibitors.

Effect of early handling of turkey poults on later responses to a dexamethasone-Escherichia coli challenge. 1. Production values and physiological response.

PubMed

Huff, G R; Huff, W E; Balog, J M; Rath, N C

2001-09-01

The stress responses of mice and rats has been shown to be permanently altered by brief, gentle handling during the first 10 d of life, resulting in increased BW and resistance to stress-induced immunosuppression. The purpose of this study was to determine whether early handling of turkey poults could permanently affect production values and physiology of adult turkeys. Turkey poults were handled 0, 1 (1x), or 2 (2x) times daily for the first 10 d after hatch. Handling consisted of gently catching each poult and holding it for 10 s. On Day 11 after hatch, half of the birds from each handling treatment were treated with three injections of 2 mg dexamethasone (DEX)/kg BW on alternating days. On the day of the third DEX injection, duplicate pens of birds were also inoculated in the airsac with 0 or 50 cfu of Escherichia coli. The same birds were treated with a second series of DEX injections at 5 wk of age. Two weeks later, all birds were weighed, and 3 wk later four birds per pen were bled and 10 birds per pen were necropsied; relative organ weights were then determined. Surviving birds were treated with a third series of DEX injections at 10 wk of age; 2 wk later, all surviving turkeys were bled, weighed, and necropsied. Feed consumption was determined weekly. There were no differences due to handling treatment on the body weights or on the relative organ weights of birds that died after the first DEX treatment. Birds treated with a second DEX injection at 5 wk of age and handled 1x daily had decreased BW. Those handled 1x or 2x daily had higher feed conversion ratios. Surviving birds that were given a third DEX treatment had higher BW and no difference in feed conversion when handled 1x or 2x daily. Relative liver, heart, and spleen weights were affected by handling of DEX-E. coli-treated birds, as were serum chemistry values for calcium, iron, glucose, total protein, blood urea nitogen, uric acid, aspartate aminotransferase, alanine aminotransferase, lactate

Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gozalo, Alfonso S.; Chavera, Alfonso; Montoya, Enrique J.

2008-02-01

The purpose of this study was to determine serum reference values for crea- tine kinase (CK), aspartate aminotransferase (AST), and lactate dehydroge- nase (LDH) in captive-born and wild-caught owl monkeys to assess their usefulness for diagnosing myocardial disease. Urine samples were also collected and semi-quantitative tests performed. There was no statistically significant difference between CK, AST, and LDH when comparing both groups. However, when comparing monkeys with proteinuria to those without proteinuria, a statistically significant difference in CK value was observed (P = 0.021). In addition, the CK/AST ratio revealed that 29% of the animals included in this study hadmore » values suggesting cardiac infarction. Grossly, cardiac concentric hypertrophy of the left ventricle and small, pitted kidneys were the most common findings. Microscopically, myocardial fibrosis, contraction band necrosis, hypertrophy and hyperplasia of coronary arteries, medium-sized renal arteries, and afferent glomerular arteriolae were the most significant lesions, along with increased mesangial matrix and hypercellularity of glomeruli, Bowman’s capsule, and peritubular space fibroplasia. These findings suggest that CK, AST, and LDH along with urinalysis provide a reliable method for diagnosing cardiomyopathies in the owl monkey. In addition, CK/AST ratio, proteinuria, and the observed histological and ultrastructural changes suggest that Aotus vociferans suffer from arterial hypertension and chronic myocardial infarction.« less

Thermal Condensation of Glycine and Alanine on Metal Ferrite Surface: Primitive Peptide Bond Formation Scenario

PubMed Central

Iqubal, Md. Asif; Sharma, Rachana; Jheeta, Sohan; Kamaluddin

2017-01-01

The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe2O4), cobalt ferrite (CoFe2O4), copper ferrite (CuFe2O4), zinc ferrite (ZnFe2O4), and manganese ferrite (MnFe2O4) nanoparticles surfaces, in the temperature range from 50–120 °C for 1–35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe2O4 produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe2O4 was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C. PMID:28346388

Non-lethal assessment of freshwater mussel physiological response to changes in environmental factors

USGS Publications Warehouse

Fritts, Andrea K.; Peterson, James T.; Wisniewski, Jason M.; Bringolf, Robert B.

2015-01-01

The development of effective nonlethal biomonitoring techniques is imperative for the preservation of imperiled freshwater mussel populations. Changes in hemolymph chemistry profiles and tissue glycogen are potential biomarkers for nonlethally monitoring stress in mussels. We sampled three species in the Flint River Basin over 2 years to evaluate how these hemolymph and tissue biomarkers responded to environmental changes. We used hierarchical linear models to evaluate the relationships between variation in the biomarkers and environmental factors and found that the responses of the hemolymph and tissue parameters were strongly related to stream discharge. Shifts in alanine aminotransferase and glycogen showed the largest relations with discharge at the time of sampling, while magnesium levels were most explained by the discharge for 5 days prior to sampling. Aspartate aminotransferase, bicarbonate, and calcium showed the strongest relations with mean discharge for 15 days prior to sampling. The modeling results indicated that biomarker responses varied substantially among individuals of different size, sex, and species and illustrated the value of hierarchical modeling techniques to account for the inherent complexity of aquatic ecosystems.

Biochemical differences in ethnic groups in Durango, Mexico.

PubMed

Lares-Asseff, Ismael; Lujín-García, Azalia; Sosa-Macías, Martha; Lazalde-Ramos, Blanca; Loera-Castañeda, Veronica; Galaviz-Hernández, Carlos; Villanueva-Fierro, Ignacio

2012-01-01

The aim of this study was to assess biochemical differences between Tepehuano indigenous people, and Mennonite and Mestizo populations of Durango, Mexico. Our study involved 334 volunteers aged 15 to 80 years; 132 Mennonite and 130 Mestizo individuals from Nuevo Ideal Municipality and 72 Tepehuano indigenous people from Mezquital Durango were evaluated. A clinical history and fast determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, urea and creatinine were performed on each studied case. Statistically significant differences between the three studied groups were found for age, weight and height (P < .05), with higher values observed in men. The highest plasma urea levels were found in Mennonite compared to Mestizo people, followed by the Tepehuano indigenous. Higher biochemical parameters were found in men (vs women) in the studied groups. The percentage of individuals with abnormal levels for AST, ALT and uric acid were higher in Tepehuano indigenous people than in Mestizo, whereas the urea and creatinine percentages were higher in Mestizo people. The differences found on biochemical tests, could be explained by differences in lifestyle such as diet and sanitary habits.

Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats

PubMed Central

Al-Attar, Atef M.; Shawush, Nessreen A.

2014-01-01

The current study was undertaken to evaluate the protective activity of olive and rosemary leaves extracts on experimental liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. Highly significant decline in the values of body weight gain and highly statistically increase of liver/body weight ratio were noted in rats treated with TAA. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase and total bilirubin were statistically increased. Additionally, light microscopic examination of liver sections from rats treated with TAA showed a marked increase in the extracellular matrix collagen content and bridging fibrosis was prominent. There were bundles of collagen surrounding the lobules that resulted in large fibrous septa and distorted tissue architecture. Interestingly, the findings of this experimental study indicated that the extracts of olive and rosemary leaves and their combination possess hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, these results suggest that the hepatoprotective effects of these extracts may be attributed to their antioxidant activities. PMID:25737646

[Study of rat blood serum biochemical indicators of cardiotoxic action of novel antitumor 4-thiazolidinone derivatives and doxorubicin in complexes with polyethylene glycol-containing polymeric carrier in the rat blood serum].

PubMed

Kobylyns'ka, L I; Havryliuk, D Ia; Riabtseva, A O; Mitina, N Ie; Zaichenko, O S; Zimenkovskyĭ, B S; Stoĭka, R S

2014-01-01

The aim of this study was to measure the activity of enzymes which reflect cardiotoxic action in rats of novel synthetic 4-thiazolidone derivatives--3882, 3288 and 3833 that demonstrated antineoplastic effect in vitro towards 60 lines of human tumor cells tested in the framework of the program of screening new anticancer drugs at the National Cancer Institute (USA). Such action of these compounds was compared with the effect of well known anticancer agent doxorubicin and after conjugation of all above mentioned substances with new polyethylenglycol-containing polymeric comb-like carrier that was synthesized by the authors. Among the biochemical indicators of cardiotoxic action of anticancer agents, activity of the following enzymes in rat blood serum showed to be the most informative: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransterase. Tenfold injection of doxorubicin in a dose of 5.5 mg/kg of weight caused rats' death, while 3882, 3288 and 3833 preparations had not such action. Application of the doxorubicin in combination with polymeric carrier prolonged the survival time to 20 days. Thus, the injection of anticancer agents in a complex with polymeric carrier provides a significant decrease in their cardiotoxicity that was confirmed by the corresponding changes in the activity of marker enzymes: creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in blood serum of treated rats.

Effects of lead shot ingestion on delta-aminolevulinic acid dehydratase activity, hemoglobin concentration, and serum chemistry in bald eagles

USGS Publications Warehouse

Hoffman, D.J.; Pattee, O.H.; Wiemeyer, Stanley N.; Mulhern, B.

1981-01-01

Lead shot ingestion by bald eagles (Haliaeetus leucocephalus) is considered to be widespread and has been implicated in the death of eagles in nature. It was recently demonstrated under experimental conditions that ingestion of as few as 10 lead shot resulted in death within 12 to 20 days. In the present study hematological responses to lead toxicity including red blood cell ALAD activity, hemoglobin concentration and 23 different blood serum chemistries were examined in five captive bald eagles that were unsuitable for rehabilitation and release. Eagles were dosed by force-feeding with 10 lead shot; they were redosed if regurgitation occurred. Red blood cell ALAD activity was inhibited by nearly 80% within 24 hours when mean blood lead concentration had increased to 0.8 parts per million (ppm). By the end of 1 week there was a significant decrease (20-25%) in hematocrit and hemoglobin, and the mean blood lead concentration was over 3 ppm. Within as little as 1-2 weeks after dosing, significant elevations in serum creatinine and serum alanine aminotransferase occurred, as well as a significant decrease in the ratio of serum aspartic aminotransferase to serum alanine aminotransferase. The mean blood lead concentration was over 5 ppm by the end of 2 weeks. These changes in serum chemistry may be indicative of kidney and liver alterations.

Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism.

PubMed

Mesa-Torres, Noel; Calvo, Ana C; Oppici, Elisa; Titelbaum, Nicholas; Montioli, Riccardo; Miranda-Vizuete, Antonio; Cellini, Barbara; Salido, Eduardo; Pey, Angel L

2016-09-01

In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

PubMed Central

la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

2013-01-01

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

PubMed

Kobayashi, Natsuko; Iijima, Hiroko; Tada, Toshifumi; Kumada, Takashi; Yoshida, Masahiro; Aoki, Tomoko; Nishimura, Takashi; Nakano, Chikage; Takata, Ryo; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Sakai, Yoshiyuki; Aizawa, Nobuhiro; Nishikawa, Hiroki; Ikeda, Naoto; Iwata, Yoshinori; Enomoto, Hirayuki; Hirota, Seiichi; Fujimoto, Jiro; Nishiguchi, Shuhei

2018-05-01

Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy. A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48). Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0-14.8), 7.4 (4.6-14.7), 5.3 (4.1-11.8), and 5.4 (4.0-13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245-278) and 229 (209-249) dB/m, respectively (P=0.020). Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.

D-alanine carboxypeptidase activity of Micrococcus lysodeikticus released into the protoplasting medium.

PubMed

Linder, R; Salton, M R

1975-06-16

Conversion of whole cells of Micrococcus lysodeikticus to protoplasts allowed the release of a soluble form of a D-alanine carboxypeptidase into the protoplasting medium. The enzyme cleaves the terminal D-alanine from the radioactively labelled UDP-N-acetylmuramyl-pentapeptide containing L-lysine as the diamino acid. However, the enzyme is only minimally active in this fraction so that it had to be enriched and partially purified before its properties could be studied. Chromatography on carboxymethyl-Sephadex removed the lysozyme used in the protoplasting of the cells. The material which was unadsorbed to the column was applied to an affinity chromatography column of Ampicillin-Sepharose. Most of the contaminating protein was washed from the column while the D-alanine carboxypeptidase adhered to the resin and could be eluted with 0.5 M Tris-HCl buffer pH 8.6. Some of the properties of the enzymic activity were studied using this preparation. The enzyme was activated by Mg2+ ions with a broad optimum from 15--35 mM. It was maximally active when NaCl at a concentrations of 0.06--0.08 M was added to the assay, and the pH curve was biphasic with an alkaline optimum. The Km for substrate was found to be 0.118 mM. Enzymic activity was completely inhibited by low concentrations of Ampicillin and penicillin G.

Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

PubMed Central

Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S. Painelli, Vitor; Harris, Roger C.; Gualano, Bruno

2015-01-01

Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists. PMID:25875297

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

PubMed

Solis, Marina Yazigi; Cooper, Simon; Hobson, Ruth M; Artioli, Guilherme G; Otaduy, Maria C; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S Painelli, Vitor; Harris, Roger C; Gualano, Bruno; Sale, Craig

2015-01-01

Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C.

PubMed

Massirer, K B; Hirata, M H; Silva, A E B; Ferraz, M L G; Nguyen, N Y; Hirata, R D C

2004-05-01

Interferon (IFN)-alpha receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-alpha therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-alpha receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-alpha in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFN-alpha 2b for one year. Those with HBV or HIV infection, or using alcohol were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-alpha response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcription-polymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/beta-actin-mRNA ratio (mean +/- SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 +/- 0.15; N = 5; P < 0.05) compared to non-responders (0.35 +/- 0.17; N = 12) and controls (0.30 +/- 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in non-responders during IFN-alpha therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-alpha response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C.

Synthesis and characterization of new nanocomposites films using alanine-Cu-functionalized graphene oxide as nanofiller and PVA as polymeric matrix for improving of their properties

NASA Astrophysics Data System (ADS)

Abdolmaleki, Amir; Mallakpour, Shadpour; Karshenas, Azam

2017-09-01

In the synthesis of polymer-graphene nanocomposites, for improving properties of nanocomposites, two factors dispersion and strong interfacial interactions between graphene and the polymer, are essential. In the present work, poly(vinyl alcohol) PVA/GO-Cu-alanine nanocomposite films were manufactured using concentrations 0, 1, 3 and 5 wt% of GO-Cu-alanine in water solution. For this purpose, L-alanine amino acid was located on the surface and edges of GO through copper(II) ion as a coordinating function. Then, flexible PVA/GO-Cu-alanine nanocomposite films were fabricated using GO-Cu-alanine as filler and PVA as matrix. Due to the existence of affective interaction between GO-Cu-alanine and PVA matrix, the acquired PVA/GO-Cu-alanine nanocomposites demonstrated great thermal and mechanical properties. Properties of manufactured materials were characterized by Fourier transform infrared, X-ray photoelectron spectroscopies (XPS), X-ray diffraction (XRD), Thermal gravimetric analysis, elemental analysis, field emission scanning electron microscopy, transmission electron microscopy and energy dispersive X-ray spectroscopy (EDX).

Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide

PubMed Central

Johnston, Heather J.; Boys, Sarah K.; Makda, Ashraff; Carragher, Neil O.

2016-01-01

Abstract Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid‐phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose‐dependent response in IRS‐1 expression. Alanine scanning reveals a structural dependence to the cytotoxicity, actin targeting and pathway inhibition, and allows a new readily synthesised lead to be proposed. PMID:27304907

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

PubMed Central

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E.; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H.; Pybus, Oliver G.; Alter, Harvey J.

2012-01-01

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis. PMID:22829669

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis.

PubMed

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H; Pybus, Oliver G; Alter, Harvey J

2012-09-04

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

Biochemical, anthropometric and body composition indicators as predictors of hepatic steatosis in obese adolescents

PubMed Central

Gobato, Amanda Oliva; Vasques, Ana Carolina J.; Yamada, Roberto Massao; Zambon, Mariana Porto; Barros-Filho, Antonio de Azevedo; Hessel, Gabriel

2014-01-01

OBJECTIVE: To describe the prevalence of hepatic steatosis and to assess the performance of biochemical, anthropometric and body composition indicators for hepatic steatosis in obese teenagers. METHODS: Cross-sectional study including 79 adolecents aged from ten to 18 years old. Hepatic steatosis was diagnosed by abdominal ultrasound in case of moderate or intense hepatorenal contrast and/or a difference in the histogram ≥7 on the right kidney cortex. The insulin resistance was determined by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index for values >3.16. Anthropometric and body composition indicators consisted of body mass index, body fat percentage, abdominal circumference and subcutaneous fat. Fasting glycemia and insulin, lipid profile and hepatic enzymes, such as aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and alkaline phosphatase, were also evaluated. In order to assess the performance of these indicators in the diagnosis of hepatic steatosis in teenagers, a ROC curve analysis was applied. RESULTS: Hepatic steatosis was found in 20% of the patients and insulin resistance, in 29%. Gamma-glutamyltransferase and HOMA-IR were good indicators for predicting hepatic steatosis, with a cutoff of 1.06 times above the reference value for gamma-glutamyltransferase and 3.28 times for the HOMA-IR. The anthropometric indicators, the body fat percentage, the lipid profile, the glycemia and the aspartate aminotransferase did not present significant associations. CONCLUSIONS: Patients with high gamma-glutamyltransferase level and/or HOMA-IR should be submitted to abdominal ultrasound examination due to the increased chance of having hepatic steatosis. PMID:25119755

Diagnosis and treatment of Sarcocystis neurona-induced myositis in a free-ranging California sea lion.

PubMed

Carlson-Bremer, Daphne P; Gulland, Frances M D; Johnson, Christine K; Colegrove, Kathleen M; Van Bonn, William G

2012-02-01

An underweight, lethargic adult female California sea lion (Zalophus californianus) became stranded along the California shore and was captured and transported to a rehabilitation hospital for assessment and care. Initial physical assessment revealed the sea lion was lethargic and in poor body condition. Active myositis was diagnosed on the basis of concurrent elevations in activities of alanine aminotransferase and creatine kinase detected during serum biochemical analysis. Infection with Sarcocystis neurona was diagnosed after serologic titers increased 4-fold over a 3-week period. Diagnosis was confirmed on the basis of histopathologic findings, positive results on immunohistochemical staining, and results of quantitative PCR assay on biopsy specimens obtained from the diaphragm and muscles of the dorsal cervical region. Anticoccidial treatment was instituted with ponazuril (10 mg/kg [4.5 mg/lb], PO, q 24 h) and continued for 28 days. Prednisone (0.2 mg/kg [0.09 mg/lb], PO, q 12 h) was administered for 2 days and then every 24 hours for 5 days to treat associated inflammation. At the end of treatment, the sea lion was clinically normal, alanine aminotransferase and creatine kinase values were within reference limits, and antibody titers against S neurona had decreased 6-fold. The sea lion was released approximately 3 months after becoming stranded. S neurona-induced myositis was diagnosed in a free-ranging California sea lion. On the basis of the successful treatment and release of this sea lion, anticoccidial treatment should be considered for marine mammals in which protozoal disease is diagnosed.

Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: comparison between theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2008-01-01

The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid-base properties in alanine-based peptides. Hence, the acid-base properties of three alanine-based peptides: Ac-KK-(A)(7)-KK-NH(2) (KAK), Ac-OO-(A)(7)-DD-NH(2) (OAD), Ac-KK-(A)(7)-EE-NH(2) (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH-metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson-Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, pK(a1) and pK(a2) correspond to the acidic side chains. For all three compounds in both solvents, the pK(a1) value is remarkably lower than the pK(a) of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method.

Antimicrobial susceptibility testing of a clinical isolate of vancomycin-dependent enterococcus using D-alanine-D-alanine as a growth supplement.

PubMed

Sng, L H; Cornish, N; Knapp, C C; Ludwig, M D; Hall, G S; Washington, J A

1998-04-01

Bacteremia due to a vancomycin-dependent enterococcus (VDE) occurred during long-term vancomycin therapy in a renal transplant recipient with underlying pancreatitis and a vancomycin-resistant enterococcal (VRE) wound infection and bacteremia. The VDE was isolated from blood during vancomycin therapy and grew only in the presence of vancomycin and D-alanine-D-alanine (DADA), a substance required for cell-wall synthesis. Colonies beyond the periphery of growth of the VDE around a vancomycin disk contained vancomycin-independent revertant mutants after 48 hours of incubation. Pulsed-field gel electrophoresis of the VDE, revertant mutant, the initial blood culture isolate of VRE, and an autopsy isolate showed that the four strains were identical. Antimicrobial susceptibility testing was performed using standard macrobroth and microbroth dilution methods. DADA was used as a growth supplement for macrobroth dilution susceptibility testing of the VDE isolate. Minimum inhibitory concentrations (MICs) were similar for the VRE isolate and the VDE revertant, which were both resistant to ampicillin, high-level gentamicin, ciprofloxacin, imipenem, vancomycin, and daptomycin, and were susceptible to fusidic acid, high-level streptomycin, rifampin, and a quinupristin-dalfopristin combination. The MICs of teicoplanin were 2 microg/mL or less and 16 microg/mL for the clinical VRE isolate and the VDE revertant, respectively. The autopsy isolate was resistant to all antimicrobials tested and showed a fourfold increase in MICs for quinupristin-dalfopristin compared with that of the original blood isolate. The VDE was susceptible to all drugs tested except vancomycin.

Hypolipidemic effect of the edible mushroom Agaricus blazei in rats subjected to a hypercholesterolemic diet.

PubMed

de Miranda, Aline M; Ribeiro, Gustavo M; Cunha, Aureliano C; Silva, Lorena S; dos Santos, Rinaldo C; Pedrosa, Maria Lúcia; Silva, Marcelo E

2014-03-01

The effects of Agaricus blazei intake on the lipid profile of animals fed a hypercholesterolemic diet were evaluated. Thirty-two female Fisher rats were divided into four groups and given the standard AIN-93 M diet (C), this diet + 1 % A. blazei (CAb), a hypercholesterolemic diet with 25 % soybean oil and 1 % cholesterol (H) or this diet + 1 % A. blazei (HAb) for 6 weeks. Food intake, weight gain, liver and serum lipid profiles, activity of aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], and creatinine and urea levels as well as abdominal fat weight were measured. Histological analysis of kidney and liver tissue was also performed. The HAb group had a higher food intake, but a lower weight gain as compared to group H. This resulted in a significant decrease in abdominal fat weight, to values close to those of groups C and CAb. Supplementing the hypercholesterolemic diet with A. blazei promoted a significant reduction in total and non-HDL cholesterol, as well as in the atherogenic index, as compared to group H, and this effect was more pronounced in the serum. There was no hepatotoxic effect caused by the supplementation of the diets with the mushroom. We conclude that in our experimental model and in the concentration used, A. blazei was effective in improving the lipid profile of the animals.

Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China.

PubMed

Huang, Rui; Wang, Guiyang; Tian, Chen; Liu, Yong; Jia, Bei; Wang, Jian; Yang, Yue; Li, Yang; Sun, Zhenhua; Yan, Xiaomin; Xia, Juan; Xiong, Yali; Song, Peixin; Zhang, Zhaoping; Ding, Weimao; Wu, Chao

2017-08-17

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

The Usefulness of Clinical-Practice-Based Laboratory Data in Facilitating the Diagnosis of Dengue Illness

PubMed Central

Liu, Jien-Wei; Lee, Ing-Kit; Wang, Lin; Chen, Rong-Fu; Yang, Kuender D.

2013-01-01

Alertness to dengue and making a timely diagnosis is extremely important in the treatment of dengue and containment of dengue epidemics. We evaluated the complementary role of clinical-practice-based laboratory data in facilitating suspicion/diagnosis of dengue. One hundred overall dengue (57 dengue fever [DF] and 43 dengue hemorrhagic fever [DHF]) cases and another 100 nondengue cases (78 viral infections other than dengue, 6 bacterial sepsis, and 16 miscellaneous diseases) were analyzed. We separately compared individual laboratory variables (platelet count [PC] , prothrombin time [PT], activated partial thromboplastin time [APTT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) and varied combined variables of DF and/or DHF cases with the corresponding ones of nondengue cases. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) in the diagnosis of DF and/or DHF were measured based on these laboratory variables. While trade-off between sensitivity and specificity, and/or suboptimal PPV/NPV was found at measurements using these variables, prolonged APTT + normal PT + PC < 100 × 109 cells/L had a favorable sensitivity, specificity, PPV, and NPV in diagnosis of DF and/or DHF. In conclusion, these data suggested that prolonged APTT + normal PT + PC < 100 × 109 cells/L is useful in evaluating the likelihood of DF and/or DHF. PMID:24455678

Hematology, plasma biochemistry, and tissue enzyme activities of invasive red lionfish captured off North Carolina, USA.

PubMed

Anderson, E T; Stoskopf, M K; Morris, J A; Clarke, E O; Harms, C A

2010-12-01

The red lionfish Pterois volitans is important not only in the aquarium trade but also as an invasive species in the western Atlantic. Introduced to waters off the southeastern coast of the United States, red lionfish have rapidly spread along much of the East Coast and throughout Bermuda, the Bahamas, and much of the Caribbean. Hematology and plasma biochemistry were evaluated in red lionfish captured from the offshore waters of North Carolina to establish baseline parameters for individual and population health assessment. Blood smears were evaluated for total and differential white blood cell counts, and routine clinical biochemical profiles were performed on plasma samples. To improve the interpretive value of routine plasma biochemistry profiles, tissue enzyme activities (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], lactate dehydrogenase [LD], and creatine kinase [CK]) were analyzed from liver, kidney, skeletal muscle, gastrointestinal tract, and heart tissues from five fish. The hematological and plasma biochemical values were similar to those of other marine teleosts except that the estimated white blood cell counts were much lower than those routinely found in many species. The tissue enzyme activity findings suggest that plasma LD, CK, and AST offer clinical relevance in the assessment of red lionfish.

Effects of 4 Weeks of β-Alanine Supplementation on Swim-Performance Parameters in Water Polo Players.

PubMed

Brisola, Gabriel Motta Pinheiro; Milioni, Fabio; Papoti, Marcelo; Zagatto, Alessandro Moura

2017-08-01

In water polo, several high-intensity efforts are performed, leading to the fatigue process due to accumulation of hydrogen ions, and thus β-alanine supplementation could be an efficient strategy to increase the intramuscular acid buffer. Purpose To investigate whether 4 wk of β-alanine supplementation enhances parameters related to water polo performance. Methods Twenty-two highly trained male water polo players of national level were randomly assigned to receive 28 d of either β-alanine or a placebo (4.8 g/d of the supplement in the first 10 d and 6.4 g/d in the final 18 d). The participants performed 30-s maximal tethered swimming (30TS), 200-m swimming (P200m), and 30-s crossbar jumps (30CJ) before and after the supplementation period. Results The β-alanine group presented significant increases in 30TS for mean force (P = .04; Δ = 30.5% ± 40.4%) and integral of force (P = .05; Δ = 28.0% ± 38.0%), as well as P200m (P = .05; Δ = -2.2% ± 2.6%), while the placebo group did not significantly differ for mean force (P = .13; Δ = 24.1% ± 33.7%), integral of force (P = .12; Δ = 24.3% ± 35.1%), or P200m (P = .10; Δ = -1.6% ± 3.8%). However, there was no significant group effect for any variable, and the magnitude-based-inference analysis showed unclear outcomes between groups (Cohen d ± 95%CL mean force = 0.16 ± 0.83, integral of force = 0.12 ± 0.84, and P200m = 0.05 ± 0.30). For 30CJ the results were similar, with improvements in both groups (placebo, Δ = 14.9% ± 14.1%; β-alanine, Δ = 16.9% ± 18.5%) but with no significant interaction effect between groups and an unclear effect (0.14 ± 0.75). Conclusion Four weeks of β-alanine supplementation does not substantially improve performance of 30TS, P200m, or 30CJ in highly trained water polo athletes compared with a control group.

Characterization of Lactobacillus salivarius alanine racemase: short-chain carboxylate-activation and the role of A131.

PubMed

Kobayashi, Jyumpei; Yukimoto, Jotaro; Shimizu, Yasuhiro; Ohmori, Taketo; Suzuki, Hirokazu; Doi, Katsumi; Ohshima, Toshihisa

2015-01-01

Many strains of lactic acid bacteria produce high concentrations of d-amino acids. Among them, Lactobacillus salivarius UCC 118 produces d-alanine at a relative concentration much greater than 50 % of the total d, l-alanine (100d/d, l-alanine). We characterized the L. salivarius alanine racemase (ALR) likely responsible for this d-alanine production and found that the enzyme was activated by carboxylates, which is an unique characteristic among ALRs. In addition, alignment of the amino acid sequences of several ALRs revealed that A131 of L. salivarius ALR is likely involved in the activation. To confirm that finding, an L. salivarius ALR variant with an A131K (ALR(A131K)) substitution was prepared, and its properties were compared with those of ALR. The activity of ALR(A131K) was about three times greater than that of ALR. In addition, whereas L. salivarius ALR was strongly activated by low concentrations (e.g., 1 mM) of short chain carboxylates, and was inhibited at higher concentrations (e.g., 10 mM), ALR(A131K) was clearly inhibited at all carboxylate concentrations tested (1-40 mM). Acetate also increased the stability of ALR such that maximum activity was observed at 35 °C and pH 8.0 without acetate, but at 50 °C in the presence of 1 mM acetate. On the other hand, maximum ALR(A131K) activity was observed at 45 °C and around pH 9.0 with or without acetate. It thus appears that A131 mediates the activation and stabilization of L. salivarius ALR by short chain carboxylates.

Reference values for biochemical parameters in blood serum of young and adult alpacas (Vicugna pacos).

PubMed

Husakova, T; Pavlata, L; Pechova, A; Hauptmanova, K; Pitropovska, E; Tichy, L

2014-09-01

The aim of this study was to establish reference interval for biochemical parameters in blood of alpacas on the basis of large population of clinically healthy animals, and to determine the influence of sex, age and season on nitrogen and lipid metabolites, enzymes, electrolytes, vitamins and minerals in blood of alpacas. Blood samples were collected from 311 alpacas (61 males and 201 females >6 months of age and 49 crias (21 males and 28 females) ⩽6 months of age). Selected farms were located in Central Europe (Czech Republic and Germany). We determined 24 biochemical parameters from blood serum. We performed the comparison of results by the sex of animals and for the older group also the comparison of the results with regard to the season, respectively, to the feeding period. We found no highly significant difference (P<0.01) between males and females with the exception of γ-glutamyl transferase (GGT), alkaline phosphatase (ALP) and cholesterol. We found 15 significantly different parameters between the group of crias 6 months of age and the older alpacas. Based on our findings we suggest for most parameters to use different reference intervals (especially ALP, cholesterol, total protein, globulin, non-esterified fatty acids (NEFA), GGT and phosphorus) for the two above-mentioned age groups. Another important finding is the differences between some parameters in older group of alpacas in summer/winter feeding period. Animals in the summer feeding period have higher values of parameters related to fat mobilization (β-hydroxybutyrate, NEFA) and liver metabolism (bilirubin, alanine aminotransferase). The winter period with increased feeding of supplements with higher amount of fat, vitamins and minerals is characteristic by increased values of cholesterol, triglycerides, vitamins A and E, and some minerals (K, Ca, Mg and Cl) in blood serum. Clinical laboratory diagnosis of metabolic disturbances may be improved with use of age-based reference values and with

Radiology case of the month. Nausea, vomiting, and diarrhea in a patient with hepatitis C and acquired immunodeficiency syndrome (AIDS). Diffuse, severe gastric-wall thickening, consistent with edema.

PubMed

Mabry, Christian; Hutchings, John; Sanders, Charles; Neitzschman, Harold

2012-01-01

The patient is a 42-year-old male with a past medical history of HIV/AIDS (his most recent CD4 count, four months before admission, was 19) and hepatitis C who presented to the Emergency Department complaining of one week of persistent nausea, vomiting, and diarrhea. His admit labs were as follows: hemoglobin of 11.8, hematocrit of 35, total protein of 6.0, albumin of 1.6, total bilirubin of 2.3, aspartate aminotransferase (AST) of 141, alkaline phosphatase (ALP) of 146, and alanine aminotransferase (ALT) of 31. Computed tomography (CT) images of the abdomen and pelvis with contrast were obtained (Figures 1 - 4).

Fast and Cost-Effective Biochemical Spectrophotometric Analysis of Solution of Insect "Blood" and Body Surface Elution.

PubMed

Łoś, Aleksandra; Strachecka, Aneta

2018-05-09

Using insect hemolymph ("blood") and insect body surface elutions, researchers can perform rapid and cheap biochemical analyses to determine the insect's immunology status. The authors of this publication describe a detailed methodology for a quick marking of the concentration of total proteins and evaluation of the proteolytic system activity (acid, neutral, and alkaline proteases and protease inhibitors), as well as a methodology for quick "liver" tests in insects: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and urea and glucose concentration analyses. The meaning and examples of an interpretation of the results of the presented methodology for biochemical parameter determination are described for the example of honey bees.

Assessing microbial utilization of free versus sorbed Alanine by using position-specific 13C labeling and 13C-PLFA analysis

NASA Astrophysics Data System (ADS)

Herschbach, Jennifer; Apostel, Carolin; Spielvogel, Sandra; Kuzyakov, Yakov; Dippold, Michaela

2016-04-01

Microbial utilization is a key transformation process of soil organic matter (SOM). Sorption of low molecular weight organic substances (LMWOS) to soil mineral surfaces blocks or delays microbial uptake and therefore mineralization of LMWOS to CO2, as well as all other biochemical transformations. We used position-specific labeling, a tool of isotope applications novel to soil science, combined with 13C-phospholipid fatty acid (PLFA) analysis, to assess microbial utilization of sorbed and non-sorbed Alanine in soil. Alanine has various functional groups enabling different sorption mechanisms via its positive charge (e.g. to clay minerals by cation exchange), as well as via its negative charge (e.g. to iron oxides by ligand exchange). To assess changes in the transformation pathways caused by sorption, we added uniformly and position-specifically 13C and 14C labeled Alanine to the Ap of a loamy Luvisol in a short-term (10 days) incubation experiment. To allow for sorption of the tracer solution to an aliquot of this soil, microbial activity was minimized in this subsample by sterilizing the soil by γ-radiation. After shaking, the remaining solutions were filtered and the non-sorbed Alanine was removed with Millipore water and then added to non-sterilized soil. For the free Alanine treatment, solutions with Alanine of similar amount and isotopic composition were prepared, added to the soil and incubated as well. The respired CO2 was trapped in NaOH and its 14C-activity was determined at increasing times intervals. Microbial utilization of Alanine's individual C positions was evaluated in distinct microbial groups classified by 13C-PLFA analysis. Sorption to soil minerals delayed respiration to CO2 and reduced initial respiration rate by 80%. Irrespective of sorption, the highest amount was respired from the carboxylic position (C-1), whereas the amino-bound (C-2) and the methylic position (C-3) were preferentially incorporated into PLFA of microorganisms due to the

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-aminoethylphosphonic acid (l-Ala-P)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Au, Kinfai; Ren, Jingshan; Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN

2008-05-01

Structures of BA0252, an alanine racemase from B. anthracis, in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) and determined by X-ray crystallography to resolutions of 2.1 and 1.47 Å, respectively, are described. Bacillus anthracis, the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high-throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) have determined by X-ray crystallo@@graphy to resolutions of 2.1 and 1.47 Å, respectively. Difficulties inmore » crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti-anthrax drugs: not only is d-alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis. These structures confirm the binding mode of l-Ala-P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti-anthrax therapies.« less

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

PubMed Central

Umpleby, A M; Trend, P S; Chubb, D; Conaglen, J V; Williams, C D; Hesp, R; Scobie, I N; Wiles, C M; Spencer, G; Sönksen, P H

1989-01-01

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect. PMID:2507747

ENDOR-Induced EPR of Disordered Systems: Application to X-Irradiated Alanine.

PubMed

Kusakovskij, Jevgenij; Maes, Kwinten; Callens, Freddy; Vrielinck, Henk

2018-02-15

The electron paramagnetic resonance (EPR) spectra of radiation-induced radicals in organic solids are generally composed of multiple components that largely overlap due to their similar weak g anisotropy and a large number of hyperfine (HF) interactions. Such properties make these systems difficult to study using standard cw EPR spectroscopy even in single crystals. Electron-nuclear double-resonance (ENDOR) spectroscopy is a powerful and widely used complementary technique. In particular, ENDOR-induced EPR (EIE) experiments are useful for separating the overlapping contributions. In the present work, these techniques were employed to study the EPR spectrum of stable radicals in X-irradiated alanine, which is widely used in dosimetric applications. The principal values of all major proton HF interactions of the dominant radicals were determined by analyzing the magnetic field dependence of the ENDOR spectrum at 50 K, where the rotation of methyl groups is frozen. Accurate simulations of the EPR spectrum were performed after the major components were separated using an EIE analysis. As a result, new evidence in favor of the model of the second dominant radical was obtained.

VUV photodynamics and chiral asymmetry in the photoionization of gas phase alanine enantiomers.

