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Sample records for aminotransferase gamma-glutamyltransferase ggt

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

    DEFF Research Database (Denmark)

    Fraser, Abigail; Thinggaard, Mikael; Christensen, Kaare

    2009-01-01

    Abstract Background/Aims: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic...

  2. Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Huang, Hao; Wang, Xue-Ping; Li, Xiao-Hui; Chen, Hao; Zheng, Xin; Lin, Jian-Hua; Kang, Ting; Zhang, Lin; Chen, Pei-Song

    2017-08-14

    The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

  3. Gamma-glutamyltransferase, aspartate aminotransferase and alkaline phosphatase as markers of alcohol consumption in out-patient alcoholics

    DEFF Research Database (Denmark)

    Gluud, C; Andersen, I; Dietrichson, O

    1981-01-01

    Serum activity of gamma-glutamyltransferase, aspartate aminotransferase and alkaline phosphatase were determined in 316 patients attending an out-patients clinic for treatment of alcoholism. The activity of gamma-glutamyltransferase was raised in 34% and that of aspartate aminotransferase...... and alkaline phosphatase in 18% and 7%. Neither the activity of gamma-glutamyltransferase, aspartate aminotransferase nor alkaline phosphatase showed any significant (P greater than 0.05) correlation with the history of alcohol consumption. The activities of gamma-glutamyltransferase and aspartate...... aminotransferase were raised significantly more often in patients with recent alcohol consumption than in patients who had abstained for more than 9 days. The concentration of alkaline phosphatase was not significantly (P greater than 0.05) different in these groups. The predictive value of raised and normal...

  4. Gamma-glutamyltransferase, aspartate aminotransferase and alkaline phosphatase as markers of alcohol consumption in out-patient alcoholics

    DEFF Research Database (Denmark)

    Gluud, C; Andersen, I; Dietrichson, O

    1981-01-01

    and alkaline phosphatase in 18% and 7%. Neither the activity of gamma-glutamyltransferase, aspartate aminotransferase nor alkaline phosphatase showed any significant (P greater than 0.05) correlation with the history of alcohol consumption. The activities of gamma-glutamyltransferase and aspartate...... aminotransferase were raised significantly more often in patients with recent alcohol consumption than in patients who had abstained for more than 9 days. The concentration of alkaline phosphatase was not significantly (P greater than 0.05) different in these groups. The predictive value of raised and normal...... activities of gamma-glutamyltransferase, in deciding whether a patient had had recent alcohol consumption or not, was not superior to the predictive value of raised and normal activities of aspartate aminotransferase....

  5. Associations of uric acid and gamma-glutamyltransferase (GGT) with obesity and components of metabolic syndrome in children and adolescents.

    Science.gov (United States)

    Kong, A P S; Choi, K C; Ho, C S; Chan, M H M; Ozaki, R; Chan, C W H; Chan, J C N

    2013-10-01

    The combined effect of uric acid, gamma-glutamyltransferase (GGT) and cardiovascular risk factors clustering in the youth remains under-explored. The objective of this study was to examine the association between uric acid, GGT, obesity and the individual components of metabolic syndrome in children and adolescents. We performed a cross-sectional observational study of 2067 children and adolescents (875 boys and 1192 girls) aged 6-20 years who were healthy volunteers and were recruited from primary and secondary schools in Hong Kong between 2007 and 2008. Subjects were divided into two strata (75th percentile as cut-off) for comparison between odds of cardiovascular risk factors. After adjustment by multivariable logistic regression, subjects in upper stratum, i.e., >75th percentile, of either serum uric acid or GGT levels were associated with obesity, low high-density lipoprotein cholesterol (HDL-C) level and high blood pressure (adjusted odds ratios [AOR] ranged from 1.63 to 5.82, all P uric acid and GGT in the association with obesity, low HDL-C and high blood pressure (AOR ranged from 2.60 to 10.69, all P Uric acid and GGT have combined effect in association with obesity and other cardiovascular risk factors in children and adolescents. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

  6. The antioxidant effects of vitamin C on liver enzymes: aspartate aminotransferase, alanine aminotranferease, alkaline phosphatase and gamma-glutamyltransferase activities in rats under Paraquat insult

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    Benjamin Nnamdi Okolonkwo

    2013-06-01

    Full Text Available Paraquat (PQ is a bipyridylium herbicide; applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the liver enzymes [aspartate aminotransferase (SGOT, alanine aminotranferease (SGPT, alkaline phosphatase (ALP, and gamma-glutamyltransferase (GGT] of rats under this toxic insult. Male rats in groups (A, B, C and D were intraperitoneally injected with different sublethal increasing doses (0, 0.02, 0.04 and 0.06 g/kg body weigh of PQ respectively on monthly basis. Subsequently, the subgroups (A2, B2, C2 and D2 were given orally, 200 mg/L vitamin C, while the subgroups A1, B1, C1, and D1, received only water. Four animals per subgroup were decapitated on monthly basis and blood samples taken for enzyme assay. The parameters studied were - SGOT, SGPT, ALP and GGT - liver enzymes. The dose and time dependent PQ toxicity effect resulted in highly elevated Liver enzymes activities. The subgroups on vitamin C had significantly lower enzyme activities when compared to the same subgroups on only PQ insult. But the values were high when compared to the control subgroups (A1 and A2. These results were indication that vitamin C when given at moderate doses and maintained for a longer period could be a life saving adjunct to toxic insult.

  7. Potential impact of joint association of alanine aminotransferase and gamma-glutamyltransferase on insulin resistance in Japan: The Toranomon Hospital Health Management Center Study 19 (TOPICS 19).

    Science.gov (United States)

    Arase, Yasuji; Heianza, Yoriko; Hara, Shigeko; Ohmoto-Sekine, Yuki; Amakawa, Kazuhisa; Tsuji, Hiroshi; Ogawa, Kyoko; Saito, Kazumi; Kodama, Satoru; Ikeda, Kenji; Kumada, Hiromitsu; Kobayashi, Tetsuro; Sone, Hirohito

    2015-03-01

    To investigate the potential impact of joint association of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) on insulin resistance and β-cell dysfunction in healthy Japanese individuals with a normal range of liver enzymes. This study included 1010 individuals (545 men and 465 women) aged 20-89 years who underwent an oral glucose tolerance test for health screening. Participants were divided into four groups on the basis of median values for ALT and GGT: (i) both ALT and GGT low (both-low); (ii) ALT high and GGT low (ALT-high); (iii) ALT low and GGT high (GGT-high); and (iv) both ALT and GGT high (both-high). Logistic regression analysis was used to investigate the relationship between liver enzyme and insulin dynamics, such as Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) and insulinogenic index (IGI). The insulin resistance was defined when HOMA-IR was 2.5 or more. IGI of less than 0.4 was considered to be decreased early-phase insulin secretion. Mean values of HOMA-IR in men was 1.5 in the both-low group, 1.8 in ALT-high, 1.8 in GGT-high and 2.8 in both-high. The mean HOMA-IR in women was 1.3 in the both-low group, 1.3 in ALT-high, 1.6 in GGT-high and 2.0 in both-high. HOMA-IR in the both-high group was significantly higher than that in the both-low group regardless of the difference of sex. Multivariate analysis showed that insulin resistance occurred when the patient had high liver enzymes. Combining the two liver function markers would be effective for identifying individuals with insulin resistance. © 2014 The Japan Society of Hepatology.

  8. Role of gamma-glutamyltransferase in cardiovascular diseases

    OpenAIRE

    Jiang, Shengyang; Jiang, Donglin; Tao, Yijia

    2013-01-01

    Cardiovascular diseases are threatening human health with rising morbidity and mortality rates. Gamma-glutamyltransferase (GGT) has been found to be involved in the pathogenesis of cardiovascular diseases, especially coronary artery disease, and the prognosis of cardiovascular disease may be predicted by increasing GGT levels. GGT levels are related to cardiovascular emergencies of chronic heart failure, and an elevated GGT level has been shown to be an independent predictive maker for cardia...

  9. [Alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase (AP) and gamma-glutamyltransferase (GGP) in intestinal diseases of dogs].

    Science.gov (United States)

    Dodurka, T; Kraft, W

    1995-07-01

    331 dogs, suffering from different intestinal diseases with diarrhea, were classified into the groups of "acute noninfectious", "infectious", "chronic" and "secondary enteropathies". The serum enzymes ALT, AST, GLDH, AP and GGT were determined. In all groups increases of enzyme activities were to be found. The highest and most frequent increases have been observed in acute noninfectious and in secondary enteropathies. The enzyme pattern in acute noninfectious enteropathies indicate a secondary liver disturbance in consequence of the intestinal disease, whereas the liver participation in secondary enteropathies is the effect of the primary disease other than intestinal disturbances. In comparison to this the height and number of increases of liver enzyme activities were low in acute infectious and in chronic enteropathies.

  10. Reference values of the enzymatic activities of the aspartate aminotransferase and gamma glutamyltransferase of Jersey breed. The influence of age and sexual factors, and of the infection by the bovine leukosis virus

    OpenAIRE

    Gregory, L.; Birgel Junior, E.H.; Mirandola, R.M.S.; Araújo, W.P.; Birgel, E.H.

    1999-01-01

    Com o objetivo de estabelecer os valores de referência de parâmetros bioquímicos que avaliem a função hepática, por meio da determinação da atividade enzimática da aspartato-aminotransferase (AST) e da gama-glutamiltransferase (GGT), de bovinos da raça Jersey, criados no Estado de São Paulo, bem como avaliar a influência dos fatores etários, sexuais e da infecção pelo vírus da leucose dos bovinos sobre os referidos parâmetros bioquímicos, foram colhidas e examinadas amostras de soro sangüíneo...

  11. Genetically elevated gamma-glutamyltransferase and Alzheimer's disease.

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    Kunutsor, Setor K; Laukkanen, Jari A; Burgess, Stephen

    2018-03-02

    Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associated with GGT in a previous genome-wide association study on liver enzymes as instruments. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR. The odds ratio of AD was 1.09 (95% confidence interval, 0.98 to 1.22; p = 0.10) per one standard deviation genetically elevated GGT based on all 26 SNPs. The results were similar in both MR-Egger and weighted median MR methods. Overall, our findings cannot confirm a strong causal effect of GGT on AD risk. Further MR investigations using individual-level data are warranted to confirm or rule out causality. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

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    Gerald Koenig

    2015-01-01

    Full Text Available Gamma-glutamyltransferase (GGT is a well-established serum marker for alcohol-related liver disease. However, GGT’s predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS, and all-cause mortality. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethnic categories. Here, we examine the relationship of GGT to other serum markers such as serum ferritin (SF levels, and we suggest a link to exposure to environmental and endogenous toxins, resulting in oxidative and nitrosative stress. We observe a general upward trend in population levels of GGT over time, particularly in the US and Korea. Since the late 1970s, both GGT and incident MetS and its related disorders have risen in virtual lockstep. GGT is an early predictive marker for atherosclerosis, heart failure, arterial stiffness and plaque, gestational diabetes, and various liver diseases, including viral hepatitis, other infectious diseases, and several life-threatening cancers. We review literature both from the medical sciences and from life insurance industries demonstrating that serum GGT is a superior marker for future disease risk, when compared against multiple other known mortality risk factors.

  13. Valores de referência da atividade enzimática da aspartato-aminotransferase e da gama-glutamiltransferase em bovinos da raça Jersey. Influência dos fatores etários, sexuais e da infecção pelo vírus da leucose dos bovinos Reference values of the enzymatic activities of the aspartate aminotransferase and gamma glutamyltransferase of Jersey breed. The influence of age and sexual factors, and of the infection by the bovine leukosis virus

    Directory of Open Access Journals (Sweden)

    L. Gregory

    1999-12-01

    Full Text Available Com o objetivo de estabelecer os valores de referência de parâmetros bioquímicos que avaliem a função hepática, por meio da determinação da atividade enzimática da aspartato-aminotransferase (AST e da gama-glutamiltransferase (GGT, de bovinos da raça Jersey, criados no Estado de São Paulo, bem como avaliar a influência dos fatores etários, sexuais e da infecção pelo vírus da leucose dos bovinos sobre os referidos parâmetros bioquímicos, foram colhidas e examinadas amostras de soro sangüíneo de 170 animais, sendo 106 fêmeas e 17 machos, considerados clinicamente sadios e não reagentes ao antígeno glicoprotéico (gp51 da cápsula do vírus da leucose dos bovinos e 47 fêmeas soro-reagentes ao mencionado vírus. Os valores de referência obtidos para a AST foram iguais a 33,91±10,99U/l enquanto para a GGT obtiveram-se valores médios de 13,21±12,72U/l. A avaliação dos resultados demonstrou que as transaminases sofreram influência dos fatores etários, pois comprovou-se que os teores séricos da AST aumentaram significativamente com o evoluir da idade, sendo o valor mínimo observado nas bezerras com até 3 meses de idade (26,39±22,17U/l e valor máximo em vacas com idade entre 48 e 72 meses de idade (38,60±11,24U/l. Para os níveis séricos da GGT observou-se que nas bezerras com até 3 meses de idade os níveis séricos (31,15±38,70U/l foram maiores do que os observados nos animais mais velhos (entre 8,70±2,40U/l e 14,24±10,37U/l. Nesta pesquisa não foram observadas influências dos fatores sexuais e da infecção pelo vírus da leucose dos bovinos sobre a atividade enzimática das transaminases.With the purpose of having the reference values established for the biochemical parameters which evaluate the hepatic function through the determination of the enzymatic activities of the aspartate aminotransferase (AST and gamma glutamyltransferase (GGT of Jersey breed, raised in the São Paulo State, as well as, to

  14. Gamma-glutamyltransferase, possible novel biomarker in colon diverticulosis: a case-control study.

    Science.gov (United States)

    Bălăeţ, Constantin; Coculescu, Bogdan Ioan; Manole, Gheorghe; Bălăeţ, Maria; Dincă, Gabi Valeriu

    2018-12-01

    The gamma-glutamyltransferase (GGT) is recognized in medical practice as a useful indicator for the detection of liver lesions, especially those induced by the excessive consumption of alcoholic or cholesterol-associated drinks. The present study, although it includes a very small number of cases diagnosed with colon diverticulosis-diverticulitis associated with polyposis at the same intestinal level, identifies the presence of increased circulating concentrations of this enzyme in the serum. Its serum levels are tracked "dynamically" throughout a year after the diagnosis and start of the therapy. The study calls into question the release of the enzyme from the edge of the enterocytes' brush-like edge, leading to the pathogenic disturbance of regional redox homeostasis. The hypothesis gives the circulating values of GGT predictive value for cellular oxidative stress, as well as for indirectly expressing the glutathione level in cytosol.