PubMed

Tia, Maurice; Cunha de Miranda, Barbara; Daly, Steven; Gaie-Levrel, François; Garcia, Gustavo A; Nahon, Laurent; Powis, Ivan

2014-04-17

The valence shell photoionization of the simplest proteinaceous chiral amino acid, alanine, is investigated over the vacuum ultraviolet region from its ionization threshold up to 18 eV. Tunable and variable polarization synchrotron radiation was coupled to a double imaging photoelectron/photoion coincidence (i(2)PEPICO) spectrometer to produce mass-selected threshold photoelectron spectra and derive the state-selected fragmentation channels. The photoelectron circular dichroism (PECD), an orbital-sensitive, conformer-dependent chiroptical effect, was also recorded at various photon energies and compared to continuum multiple scattering calculations. Two complementary vaporization methods-aerosol thermodesorption and a resistively heated sample oven coupled to an adiabatic expansion-were applied to promote pure enantiomers of alanine into the gas phase, yielding neutral alanine with different internal energy distributions. A comparison of the photoelectron spectroscopy, fragmentation, and dichroism measured for each of the vaporization methods was rationalized in terms of internal energy and conformer populations and supported by theoretical calculations. The analytical potential of the so-called PECD-PICO detection technique-where the electron spectroscopy and circular dichroism can be obtained as a function of mass and ion translational energy-is underlined and applied to characterize the origin of the various species found in the experimental mass spectra. Finally, the PECD findings are discussed within an astrochemical context, and possible implications regarding the origin of biomolecular asymmetry are identified.

Thermodynamics of DL-alanine solvation in water-dimethylsulfoxide mixtures at 298.15 K

NASA Astrophysics Data System (ADS)

Roy, S.; Mahali, K.; Mondal, S.; Dolui, B. K.

2015-04-01

In this study we mainly discuss the transfer Gibbs free energy Δ G {/t 0}( i) and Δ S {/t 0}( i)entropy of DL-alanine at 298.15 K and consequently the involved chemical transfer free energy (Δ G {/t,ch 0}( i)) and entropy ( TΔ S {/t,ch 0}( i)) in aqueous mixtures of dimethylsulfoxide are discussed to clarify the solvation chemistry of DL-alanine. For the evaluation of these energy terms, solubility of this amino acid has been measured by formol titrimetry at five equidistant temperatures i.e., from 288.15 to 308.15 K in different composition of this mixed solvent system. The various solvent parameters as well as thermodynamic parameters like molar volume, density, dipole moment and solvent diameter of this solvent system have also been reported here. The chemical effects of the transfer Gibbs energies (Δ G {/t,ch 0}( i)) and entropies of transfer ( TΔ S {/t,ch 0}( i)) have been obtained after elimination of cavity effect and dipole-dipole interaction effects from the total transfer energies. Here the chemical contribution of transfer energetics of DL-alanine is mainly guided by the composite effects of increased dispersion interaction, basicity effect and decreased acidity, hydrogen bonding effects, hydrophilic hydration and hydrophobic hydration of aqueous DMSO mixtures as compared to that of reference solvent, water.

Effect of increasing maximal aerobic exercise on serum muscles enzymes in professional field hockey players.

PubMed

Hazar, Muhsin; Otag, Aynur; Otag, Ilhan; Sezen, Mehmet; Sever, Ozan

2014-11-04

Exercise results in oxidative enzyme increase and micro-injuries in skeletal muscles. The aim of this study was to investigate the effect of maximal aerobic exercise on serum muscle enzymes in professional field hockey players. This study aims to determine the effect of increasing maximal aerobic exercise on creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. 31 young professional field hockey players (13 female and 18 male players) volunteered for this study. All participants underwent the shuttle run test. Blood samples were taken from each participant before the shuttle run test. Post test blood samples were taken immediately after exercise and one hour after respectively. Pre and post test CK, CK-MB, AST and ALT values were measured by means of auto analyzer using original kits. The acute post test measure of the CK level increased in male (p=0.002) and female (p=0.00) sportsmen. CK-MB values obtained one hour after the exercise was lower than those before the exercise in males (p=0.02). In females (p=0.017) and males (p=0.05) AST activity significantly increased immediately after exercise and decreased to resting activity 1 h recovery. ALT significantly increased immediately after exercise in female (p=0.03) and male (p=0.00) athletes and after 1 h recovery ALT activities decreased below resting values. The timing and severity of exercise used in our study increased CK values, decreased CK-MB values and AST, ALT values increased in female and male field hockey players.

Adsorption of alanine with heteroatom substituted fullerene for solar cell application: A DFT study.

PubMed

Dheivamalar, S; Sugi, L; Ravichandran, K; Sriram, S

2018-09-05

C 20 is the most important fullerene cage and alanine is the simplest representation of a backbone unit of the protein. The absorption feasibility of alanine molecule in the Si-doped C 20 and B-doped C 20 fullerenes has been studied based on calculated electronic properties of fullerenes using density functional theory (DFT). In this work, we explore the ability of Si-doped C 20 , B-doped C 20 fullerene to interact with alanine at the DFT-B3LYP/6-31G, RHF level of theory. We find that noticeable structural change takes place in C 20 when one of its carbon is substituted with Si or B. The molecular geometry, electronic properties and vibrational analysis have also been performed on the title compounds. The NMR study reveals the aromaticity of the pure and doped fullerene compounds. Stability of the doped fullerene - alanine compound arises from hyper conjugative interactions. It leads to one of the major property of bioactivity, charge transfer and delocalization of charge and this properties has been analyzed using Natural Bond Orbital (NBO) analysis. The energy gap of the doped fullerene reveals that there is a decrease in the size of energy gap significantly, making them more reactive as compared to C 20 fullerene. Theoretical studies of the electronic spectra by using time - dependent density functional theory (TD-DFT) method were helpful to interpret the observed electronic transition state. We aim to optimize the performance of the solar cells by altering the frontier orbital energy gaps. Considering all studied properties, it may be inferred that the applicability of C 20 fullerene as the non-linear optical (NLO) material and its NLO property would increase on doping fullerene with Si and B atom. Specifically C 19 Si would be better among them. Copyright © 2018. Published by Elsevier B.V.

Radiochemical microassay for aspartate aminotransferase activity in the nervous system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garrison, D.; Beattie, J.; Namboodiri, M.A.

1988-07-01

A radiochemical procedure for measuring aspartate aminotransferase activity in the nervous system is described. The method is based on the exchange of tritium atoms at positions 2 and 3 of L-2,3-(/sup 3/H)aspartate with water when this amino acid is transaminated in the presence of alpha-ketoglutarate to form oxaloacetate. The tritiated water is separated from the radiolabeled aspartate by passing the reaction mixture over a cation exchange column. Confirmation that the radioactivity in the product is associated with water was obtained by separating it by anion exchange HPLC and by evaporation. The product formation is linear with time up to 120more » min and with tissue in the 0.05- to 10-micrograms range. The apparent Km for aspartate in the rat brain homogenate is found to be 0.83 mM and that for alpha-ketoglutarate to be 0.12 mM. Methods that further improve the sensitivity of the assay are also discussed.« less

Anaerobic Metabolism in the N-Limited Green Alga Selenastrum minutum: III. Alanine Is the Product of Anaerobic Ammonium Assimilation.

PubMed

Vanlerberghe, G C; Joy, K W; Turpin, D H

1991-02-01

We have determined the flow of (15)N into free amino acids of the N-limited green alga Selenastrum minutum (Naeg.) Collins after addition of (15)NH(4) (+) to aerobic or anaerobic cells. Under aerobic conditions, only a small proportion of the N assimilated was retained in the free amino acid pool. However, under anaerobic conditions almost all assimilated NH(4) (+) accumulates in alanine. This is a unique feature of anaerobic NH(4) (+) assimilation. The pathway of carbon flow to alanine results in the production of ATP and reductant which matches exactly the requirements of NH(4) (+) assimilation. Alanine synthesis is therefore an excellent strategy to maintain energy and redox balance during anaerobic NH(4) (+) assimilation.

Multiphoton manipulations of enzymatic photoactivity in aspartate aminotransferase.

PubMed

Hill, Melissa P; Freer, Lucy H; Vang, Mai C; Carroll, Elizabeth C; Larsen, Delmar S

2011-04-21

The aspartate aminotransferase (AAT) enzyme utilizes the chromophoric pyridoxal 5'-phosphate (PLP) cofactor to facilitate the transamination of amino acids. Recently, we demonstrated that, upon exposure to blue light, PLP forms a reactive triplet state that rapidly (in microseconds) generates the high-energy quinonoid intermediate when bound to PLP-dependent enzymes [J. Am. Chem. Soc.2010, 132 (47), 16953-16961]. This increases the net catalytic activity (k(cat)) of AAT, since formation of the quinonoid is partially rate limiting via the thermally activated enzymatic pathway. The magnitude of observed photoenhancement initially scales linearly with pump fluence; however when a critical threshold is exceeded, the photoactivity saturates and is even suppressed at greater excitation fluences. The photodynamic mechanisms associated with this suppression behavior are characterized with the use of ultrafast multipulse pump-dump-probe and pump-repump-probe transient absorption techniques in combination with complementary two-color, steady-state excitation assays. Via multistate kinetic modeling of the transient ultrafast data and the steady-state assay data, the nonmonotonic incident power dependence of the photoactivty in AAT is decomposed into contributions from high-intensity dumping of the excited singlet state and repumping of the excited triplet state with induces the repopulation of the ground state via rapid intersystem crossing in the higher-lying triplet electronic manifold.

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

PubMed

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.

Aspartate aminotransferase is potently inhibited by copper complexes: Exploring copper complex-binding proteome.

PubMed

Jia, Yuqi; Lu, Liping; Yuan, Caixia; Feng, Sisi; Zhu, Miaoli

2017-05-01

Recent researches indicated that a copper complex-binding proteome that potently interacted with copper complexes and then influenced cellular metabolism might exist in organism. In order to explore the copper complex-binding proteome, a copper chelating ion-immobilized affinity chromatography (Cu-IMAC) column and mass spectrometry were used to separate and identify putative Cu-binding proteins in primary rat hepatocytes. A total of 97 putative Cu-binding proteins were isolated and identified. Five higher abundance proteins, aspartate aminotransferase (AST), malate dehydrogenase (MDH), catalase (CAT), calreticulin (CRT) and albumin (Alb) were further purified using a SP-, and (or) Q-Sepharose Fast Flow column. The interaction between the purified proteins and selected 11 copper complexes and CuCl 2 was investigated. The enzymes inhibition tests demonstrated that AST was potently inhibited by copper complexes while MDH and CAT were weakly inhibited. Schiff-based copper complexes 6 and 7 potently inhibited AST with the IC 50 value of 3.6 and 7.2μM, respectively and exhibited better selectivity over MDH and CAT. Fluorescence titration results showed the two complexes tightly bound to AST with binding constant of 3.89×10 6 and 3.73×10 6 M -1 , respectively and a stoichiometry ratio of 1:1. Copper complex 6 was able to enter into HepG2 cells and further inhibit intracellular AST activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultra-Rapid Crystallization of L-alanine Using Monomode Microwaves, Indium Tin Oxide and Metal-Assisted and Microwave-Accelerated Evaporative Crystallization.

PubMed

Lansiquot, Carisse; Boone-Kukoyi, Zainab; Shortt, Raquel; Thompson, Nishone; Ajifa, Hillary; Kioko, Bridgit; Constance, Edward Ned; Clement, Travis; Ozturk, Birol; Aslan, Kadir

2017-01-01

The use of indium tin oxide (ITO) and focused monomode microwave heating for the ultra-rapid crystallization of L-alanine (a model amino acid) is reported. Commercially available ITO dots (< 5 mm) attached to blank poly(methyl)methacrylate (PMMA, 5 cm in diameter with 21-well silicon isolators: referred to as the iCrystal plates) were found to withstand prolonged microwave heating during crystallization experiments. Crystallization of L-alanine was performed at room temperature (a control experiment), with the use of two microwave sources: a 2.45 GHz conventional microwave (900 W, power level 1, a control experiment) and 8 GHz (20 W) solid state, monomode microwave source with an applicator tip that focuses the microwave field to a 5-mm cavity. Initial appearance of L-alanine crystals and on iCrystal plates with ITO dots took 47 ± 2.9 min, 12 ± 7.6 min and 1.5 ± 0.5 min at room temperature, using a conventional microwave and focused monomode microwave heating, respectively. Complete evaporation of the solvent using the focused microwaves was achieved in 3.2 ± 0.5 min, which is ~52-fold and ~172-fold faster than that observed at room temperature and using conventional microwave heating, respectively. The size and number of L-alanine crystals was dependent on the type of the 21-well iCrystal plates and the microwave heating method: 33 crystals of 585 ± 137 μm in size at room temperature > 37 crystals of 542 ± 100 μm in size with conventional microwave heating > 331 crystals of 311 ± 190 μm in size with focused monomode microwave. FTIR, optical microscopy and powder X-ray diffraction analysis showed that the chemical composition and crystallinity of the L-alanine crystals did not change when exposed to microwave heating and ITO surfaces. In addition, theoretical simulations for the binding of L-alanine molecules to ITO and other metals showed the predicted nature of hydrogen bonds formed between L-alanine and these surfaces.

Ultra-Rapid Crystallization of L-alanine Using Monomode Microwaves, Indium Tin Oxide and Metal-Assisted and Microwave-Accelerated Evaporative Crystallization

PubMed Central

Lansiquot, Carisse; Boone-Kukoyi, Zainab; Shortt, Raquel; Thompson, Nishone; Ajifa, Hillary; Kioko, Bridgit; Constance, Edward Ned; Clement, Travis; Ozturk, Birol; Aslan, Kadir

2018-01-01

The use of indium tin oxide (ITO) and focused monomode microwave heating for the ultra-rapid crystallization of L-alanine (a model amino acid) is reported. Commercially available ITO dots (< 5 mm) attached to blank poly(methyl)methacrylate (PMMA, 5 cm in diameter with 21-well silicon isolators: referred to as the iCrystal plates) were found to withstand prolonged microwave heating during crystallization experiments. Crystallization of L-alanine was performed at room temperature (a control experiment), with the use of two microwave sources: a 2.45 GHz conventional microwave (900 W, power level 1, a control experiment) and 8 GHz (20 W) solid state, monomode microwave source with an applicator tip that focuses the microwave field to a 5-mm cavity. Initial appearance of L-alanine crystals and on iCrystal plates with ITO dots took 47 ± 2.9 min, 12 ± 7.6 min and 1.5 ± 0.5 min at room temperature, using a conventional microwave and focused monomode microwave heating, respectively. Complete evaporation of the solvent using the focused microwaves was achieved in 3.2 ± 0.5 min, which is ~52-fold and ~172-fold faster than that observed at room temperature and using conventional microwave heating, respectively. The size and number of L-alanine crystals was dependent on the type of the 21-well iCrystal plates and the microwave heating method: 33 crystals of 585 ± 137 μm in size at room temperature > 37 crystals of 542 ± 100 μm in size with conventional microwave heating > 331 crystals of 311 ± 190 μm in size with focused monomode microwave. FTIR, optical microscopy and powder X-ray diffraction analysis showed that the chemical composition and crystallinity of the L-alanine crystals did not change when exposed to microwave heating and ITO surfaces. In addition, theoretical simulations for the binding of L-alanine molecules to ITO and other metals showed the predicted nature of hydrogen bonds formed between L-alanine and these surfaces. PMID:29657884

A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

PubMed

Uchio, Ryusei; Higashi, Yohei; Kohama, Yusuke; Kawasaki, Kengo; Hirao, Takashi; Muroyama, Koutarou; Murosaki, Shinji

2017-01-01

Turmeric ( Curcuma longa ) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates.

PubMed

Clark, D B; Lynch, K G; Donovan, J E; Block, G D

2001-09-01

Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.

Effects of dietary milk thistle on blood parameters, liver pathology, and hepatobiliary scintigraphy in white carneaux pigeons (Columba livia) challenged with B1 aflatoxin.

PubMed

Grizzle, Judith; Hadley, Tarah L; Rotstein, David S; Perrin, Shannon L; Gerhardt, Lillian E; Beam, James D; Saxton, Arnold M; Jones, Michael P; Daniel, Gregory B

2009-06-01

Milk thistle (Silybum marianum) has been used in humans for the treatment of liver disease because of its antioxidant properties and its ability to stabilize cell membranes and regulate cell permeability. To investigate possible hepatoprotective effects in birds, standardized extracts (80%) of silymarin from milk thistle were tested in white Carneaux pigeons (Columba livia). Pigeons were separated into 3 groups and fed diets formulated to provide milk thistle at a level of 0, 10, or 100 mg/kg body weight per day. After acclimation, the birds were challenged with B1 aflatoxin (3 mg/kg body weight for 2 consecutive days) by oral gavage. Liver function then was assessed by hematologic testing and plasma biochemical analysis, liver histopathology, and hepatobiliary scintigraphy. Results of histopathology and hepatobiliary scintigraphy showed no protective effects from milk-thistle administration. Aflatoxin challenge resulted in hepatic inflammation and necrosis, biliary-duct hyperplasia, and lymphocyte infiltration. All hepatobiliary scintigraphy elements increased significantly after aflatoxin challenge. Bile acid levels and plasma enzyme concentrations of aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase all increased after aflatoxin exposure and were mostly unchanged with consumption of milk thistle. Only birds fed 10 mg/kg body weight milk thistle showed significant reductions in lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase concentrations after aflatoxin exposure. Our results show that consumption of milk thistle is not associated with hepatoprotective effects against acute B1 aflatoxin exposure in pigeons.

Effect of early fasting and total parenteral nutrition support on the healing of incision and nutritional status in patients after sacrectomy.

PubMed

Gao, S; Zheng, Y; Liu, X; Tian, Z; Zhao, Y

2018-06-01

Surgical site infection is one of the most common complications for patients after sacrectomy, which often accompanied by poor wound healing, sinus formation and serious metabolic disturbance. We tried to avoid the surgical site infection caused by feces during early period after surgery through early fasting and total parenteral nutrition (TPN) support, then compared the clinical results of these patients with other patients that received enteral nutrition (EN) early after sacrectomy. Forty-eight patients after sacrectomy (the level of sacrectomy above S 2 ) were randomly divided into two groups: TPN group and EN group. The patients of two groups received different nutrition support from the first day to the seventh day after surgery, then the factors such as nutritional and metabolic status after surgery, incidence of complications as well as the time of incision healing and hospitalization were observed. The p-value of total serum protein, albumin, serum alanine aminotransferase, total bilirubin at seventh day after sacrectomy between TPN group and EN group is <0.0005. The p-value of hemoglobin at seventh day after sacrectomy between TPN group and EN group is 0.001. The p-value of total serum protein at fourteenth day after sacrectomy between TPN group and EN group is 0.003. The p-value of albumin and total bilirubin at fourteenth day after sacrectomy between TPN group and EN group is 0.001. The p-value of hemoglobin, serum alanine aminotransferase at fourteenth day after sacrectomy between TPN group and EN group is <0.0005. The incidence of gastrointestinal complication and delay of apparition of feces in EN group were lower than that in TPN group (p=0.041, p<0.0005). The incidence of surgical site infection, the time of incision healing and hospitalization in TPN group were lower than that in EN group (p=0.048, p=0.008, p<0.0005). The method of fasting and supported by TPN during the early period after sacrectomy contribute to the incision healing, meanwhile

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

PubMed Central

Hu, Yan-Chao; Liu, Hao; Liu, Xiao-Yan; Ma, Li-Na; Guan, Yu-Hua; Luo, Xia; Ding, Xiang-Chun

2017-01-01

AIM To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated with CHB patients’ age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4

Prevalence of abnormal serum alanine aminotransferase levels in type 2 diabetic patients in Iran.