  15. Comparison of gamma glutamyltransferase in normal and in type 2 diabetics

    International Nuclear Information System (INIS)

    Iqbal, A.

    2010-01-01

    Objective: Comparison of gamma glutamyltransferase in normal and type 2 diabetics. Methods: In a cross-sectional study, 100 apparently normal healthy subjects and, 47 type 2 diabetic subjects were selected from either sex with ages between 18-65 years. Subjects were measured for waist/hip ratio, BMI and serum levels of ALT, AST, Alk Phosphatase and Glutamyl Transferase (GGT). The study excluded by screening for Anti HCV, HBsAg and patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), GGT levels more than three times the normal and subject with a total leukocyte count more than 10,000/ mu l. Results: The levels of GGT levels were found to be most significant among all the liver enzymes (P = 0.001). The levels of GGT compared with type 2 diabetics was found to be significantly increased when compared with BMI, waist/circumference, cholesterol, triglycerides (TG), High Density Lipoprotein (HDL), Low density Lipoprotein (LDL), fasting blood sugar level and blood pressure (P = 0.001). The pearson regression analysis showed a positive relation with systolic, diastolic blood pressure and fasting blood sugar. Conclusion: These results indicate that levels of GGT were raised with increased waist girth, BMI, blood pressure TG and low HDL, all of these are the features of metabolic syndrome according to ATP III criteria. Hence, serum GGT may be an important investigation for diabetes and metabolic syndrome. (author)

  16. The association of plasma cysteine and gamma-glutamyltransferase with BMI and obesity.

    LENUS (Irish Health Repository)

    Elshorbagy, Amany K

    2009-07-01

    We recently reported a strong positive association of plasma total cysteine (tCys) with fat mass in over 5,000 subjects. As gamma-glutamyltransferase (GGT) enzyme increases cysteine availability by catalyzing glutathione breakdown and is positively associated with BMI and adiposity, we hypothesized that GGT might explain the association of tCys with adiposity. To study whether the associations of tCys and serum GGT with BMI and obesity were interrelated we conducted a cross-sectional study using data from 1,550 subjects recruited from nine European countries in the COMAC project. Multiple linear and logistic regression models and concentration-response curves were used. In age and sex-adjusted analyses, tCys showed strong positive associations with BMI (partial r = 0.19, P < 0.001), and obesity (odds ratio (OR) for 4th vs. 1st tCys quartile: 2.8; 95% confidence interval: 1.6-5.0, P < 0.001), both of which remained robust after adjustment for GGT and other metabolic and lifestyle confounders. Serum GGT was also a positive predictor of BMI (partial r = 0.17, P < 0.001) and obesity (OR for 4th vs. 1st GGT quartile: 4.8; 95% confidence interval: 2.5-9.2, P < 0.001), independent of tCys. However, the associations of GGT with BMI and obesity were weakened by adjustment for obesity-related factors such as serum lipids and blood pressure. These results indicate that tCys is a strong positive predictor of BMI and obesity, independent of GGT and other obesity-related factors. We also suggest that the association of serum GGT with BMI and obesity is unrelated to the role of GGT in cysteine turnover. The potential link between cysteine and fat metabolism should be further evaluated.

  17. Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Yue-Feng Wen

    Full Text Available Gamma-glutamyltransferase (GGT is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC.Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L. The association of pretherapeutic serum GGT levels with clinical-pathological parameters was examined. Univariate and multivariate survival analyses were performed.The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001. Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007 times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001 times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001 times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001 times the risk of metastasis compared with those in the low-risk GGT group.The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant metastasis-free survival in patients

  18. Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study.

    Science.gov (United States)

    Ceriotti, Ferruccio; Henny, Joseph; Queraltó, Josep; Ziyu, Shen; Özarda, Yeşim; Chen, Baorong; Boyd, James C; Panteghini, Mauro

    2010-11-01

    Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 μkat/L), allowing a single RI of 11-34 U/L (0.18-0.57 μkat/L) to be defined. Interregional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 μkat/L) for females and 9-59 U/L (0.15-0.99 μkat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 μkat/L) for females and 12-68 U/L (0.20- 1.13 μkat/L) for males, respectively. For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is

  19. Assessement of glycaemia and serum activities of aspartate aminotransferase, creatinekinase, gamma glutamyltransferase and lactate dehydrogenase in thoroughbred horses submitted to exercise of different intensities/ Avaliação da glicemia e da atividade sérica de aspartato aminotransferase, creatinoquinase, gama-glutamiltransferase e lactato desidrogenase em eqüinos puro sangue inglês (PSI submetidos a exercícios de diferentes intensidades

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    Joandes Henrique Fonteque

    2005-06-01

    Full Text Available In order to evaluate the influence of exercise of different intensities on biochemical parameters in Thoroughbred horses blood was collected from 60 animals, 30 males and 30 females.The animals were subdivided in two groups : 30 horses, 15 males and 15 females with 24 to 36 months of age and not in training, and after 12 months of training; 30 horses, 15 males and 15 females with 36 to 48 months of age in training. Blood samples were collected before and after trot and gallop. Plasmatic glucose was analyzed through a colorimetric method, while aspartate aminotransferase (AST, creatine kinase (CK, lactate dehydrogenase (LDH and gammaglutamyltransferase (GGT were analyzed through kinetic methods. Results show a statistically significant increase in plasmatic glucose after trot and gallop independent of gender, while the increases in CK and LDH were different for males and females. Variations for AST and GGT were not statistically significant.O objetivo do presente estudo foi avaliar as alterações na bioquímica sérica em eqüinos PSI submetidos a exercícios de diferentes intensidades. Foram colhidas amostras de sangue de 60 eqüinos PSI, distribuídos nos seguintes grupos: 30 animais sendo 15 machos e 15 fêmeas, com idade de 24 a 36 meses, não submetidos a treinamento e após um período de 12 meses de treinamento e 30 eqüinos de 36 a 48 meses, em fase de treinamento, antes e após o trote . Dos animais de 36 a 48 meses foram selecionados 20 machos e 10 fêmeas e colhido sangue antes e após o galope. Determinou-se, por métodos colorimétricos, os valores da glicose plasmática e, por métodos cinéticos, as enzimas aspartato aminotransferase (AST, creatinoquinase (CK, lactato desidrogenase (LDH e gama-glutamiltransferase (GGT. A análise estatística dos resultados comprovou a ocorrência de aumento significativo (p < 0,05 dos valores da glicose plasmática após o trote e galope para ambos os sexos. Para as enzimas CK e LDH ocorreram

  20. Lack of a relationship between circulating gamma-glutamyltransferase levels and carotid intima media thickness in hypertensive and diabetic patients.

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    Nuti, Marco; Spontoni, Paolo; Grigoratos, Chrysanthos; Dell'Omo, Giulia; Balbarini, Alberto; Pedrinelli, Roberto

    2012-01-01

    By increasing the intracellular prooxidant burden, gamma-glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That noxious influence may be reflected by circulating enzyme levels, a correlate of cardiovascular risk factors, and a predictor of incident events. To evaluate this hypothesis, we tested the association between circulating GGT and common carotid intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic involvement, in a large and well-characterized group of patients at risk of cardiovascular disease (CVD). This study analyzed 548 patients with hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with known hepatic disease and abnormal GGT values were excluded. CIMT (B-mode ultrasonography) values were the mean of four far-wall measurements at both common carotids. Metabolic syndrome (MetS) was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent sex-related differences in GGT levels, the data were analyzed separately in males and females in samples dichotomized by the median. The age-adjusted CIMT values did not differ by GGT levels in males or females. In contrast, the carotid wall was consistently thicker in patients with a history of CVD and MetS independent of age and concurrent GGT values. In both sexes, GGT was associated with key components of the MetS such as triglycerides, fasting plasma glucose, and body mass index. The data collected in this mixed group of hypertensive and/or diabetic patients with widely prevalent history of CVD do not support the concept of a direct pathophysiological link between GGT levels within reference limits and atherosclerotic involvement.

  1. Lack of a relationship between circulating gamma-glutamyltransferase levels and carotid intima media thickness in hypertensive and diabetic patients

    Science.gov (United States)

    Nuti, Marco; Spontoni, Paolo; Grigoratos, Chrysanthos; Dell’Omo, Giulia; Balbarini, Alberto; Pedrinelli, Roberto

    2012-01-01

    Background By increasing the intracellular prooxidant burden, gamma-glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That noxious influence may be reflected by circulating enzyme levels, a correlate of cardiovascular risk factors, and a predictor of incident events. To evaluate this hypothesis, we tested the association between circulating GGT and common carotid intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic involvement, in a large and well-characterized group of patients at risk of cardiovascular disease (CVD). Patients This study analyzed 548 patients with hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with known hepatic disease and abnormal GGT values were excluded. Methods CIMT (B-mode ultrasonography) values were the mean of four far-wall measurements at both common carotids. Metabolic syndrome (MetS) was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent sex-related differences in GGT levels, the data were analyzed separately in males and females in samples dichotomized by the median. Results The age-adjusted CIMT values did not differ by GGT levels in males or females. In contrast, the carotid wall was consistently thicker in patients with a history of CVD and MetS independent of age and concurrent GGT values. In both sexes, GGT was associated with key components of the MetS such as triglycerides, fasting plasma glucose, and body mass index. Conclusion The data collected in this mixed group of hypertensive and/or diabetic patients with widely prevalent history of CVD do not support the concept of a direct pathophysiological link between GGT levels within reference limits and atherosclerotic involvement. PMID:22661894

  2. Atividade sérica das enzimas AST, CK e GGT em cavalos Crioulos AST, CK and GGT enzymes serum activities in Crioulo horses

    Directory of Open Access Journals (Sweden)

    Carina Franciscato

    2006-10-01

    Full Text Available O objetivo deste trabalho foi verificar a influência da idade, sexo, manejo e estado gestacional sobre a atividade sérica das enzimas: aspartato aminotransferase (AST, creatina quinase (CK e gama-glutamiltransferase (GGT em cavalos da raça Crioula. Foram utilizados 142 eqüinos, divididos em seis grupos: potros até um ano de idade; cavalos adultos em regime de atividade livre; cavalos adultos em treinamento; machos adultos; fêmeas não gestantes; fêmeas gestantes. O valor da CK foi mais elevado em animais adultos do que em potros, o mesmo tendo ocorrido em animais em atividade livre, comparados a animais em treinamento. Fêmeas não gestantes apresentaram valores das enzimas CK e GGT maiores que os machos; o valor da CK em fêmeas gestantes foi mais elevado do que em fêmeas não gestantes. A idade, o sexo, o manejo e o estado gestacional influenciam a atividade sérica da CK, e o sexo influencia a atividade sérica da GGT.The objective of this work was to evaluate the influence of age, sex, management and pregnancy status on aspartate aminotransferase (AST, creatine kinase (CK and gamma-glutamyltransferase (GGT enzymes serum activities of Crioulo horses. One hundred and forty-two horses, divided into six group were analyzed: yearlings; free activity of adult horses; training adult horses; male adult horses; nonpregnant and pregnant females. The CK enzyme activity value was higher in adult horses than in yearlings, and the same result was found when comparing free activity and training horses. Nonpregnant females had higher values for CK and GGT comparing to male horses, and CK values were higher in pregnant comparing to nonpregnant females. Age, sex, management and pregnancy status influence on CK serum activity, and sex influences on GGT serum activity.

  3. Relationship between alcohol drinking and aspartate aminotransferase:alanine aminotransferase (AST:ALT) ratio, mean corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), and apolipoprotein A1 and B in the U.S. population.

    Science.gov (United States)

    Liangpunsakul, Suthat; Qi, Rong; Crabb, David W; Witzmann, Frank

    2010-03-01

    The misuse of alcohol, even at levels just above two drinks per day, is a public health problem, but identifying patients with this potentially unhealthy drinking is hindered by the lack of tests. Several blood tests, such as those testing for gamma-glutamyl transpeptidase (GGT) or mean corpuscular volume (MCV), are among the commonly used markers to identify very heavy drinking, but combinations of these markers have rarely been tested in lighter drinkers. We examined the relationship between alcohol drinking and the levels of these markers in a national population-based study composed primarily of lighter drinkers. Data were analyzed from 8,708 adult participants in the third U.S. National Health and Nutrition Examination Survey after excluding subjects with iron overload; with hepatitis B and C; who were pregnant; and who were taking prescription drugs such as phenytoin (Dilantin), barbiturates, and hydroxyurea (Droxia and Hydrea). The relationship between the amount of alcohol drinking and GGT, aspartate aminotransferase:alanine aminotransferase ratio, MCV of erythrocytes, and apolipoprotein A1 and B were analyzed and adjusted for potential liver injury risk factors. The prevalence of unhealthy alcohol drinking (defined as consumption of more than two standard drinks per day) was 6.7%. Heavier drinkers tended to be younger and reported an average of 4.2 drinks per day. When tested alone or in combination, the sensitivity and positive predictive values for these blood tests were too low to be clinically useful in identifying the subjects in the heavier drinking category. In this large, national, population-based study, the markers of heavy drinking studied here, either alone or in combination, did not appear to be useful in identifying unhealthy drinking. More work is needed to find the novel marker(s) associated with risky alcohol drinking.