PubMed

Meybodi, M A; Afkhami-Ardekani, M; Rashidi, M

2008-09-15

This study was performed to estimate prevalence of transaminase levels in type 2 diabetic patients and identify contributing risk factors. In this cross-sectional study 348 patients with type 2 diabetes, who attended the diabetic clinic of Yazd Diabetes Research Center, were studied from October 2004 to December 2005. Patients with history of viral hepatitis, alcohol abuse and use of drug such as Amiodarone, Bleomycin, methotrexate, tamoxifen and sodium valporate was excluded. To examine the relationships between ALT, AST in individuals with type II diabetes and relation to various metabolic parameters like triglyceride, cholesterol, age, duration of diabetes, gender and BMI. Of 348 patients that entered the study, mean age was 58.8 +/- 11.5. Elevated ALT and AST were found in 10.4 and 3.3% of type 2 diabetic patients, respectively. Although the prevalence of elevated ALT increased with increasing age, FBS and triglyceride levels in subjects, but it was not statistically significant. There was a significant association between elevated ALT and gender as well as diabetes duration. The prevalence of elevated of ALT in type 2 diabetic patients is 1.6 times higher than general population in Iran unrelated to age, BMI, glycemic control, triglyceride levels. Identification risk factors and mechanisms of these elevations are very important and require further evaluation.

Effects of pretransport handling stress on physiological and behavioral response of ostriches.

PubMed

Bejaei, M; Cheng, K M

2014-05-01

Ostrich (Struthio camelus) production is a relatively young industry and there has been little research on ostrich welfare during pretransport handling and the transportation process. A heavy body with a high center of gravity makes ostriches' handling and transportation problems different from other livestock. The main objective of this study was to investigate the effects of the pretransport holding time duration on ostrich behavior and physiological responses. A second objective was to identify and validate behavioral indicator(s) that could be used to identify stressed birds during pretransport handling. Prior to shipping, twenty-four 2.5-yr-old ostriches were moved into a holding pen. Birds were then individually restrained, hooded, and walked from the holding pen (approximately 12 min/bird) to a sampling pen (visually isolated from the holding pen) where they were weighed and a 10-mL blood sample obtained. A second blood sample was taken from each bird after a 1,100-km transportation. Blood samples were analyzed for concentrations of blood metabolites, enzymes, corticosterone, and white blood cell and differential counts. Behavioral responses and physical damages of ostriches were also recorded before and after transport. Results indicated that birds that spent longer time in the pretransport holding pen had higher pretransport plasma concentrations of aspartate aminotransferase, alanine aminotransferase, sodium, and packed cell volume. Immobile sitting behavior, observed in 5 out of the last 11 birds handled, was positively correlated with higher pretransport handling stress, higher posttransport aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, and glucose concentrations, and transport losses. Knowledge of pretransport handling impacts on ostrich stress and availability of behavioral indicators (e.g., immobile sitting response) could be used to improve handing processes, thereby decreasing potential weight loss, injury, and

Hepatoprotective Effects of Corilagin Following Hemorrhagic Shock are Through Akt-Dependent Pathway

PubMed Central

Liu, Fu-Chao; Chaudry, Irshad H.; Yu, Huang-Ping

2017-01-01

ABSTRACT Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague–Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin-treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway. PMID:27559697

Atherosclerosis and Liver Function Tests in Coronary Angiography Patients.

PubMed

Doganer, Y C; Rohrer, J E; Aydogan, U; Agerter, D C; Cayci, T; Barcin, C

2015-09-01

Elevated aminotransferase levels indicating liver function, even in the normal range, have attracted great concern as potential novel markers of cardiovascular risk assessment. We hypothesized the possibility that liver function test variations in the normal range might be meaningfully associated to coronary artery disease (CAD). Eighty-eight patients were randomly selected from those who underwent coronary angiography from June 2010 to June 2011 after applying to the outpatient cardiology clinic in Gulhane Military Medical Academy. According to the results of angiographies, patients were classified into three groups as normal, non-critical (< 50% involvement in coronaries), and critical (≥ 50% involvement in coronaries). In addition to angiographic intervention, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, albumin and the other serum parameters were performed in all patients. The patient groups of CAD were balanced (28 critical cases, 30 non-critical cases and 30 normal cases). Mean age was 51.93 ± 9.3 (range 32-65) years and 19.3 per cent (n = 17) were females. Multiple linear regression analysis of all three liver function tests explained a significant portion of the variance, but adjusted r-squares were small (AST = 0.174, ALT = 0.242, albumin = 0.124). Albumin was significantly higher for patients with critical CAD than for patients with no CAD (beta = 3.205, p = 0.002). Non-critical CAD was not significantly different from no CAD for any of the dependent variables. Mean AST was significantly higher for patients taking aspirin (beta = 0.218, p = 0.049), as was mean ALT (beta = 0.264, p = 0.015). Alanine aminotransferase and AST may not be associated with angiographically determined coronary atherosclerosis. Albumin may be more sensitive to demonstrate the burden of atherosclerosis. These results indicate that the association between the liver function tests and coronary atherosclerosis may be more

Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.

PubMed

Akashi, Iwao; Kagami, Keisuke; Hirano, Toshihiko; Oka, Kitaro

2009-04-01

The protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced acute liver injury in rats were investigated. Wistar rats were orally administered saline (control) or one of the test compounds (caffeine, chlorogenic acid, trigonelline, nicotinic acid or eight pyrazinoic acids) at a dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mug/kg)/D-GalN (250 mg/kg) 1 h after administration of the test compounds. Blood samples were collected up to 12 h after LPS/D-GalN injection, followed by determination of plasma aspartate aminotransferase, alanine aminotransferase, tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels. Plasma aspartate aminotransferase and alanine aminotransferase levels were significantly increased after LPS/D-GalN-treatment, but were suppressed by pretreatment with caffeine (n = 5), nicotinic acid, non-substituted pyrazinoic acid or 5-methylpyrazinoic acid (n = 6, respectively) 12 h after LPS/D-GalN-treatment (P < 0.01, respectively). Moreover, the animals pretreated with these test compounds showed significantly higher survival rates (83-100%) compared with the control (23%). Only pretreatment with caffeine significantly suppressed the LPS/D-GalN induced elevation of plasma TNF-alpha levels 1 and 2 h after LPS/D-GalN-treatment (P < 0.01, respectively). Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats. The results suggest that caffeine, nicotinic acid, non-substituted pyrazinoic acid and 5-methylpyrazinoic acid can protect against LPS/D-GalN induced acute liver injury, which may be mediated by the reduction of TNF-alpha production and/or increasing IL-10 production.

Protein linear indices of the 'macromolecular pseudograph alpha-carbon atom adjacency matrix' in bioinformatics. Part 1: prediction of protein stability effects of a complete set of alanine substitutions in Arc repressor.

PubMed

Marrero-Ponce, Yovani; Medina-Marrero, Ricardo; Castillo-Garit, Juan A; Romero-Zaldivar, Vicente; Torrens, Francisco; Castro, Eduardo A

2005-04-15

TOMOCOMD-CAMPS method produced a linear piecewise regression (R=0.97) between protein backbone descriptors and tm values for alanine mutants of the Arc repressor. A break-point value of 51.87 degrees C characterized two mutant clusters and coincided perfectly with the experimental scale. For this reason, we can use the linear discriminant analysis and piecewise models in combination to classify and predict the stability of the mutant Arc homodimers. These models also permitted the interpretation of the driving forces of such folding process, indicating that topologic/topographic protein backbone interactions control the stability profile of wild-type Arc and its alanine mutants.

The effect of taurine and β-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice.

PubMed

Horvath, Deanna M; Murphy, Robyn M; Mollica, Janelle P; Hayes, Alan; Goodman, Craig A

2016-11-01

This study investigated the effect of taurine and β-alanine supplementation on muscle function and muscle taurine transporter (TauT) protein expression in mdx mice. Wild-type (WT) and mdx mice (5 months) were supplemented with taurine or β-alanine for 4 weeks, after which in vitro contractile properties, fatigue resistance and force recovery, and the expression of the TauT protein and proteins involved in excitation-contraction (E-C) coupling were examined in fast-twitch muscle. There was no difference in basal TauT protein expression or basal taurine content between mdx than WT muscle. Supplementation with taurine and β-alanine increased and reduced taurine content, respectively, in muscle from WT and mdx mice but had no effect of TauT protein. Taurine supplementation reduced body and muscle mass, and enhanced fatigue resistance and force recovery in mdx muscle. β-Alanine supplementation enhanced fatigue resistance in WT and mdx muscle. There was no difference in the basal expression of key E-C coupling proteins [ryanodine receptor 1 (RyR1), dihydropyridine receptor (DHPR), sarco(endo)plasmic reticulum Ca 2+ -ATPase 1 (SERCA1) or calsequestrin 1 (CSQ1)] between WT and mdx mice, and the expression of these proteins was not altered by taurine or β-alanine supplementation. These findings suggest that TauT protein expression is relatively insensitive to changes in muscle taurine content in WT and mdx mice, and that taurine and β-alanine supplementation may be viable therapeutic strategies to improve fatigue resistance of dystrophic skeletal muscle.

Short-duration beta-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players.

PubMed

Hoffman, Jay R; Ratamess, Nicholas A; Faigenbaum, Avery D; Ross, Ryan; Kang, Jie; Stout, Jeffrey R; Wise, John A

2008-01-01

The purpose of this study was to examine the effect of 30 days of beta-alanine supplementation in collegiate football players on anaerobic performance measures. Subjects were randomly divided into a supplement (beta-alanine group [BA], 4.5 g x d(-1) of beta-alanine) or placebo (placebo group [P], 4.5 g x d(-1) of maltodextrin) group. Supplementation began 3 weeks before preseason football training camp and continued for an additional 9 days during camp. Performance measures included a 60-second Wingate anaerobic power test and 3 line drills (200-yd shuttle runs with a 2-minute rest between sprints) assessed on day 1 of training camp. Training logs recorded resistance training volumes, and subjects completed questionnaires on subjective feelings of soreness, fatigue, and practice intensity. No difference was seen in fatigue rate in the line drill, but a trend (P = .07) was observed for a lower fatigue rate for BA compared with P during the Wingate anaerobic power test. A significantly higher training volume was seen for BA in the bench press exercise, and a trend (P = .09) for a greater training volume was seen for all resistance exercise sessions. In addition, subjective feelings of fatigue were significantly lower for BA than P. In conclusion, despite a trend toward lower fatigue rates during 60 seconds of maximal exercise, 3 weeks of beta-alanine supplementation did not result in significant improvements in fatigue rates during high-intensity anaerobic exercise. However, higher training volumes and lower subjective feelings of fatigue in BA indicated that as duration of supplementation continued, the efficacy of beta-alanine supplementation in highly trained athletes became apparent.

Liver enzymes and blood metabolites in a population of free-ranging red deer (Cervus elaphus) naturally infected with Fascioloides magna.

PubMed

Severin, K; Mašek, T; Janicki, Z; Konjević, D; Slavica, A; Marinculić, A; Martinković, F; Vengušt, G; Džaja, P

2012-06-01

We investigated the effects of Fascioloides magna infection on the serum biochemistry values of the naturally infected red deer population in eastern Croatia. The investigation was performed on 47 red deer with F. magna infection confirmed patho-anatomically in 27 animals (57.4%). Fibrous capsules and migratory lesions were found in 14 deer while only fibrous capsules without migratory lesions were found in 13 deer. In 13 deer both immature and mature flukes were found, in 5 deer only immature flukes were found and in 9 deer only mature flukes were found. Fascioloides magna infected deer with fibrous capsules and migratory lesions had significantly higher values for lactate dehydrogenase (LDH), glutamate dehydrogenase (GLDH) and globulin, and lower values for albumin/globulin ratio and glucose compared to uninfected deer. Fascioloides magna infected deer with fibrous capsules without the presence of migratory lesions had higher values for alanine aminotransferase (ALT) and globulin, and lower values for albumin/globulin ratio and glucose, than the uninfected deer. The number of immature flukes was positively correlated with values of aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), LDH, GLDH, urea and triglycerides. The number of migratory lesions was positively correlated with GGT, GLDH, globulin and urea values. The creatinine value was positively correlated with the number of mature flukes. The trial showed that F. magna infection causes significant changes in serum biochemistry. Moreover, these changes do not completely resemble changes following F. hepatica infection. Further investigation of changes in liver enzymes and other serum metabolites in controlled, experimentally induced fascioloidosis in red deer is needed to better understand the pathogenesis of F. magna.

Evaluation of coagulation parameters and liver enzymes among alcohol drinkers in Port Harcourt, Nigeria.

PubMed

Adias, Teddy Charles; Egerton, Everton; Erhabor, Osaro

2013-01-01

Alcohol is a major contributor to the global burden of disease, disability, and death in high, middle, and low-income countries. Harmful use of alcohol is one of the main factors contributing to premature deaths and avoidable disease burden worldwide and has a major impact on public health. The aim of this present cross-sectional study was to investigate the effect of alcohol consumption on coagulation parameters and liver enzymes of subjects in Port Harcourt, Nigeria. Two hundred adults consisting of 120 alcohol dependent subjects and 80 age, gender-matched nondrinkers aged 25-65 years (mean age 45.25 ± 11.50 years) were enrolled in this study. Of the 120 chronic alcohol drinkers, 37 were dependent on local dry gin, while 83 were dependent on other alcoholic beverages. The mean values of the liver enzymes, aspartate aminotransferase and gamma glutamyl transferase, were significantly higher (P = 0.002 and P = 0.02 respectively) among the chronic alcohol consumers compared with their nondrinker counterparts. Although the value of alanine aminotransferase was higher in the chronic drinkers, it did not reveal any significant difference (P = 0.11). The coagulation parameters, prothrombin time and activated partial thromboplastin time were investigated among chronic drinkers and nondrinkers. The mean value of prothrombin time and activated partial thromboplastin time was significantly higher in the chronic alcohol drinkers compared to the nondrinkers (P = 0.04 and P = 0.02 respectively). We observed a positive and significant correlation between values of liver enzymes, serum gamma glutamyl transferase and aspartate aminotransferase, and values of prothrombin time among alcohol consumers (r = 0.72 and r = 0.68 respectively). The implementation of policies to target harm reduction strategies among alcoholics is urgently needed, alongside the building of a strong base of public awareness and community support required for the continuity and sustainability of alcohol

Evaluation of coagulation parameters and liver enzymes among alcohol drinkers in Port Harcourt, Nigeria

PubMed Central

Adias, Teddy Charles; Egerton, Everton; Erhabor, Osaro

2013-01-01

Alcohol is a major contributor to the global burden of disease, disability, and death in high, middle, and low-income countries. Harmful use of alcohol is one of the main factors contributing to premature deaths and avoidable disease burden worldwide and has a major impact on public health. The aim of this present cross-sectional study was to investigate the effect of alcohol consumption on coagulation parameters and liver enzymes of subjects in Port Harcourt, Nigeria. Two hundred adults consisting of 120 alcohol dependent subjects and 80 age, gender-matched nondrinkers aged 25–65 years (mean age 45.25 ± 11.50 years) were enrolled in this study. Of the 120 chronic alcohol drinkers, 37 were dependent on local dry gin, while 83 were dependent on other alcoholic beverages. The mean values of the liver enzymes, aspartate aminotransferase and gamma glutamyl transferase, were significantly higher (P = 0.002 and P = 0.02 respectively) among the chronic alcohol consumers compared with their nondrinker counterparts. Although the value of alanine aminotransferase was higher in the chronic drinkers, it did not reveal any significant difference (P = 0.11). The coagulation parameters, prothrombin time and activated partial thromboplastin time were investigated among chronic drinkers and nondrinkers. The mean value of prothrombin time and activated partial thromboplastin time was significantly higher in the chronic alcohol drinkers compared to the nondrinkers (P = 0.04 and P = 0.02 respectively). We observed a positive and significant correlation between values of liver enzymes, serum gamma glutamyl transferase and aspartate aminotransferase, and values of prothrombin time among alcohol consumers (r = 0.72 and r = 0.68 respectively). The implementation of policies to target harm reduction strategies among alcoholics is urgently needed, alongside the building of a strong base of public awareness and community support required for the continuity and sustainability of alcohol

The primary structure of aspartate aminotransferase from pig heart muscle. Digestion with a proteinase having specificity for lysine residues.

PubMed Central

Doonan, S; Doonan, H J; Hanford, R; Vernon, C A; Walker, J M; da Airold, L P; Bossa, F; Barra, D; Carloni, M; Fasella, P; Riva, F

1975-01-01

Carboxymethylated aspartate aminotransferase was digested with a proteinase claimed to be specific for lysine residues. Complete cleavage occurred at 12 of the 19 lysine residues in the protein, but at the remaining seven residues cleavage was either restricted or absent. In addition, cleavage was observed at three of the 26 arginine residues. These results are discussed with reference to the amino acid residues adjacent to points of complete or restricted cleavage. The complete primary structure of aspartate aminotransferase, based on these and other studies, is given. Evidence for the assignment of some acid and amide side chains has been deposited as Supplementary Publication SUP 50050 (11 pp.) at the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1975) 145, 5. The evidence for the assignment of residue 366 was less conclusive than for the other acid and amide side chains and is, therefore, given in the main paper. PMID:1239277

Analysis of some biochemical and haematological parameters for Mucuna pruriens (DC) seed powder in male rats.

PubMed

Chukwudi, Ndukwe Henry; Simeon, Omale; Chinyere, Aguiyi John

2011-10-01

The biochemical and haematological effects of the seed powder of Mucuna pruriens in male rats were evaluated to establish some biological properties of this potential biopesticide currently undergoing investigation. The result showed that Mucuna pruriens seed extract produced a significant (p<0.05) increase in white blood cell (WBC) count, as well as in bilirubin concentrations, alkaline phosphatase (ALP), protein and creatinine levels measured. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced (P<0.05) in comparison with the experimental control. PCV, Hb, albumin level and WBC differential counts gave no significant difference between treated and control groups. The results revealed metabolic imbalance in the rats which suggests a mild cholestasis effect of the extract.