  4. Relationship Between Alcohol Drinking and Aspartate Aminotransferase:Alanine Aminotransferase (AST:ALT) Ratio, Mean Corpuscular Volume (MCV), Gamma-Glutamyl Transpeptidase (GGT), and Apolipoprotein A1 and B in the U.S. Population*

    Science.gov (United States)

    Liangpunsakul, Suthat; Qi, Rong; Crabb, David W.; Witzmann, Frank

    2010-01-01

    Objective: The misuse of alcohol, even at levels just above two drinks per day, is a public health problem, but identifying patients with this potentially unhealthy drinking is hindered by the lack of tests. Several blood tests, such as those testing for gamma-glutamyl transpeptidase (GGT) or mean corpuscular volume (MCV), are among the commonly used markers to identify very heavy drinking, but combinations of these markers have rarely been tested in lighter drinkers. We examined the relationship between alcohol drinking and the levels of these markers in a national population-based study composed primarily of lighter drinkers. Method: Data were analyzed from 8,708 adult participants in the third U.S. National Health and Nutrition Examination Survey after excluding subjects with iron overload; with hepatitis B and C; who were pregnant; and who were taking prescription drugs such as phenytoin (Dilantin), barbiturates, and hydroxyurea (Droxia and Hydrea). The relationship between the amount of alcohol drinking and GGT, aspartate aminotransferase:alanine aminotransferase ratio, MCV of erythrocytes, and apolipoprotein A1 and B were analyzed and adjusted for potential liver injury risk factors. Results: The prevalence of unhealthy alcohol drinking (defined as consumption of more than two standard drinks per day) was 6.7%. Heavier drinkers tended to be younger and reported an average of 4.2 drinks per day. When tested alone or in combination, the sensitivity and positive predictive values for these blood tests were too low to be clinically useful in identifying the subjects in the heavier drinking category. Conclusions: In this large, national, population-based study, the markers of heavy drinking studied here, either alone or in combination, did not appear to be useful in identifying unhealthy drinking. More work is needed to find the novel marker(s) associated with risky alcohol drinking. PMID:20230722

  5. Association between plasma gamma-glutamyltransferase fractions and metabolic syndrome among hypertensive patients.

    Science.gov (United States)

    Franzini, Maria; Scataglini, Ilenia; Ricchiuti, Angelo; Fierabracci, Vanna; Paolicchi, Aldo; Pompella, Alfonso; Dell'Omo, Giulia; Pedrinelli, Roberto; Corti, Alessandro

    2017-09-20

    Among the risk factors associated to metabolic syndrome (MetS), hypertension shows the highest prevalence in Italy. We investigated the relationship between the newly identified serum γ-glutamyltransferase (GGT) fractions, b- s- m- f-GGT, and risk factors associated to MetS in hypertensive patients. A total of ninety-five consecutive hypertensive patients were enrolled. GGT fractions were analysed by gel-filtration chromatography, and hepatic steatosis was evaluated by ultrasound. MetS was diagnosed in 36% of patients. Considering the whole group, b- and f-GGT showed the highest positive correlation with BMI, glucose, triglycerides and insulin, and the highest negative correlation with HDL cholesterol. While both serum triglycerides and insulin were independently associated with b-GGT levels, only triglycerides were independently associated with f-GGT. The values of b-GGT activity increased with steatosis grade (g0 = 1.19; g2 = 3.29; ratio g2/g0 = 2.75, p < 0.0001 linear trend). Patients with MetS showed higher levels of b-GGT, m-GGT and f-GGT [median (25 th -75 th ) U/L: 3.19 (1.50-6.59); 0.55 (0.26-0.81); 10.3 (9.1-13.6); respectively] as compared to subjects presenting with one or two MetS criteria [1.75 (0.95-2.85), p < 0.001; 0.33 (0.19-0.60), p < 0.05; 8.8 (7.0-10.6), p < 0.001]. Our data point to a potential role for b- and f-GGT fractions in identifying MetS patients among hypertensive subjects, thus providing a minimally invasive blood-based tool for MetS diagnosis.

  6. Serum Gamma - Glutamyltransferase Is Associated with Albuminuria: A Population-Based Study

    Science.gov (United States)

    Lin, Diaozhu; Qi, Yiqin; Xu, Mingtong; Li, Na; Huang, Chulin; Ren, Meng; Li, Yan; Yan, Li

    2014-01-01

    Background Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population. Materials and Methods We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion. Results The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend albuminuria and 1.55 (95% CI, 1.18–2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05). Conclusion Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese. PMID:25500578

  7. Biomarkers of Oxidative Stress and Personalized Treatment of Pulmonary Tuberculosis: Emerging Role of Gamma-Glutamyltransferase

    Directory of Open Access Journals (Sweden)

    Etienne Mokondjimobe

    2012-01-01

    Full Text Available Background. The objectives were (i to evaluate the impact of acute pulmonary tuberculosis (PTB and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7±5.8 years with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n=1 developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR.

  8. Relationship between elevated serum gamma-glutamyltransferase activity and slow coronary flow

    DEFF Research Database (Denmark)

    Sen, Nihat; Ozlü, Mehmet F; Basar, Nurcan

    2009-01-01

    . The results were compared with those of a control group consisting of 86 age- and sex-matched patients who had normal coronary arteries and normal coronary flow. RESULTS: The three groups were similar with respect to body mass index, presence of hypertension and diabetes mellitus, lipid profiles, and fasting...... was found as the only independent predictor of the mean TFC (beta=0.309; pphysiopathologic role of serum GGT activity in SCF....

  9. Monitoring of milk production and total cholesterol concentration, gamma-glutamyltransferase, and glutathione peroxidase in Simmental cows blood

    Directory of Open Access Journals (Sweden)

    Terezija Silvija Marenjak

    2007-06-01

    Full Text Available Milk production, total blood cholesterol concentration and activity ofgamma-glutamyl-transferase (GGT and glutation peroxidase (GPx in blood of Simmental cows was monitored during two control periods (first control period - May 2004; second control period - June 2004. The objective was to determine a relationship between milk production and particular blood parameters, and their possible implementation as an indicator of milk production. Twelve Simmental cows from small-scale dairy farm in Zagreb County were included in the study. Cows originated from the same herd andwere roughly of the same parity and stage of lactation. The average milk production and total blood cholesterol concentration were significantly higher in May then in June (20,55 L/d vs. 15,44 L/d; 4,55 mmol/L vs. 3,96 mmol/L, respectively, whereas the GPx and GGT activity was significantly lower in May in comparison with June (GPx=1720,66 U/L vs. GPx=1808 U/L, and GGT = 20,11 U/L vs. 23,22 U/L, respectively. A positive correlation between the milk production and the total blood cholesterol level was detected (r=0,58. The total blood cholesterol concentration in the blood plasma mighthave been one of the indicators of production performance in the Simmental cows herd, whereas the activity of stated enzymes may specify the nutritional status thereof the milk production depends on.

  10. Gamma-glutamyl transpeptidase (GGT) blood test

    Science.gov (United States)

    ... ency/article/003458.htm Gamma-glutamyl transferase (GGT) blood test To use the sharing features on this page, please enable JavaScript. The gamma-glutamyl transferase (GGT) blood test measures the level of the enzyme GGT in ...