Amhezole, A Novel Fungal Secondary Metabolite from Aspergillus terreus for Treatment of Microbial Mouth Infection.

PubMed

Awaad, Amani S; Al-Mudhayyif, Hind A; Al-Othman, Monerah R; Zain, Mohamed E; El-Meligy, Reham M

2017-03-01

Bio-guided fractionation of Aspergillus terreus extract leads to isolation of a novel terpenoidal secondary metabolite. The isolated compound and the total alcoholic extract of Aspergillus terreus showed a remarkable activity against microbial mouth infections; namely, Candida albicans, Lactobacillus acidophilus, Streptococcus gordonii, and S. mutan. Moreover, the Minimum Inhibitory Concentration of the isolated compound was determined and showed low values. The combination of each of the alcoholic extract of A. terreus and the isolated compound Coe-Comfort tissue conditioner inhibited the growth of Candida albicans at concentrations of 500 and 7.81 µg/mL, respectively, Lactobacillus acidophilus at concentrations of 250 and 7.81 µg/mL, respectively, Streptococcus gordonii at concentrations of 1000 and 62.50 µg/mL, respectively, and S. mutans at concentrations of 1000 and 125 µg/mL, respectively. The oral dosing of the extract and the isolated compound did not show any significant effect on the activity of alanine aminotransferase, aspirate aminotransferase, and the levels of blood urea and serum creatinine. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Hypolipidemic Effect of Moringa oleifera Lam Leaf Powder and its Extract in Diet-Induced Hypercholesterolemic Rats.

PubMed

Helmy, Shahinaz A; Morsy, Nashwa F S; Elaby, Shahenda M; Ghaly, Mohammed A A

2017-08-01

The leaves of Moringa oleifera Lam possess some potential medicinal value. The aim of this study was to evaluate the protective effect of M. oleifera leaf powder and its extract against hyperlipidemia in rats. Adult male albino rats were divided into six groups. The first group was fed on a basal diet that served as a negative control, whereas the others were fed on a high-fat diet (HFD) containing moringa leaf powder at 0.737% or 1.475% or administered daily with 200 or 400 mg dry moringa leaf extract/kg bw for 60 days. A positive control group was fed on the HFD. Serum indices related to lipid profile, oxidative status, and liver function were analyzed. Feeding rats on an HFD containing moringa leaf powder at 0.737% or an oral dose of its dry extract at 400 mg/kg bw alleviated the harmful elevation of cholesterol, triglycerides, low-density lipoprotein cholesterol, malondialdehyde, and the activities of alanine aminotransferase and aspartate aminotransferase in serum that were induced by the HFD. This is the first study demonstrating the hypocholesterolemic effect of M. oleifera leaf powder.

Effect of Red Ginseng on Genotoxicity and Health-Related Quality of Life after Adjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer: A Randomized, Double Blind, Placebo-Controlled Trial.

PubMed

Kim, Hee Seung; Kim, Mi-Kyung; Lee, Maria; Kwon, Byung-Su; Suh, Dong Hoon; Song, Yong Sang

2017-07-19

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo ( n = 15) and red ginseng groups ( n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Effect of tea (Camellia sinensis) and olive (Olea europaea L.) leaves extracts on male mice exposed to diazinon.

PubMed

Al-Attar, Atef M; Abu Zeid, Isam M

2013-01-01

The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors.

Effect of Tea (Camellia sinensis) and Olive (Olea europaea L.) Leaves Extracts on Male Mice Exposed to Diazinon

PubMed Central

Al-Attar, Atef M.; Abu Zeid, Isam M.

2013-01-01

The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors. PMID:23691503

Effects of dietary ABATE® on reproductive success, duckling survival, behavior, and clinical pathology in game-farm mallards

USGS Publications Warehouse

Franson, J. Christian; Spann, James W.; Heinz, Gary; Bunck, Christine M.; Lamont, Thair

1983-01-01

Forty-four pairs of game-farm mallards (Anas platyrhynchos) were fed ABATE® 4E (temephos) to yield 0, 1, or 10 ppm ABATE® beginning before the initiation of lay, and terminating when ducklings were 21 days of age. The mean interval between eggs laid was greater for hens fed 10 ppm ABATE® than for controls. Clutch size, fertility, hatchability, nest attentiveness of incubating hens, and avoidance behavior of ducklings were not significantly affected by ABATE® ingestion. The percentage survival of ducklings to 21 days of age was significantly lower in both treated groups than in controls, but brain acetylcholinesterase (AChE) activity was not inhibited in young which died before termination of the study. In 21-day-old ducklings, aspartate aminotransferase (AST) activity increased and plasma nonspecific cholinesterase (ChE) activity was inhibited by about 20% in both treatment groups, but there were no significant differences in brain AChE or plasma alanine aminotransferase (ALT) activities, or plasma uric acid concentration. Clinical chemistry values of adults were not affected. No ABATE®, ABATE® sulfoxide, or ABATE® sulfone residues were found in eggs or tissue samples.

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

PubMed Central

Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

2012-01-01

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

Exercise Training and Calorie Restriction Influence the Metabolic Parameters in Ovariectomized Female Rats

PubMed Central

Pósa, Anikó; Kupai, Krisztina; Szalai, Zita; Veszelka, Médea; Török, Szilvia; Varga, Csaba

2015-01-01

The estrogen deficiency after menopause leads to overweight or obesity, and physical exercise is one of the important modulators of this body weight gain. Female Wistar rats underwent ovariectomy surgery (OVX) or sham operation (SO). OVX and SO groups were randomized into new groups based on the voluntary physical activity (with or without running) and the type of diet for 12 weeks. Rats were fed standard chow (CTRL), high triglyceride diet (HT), or restricted diet (CR). The metabolic syndrome was assessed by measuring the body weight gain, the glucose sensitivity, and the levels of insulin, triglyceride, leptin, and aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT). The exercise training combined with the CR resulted in improvements in the glucose tolerance and the insulin sensitivity. Plasma TG, AST, and ALT levels were significantly higher in OVX rats fed with HT but these high values were suppressed by exercise and CR. Compared to SO animals, estrogen deprivation with HT caused a significant increase in leptin level. Our data provide evidence that CR combined with voluntary physical exercise can be a very effective strategy to prevent the development of a metabolic syndrome induced by high calorie diet. PMID:25874022

Babao Dan attenuates hepatic fibrosis by inhibiting hepatic stellate cells activation and proliferation via TLR4 signaling pathway.

PubMed

Liang, Lei; Yang, Xue; Yu, Yang; Li, Xiaoyong; Wu, Yechen; Shi, Rongyu; Jiang, Jinghua; Gao, Lu; Ye, Fei; Zhao, Qiudong; Li, Rong; Wei, Lixin; Han, Zhipeng

2016-12-13

Babao Dan (BBD), a traditional Chinese medicine, has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the protective effect of BBD on rat hepatic fibrosis induced by diethylnitrosamine (DEN) and explore it possible mechanism. BBD was administrated while DEN was given. After eight weeks, values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicated that BBD significantly protected liver from damaging by DEN and had no obvious side effect on normal rat livers. Meanwhile, BBD attenuated hepatic inflammation and fibrosis in DEN-induced rat livers through histopathological examination and hepatic hydroxyproline content. Furthermore, we found that BBD inhibited hepatic stellate cells activation and proliferation without altering the concentration of lipopolysaccharide (LPS) in portal vein. In vitro study, serum from BBD treated rats (BBD-serum) could also significantly suppress LPS-induced HSCs activation through TLR4/NF-κB pathway. In addition, BBD-serum also inhibited the proliferation of HSCs by regulating TLR4/ERK pathway. Our study demonstrated that BBD may provide a new therapy strategy of hepatic injury and hepatic fibrosis.

Bioassay-guided fractionation of a hepatoprotective and antioxidant extract of pea by-product.

PubMed

Seida, Ahmed A; El Tanbouly, Nebal D; Islam, Wafaa T; Eid, Hanaa H; El Maraghy, Shohda A; El Senousy, Amira S

2015-01-01

The hepatoprotective and antioxidant activities of the hydroalcoholic extract (PE) of pea (Pisum sativum L.) by-product were evaluated, using CCl4-induced oxidative stress and hepatic damage in rats. These activities were assessed via measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin, malondialdehyde (MDA), reduced glutathione (GSH), protein thiols (PSH), nitrite/nitrate levels, glutathione-peroxidase (GSH-Px), glutathione-S-transferase (GST) activities, as well as, histopathological evaluation. PE revealed significant hepatoprotective and antioxidant activities mostly found in n-butanol fraction. Chromatographic fractionation of this active fraction led to the isolation of five flavonoid glycosides namely, quercetin-3-O-sophorotrioside (1), quercetin-3-O-rutinoside (2), quercetin-3-O-(6″″-O-E sinapoyl)-sophorotrioside (3), quercetin-3-O-(6″″-O-E feruloyl)-sophorotrioside (4) and quercetin-3-O-β-D-glucopyranoside (5). The isolated compounds were quantified in PE, using a validated HPLC method and the nutritional composition of pea by-product was also investigated. Our results suggest that pea by-product contained biologically active constituents which can be utilised to obtain high value added products for nutraceutical use.

Acute hepatitis C in an HIV-infected patient: a case report and review of literature.

PubMed

Driver, Todd H; Terrault, Norah; Saxena, Varun

2013-05-01

With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

Anaerobic metabolism in the N-limited green alga Selenastrum minutum. 3. Alanine is the product of anaerobic ammonium assimilation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vanlerberghe, G.C.; Turpin, D.H.; Joy, K.W.

The authors have determined the flow of {sup 15}N into free amino acids of the N-limited green alga Selenastrum minutum (Naeg.) Collins after addition of {sup 15}NH{sub 4}{sup +} to aerobic or anaerobic cells. Under aerobic conditions, only a small proportion of the N assimilated was retained in the free amino acid pool. However, under anaerobic conditions almost all assimilated NH{sub 4}{sup +} accumulates in alanine. This is a unique feature of anaerobic NH{sub 4}{sup +} assimilation. The pathway of carbon flow to alanine results in the production of ATP and reductant which matches exactly the requirements of NH{sub 4}{supmore » +} assimilation. Alanine synthesis is therefore an excellent strategy to maintain energy and redox balance during anaerobic NH{sub 4}{sup +} assimilation.« less

Laboratory and Molecular Characterization of Dengue Viruses in a 2014 Outbreak in Guangfo Region, Southern China.

PubMed

Luo, Zhao-Fan; Hu, Bo; Zhang, Feng-Yi; Lin, Xiang-Hua; Xie, Xiao-Ying; Pan, Kun-Yi; Li, Hong-Yu; Ren, Rui-Wen; Zhao, Wen-Zhong

2017-09-25

Non-specific symptoms and low viremia levels make early diagnosis of dengue virus (DENV) infection challenging. This study aimed to i) identify laboratory markers that can be used to predict a DENV-positive diagnosis and ii) perform a molecular characterization of DENVs from the 2014 Guangdong epidemic. This retrospective study analyzed 1,044 patients from the Guangdong epidemic who were clinically suspected cases of dengue. Viral RNA was detected by real-time RT-PCR, and viral-specific NS1 antigen was detected using enzyme-linked immuno sorbent assay. A molecular phylogenetic analysis was performed for the with the DENV C-prM gene junction. Patients with dengue infection had leukopenia (2.8 × 10 9 /L), thrombocytopenia (109.0 × 10 9 /L), elevated aspartate aminotransferase (56.0 IU/L) and alanine aminotransferase (43.5 IU/L), and prolonged activated partial thromboplastin time (APTT, 33.5 s) (all P ＜ 0.001) compared to patients without dengue. The positive predictive value of leukopenia and thrombocytopenia for DENV infection were 96.9% and 93.0%, respectively. Leukopenia, thrombocytopenia, elevated aminotransferases, and prolonged APTT were useful predictive markers for an early diagnosis of DENV infection. Phylogenetic analysis indicated that the DENVs from the 2014 epidemic were closely related to a 2010 New Delhi strain and a 2013 Guangzhou strain. The 2014 epidemic consisted of co-circulating DENV-1 genotypes I and V from multiple origins. Efficient dengue surveillance can facilitate rapid response to future outbreaks.

Two continuous coupled assays for ornithine-δ-aminotransferase.

PubMed

Juncosa, Jose I; Lee, Hyunbeom; Silverman, Richard B

2013-09-15

We have developed two new continuous coupled assays for ornithine-δ-aminotransferase (OAT) that are more sensitive than previous methods, measure activity in real time, and can be carried out in multiwell plates for convenience and high throughput. The first assay is based on the reduction of Δ(1)-pyrroline-5-carboxylate (P5C), generated from ornithine by OAT, using human pyrroline 5-carboxylate reductase 1 (PYCR1), which results in the concomitant oxidation of NADH (nicotinamide adenine dinucleotide, reduced form) to NAD⁺ (nicotinamide adenine dinucleotide, oxidized form). This procedure was found to be three times more sensitive than previous methods and is suitable for the study of small molecules as inhibitors or inactivators of OAT or as a method to determine OAT activity in unknown samples. The second method involves the detection of L-glutamate, produced during the regeneration of the cofactor pyridoxal 5'-phosphate (PLP) of OAT by an unamplified modification of the commercially available Amplex Red L-glutamate detection kit (Life Technologies). This assay is recommended for the determination of the substrate activity of small molecules against OAT; measuring the transformation of L-ornithine at high concentrations by this assay is complicated by the fact that it also acts as a substrate for the L-glutamate oxidase (GluOx) reporter enzyme. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of inflammation during fixed orthodontic treatment.

PubMed

Bilgic, Fundagul; Akinci Sozer, Ozlem; Ozcan, Oguzhan; Gurpinar, Ahmet Burak; Yilmaz, Hakki; Ay, Yazgi

2016-11-01

The aim of this study was to assess effects of fixed orthodontic therapy on high-sensitivity C-reactive protein (hs-CRP) level, CBC parameters and levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), urea, creatinine, sodium (Na), potassium (K), calcium (Ca), total protein (TP), and albumin (Alb). Blood samples (7ml) were drawn at baseline, on days 1 and 7, and three months after placement of braces in the study group, while only one blood sample was drawn at baseline in the control group. Serum hs-CRP levels were measured by nephelometric method. Friedman two-way variance analysis was used to assess values with skewed distribution obtained at baseline, on days 1 and 7, in the third month. Wilcoxon rank sign test was performed if median values were unequal. During measurement periods, there were significant increases in hs-CRP level, WBC count and neutrophil count while a significant decrease in Na level (p<0.05). K level was significantly decreased on the day 1. No significant differences were detected in other biochemical parameters evaluated. Elevation in serum hs-CRP levels and neutrophil: lymphocyte ratio within first 3 months indicates that a systemic immune response develops against therapy in patients undergoing fixed orthodontic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Resting and post-exercise serum biomarkers of cardiac and skeletal muscle damage in adolescent runners.

PubMed

Nie, J; Tong, T K; George, K; Fu, F H; Lin, H; Shi, Q

2011-10-01

This study examined the response of serum biomarkers of cardiac and skeletal muscle damage at rest and after a routine workout of 21 km run in 12 male adolescent (16.2±0.6 years) long-distance runners. Biomarkers of cardiac [troponins (cTnT, cTnI), creatine kinase MB mass (CK-Mbmass)] and skeletal muscle [creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hydroxybutyrate dehydrogenase (HBD)] damage were assayed at rest, 2, 4 and 24 h post-exercise. At rest, cTnT and cTnI were not detectable; however, CK, CK-MBmass, AST, ALT and HBD were above corresponding clinical cut-off values. Post-exercise significant elevations above rest were observed for all biomarkers, except ALT, 2 and 4 h following the run, and remained elevated in cTnI, CK, CK-MBmass, LDH and AST 24 h post-workout. A significant increase in data points above clinical cut-off values from rest to post-exercise was reported for cTnT, cTnI and CK at 2 and 4 h, and in cTnI and CK 24 h post-exercise. In conclusion, a 21 km run in adolescent runners increased post-exercise biomarkers of cardiac and skeletal muscle damage. © 2010 John Wiley & Sons A/S.

Waist circumference as a marker for screening nonalcoholic fatty liver disease in obese adolescents

PubMed Central

Clemente, Ana Paula Grotti; Dal Molin, Bárbara; de Carvalho-Ferreira, Joana Pereira; Campos, Raquel Munhoz da Silveira; Ganen, Aline de Piano; Tock, Lian; de Mello, Marco Túlio; Dâmaso, Ana Raimunda

2016-01-01

Abstract Objective: To assess the relationship between the degree of waist circumference (WC) and nonalcoholic fatty liver disease (NAFLD) in obese adolescents of both genders, analyzed according to quartiles of WC. Methods: Cross-sectional study that involved 247 obese adolescents aged 12–19 years. Mean values of the nutritional parameters and serum analyses were compared with the groups using the independent t-test. Pearson correlation coefficient was used to determine the relationship of the parameters studied. Chi-square test for trend was used to determine the relationship between the prevalence of the NAFLD and WC quartile by gender. Results: NAFLD were presented in 60% of the study participants. Obese adolescents in the 3rd and 4th quartiles of WC presented higher prevalence of NAFLD when compared with that in the 1st quartile in both genders. The NAFLD patients had significantly higher values for body weight, BMI (body mass index), BAZ-score (BMI-for-age z-scores), total fat (% and kg), WC, visceral fat, insulin, insulin resistance index (HOMA-IR), aspartate aminotransferase and alanine aminotransferase, when compared with non-NAFLD obese adolescents. Conclusions: In conclusion, the results presented here suggest that an increase in WC can reliably predict the risk of NAFLD in obese adolescents. This is a low cost and easy-to-use tool that can help in screening in adolescents. PMID:26830602

Alanine and proline content modulate global sensitivity to discrete perturbations in disordered proteins

PubMed Central

Perez, Romel B.; Tischer, Alexander; Auton, Matthew; Whitten, Steven T.

2014-01-01

Molecular transduction of biological signals is understood primarily in terms of the cooperative structural transitions of protein macromolecules, providing a mechanism through which discrete local structure perturbations affect global macromolecular properties. The recognition that proteins lacking tertiary stability, commonly referred to as intrinsically disordered proteins, mediate key signaling pathways suggests that protein structures without cooperative intramolecular interactions may also have the ability to couple local and global structure changes. Presented here are results from experiments that measured and tested the ability of disordered proteins to couple local changes in structure to global changes in structure. Using the intrinsically disordered N-terminal region of the p53 protein as an experimental model, a set of proline and alanine to glycine substitution variants were designed to modulate backbone conformational propensities without introducing non-native intramolecular interactions. The hydrodynamic radius (Rh) was used to monitor changes in global structure. Circular dichroism spectroscopy showed that the glycine substitutions decreased polyproline II (PPII) propensities relative to the wild type, as expected, and fluorescence methods indicated that substitution-induced changes in Rh were not associated with folding. The experiments showed that changes in local PPII structure cause changes in Rh that are variable and that depend on the intrinsic chain propensities of proline and alanine residues, demonstrating a mechanism for coupling local and global structure changes. Molecular simulations that model our results were used to extend the analysis to other proteins and illustrate the generality of the observed proline and alanine effects on the structures of intrinsically disordered proteins. PMID:25244701

Reference values of blood parameters in beef cattle of different ages and stages of lactation.

PubMed Central

Doornenbal, H; Tong, A K; Murray, N L

1988-01-01

Reference (normal) values for 12 blood serum components were determined for 48 Shorthorn cows (2-10 years old) and their 48 calves, 357 crossbred cows (12-14 years old), 36 feedlot bulls and 36 feedlot steers. In addition, hemoglobin, hematocrit, triiodothyronine, thyroxine and cortisol levels were determined for the crossbred cows, and feedlot bulls and steers. Reference values were tabulated according to sex, age and stage of lactation. Serum concentrations of urea, total protein and bilirubin, and serum activity of aspartate aminotransferase and lactate dehydrogenase increased with age (P less than 0.05), while calcium, phosphorus and alkaline phosphatase decreased with age (P less than 0.05) from birth to the age of ten years. The Shorthorn cows had the highest levels of glucose at parturition (P less than 0.05) with decreasing levels during lactation. Creatinine concentration decreased during lactation and increased during postweaning. Both lactate dehydrogenase and aspartate aminotransferase levels increased (P less than 0.05) during lactation. Urea and uric acid were present at higher concentrations in lactating than nonlactating cows (P less than 0.05). The values reported, based on a wide age range and large number of cattle, could serve as clinical guides and a basis for further research. PMID:3349406

Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

PubMed

Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

2017-04-01

The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Theoretical studies on the inactivation mechanism of γ-aminobutyric acid aminotransferase.

PubMed

Durak, A T; Gökcan, H; Konuklar, F A S

2011-07-21

The inactivation mechanism of γ-aminobutyric acid aminotransferase (GABA-AT) in the presence of γ-vinyl-aminobutyric acid, an anti-epilepsy drug, has been studied by means of theoretical calculations. Density functional theory methods have been applied to compare the three experimentally proposed inactivation mechanisms (Silverman et al., J. Biol. Chem., 2004, 279, 363). All the calculations were performed at the B3LYP/6-31+G(d,p) level of theory. Single point solvent calculations were carried out in water, by means of an integral equation formalism-polarizable continuum model (IEFPCM) at the B3LYP/6-31+G(d,p) level of theory. The present calculations provide an insight into the mechanistic preferences of the inactivation reaction of GABA-AT. The results also allow us to elucidate the key factors behind the mechanistic preferences. The computations also confirm the importance of explicit water molecules around the reacting center in the proton transfer steps.

Scrub typhus associated hepatic dysfunction and abdominal CT findings

PubMed Central

Park, Man Je; Lee, Hyoun Soo; Shim, Sang Goon; Kim, So Hee

2015-01-01

Objective: This retrospective study investigated abnormal hepatic dysfunction and abdominal computed tomography (CT) findings in scrub typhus. Methods: Three hundred forty nine adult patients were diagnosed with scrub typhus. Ninety four underwent abdominal CT. The CT images were reviewed by the attending radiologist. Patient data of history, symptoms, signs, and results of laboratory tests were collected from the electronic medical records. Results: In 349 patients with scrub typhus, elevation of aspartate aminotransferase (78.5%) and alanine aminotransferase (63.0%) were dominant compared to alkaline phosphatase (27.2%) and total bilirubin (16.1%). Abdominal CT findings of 94 patients were, in descending order of frequency, enlarged lymph node (53.2%), inhomogeneous enhancement of liver (47.9%), splenomegaly (46.8%), ascites (28.7%), low attenuation of periportal areas (27.7%), gallbladder wall thickening (17.0%), and splenic infarct (6.4%). Also, the level of aspartate aminotransferase tended to be elevated according to the number of CT findings (P= 0.028) Conclusions: We found that abdominal CT manifestations of scrub typhus with elevated aminotransferases were varied and not specific. However, knowledge of these findings may evoke the recognition of scrub typhus by clinicians in endemic areas. PMID:26101478

Biochemical and genetic analyses of N metabolism in maize testcross seedlings: 2. Roots.

PubMed

Silva, Ignacio Trucillo; Abbaraju, Hari Kishan R; Fallis, Lynne P; Liu, Hongjun; Lee, Michael; Dhugga, Kanwarpal S

2018-06-01

Intracellular factors differentially affected enzyme activities of N assimilation in the roots of maize testcrosses where alanine aminotransferase and glutamate synthase were the main enzymes regulating the levels of glutamate. N is a key macronutrient for plant growth and development. Breeding maize with improved efficiency in N use could help reduce environmental contamination as well as increase profitability for the farmers. Quantitative trait loci (QTL) mapping of traits related to N metabolism in the root tissue was undertaken in a maize testcross mapping population grown in hydroponic cultures. N concentration was negatively correlated with root and total dry mass. Neither the enzyme activities nor metabolites were appreciably correlated between the root and leaf tissues. Repeatability measures for most of the enzymes were lower than for dry mass. Weak negative correlations between most of the enzymes and dry mass resulted likely from dilution and suggested the presence of excess of enzyme activities for maximal biomass production. Glutamate synthase and alanine aminotransferase each explained more variation in glutamate concentration than either aspartate aminotransferase or asparagine synthetase whereas glutamine synthetase was inconsequential. Twenty-six QTL were identified across all traits. QTL models explained 7-43% of the variance with no significant epistasis between the QTL. Thirteen candidate genes were identified underlying QTL within 1-LOD confidence intervals. All the candidate genes were located in trans configuration, unlinked or even on different chromosomes, relative to the known genomic positions of the corresponding structural genes. Our results have implications in improving NUE in maize and other crop plants.

N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats.

PubMed

Abu El-Saad, Ahmed M; Al-Kahtani, Mohammed A; Abdel-Moneim, Ashraf M

2016-01-01

Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.

Morbidity study of extruder personnel with potential exposure to brominated dioxins and furans. II. Results of clinical laboratory studies.

PubMed Central

Ott, M G; Zober, A

1996-01-01

OBJECTIVE: To test whether dioxins affect liver and thyroid function, lipid metabolism and glucose or immunological variables, in workers exposed to brominated dioxins and furans. METHODS: 34 male production employees (29 were extruder operators) and eight technical support personnel were studied, all of whom were potentially exposed to polybrominated dibenzo-p-dioxins (PBDDs) and furans (PBDFs) during production of resins containing polybrominated diphenyl ethers (PBDEs). Controls were from a similar resin producing plant that did not use PBDEs. Blood samples were analysed for tetra, penta, and hexabrominated congeners, but 2,3,7,8-TBDD was the only exposure measure used in the regression analyses. Seven liver function indicators, five measures of blood lipids and glucose, four haematology and blood coagulation measures, and three measures of thyroid function were examined. RESULTS: None of the variables was statistically related to concentration of 2,3,7,8-TBDD in the regression analyses. Cigarette smoking was related to several outcomes at the 0.05 level: aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase (GLDH), erythrocyte sedimentation rate, and white blood cell count. Body mass index was also related to alanine aminotransferase, gamma-glutamyltranspeptidase, cholinesterase, GLDH, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, and glucose concentrations. No definitive associations between liver, blood lipid, thyroid, or immunological variables and exposure to brominated dioxins or blood lipid concentration of 2,3,7,8-TBDD were found. CONCLUSIONS: The study population was small and hence the findings must be interpreted with caution. Nevertheless, these results provide a base for interpreting the results of clinical studies in similarly exposed populations. PMID:8994404

Morbidity study of extruder personnel with potential exposure to brominated dioxins and furans. II. Results of clinical laboratory studies.

PubMed

Ott, M G; Zober, A

1996-12-01

To test whether dioxins affect liver and thyroid function, lipid metabolism and glucose or immunological variables, in workers exposed to brominated dioxins and furans. 34 male production employees (29 were extruder operators) and eight technical support personnel were studied, all of whom were potentially exposed to polybrominated dibenzo-p-dioxins (PBDDs) and furans (PBDFs) during production of resins containing polybrominated diphenyl ethers (PBDEs). Controls were from a similar resin producing plant that did not use PBDEs. Blood samples were analysed for tetra, penta, and hexabrominated congeners, but 2,3,7,8-TBDD was the only exposure measure used in the regression analyses. Seven liver function indicators, five measures of blood lipids and glucose, four haematology and blood coagulation measures, and three measures of thyroid function were examined. None of the variables was statistically related to concentration of 2,3,7,8-TBDD in the regression analyses. Cigarette smoking was related to several outcomes at the 0.05 level: aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase (GLDH), erythrocyte sedimentation rate, and white blood cell count. Body mass index was also related to alanine aminotransferase, gamma-glutamyltranspeptidase, cholinesterase, GLDH, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, and glucose concentrations. No definitive associations between liver, blood lipid, thyroid, or immunological variables and exposure to brominated dioxins or blood lipid concentration of 2,3,7,8-TBDD were found. The study population was small and hence the findings must be interpreted with caution. Nevertheless, these results provide a base for interpreting the results of clinical studies in similarly exposed populations.

Survivability and reactivity of glycine and alanine in early oceans: effects of meteorite impacts.

PubMed

Umeda, Yuhei; Fukunaga, Nao; Sekine, Toshimori; Furukawa, Yoshihiro; Kakegawa, Takeshi; Kobayashi, Takamichi; Nakazawa, Hiromoto

2016-01-01

Prebiotic oceans might have contained abundant amino acids, and were subjected to meteorite impacts, especially during the late heavy bombardment. It is so far unknown how meteorite impacts affected amino acids in the early oceans. Impact experiments were performed under the conditions where glycine was synthesized from carbon, ammonia, and water, using aqueous solutions containing (13)C-labeled glycine and alanine. Selected amino acids and amines in samples were analyzed with liquid chromatography-mass spectrometry (LC/MS). In particular, the (13)C-labeled reaction products were analyzed to distinguish between run products and contaminants. The results revealed that both amino acids survived partially in the early ocean through meteorite impacts, that part of glycine changed into alanine, and that large amounts of methylamine and ethylamine were formed. Fast decarboxylation was confirmed to occur during such impact processes. Furthermore, the formation of n-butylamine, detected only in the samples recovered from the solutions with additional nitrogen and carbon sources of ammonia and benzene, suggests that chemical reactions to form new biomolecules can proceed through marine impacts. Methylamine and ethylamine from glycine and alanine increased considerably in the presence of hematite rather than olivine under similar impact conditions. These results also suggest that amino acids present in early oceans can contribute further to impact-induced reactions, implying that impact energy plays a potential role in the prebiotic formation of various biomolecules, although the reactions are complicated and depend upon the chemical environments as well.

Cellular and Physiological Effects of Dietary Supplementation with β-Hydroxy-β-Methylbutyrate (HMB) and β-Alanine in Late Middle-Aged Mice.

PubMed

Vallejo, Julian; Spence, Madoka; Cheng, An-Lin; Brotto, Leticia; Edens, Neile K; Garvey, Sean M; Brotto, Marco

2016-01-01

There is growing evidence that severe decline of skeletal muscle mass and function with age may be mitigated by exercise and dietary supplementation with protein and amino acid ingredient technologies. The purposes of this study were to examine the effects of the leucine catabolite, beta-hydroxy-beta-methylbutyrate (HMB), in C2C12 myoblasts and myotubes, and to investigate the effects of dietary supplementation with HMB, the amino acid β-alanine and the combination thereof, on muscle contractility in a preclinical model of pre-sarcopenia. In C2C12 myotubes, HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of all SR agonists tested (KCl, P<0.01; caffeine, P = 0.03; ionomycin, P = 0.03). HMB also improved C2C12 myoblast viability (25 μM HMB, P = 0.03) and increased proliferation (25 μM HMB, P = 0.04; 125 μM HMB, P<0.01). Furthermore, an ex vivo muscle contractility study was performed on EDL and soleus muscle from 19 month old, male C57BL/6nTac mice. For 8 weeks, mice were fed control AIN-93M diet, diet with HMB, diet with β-alanine, or diet with HMB and β-alanine. In β-alanine fed mice, EDL muscle showed a 7% increase in maximum absolute force compared to the control diet (202 ± 3vs. 188± 5 mN, P = 0.02). At submaximal frequency of stimulation (20 Hz), EDL from mice fed HMB plus β-alanine showed an 11% increase in absolute force (88.6 ± 2.2 vs. 79.8 ± 2.4 mN, P = 0.025) and a 13% increase in specific force (12.2 ± 0.4 vs. 10.8 ± 0.4 N/cm2, P = 0.021). Also in EDL muscle, β-alanine increased the rate of force development at all frequencies tested (P<0.025), while HMB reduced the time to reach peak contractile force (TTP), with a significant effect at 80 Hz (P = 0.0156). In soleus muscle, all experimental diets were associated with a decrease in TTP, compared to control diet. Our findings highlight beneficial effects of HMB and β-alanine supplementation on skeletal muscle function in aging mice.

Assessment of non-invasive models for liver fibrosis in chronic hepatitis B virus related liver disease patients in resource limited settings.

PubMed

Shrivastava, Rakesh; Sen, Sourav; Banerji, Debabrata; Praharaj, Ashok K; Chopra, Gurvinder Singh; Gill, Satyajit Singh

2013-01-01

A total of 350 million individuals are affected by chronic hepatitis B virus infection world-wide. Historically, liver biopsy has been instrumental in adequately assessing patients with chronic liver disease. A number of non-invasive models have been studied world-wide. The aim of this study is to assess the utility of non-invasive mathematical models of liver fibrosis in chronic hepatitis B (CHB). Indian patients in a resource limited setting using routinely performed non-invasive laboratory investigations. A cross-sectional study carried out at a tertiary care center. A total of 52 consecutive chronic liver disease patients who underwent percutaneous liver biopsy and 25 healthy controls were enrolled in the study. Routine laboratory investigations included serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gama glutamyl transpeptidase (GGT), total bilirubin, total cholesterol, prothrombin time and platelet count. Three non-invasive models for namely aspartate aminotransferase to platelet ratio index (APRI), Fibrosis 4 (FIB-4) and Forn's index were calculated. Outcomes were compared for the assessment of best predictor of fibrosis by calculating the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each index. Medcalc online software and by Microsoft Excel Worksheet. Chi-square test was used for significance. P value < 0.05 was taken as significant. While the serum levels of AST, ALT and GGT were significantly higher in patients group as compare with the healthy controls (P < 0.01), the platelet counts were significantly lower in patient group as compared to the control group (P < 0.01). Mean value of all 3 indices were significantly higher in patients group as compare with the controls (P < 0.01). Out of the three indices, APRI index with a NPV of 95% appeared to be a better model for excluding significant liver fibrosis while FIB-4 with a PPV of 61% showed fair correlation with significant

Design and Mechanism of Tetrahydrothiophene-based GABA Aminotransferase Inactivators

PubMed Central

Le, Hoang V.; Hawker, Dustin D.; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L.; Silverman, Richard B.

2015-01-01

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally-restricted, tetrahydrothiophene-based GABA analogs with a properly-positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is eight times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bond interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O=C interaction with Glu-270, thereby inactivating the enzyme. PMID:25781189

[Visual field defect in a patient given sodium valporate then carbamazepine: possible effect of aminotransferase inhibition].

PubMed

Jung, Ph; Doussard-Lefaucheux, S

2002-04-01

We report the case of a 25-years old woman with anti-epileptic drugs who presents a visual field defect similar to those described with vigabatrin even though she was successfully treated with valproic acid then carbamazepine without vigabatrin. The association with trichorrhexis nodosa, a hair disease sometimes associated with inherited perturbation of metabolism of urea cycle in which visual loss can occur, could suggest an aspecific inhibition of several aminotransferases which could explain different adverse effects of some anti-epileptic drugs (visual abnormalities, alopecia) perhaps in genetic predisposed patients.

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

PubMed

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 from<0.0001s(-1) to 0.07s(-1), whereas k(cat)' 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.

Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players.

PubMed

Rosas, Fabián; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Caniuqueo, Alexis; Cañas-Jamet, Rodrigo; McCrudden, Emma; Meylan, Cesar; Moran, Jason; Nakamura, Fábio Y; Pereira, Lucas A; Loturco, Irineu; Diaz, Daniela; Izquierdo, Mikel

2017-09-01

Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability.

Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players

PubMed Central

Rosas, Fabián; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Cañas-Jamet, Rodrigo; McCrudden, Emma; Meylan, Cesar; Moran, Jason; Nakamura, Fábio Y.; Pereira, Lucas A.; Loturco, Irineu; Diaz, Daniela; Izquierdo, Mikel

2017-01-01

Abstract Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability. PMID:28828081

In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1-13 C]Alanine.

PubMed

Park, Jae Mo; Khemtong, Chalermchai; Liu, Shie-Chau; Hurd, Ralph E; Spielman, Daniel M

2017-05-01

The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD + ]. In this study, we assessed the use of hyperpolarized [1- 13 C]alanine and the subsequent detection of the intracellular products of [1- 13 C]pyruvate and [1- 13 C]lactate as a useful substrate for assessing redox levels in the liver in vivo. Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion. A solution of 80-mM hyperpolarized [1- 13 C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of 13 C MRS spectra. In vivo rat liver spectra showed peaks from [1- 13 C] alanine and the products of [1- 13 C]lactate, [1- 13 C]pyruvate, and 13 C-bicarbonate. A significantly increased 13 C-lactate/ 13 C-pyruvate ratio was observed after ethanol infusion (8.46 ± 0.58 at baseline versus 13.58 ± 0.69 after ethanol infusion; P < 0.001) consistent with the increased NADH produced by liver metabolism of ethanol to acetaldehyde and then acetate. A decrease in 13 C-bicarbonate production was also noted, potentially reflecting ethanol-induced mitochondrial redox changes. A method to measure in vivo tissue redox using hyperpolarized [1- 13 C]alanine is presented, with the validity of the proposed 13 C-pyruvate/ 13 C-lactate metric tested using an ethanol challenge to alter liver redox state. Magn Reson Med 77:1741-1748, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

β-Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro

PubMed Central

Mori, Masahiro; Gähwiler, Beat H; Gerber, Urs

2002-01-01

Electrophysiological and pharmacological properties of glycine receptors were characterized in hippocampal organotypic slice cultures. In the presence of ionotropic glutamate and GABAB receptor antagonists, pressure-application of glycine onto CA3 pyramidal cells induced a current associated with increased chloride conductance, which was inhibited by strychnine. Similar chloride currents could also be induced with β-alanine or taurine. Whole-cell glycine responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal cells and dentate granule cells, while responses to GABA were similar among these three cell types. Although these results demonstrate the presence of functional glycine receptors in the hippocampus, no evidence for their activation during synaptic stimulation was found. Gabazine, a selective GABAA receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor activation is not dependent on transporter-controlled levels of extracellular glycine, as no chloride current was observed in response to sarcosine, an inhibitor of glycine transporters. In contrast, application of guanidinoethanesulfonic acid, an uptake inhibitor of β-alanine and taurine, induced strychnine-sensitive chloride current in the presence of gabazine. These data indicate that modulation of transporters for the endogenous amino acids, β-alanine and taurine, can regulate tonic activation of glycine receptors, which may function in maintenance of inhibitory tone in the hippocampus. PMID:11850512

[Elevated transaminases - what to do if everything was done?].