  11. Individual differences in plasma ALT, AST and GGT: contributions of genetic and environmental factors, including alcohol consumption.

    Science.gov (United States)

    Whitfield, J B; Martin, N G

    1985-01-01

    The causes of individuality of the plasma enzymes alanine aminotransferase (ALT; EC 2.6.1.2), aspartate aminotransferase (AST; EC 2.6.1.1) and gamma-glutamyl transferase (GGT; EC 2.3.2.2) were investigated in a study of 206 pairs of twins. Between-person variance was greater in men than women, while within-person variation was similar in both sexes. Plasma ALT and AST levels were affected by genetic factors, while GGT was affected by some environmental factor shared by co-twins. In the men, alcohol intake had a significant but small effect on all three enzyme levels, and since alcohol consumption was highly heritable, this appeared as a genetic influence on enzyme activities. The major factors involved in the observed correlations between these enzymes were a non-shared environmental factor other than alcohol affecting ALT, AST and GGT, and a genetic factor affecting only ALT and AST.

  12. Serum γ-Glutamyltransferase, Alanine Aminotransferase and Aspartate Aminotransferase Activity in Healthy Blood Donor of Different Ethnic Groups in Gorgan.

    Science.gov (United States)

    Marjani, Abdoljalal; Mehrpouya, Masoumeh; Pourhashem, Zeinab

    2016-07-01

    Measure of liver enzymes may help to increase safety of blood donation for both blood donor and recipient. Determination of liver enzymes may prepare valuable clinical information. To assess serum γ-Glutamyltransferase (GGT), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) activities in healthy blood donors in different ethnic groups in Gorgan. This study was performed in 450 healthy male blood donors, in three ethnic groups (Fars, Sistanee and Turkman) who attended Gorgan blood transfusion center. Liver enzymes (GGT, ALT and AST) were determined. Serum AST and ALT in three ethnic groups were significant except for serum GGT levels. There was significant correlation between family histories of liver disease and systolic blood pressure and AST in Fars, and GGT in Sistanee ethnic groups. Several factors, such as age, family history of diabetes mellitus, family history of liver disease and smoking habit had no effect on some liver enzymes in different ethnic groups in this area. Variation of AST, ALT, and GGT enzyme activities in healthy subjects was associated with some subjects in our study groups. According to our study, it suggests that screening of AST and GGT enzymes in subjects with family history of liver disease is necessary in different ethnic groups.

  13. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S

    2002-01-01

    It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated...

  14. Vanadium air-pollution - a cause of malabsorption and immunosuppression in cattle

    CSIR Research Space (South Africa)

    Gummow, B

    1994-12-01

    Full Text Available blood was collected for the determination of the following parameters: Total serum protein (TSP) Albumin (Alb) Globulin (Glob) Blood-urea nitrogen (BUN) Gamma-glutamyltransferase (GGT) Aspartate aminotransferase (AST) Creatine phosphokinase (CK... TSP levels were probably as a result of low levels of both alb and glob. This would occur with protein losing enteropathies, malabsorption, malnutrition or chronic liver disease together with immunodeficiency and/or failure of passive colostral...

  15. New pediatric percentiles of liver enzyme serum levels (ALT, AST, GGT): Effects of age, sex, BMI and pubertal stage.

    Science.gov (United States)

    Bussler, Sarah; Vogel, Mandy; Pietzner, Diana; Harms, Kristian; Buzek, Theresa; Penke, Melanie; Händel, Norman; Körner, Antje; Baumann, Ulrich; Kiess, Wieland; Flemming, Gunter

    2017-09-19

    The present study aims to clarify the effects of sex, age, BMI and puberty on transaminase serum levels in children and adolescents and to provide new age- and sex-related percentiles for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). Venous blood and anthropometric data were collected from 4,126 cases. Excluded were cases of participants with potential hepatotoxic medication, with evidence of potential illness at the time of blood sampling and non-normal BMI (BMI  90 th ). The resulting data (N = 3,131 cases) were used for the calculations of ALT, AST, and GGT percentiles. Age- and sex-related reference intervals were established by using an LMSP-type method. Serum levels of transaminases follow age-specific patterns and relate to the onset of puberty. This observation is more pronounced in girls than in boys. The ALT percentiles showed similar shaped patterns in both sexes. Multivariate regression confirmed significant effects of puberty and BMI-SDS (β = 2.21) on ALT. Surprisingly, AST serum levels were negatively influenced by age (β = -1.42) and BMI-SDS (β = -0.15). The GGT percentiles revealed significant sex-specific differences, correlated positively with age (β = 0.37) and showed significant association with BMI-SDS (β = 1.16). Current reference values of ALT, AST and GGT serum levels were calculated for children between 11 months and 16.0 years, using modern analytical and statistical methods. This study extends the current knowledge about transaminases by revealing influences of age, sex, BMI, and puberty on the serum concentrations of all three parameters and has for these parameters one of the largest sample sizes published so far. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  16. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S

    2002-01-01

    It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated...... with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat...... 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO...

  17. Aspartate aminotransferase (AST) blood test

    Science.gov (United States)

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

  18. Feasibility of alanine aminotransferase/aspartate aminotransferase ratio in predicting hepatic steatosis in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    ZHANG Xiuli

    2017-06-01

    Full Text Available ObjectiveTo investigate the feasibility of alanine aminotransferase (ALT/aspartate aminotransferase (AST ratio in predicting the degree of hepatic steatosis in chronic hepatitis C (CHC patients. MethodsA total of 231 CHC patients who visited The First People′s Hospital of Nanyang from May 2012 to June 2016 were enrolled, among whom 105 (45.45% had nonalcoholic fatty liver disease (NAFLD and 126 (54.55% did not have NAFLD. According to the ultrasound score, the NAFLD group was divided into mild-to-moderate (1-2 points hepatic steatosis group(n=67 and severe (3 points hepatic steatosis group(n=38. The two groups were compared in terms of demographic data and disease data including creatinine, fasting blood glucose, ALT, AST, ALT/AST ratio, γ-glutamyltransferase (GGT, uric acid, low-density lipoprotein, high-density lipoprotein (HDL, cholesterol (CHO, and triglyceride (TG to screen out independent risk factors for NAFLD in CHC patients. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; with severe NAFLD as the dependent variable, different factors were introduced into the logistic regression equation to screen out independent risk factors. ResultsCompared with the non-NAFLD group, the NAFLD group had significantly higher systolic pressure, diastolic pressure, fasting blood glucose, ALT/AST ratio, and levels of ALT, GGT, HDL, CHO, and TG, as well as a significantly higher proportion of patients with diabetes, hypertension, or metabolic syndrome (all P<0.05. Compared with the severe hepatic steatosis group, the mild-to-moderate hepatic steatosis group had significantly lower systolic pressure, diastolic pressure, fasting blood glucose, ALT/AST ratio, and levels of ALT, GGT, HDL, CHO, and TG, as

  19. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels: Evidence for correlated genetic effects

    NARCIS (Netherlands)

    van Beek, J.H.D.A.; de Moor, M.H.M.; Geels, L.M.; Sinke, M.R.T.; de Geus, E.J.C.; Lubke, G.H.; Kluft, C.; Neuteboom, J.; Vink, J.M.; Willemsen, G.; Boomsma, D.I.

    2014-01-01

    Background: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT

  20. Gamma-glutamyltranspeptidase (GGT) in experimental liver cirrhosis induced by thioacetamide: a biochemical and enzymehistochemical study.

    Science.gov (United States)

    Kretzschmar, M; Machnik, G; Oesterle, D; Zimmermann, T; Klinger, W

    1991-01-01

    Micro- and macronodular experimental cirrhosis-like liver lesion was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months. The activity of gamma-glutamyltranspeptidase (GGT) and the distribution pattern of this enzyme within the liver structure were investigated 14 d after withdrawal of TAA in comparison to neonatal and adult normal liver. GGT activity was extremely high at birth. Chronic TAA administration led to a strong increase in hepatic GGT activity in dependence on duration of TAA administration in comparison to adult controls. In accordance to these results we observed by enzyme-histochemistry a small to moderate hepatocellular GGT activity after 3 months of TAA treatment. GGT activity was also demonstrable in epithelia of proliferated ductuli biliferi of single enlarged portal tracts. After 6 months of TAA administration the hepatocellular GGT activity was moderate to strong. It was demonstrable both in parenchymal (preneo-plastic) nodules and in cholangiocellular/cholangioductular proliferates. A GGT activity of mesenchymal cells was not demonstrable. We conclude that the increased hepatic GGT activity after chronic TAA administration can be correlated with the process of development of preneoplastic nodules. A relation between increased GGT activity and the process of cirrhogenesis does not seem to be probable in this animal cirrhosis model.

  1. Blood markers of alcohol use in epistaxis patients.

    Science.gov (United States)

    Soyka, Michael B; Schrepfer, Thomas; Holzmann, David

    2012-08-01

    Epistaxis and alcohol overconsumption are frequently encountered in patients admitted to emergency wards. The aim of the study was to analyze indirect markers of alcohol overconsumption in epistaxis patients and evaluate its role as a risk factor. In a cohort of 510 epistaxis patients indirect markers of alcohol overuse were measured including the mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase and alanine aminotransferase. The results were compared to the normal findings in literature. Pathologic mean levels of GGT were found in epistaxis patients. Almost 5% had macrocytosis and MCV correlated positively with liver enzyme levels. Platelet counts were negatively correlated with both corpuscular volumes and liver enzymes. Indirect markers of alcohol overconsumption were found to be elevated in epistaxis patients. These results suggest that a subgroup of epistaxis patients overconsumes alcoholic beverages supporting the idea of alcohol abuse being a risk factor in epistaxis. Questioning about drinking habits should be employed and help offered to affected patients.

  2. The Genetic Architecture of Liver Enzyme Levels: GGT, ALT and AST

    NARCIS (Netherlands)

    van Beek, J.H.D.A.; de Moor, M.H.M.; de Geus, E.J.C.; Lubke, G.H.; Vink, J.M.; Willemsen, G.; Boomsma, D.I.

    2013-01-01

    High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often

  3. The genetic architecture of liver enzyme levels: GGT, ALT and AST

    NARCIS (Netherlands)

    Beek, J.H.D.H. van; Moor, M.H.M. de; Geus, E.J.C. de; Lubke, G.H.; Vink, J.M.; Willemsen, G.; Boomsma, D.I.

    2013-01-01

    %High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often

  4. Rule of changes in serum GGT levels and GGT/ALT and AST/ALT ratios in primary hepatic carcinoma patients with different AFP levels.

    Science.gov (United States)

    Yang, Jian-Gong; He, Xiao-Feng; Huang, Bing; Zhang, Hui-Ai; He, Yong-Kang

    2017-12-22

    This study aims to explore the rule of changes in serum GGT activity, as well as GGT/ALT and AST/ALT ratios, in primary hepatic carcinoma (PHC) patients with different alpha-fetal protein (AFP) levels. GGT, AST and ALT were detected in 370 PHC patients with positive HBs-Ag using a automatic biochemical analyzer, and AFP was detected using a Roche E170 modular analytics immunoassay analyzer. GGT level, as well as AST/ALT and GGT/ALT, ratios were compared among PHC patients with different AFP levels. As shown in Table 1, GGT levels were 109.59 ± 111.06, 151.13 ± 190.43, 135.86 ± 107.62, 151.36 ± 176.59 and 172.58 ± 188.84, respectively, in the groups of primary PHC patients with AFP levels of ⩽ 10, 10-100, 100-200, 200-400 and ⩾ 400 ng/ml; and the differences among these groups were not statistically significant (P> 0.05). AST/ALT ratios were 1.55 ± 1.02, 1.30 ± 0.81, 2.02 ± 1.89, 2.12 ± 1.11 and 1.73 ± 1.25, respectively; and the differences among these groups were not statistically significant (P> 0.05). GGT/ALT ratios were 3.43 ± 3.12, 3.57 ± 5.70, 3.57 ± 2.94, 3.89 ± 4.58 and 3.43 ± 3.61, respectively; and the differences among these groups were not statistically significant (P> 0.05). For patients with chronic hepatitis B and cirrhosis after hepatitis B, no matter how AFP level is, when liver function report reveals increased GGT, AST/ALT > 1 and GGT/ALT > 1 (that is, AST > ALT and GGT > ALT), even if AFP is negative, we should also be alert to the existence of PHC.

  5. The genetic architecture of liver enzyme levels: GGT, ALT and AST.

    Science.gov (United States)

    van Beek, Jenny H D A; de Moor, Marleen H M; de Geus, Eco J C; Lubke, Gitta H; Vink, Jacqueline M; Willemsen, Gonneke; Boomsma, Dorret I

    2013-07-01

    High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h(2) 60 %) and AST in both sexes (total h(2) 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age.

  6. The Genetic Architecture of Liver Enzyme Levels: GGT, ALT and AST

    OpenAIRE

    van Beek, Jenny H. D. A.; de Moor, Marleen H. M.; de Geus, Eco J. C.; Lubke, Gitta H.; Vink, Jacqueline M.; Willemsen, Gonneke; Boomsma, Dorret I.

    2013-01-01

    High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were ass...

  7. Circulating soluble CD36 is a novel marker of liver injury in subjects with altered glucose tolerance

    DEFF Research Database (Denmark)

    Fernández-Real, Jose-Manuel; Handberg, Aase; Ortega, Francisco

    2008-01-01

    ) and indicators of liver health. We evaluated a cohort of men from the general population (n=117). As expected, serum (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were associated positively with body mass index (BMI) and age and negatively with SI (minimal model method). Circulating...... sCD36 was positively associated with ALT, AST and GGT in subjects with altered glucose tolerance, but not in those with normal glucose tolerance. The difference in the slope of the relationships was significant (P=.01). Age, BMI and triglycerides (but not sCD36) contributed independently to 29......% of ALT variance in subjects with normal glucose tolerance. In contrast, SI and sCD36 contributed independently to 39% of ALT variance in subjects with altered glucose tolerance. The correlation between ALT activity and sCD36 was confirmed in an independent, replication study. In summary, circulating s...