PubMed

Lepper, P M; Dufour, J-F

2009-03-18

Transaminases, gamma-GT and alcalic phosphatase are classically termed as liver enzymes, however they can be found in almost every organ. Elevated levels of the transaminases ALAT (alanin-aminotransferase) and ASAT (aspartat-aminotransferase) are signs of disturbed permeability of the cells, in which these enzymes can be found. In contrast to ALAT, which is mainly liver-specific, the ASAT is found in other organs as well, e.g. heart and skeletal muscle. At a mild elevation of these enzymes a reevaluation is recommended, however if an elevation persists and is suspicious for a liver disease, a specific work up is necessary. In this manuscript, we discuss often overlooked problems and provide a diagnostic algorithm for the workup of elevated liver enzymes.

The effect of trans-ferulic acid and gamma-oryzanol on ethanol-induced liver injury in C57BL mouse.

PubMed

Chotimarkorn, Chatchawan; Ushio, Hideki

2008-11-01

The effects of the oral administration of trans-ferulic acid and gamma-oryzanol (mixture of steryl ferulates) with ethanol (5.0 g per kg) for 30 days to c57BL mice on ethanol-induced liver injury were investigated. Preventions of ethanol-induced liver injury by trans-ferulic acid and gamma-oryzanol were reflected by markedly decreased serum activities of plasma aspartate aminotransferase, alanine aminotransferase and significant decreases in hepatic lipid hydroperoxide and TBARS levels. Furthermore, the trans-ferulic acid- and gamma-oryzanol-treated mice recovered ethanol-induced decrease in hepatic glutathione level together with enhancing superoxide dismutase activity. These results demonstrate that both trans-ferulic acid and gamma-oryzanol exert a protective action on liver injury induced by chronic ethanol ingestion.

Ultraviolet radiation induces stress in etiolated Landoltia punctata, as evidenced by the presence of alanine, a universal stress signal: a ¹⁵N NMR study.

PubMed

Monselise, E B-I; Levkovitz, A; Kost, D

2015-01-01

Analysis with (15) N NMR revealed that alanine, a universal cellular stress signal, accumulates in etiolated duckweed plants exposed to 15-min pulsed UV light, but not in the absence of UV irradiation. The addition of 10 mm vitamin C, a radical scavenger, reduced alanine levels to zero, indicating the involvement of free radicals. Free D-alanine was detected in (15) N NMR analysis of the chiral amino acid content, using D-tartaric acid as solvent. The accumulation of D-alanine under stress conditions presents a new perspective on the biochemical processes taking place in prokaryote and eukaryote cells. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Tuning electronic transport via hepta-alanine peptides junction by tryptophan doping.

PubMed

Guo, Cunlan; Yu, Xi; Refaely-Abramson, Sivan; Sepunaru, Lior; Bendikov, Tatyana; Pecht, Israel; Kronik, Leeor; Vilan, Ayelet; Sheves, Mordechai; Cahen, David

2016-09-27

Charge migration for electron transfer via the polypeptide matrix of proteins is a key process in biological energy conversion and signaling systems. It is sensitive to the sequence of amino acids composing the protein and, therefore, offers a tool for chemical control of charge transport across biomaterial-based devices. We designed a series of linear oligoalanine peptides with a single tryptophan substitution that acts as a "dopant," introducing an energy level closer to the electrodes' Fermi level than that of the alanine homopeptide. We investigated the solid-state electron transport (ETp) across a self-assembled monolayer of these peptides between gold contacts. The single tryptophan "doping" markedly increased the conductance of the peptide chain, especially when its location in the sequence is close to the electrodes. Combining inelastic tunneling spectroscopy, UV photoelectron spectroscopy, electronic structure calculations by advanced density-functional theory, and dc current-voltage analysis, the role of tryptophan in ETp is rationalized by charge tunneling across a heterogeneous energy barrier, via electronic states of alanine and tryptophan, and by relatively efficient direct coupling of tryptophan to a Au electrode. These results reveal a controlled way of modulating the electrical properties of molecular junctions by tailor-made "building block" peptides.

Six weeks of β-alanine supplementation did not enhance repeated-sprint ability or technical performances in young elite basketball players.

PubMed

Milioni, Fabio; Redkva, Paulo E; Barbieri, Fabio A; Zagatto, Alessandro M

2017-06-01

Supplementation with β-alanine plays an important role as a precursor of carnosine, the most effective intramuscular buffer, and has been seen as a potential ergogenic aid, especially for high-intensity modalities such as basketball. Thus, the aim of the present study was to investigate the effects of 6 weeks of β-alanine supplementation on repeated sprint ability (RSA) and technical performances in young elite Brazilian basketball players. In total, 27 young basketball players (17±1 years) were randomized into a β-alanine group (Gβ - 6.4 g day -1 of β-alanine) and a placebo group (GP - 6.4 g day -1 of dextrose). Before and after the supplementation period the athletes performed a RSA test composed of ten 30 m sprints with two 180° changes of direction interspaced by 30 s of recovery. During the recovery period (i.e., after the sprints) the athletes performed a countermovement jump (CMJ) and a set of three free throws. After 48 h they performed a Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). Both groups increased the distance covered in the Yo-Yo IR1 after the supplementation period ( p = 0.001). On the other hand, both groups presented impairment in RSA time-performance (total time, best time, and mean time, p ≤ 0.04), while no significant changes were observed for technical task performances (i.e., CMJ and free throws) ( p ≥ 0.07). No between-group interactions were observed for any variable measured ( p ≥ 0.31). Thus, 6 weeks of β-alanine supplementation did not improve RSA or technical performances in young elite basketball players.

Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis.

PubMed

Wood, C M; Milligan, C L; Walsh, P J

1999-08-01

Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.

SU-E-T-799: Verification of a Simultaneous Treatment of Multiple Brain Metastases Using VMAT Technique by a Composite Alanine-Gel Dosimeter Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavoni, J; Silveira, M; Filho, O Baffa

Purpose: This work presents an end-to-end test using a Gel-Alanine phantom to validate the three-dimensional (3D) dose distribution (DD) delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. Methods: Three cylindrical phantons containing MAGIC-f gel dosimeter were used to measure the 3D DD of a VMAT treatment, the first two were filled with the gel dosimeter (Gel 1 and 2) and the third one was filled with gel and 12 alanine dosimeters distributed along it (Gel 3). Gels 1 and 3 were irradiated and gel 2 was used to map the magnetic resonance imagemore » (MRI) scanner field inomogeneities. A CT scan of gel 3 was used for the VMAT treatment planning and 5 alanine pellets were chosen as lesions, around them a PTV was grown and different dose prescriptions were assigned for each one, varying from 5 to 9Gy. Before treatment, the plan was approved in a QA based on an ionization chamber absolute dose measurement, a radiochromic film planar dose measurement and a portal dosimetry per field verification; and also the phantons positioning were verified by ExacTrac 6D correction and OBI kV Cone Beam CT. The gels were irradiated, the MRIs were acquired 24 hours after irradiation and finally, the alanine dosimeters were analysed in a X-band Electron Spin Resonance spectrometer. Results: The association of the two detectors enabled the 3D dose evaluation by gel and punctually inside target volumes by alanine. In the gamma analyses (3%/3mm) comparing the 5 PTVs’ central images DD with TPS expected DD more than 95% of the points were approved. The alanine absolute dose measurements were in agreement with TPS by less than 5%. Conclusion: The gel-alanine phantom enabled the dosimetric validation of multiple brain metastases treatment using VMAT, being an almost ideal tool for this application. This work is partially supported by FAPESP.« less

Identification and Partial Characterization of a Novel UDP-N-Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase Fusion Enzyme from Verrucomicrobium spinosum DSM 4136(T).

PubMed

Naqvi, Kubra F; Patin, Delphine; Wheatley, Matthew S; Savka, Michael A; Dobson, Renwick C J; Gan, Han Ming; Barreteau, Hélène; Blanot, Didier; Mengin-Lecreulx, Dominique; Hudson, André O

2016-01-01

The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/C Vs ) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44-46°C. Its apparent K m values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum.

Identification and Partial Characterization of a Novel UDP-N-Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase Fusion Enzyme from Verrucomicrobium spinosum DSM 4136T

PubMed Central

Naqvi, Kubra F.; Patin, Delphine; Wheatley, Matthew S.; Savka, Michael A.; Dobson, Renwick C. J.; Gan, Han Ming; Barreteau, Hélène; Blanot, Didier; Mengin-Lecreulx, Dominique; Hudson, André O.

2016-01-01

The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/CVs) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44–46°C. Its apparent Km values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum. PMID:27047475

Crystallization and preliminary X-ray data analysis of β-alanine synthase from Drosophila melanogaster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundgren, Stina; Andersen, Birgit; Piškur, Jure

2007-10-01

β-Alanine synthase catalyzes the last step in the reductive degradation pathway for uracil and thymine. Crystals of the recombinant enzyme from D. melanogaster belong to space group C2. Diffraction data to 3.3 Å resolution were collected and analyzed. β-Alanine synthase catalyzes the last step in the reductive degradation pathway for uracil and thymine, which represents the main clearance route for the widely used anticancer drug 5-fluorouracil. Crystals of the recombinant enzyme from Drosophila melanogaster, which is closely related to the human enzyme, were obtained by the hanging-drop vapour-diffusion method. They diffracted to 3.3 Å at a synchrotron-radiation source, belong tomore » space group C2 (unit-cell parameters a = 278.9, b = 95.0, c = 199.3 Å, β = 125.8°) and contain 8–10 molecules per asymmetric unit.« less

Thermal inactivation and chaperonin-mediated renaturation of mitochondrial aspartate aminotransferase.

PubMed Central

Lawton, J M; Doonan, S

1998-01-01

Mitochondrial aspartate aminotransferase is inactivated irreversibly on heating. The inactivated protein aggregates, but aggregation is prevented by the presence of the chaperonin 60 from Escherichia coli (GroEL). The chaperonin increases the rate of thermal inactivation in the temperature range 55-65 degrees C but not at lower temperatures. It has previously been shown [Twomey and Doonan (1997) Biochim. Biophys. Acta 1342, 37-44] that the enzyme switches to a modified, but catalytically active, conformation at approx. 55-60 degrees C and the present results show that this conformation is recognized by and binds to GroEL. The thermally inactivated protein can be released from GroEL in an active form by the addition of chaperonin 10 from E. coli (GroES)/ATP, showing that inactivation is not the result of irreversible chemical changes. These results suggest that the irreversibility of thermal inactivation is due to the formation of an altered conformation with a high kinetic barrier to refolding rather than to any covalent changes. In the absence of chaperonin the unfolded molecules aggregate but this is a consequence, rather than the cause, of irreversible inactivation. PMID:9693123

Effect of chronic hypo and hypervitaminosis C on the brush border enzymes and the intestinal uptake of glucose and alanine.

PubMed

Mahmood, A; Chauhan, V P; Lyall, V; Sarkar, A K

1979-08-15

Brush border sucrase and alkaline phosphatase activities are considerably enhanced in the intestine of ascorbic acid deficient guinea-pigs. Similar increase in the uptake of D-glucose and L-alanine also occurs in chronic vitamin C deficiency. However the permeability of D-glucose and L-alanine in the intestine of animals fed with large doses of vitamin C is severely depressed, with a reduction in the levels of sucrase and alkaline phosphatase activities.

Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein Level Predicts Liver Fibrosis and Prognosis in Primary Biliary Cirrhosis.

PubMed

Umemura, Takeji; Joshita, Satoru; Sekiguchi, Tomohiro; Usami, Yoko; Shibata, Soichiro; Kimura, Takefumi; Komatsu, Michiharu; Matsumoto, Akihiro; Ota, Masao; Tanaka, Eiji

2015-06-01

Noninvasive markers of liver fibrosis in patients with primary biliary cirrhosis (PBC) are needed for predicting disease progression. As the Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA(+)-M2BP) was recently established as a liver fibrosis glycobiomarker in chronic hepatitis C, we assessed its efficacy in evaluating liver fibrosis stage and disease progression in PBC. A total of 137 patients with PBC who underwent liver biopsy and serological tests for WFA(+)-M2BP were enrolled. All patients were treated with ursodeoxycholic acid. Clinical data were compared with those for other noninvasive markers (aspartate aminotransferase-to-platelet ratio, FIB-4 index, aspartate aminotransferase/alanine aminotransferase ratio, Forn's index, and Mayo score) for estimating liver fibrosis using receiver operating characteristic analysis. The association between WFA(+)-M2BP and clinical outcome (liver decompensation, liver transplantation, or death) was evaluated using the Cox proportional hazards model with stepwise method. WFA(+)-M2BP was independently associated with liver fibrosis stage as determined by liver biopsy. The cutoff values of WFA(+)-M2BP for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.7, 1.0, 1.4, and 2.0, respectively. The area under the receiver operating characteristic curve values for significant fibrosis, severe fibrosis, and cirrhosis were 0.979, 0.933, and 0.965, respectively. WFA(+)-M2BP was significantly superior to the other indices for the determination of significant and severe fibrosis stages. Furthermore, the WFA(+)-M2BP level at enrollment was strongly and independently associated with clinical outcome (hazard ratio 18.59, P=0.021). Baseline measurements of WFA(+)-M2BP represent a simple and reliable noninvasive surrogate marker of liver fibrosis and prognosis in patients with PBC.

General Lack of Correlations between Age and Signs of the Metabolic Syndrome in Subjects with Non-diabetic Fasting Glucose Values.

PubMed

Preuss, Harry G; Mrvichin, Nate; Clouatre, Dallas; Bagchi, Debasis; Preuss, Jeffrey M; Perricone, Nicholas V; Swaroop, Anand; Kaats, Gilbert R

2017-01-01

Insulin resistance and advancing age are well-recognized risk factors for metabolic syndrome. Recent reports indicate that fasting glucose levels in non-diabetic patients correlate appropriately with the development of certain elements in metabolic syndrome, which suggest a cause-effect relationship with insulin resistance. The present investigation assessed whether a significant association exists between chronological age and various elements of metabolic syndrome in this same group of subjects possessing non-diabetic fasting glucose levels. Baseline data were taken from 288 subjects (age 17-87 years) with fasting glucose levels ≤ 125 mg/dl. Correlations between chronological age and different metabolic parameters were assessed to determine any statistically significant relationships and compare these with previously demonstrated metabolic parameters. With the exception of systolic blood pressure, the following correlations between age and components of metabolic syndrome were not significant or even significant in the opposite direction compared to those found in the same population using fasting glucose as the independent variable: body weight, body fat, diastolic blood pressure, white blood cell count (WBC)/neutrophil count, and circulating levels of insulin, high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Although systolic blood pressure still increased, it was to a lesser extent than might be expected. In the present investigation, a cross-sectional analysis was carried out over a wide age range of subjects. It is noteworthy that fasting glucose levels and the other major elements of metabolic syndrome did not change significantly with advancing age. These results demonstrate that decreasing insulin resistance and fasting glucose levels may be an important way to overcome the adverse effects and perturbations of advancing age

Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

PubMed

Tan, Ge; Yuan, Ruozhen; Hao, Zilong; Lei, Chunyan; Xiong, Yao; Xu, Mangmang; Liu, Ming

2017-01-01

Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function

PubMed Central

Lee, Shirley Y.; Pullen, Lester; Virgil, Daniel J.; Castañeda, Carlos A.; Abeykoon, Dulith; Bolon, Daniel N. A.; Fushman, David

2014-01-01

Mutations at solvent inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understood for most systems. Here, we determined the effects of alanine mutations at all 15 core positions in ubiquitin on function in yeast. The majority (13 of 15) of alanine substitutions supported yeast growth as the sole ubiquitin. The two null mutants (I30A and L43A) were both less stable to temperature-induced unfolding in vitro than wild-type, but were well folded at physiological temperatures. Heteronuclear NMR studies indicated that the L43A mutation reduces temperature stability while retaining a ground-state structure similar to wild-type. This structure enables L43A to bind to common ubiquitin receptors in vitro. Many of the core alanine ubiquitin mutants, including one of the null variants (I30A), exhibited an increased accumulation of high molecular weight species, suggesting that these mutants caused a defect in the processing of ubiquitin-substrate conjugates. In contrast, L43A exhibited a unique accumulation pattern with reduced levels of high molecular weight species and undetectable levels of free ubiquitin. When conjugation to other proteins was blocked, L43A ubiquitin accumulated as free ubiquitin in yeast. Based on these findings we speculate that ubiquitin's stability to unfolding may be required for efficient recycling during proteasome-mediated substrate degradation. PMID:24361330

Cellular and Physiological Effects of Dietary Supplementation with β-Hydroxy-β-Methylbutyrate (HMB) and β-Alanine in Late Middle-Aged Mice

PubMed Central

Vallejo, Julian; Spence, Madoka; Cheng, An-Lin; Brotto, Leticia; Edens, Neile K.; Garvey, Sean M.; Brotto, Marco

2016-01-01

There is growing evidence that severe decline of skeletal muscle mass and function with age may be mitigated by exercise and dietary supplementation with protein and amino acid ingredient technologies. The purposes of this study were to examine the effects of the leucine catabolite, beta-hydroxy-beta-methylbutyrate (HMB), in C2C12 myoblasts and myotubes, and to investigate the effects of dietary supplementation with HMB, the amino acid β-alanine and the combination thereof, on muscle contractility in a preclinical model of pre-sarcopenia. In C2C12 myotubes, HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of all SR agonists tested (KCl, P<0.01; caffeine, P = 0.03; ionomycin, P = 0.03). HMB also improved C2C12 myoblast viability (25 μM HMB, P = 0.03) and increased proliferation (25 μM HMB, P = 0.04; 125 μM HMB, P<0.01). Furthermore, an ex vivo muscle contractility study was performed on EDL and soleus muscle from 19 month old, male C57BL/6nTac mice. For 8 weeks, mice were fed control AIN-93M diet, diet with HMB, diet with β-alanine, or diet with HMB and β-alanine. In β-alanine fed mice, EDL muscle showed a 7% increase in maximum absolute force compared to the control diet (202 ± 3vs. 188± 5 mN, P = 0.02). At submaximal frequency of stimulation (20 Hz), EDL from mice fed HMB plus β-alanine showed an 11% increase in absolute force (88.6 ± 2.2 vs. 79.8 ± 2.4 mN, P = 0.025) and a 13% increase in specific force (12.2 ± 0.4 vs. 10.8 ± 0.4 N/cm2, P = 0.021). Also in EDL muscle, β-alanine increased the rate of force development at all frequencies tested (P<0.025), while HMB reduced the time to reach peak contractile force (TTP), with a significant effect at 80 Hz (P = 0.0156). In soleus muscle, all experimental diets were associated with a decrease in TTP, compared to control diet. Our findings highlight beneficial effects of HMB and β-alanine supplementation on skeletal muscle function in aging mice. PMID

Transferability of ASTM/NIST alanine-polyethylene recipe at ISS. American Society for Testing and Materials/National Institute for Standards and Technology. Istituto Superiore de Sanita

PubMed

De Angelis C; Fattibene; Onori; Petetti; Bartolotta; Sansone Santamaria A

2000-05-01

Alanine-polyethylene solid state dosimeters were prepared at Istituto Superiore di Sanita (ISS) following the recipe proposed by National Institute of Standards and Technology (NIST) with the goal of testing its transferability. Dosimeters were prepared using 95% alanine and 5% polyethylene, by weight. They are rugged and of increased sensitivity, repeatability and reproducibility as respect to the ISS alanine-paraffin pellets. Reproducibility of about 1% was obtained at 10 Gy and at 3 Gy if one single pellet or a stack of five dosimeters were used, respectively.

Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of D-alanine in their biological activity.

PubMed

Villéger, Romain; Saad, Naima; Grenier, Karine; Falourd, Xavier; Foucat, Loïc; Urdaci, Maria C; Bressollier, Philippe; Ouk, Tan-Sothea

2014-10-01

Probiotics represent a potential strategy to influence the host's immune system thereby modulating immune response. Lipoteichoic Acid (LTA) is a major immune-stimulating component of Gram-positive cell envelopes. This amphiphilic polymer, anchored in the cytoplasmic membrane by means of its glycolipid component, typically consists of a poly (glycerol-phosphate) chain with D-alanine and/or glycosyl substitutions. LTA is known to stimulate macrophages in vitro, leading to secretion of inflammatory mediators such as Nitric Oxide (NO). This study investigates the structure-activity relationship of purified LTA from three probiotic Bacillus strains (Bacillus cereus CH, Bacillus subtilis CU1 and Bacillus clausii O/C). LTAs were extracted from bacterial cultures and purified. Chemical modification by means of hydrolysis at pH 8.5 was performed to remove D-alanine. The molecular structure of native and modified LTAs was determined by (1)H NMR and GC-MS, and their inflammatory potential investigated by measuring NO production by RAW 264.7 macrophages. Structural analysis revealed several differences between the newly characterized LTAs, mainly relating to their D-alanylation rates and poly (glycerol-phosphate) chain length. We observed induction of NO production by LTAs from B. subtilis and B. clausii, whereas weaker NO production was observed with B. cereus. LTA dealanylation abrogated NO production independently of the glycolipid component, suggesting that immunomodulatory potential depends on D-alanine substitutions. D-alanine may control the spatial configuration of LTAs and their recognition by cell receptors. Knowledge of molecular mechanisms behind the immunomodulatory abilities of probiotics is essential to optimize their use.

Retrospective evaluation of xylitol ingestion in dogs: 192 cases (2007-2012).

PubMed

DuHadway, Meghan R; Sharp, Claire R; Meyers, Katherine E; Koenigshof, Amy M

2015-01-01

To summarize the signalment, clinical signs, prevalence of decreased blood glucose concentration (BG), prevalence of increased liver values, treatment, and outcome in dogs known to have ingested xylitol. Retrospective study from December 2007 to February 2012 SETTING: Three university teaching hospitals. One hundred ninety-two client-owned dogs with known or suspected xylitol ingestion. None. The median ingested xylitol dose was 0.32 g/kg (range 0.03-3.64 g/kg). Clinical signs were present in 39 (20%) dogs on presentation to the veterinary teaching hospitals. The most common clinical sign was vomiting (n = 25), followed by lethargy (12). The median duration of clinical signs prior to presentation was 93 minutes (range 0-5,040 minutes). Dogs that developed clinical signs ingested a significantly higher dose of xylitol than those that were asymptomatic. Thirty dogs became hypoglycemic (BG ≤ 3.3 mmol/L [60 mg/dL]) at some time point during their hospitalization. When evaluating all dogs, there was a significant difference between the initial and lowest BGs. Thirty dogs had increased alanine aminotransferase activity or total serum bilirubin concentration. Dogs with increases in alanine aminotransferase activity or total serum bilirubin concentration had a significantly lower nadir BG. All dogs survived to discharge and 158 were known to be alive at 28 days. The rest were lost to follow up. The prognosis for dogs evaluated by a veterinarian that ingest lower doses of xylitol and do not develop liver failure is excellent. Dogs ingesting xylitol should be hospitalized and monitored for variations in BG, because BG drops in most dogs following presentation. Additional studies are needed in dogs ingesting higher doses of xylitol before correlations between dose and the development of clinical signs or liver failure can be established. Treatment and prognosis for these dogs warrants further investigation. © Veterinary Emergency and Critical Care Society 2015.

Randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection.

PubMed

Colvin, Richard A; Tanwandee, Tawesak; Piratvisuth, Teerha; Thongsawat, Satawat; Hui, Aric Josun; Zhang, Hongfei; Ren, Hong; Chen, Pei-Jer; Chuang, Wan-Long; Sobhonslidsuk, Abhasnee; Li, Ruobing; Qi, Yin; Praestgaard, Jens; Han, Yi; Xu, Junfang; Stein, Daniel S

2015-01-01

Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections. This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e-antigen (HBeAg) positive. One hundred and forty-one patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV-DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events. The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV-DNA from baseline. Reductions in HBV-DNA were not significantly different, except the 1200 μg every 4 weeks albinterferon dose which was inferior compared with pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups. Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665). © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Selection of tRNA(Asp) amber suppressor mutants having alanine, arginine, glutamine, and lysine identity.

PubMed Central

Martin, F; Reinbolt, J; Dirheimer, G; Gangloff, J; Eriani, G

1996-01-01

Elements that confer identity to a tRNA in the cellular environment, where all aminoacyl-tRNA synthetases are competing for substrates, may be delineated by in vivo experiments using suppressor tRNAs. Here we describe the selection of active Escherichia coli tRNAAsp amber mutants and analyze their identity. Starting from a library containing randomly mutated tRNA(CUA)Asp genes, we isolated four amber suppressors presenting either lysine, alanine, or glutamine activity. Two of them, presenting mainly alanine or lysine activity, were further submitted to a second round of mutagenesis selection in order to improve their efficiency of suppression. Eleven suppressors were isolated, each containing two or three mutations. Ten presented identities of the two parental mutants, whereas one had switched from lysine to arginine identity. Analysis of the different mutants revealed (or confirmed for some nucleotides) their role as positive and/or negative determinants in AlaRS, LysRS, and ArgRS recognition. More generally, it appears that tRNAAsp presents identity characteristics closely related to those of tRNALys, as well as a structural basis for acquiring alanine or arginine identity upon moderate mutational changes; these consist of addition or suppression of the corresponding positive or negative determinants, as well as tertiary interactions. Failure to isolate aspartic acid-inserting suppressors is probably due to elimination of the important G34 identity element and its replacement by an antideterminant when changing the anticodon of the tRNAAsp to the CUA triplet. PMID:8809018

The role of metal ions in chemical evolution - Polymerization of alanine and glycine in a cation-exchanged clay environment

NASA Technical Reports Server (NTRS)

Lawless, J. G.; Levi, N.

1979-01-01

The effect of the exchangeable cation on the condensation of glycine and alanine was investigated using a series of homoionic bentonites. A cycling procedure of drying, warming and wetting was employed. Peptide bond formation was observed, and the effectiveness of metal ions to catalyze the condensation was Cu(2+) greater than Ni(2) approximately equals Zn(2+) greater than Na(+). Glycine showed 6% of the monomer incorporated into oligomers with the largest detected being the pentamer. Alanine showed less peptide bond formation (a maximum of 2%) and only the dimer was observed.

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed

Dennis, V W; Brazy, P C

1978-08-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport.

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed Central

Dennis, V W; Brazy, P C

1978-01-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport. PMID:670399

Partial alanine scan of mast cell degranulating peptide (MCD): importance of the histidine- and arginine residues.

PubMed

Buku, Angeliki; Mendlowitz, Milton; Condie, Barry A; Price, Joseph A

2004-06-01

The influence of the two histidine and two arginine residues of mast cell degranulating peptide (MCD) in activity and binding was studied by replacing these amino acids in the MCD sequence with L-alanine. Their histamine releasing activity was determined on rat peritoneal mast cells. Their binding affinity to the FcepsilonRIalpha binding subunit of the human mast cell receptor protein, was carried out using fluorescence polarization. The histamine assay showed that replacement of His13 by Ala o ccurred without loss of activity compared with the activity of MCD. Alanine substitutions for Arg7 and His8 resulted in an approximately 40 fold increase, and for Arg16 in a 14-fold increase in histamine-releasing activity of MCD. The binding affinities of the analogs were tested by competitive displacement of bound fluorescent MCD peptide from the FcepsilonRIalpha binding protein of the mast cell receptor by the Ala analogs using fluorescence polarization. The analogs Ala8 (for His) and Ala16 (for Arg) showed the same binding affinities as MCD, whereas analog Ala7 (for Arg) and analog Ala13 (for His) showed slightly better binding affinity than the parent compound. This study showed that the introduction of alanine residues in these positions resulted in MCD agonists of diverse potency. These findings will be useful in further MCD structure-activity studies.

Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values

PubMed Central

Veeraselvam, M.; Sridhar, R.; Perumal, P.; Jayathangaraj, M. G.

2014-01-01

The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase (AST), and so forth were estimated in 11 (5 males and 6 females) apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P < 0.05) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). The study might help to evaluate health profiles of sloth bears for appropriate line treatment. PMID:24876990

Andrographis paniculata ameliorates carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity: diminution of oxidative stress.

PubMed

Koh, Pei Hoon; Mokhtar, Ruzaidi Azli Mohd; Iqbal, Mohammad

2011-01-01

Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P < 0.05). Parrallel to these changes, CCl(4) challenge too, enhanced hepatic damage as evidenced by sharp increase in serum transaminases (e.g. alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) (P < 0.05). Additionally, the impairment of liver function corresponded to histolopathological changes. However, most of these changes were reversed in a dose-dependent fashion by pre-treatment of animals with A. paniculata (P < 0.05). The ability of A. paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.

Improved clinicopathologic assessments of acute liver damage due to trauma in Indian ring-necked parakeets (Psittacula krameri manillensis).

PubMed

Williams, Susan M; Holthaus, Lisa; Barron, Heather Wilson; Divers, Stephen J; McBride, Michael; Almy, Frederic; Bush, Sharon; Latimer, Kenneth S

2012-06-01

Increased activities of certain biochemical enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], alkaline phosphatase [ALP]) have been associated with blunt liver injury in many species. To evaluate changes in plasma hepatic biochemical parameters in acute avian liver disease caused by trauma and to compare biochemical changes with histologic lesions in hepatic parenchyma, 30 healthy fasted Indian ring-necked parakeets (Psittacula krameri manillensis) were divided into 2 groups, and traumatic liver injury was caused by endoscopic liver biopsy (group 1) or by liver biopsy and crushing injury to the hepatic parenchyma with endoscopic forceps (group 2) in anesthetized birds. Blood samples were collected at baseline and at 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120 hours in alternate groups to compare analyte values after injury with those at baseline. Results showed consistently decreased plasma ALP activity (excluding 1 time point) throughout the study, which was thought to be associated with isoflurane administration. Plasma glutamate dehydrogenase activity initially increased but rapidly declined thereafter and was attributed to acute focal hepatocellular injury. In both groups, increases in plasma AST, ALT, and LDH activities was most likely caused by muscle injury because creatine kinase activity was concurrently increased. Compared with baseline values, bile acid concentration and y-glutamyl transferase activity were not affected by liver biopsy or crush injury. Plasma sorbitol dehydrogenase activity was the most specific indicator of liver injury in both groups. Histologic changes correlated poorly with biochemical results, possibly because the small area of hepatic parenchyma that was damaged did not affect enzyme values substantially.

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

PubMed Central

Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro

2015-01-01

Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668

Antidiabetic Effects of Aqueous and Dichloromethane/Methanol Stem Bark Extracts of Pterocarpus soyauxii Taub (Papilionaceae) on Streptozotocin-induced Diabetic Rats

PubMed Central

Tchamadeu, Marie Claire; Dzeufiet, Paul Désiré Djomeni; Blaes, Nelly; Girolami, Jean-Pierre; Kamtchouing, Pierre; Dimo, Théophile

2017-01-01

Aim of the Study: The aim is to evaluate the hypoglycemic and antidiabetic effects of aqueous and CH2Cl2/CH3OH stem bark extracts of Pterocarpus soyauxii Taub in normal and diabetic rats. Materials and Methods: Streptozotocin (STZ)-induced diabetic and normal adult Wistar rats were orally administered with aqueous and CH2Cl2/CH3OH plant extracts of P. soyauxii at various doses (38–300 mg/kg) in a single administration. In addition, STZ-induced diabetic rats received prolonged daily administration for 14 days. Glibenclamide (GB) (10 mg/kg) was used as reference treatment. In acute test, fasting blood glucose was followed for 5 h. In subacute test, body weight, food and water intakes, and blood glucose were followed weekly and serum biochemical parameters evaluated after 14 days treatment. Results: Acute administration of aqueous and CH2Cl2/CH3OH stem bark extracts moderately decreased fasting blood glucose compared to GB, significantly in normal rats (P < 0.05 to P < 0.01) but, as GB, not significantly in diabetic rats. Prolonged treatments in diabetic rats with aqueous and CH2Cl2/CH3OH extracts reduced blood glucose to an extent, respectively, superior or similar to GB. Moreover, P. soyauxii also significantly (P < 0.01) reduced weight loss, and diabetes increased serum triglycerides, total cholesterol, and transaminases (alanine aminotransferase/aspartate aminotransferase) elevations. Conclusion: P. soyauxii Taub stem bark extracts have possible value for antidiabetic oral medication. SUMMARY Aqueous and Dichloromethane/Methanol stem bark extracts of Pterocarpus soyauxii Taub have potent (compared to Glibenclamide) antidiabetic effects in STZ-diabetic rats, with specific kinetics and dose-responses.Moderate hypoglycemia effects upon acute P. soyauxii administration.Potent anti-hyperglycemic effects of sub-acute P. soyauxii administration in STZ-diabetic rats.Potent anti-hyperlipidemic effects of sub-acute P. soyauxii administration in STZ-diabetic rats

Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice.

PubMed

Sena, Maria Clecia P; Nunes, Fabíola C; Salvadori, Mirian G S Stiebbe; Carvalho, Cleyton Charles D; Morais, Liana Clebia S L; Braga, Valdir A

2011-01-01

Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 ± 8 vs. 7 ± 2 s, n = 9) or sugarcane spirit (36 ± 9 vs. 7 ± 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 ± 1 for the control group, 27 ± 2 for the ethanol group, and 31 ± 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 ± 0.17 for the control group and 2.67 ± 0.17 for the sugarcane spirit group; n = 8 for each group). The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study).

PubMed

Gómez, Henry L; Neciosup, Silvia; Tosello, Célia; Mano, Max; Bines, José; Ismael, Gustavo; Santi, Patrícia X; Pinczowski, Hélio; Nerón, Yeni; Fanelli, Marcello; Fein, Luis; Sampaio, Carlos; Lerzo, Guillermo; Capó, Adolfo; Zarba, Juan J; Blajman, César; Varela, Mirta S; Martínez-Mesa, Jeovany; Werutsky, Gustavo; Barrios, Carlos H

2016-02-01

Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a study in 1744 patients.

PubMed

Sánchez-Armengol, A; Villalobos-López, P; Caballero-Eraso, C; Carmona-Bernal, C; Asensio-Cruz, M; Barbé, F; Capote, F

2015-09-01

We analyze a large population of patients to determine whether gamma glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome (OSA) and whether these levels are related to clinical characteristics or polygraphic indexes. A cross-sectional study in a population of 1744 patients referred for OSA suspicion was conducted. The following variables were determined: glucose, cholesterol, triglycerides, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), GGT, body mass index, waist-hip ratio (WHR), and overnight sleep study. The 483 patients with GGT ≥40 IU/l were younger and more obese, and had a pattern of more centrally distributed fat than the 1261 with GGT <40 IU/l. Patients with high levels of GGT also consumed more alcohol, had a poorer biochemical profile, and had more respiratory and oximetric alterations during sleep. GGT levels were significantly correlated with AHI, DI, and CT90. In the binary regression test, WHR, glucose, cholesterol, triglycerides, and grams of alcohol consumed per day predicted GGT levels ≥40 IU/l, while none of the polygraphic variables had predictive value. High GGT levels were associated with the severity of OSA. However, this relationship seems to be due to the coexistence of other associated factors, mainly central obesity, rather than to the respiratory disorders found in this disease.

Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

PubMed

Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

2015-03-01

1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

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

PubMed

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.

Quality specifications for the extra-analytical phase of laboratory testing: Reference intervals and decision limits.

PubMed

Ceriotti, Ferruccio

2017-07-01

Reference intervals and decision limits are a critical part of the clinical laboratory report. The evaluation of their correct use represents a tool to verify the post analytical quality. Four elements are identified as indicators. 1. The use of decision limits for lipids and glycated hemoglobin. 2. The use, whenever possible, of common reference values. 3. The presence of gender-related reference intervals for at least the following common serum measurands (besides obviously the fertility relate hormones): alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatine kinase (CK), creatinine, gamma-glutamyl transferase (GGT), IgM, ferritin, iron, transferrin, urate, red blood cells (RBC), hemoglobin (Hb) and hematocrit (Hct). 4. The presence of age-related reference intervals. The problem of specific reference intervals for elderly people is discussed, but their use is not recommended; on the contrary it is necessary the presence of pediatric age-related reference intervals at least for the following common serum measurands: ALP, amylase, creatinine, inorganic phosphate, lactate dehydrogenase, aspartate aminotransferase, urate, insulin like growth factor 1, white blood cells, RBC, Hb, Hct, alfa-fetoprotein and fertility related hormones. The lack of such reference intervals may imply significant risks for the patients. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Spondias mombin L. (Anacardiaceae) enhances detoxification of hepatic and macromolecular oxidants in acetaminophen-intoxicated rats.

PubMed