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

  9. Determination of urinary GGT and ultrasonography Doppler in renal evaluation of anemic dogs

    Directory of Open Access Journals (Sweden)

    Suellen Ramos Barboza

    2016-06-01

    Full Text Available ABSTRACT. Barboza S.R., dos Santos R.V., Alves A., Rassele A.C., Dessaune Filho N., Barbosa T.S., Hiura E. & Machado F.M. [Determination of urinary GGT and ultrasonography Doppler in renal evaluation of anemic dogs.] Determinação da GGT urinária e ultrassonografia Doppler na avaliação renal de cães anêmicos. Revista Brasileira de Medicina Veterinária, 38(2:137-142, 2016. Setor de Clínica Médica de Animais de Pequeno Porte, Universidade Vila Velha, Av. Comissário José Dantas de Melo, 21, Boa Vista, Vila Velha, ES 29102-920, Brasil. Email: suellenramosvet@hotmail.com The anemia is the most common disorder in dogs erythrocytes, may cause acute renal failure, as the kidneys are very sensitive to ischemia, requiring extensive blood supply. Sonner the IRA induction phase is detected, the greater chance of success in the reversibility of the injury. The objective of this study was to analyze the behavior of GGT (gamma glutamyl transpeptidase urinary and renal blood flow from the Doppler ultrasound in order to detect tissue hypoxia in 21 anemic dogs of 8 months to 14 years old, who were divided into two groups according to the degree of anemia: Group I with moderate to severe anemia; and group II with mild anemia. In this experiment the degree of anemia little interference elimination urinary GGT; It was verified that the resistivity index was greater in animals with lower hematocrit; and that the greater the increased urinary elimination of GGT was the resistivity index.

  10. The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B.

    Science.gov (United States)

    Eminler, Ahmet Tarik; Irak, Kader; Ayyildiz, Talat; Keskin, Murat; Kiyici, Murat; Gurel, Selim; Gulten, Macit; Dolar, Enver; Nak, Selim Giray

    2014-08-01

    To investigate the relationship between gamma-glutamyl transpeptidase (GGT) levels and histopathological status determined by biopsy in patients with chronic hepatitis B and C. Patients with chronic hepatitis B and C who were referred to the Uludağ University Faculty of Medicine Gastroenterology outpatient clinic between January 2005-January 2011 and underwent liver biopsy were included in the study. Overall, 246 patients with hepatitis B and 151 patients with hepatitis C were enrolled. According to the evaluation based on the Ishak score, patients with a histological activity index (HAI) between 0-12 were defined as low activity, and those with an HAI between 13-18 were defined as high activity. In addition, patients with a fibrosis score of 0-2 were defined as low fibrosis, and those with a score between 3-6 were defined as high fibrosis; comparisons were made accordingly. In patients with hepatitis B, the mean GGT level was 38.86±42.4 (IU/L) in the low activity group and 60.44±44.4 (IU/L) in the high activity group (p<0.05). In hepatitis B patients, the mean GGT level was 26.89±14.83 (IU/L) in the low fibrosis group, whereas it was 65.60±59.7 (IU/L) in the high fibrosis group (p<0.001). There was no significant difference between HAI and fibrosis group with regard to GGT levels in the hepatitis C patients. In conclusion, it is proposed that in patients with chronic viral hepatitis, GGT levels can be taken into consideration to predict advanced histological liver damage, especially in patients with hepatitis B.

  11. Increased liver markers are associated with higher risk of type 2 diabetes.

    Science.gov (United States)

    Ko, Sun-Hye; Baeg, Myong Ki; Han, Kyung-Do; Ko, Seung-Hyun; Ahn, Yu-Bae

    2015-06-28

    To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG). A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers. The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829-5.622, P AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG. Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG.

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

    Directory of Open Access Journals (Sweden)

    LI Qiang

    2016-06-01

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

  13. Increased liver alkaline phosphatase and aminotransferase ...

    African Journals Online (AJOL)

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

  14. Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) Detection Techniques

    OpenAIRE

    Huang, Xing-Jiu; Choi, Yang-Kyu; Im, Hyung-Soon; Yarimaga, Oktay; Yoon, Euisik; Kim, Hak-Sung

    2006-01-01

    The levels of aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) in serum can help people diagnose body tissues especially the heart and the liver are injured or not. This article provides a comprehensive review of research activities that concentrate on AST/GOT and ALT/GPT detection techniques due to their clinical importance. The detection techniques include colorimetric, spectrophotometric, chemiluminescence, chromatography, fluorescence and UV absorbance, radioche...

  15. Alanine aminotransferase is more sensitive to the decrease in hepatitis B virus-DNA load than other liver markers in chronic hepatitis B patients.

    Science.gov (United States)

    Wang, Hua-Bin; Wang, Qiong-Yu; Yuan, Qing; Shan, Xiao-Yun; Fu, Guan-Hua

    2017-11-01

    A direct correlation between hepatitis B virus DNA (HBV-DNA) and liver markers has not been identified in chronic hepatitis B (CHB) patients. However, the effect of HBV-DNA changes on liver markers remains unclear. We explored the association between decreased HBV-DNA and liver makers in CHB patients. Chronic hepatitis B patients who visited Jinhua Central Hospital twice were selected for analysis. Finally, 171 participants with a 1-log reduction in HBV-DNA between the two visits were enrolled as the case group, and 158 participants with no significant changes in HBV-DNA were enrolled as the control group. There was no significant correlation between HBV-DNA and liver markers (P>.05). However, in longitudinal analysis, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) were significantly different between the two tests (P26 times, ALT was reduced by half or more. A similar trend was observed with a decrease of >63 times for AST and a decrease of >76 times for GGT. A large change in HBV-DNA can lead to a significant variation in liver markers. In particular, ALT was more sensitive than other liver markers to a reduction in HBV-DNA. © 2017 Wiley Periodicals, Inc.

  16. Effects of Omega-3 Fatty Acid in Nonalcoholic Fatty Liver Disease: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Wenxia Lu

    2016-01-01

    Full Text Available A meta-analysis was conducted to assess the effect of omega-3 fatty acid supplementation (n-3 PUFAs in lowering liver fat, liver enzyme (alanine aminotransferase (ALT, aspartate aminotransferase (AST, and gamma-glutamyltransferase (GGT levels, and blood lipids (triglyceride (TG, total cholesterol (TC, high density lipoprotein (HDL, and low density lipoprotein (LDL in patients with nonalcoholic fatty liver disease (NAFLD or nonalcoholic steatohepatitis (NASH. Methods. MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Science Citation Index (ISI Web of Science, Chinese Biomedical Literature Database (CBM, and Chinese National Knowledge Infrastructure (CNKI were searched for relevant randomized controlled trials on the effects of n-3 polyunsaturated fatty acids (PUFAs in patients with NAFLD from inception to May 2015. Ten studies were included in this meta-analysis. Results. 577 cases of NAFLD/NASH in ten randomized controlled trials (RCTs were included. The results of the meta-analysis showed that benefit changes in liver fat favored PUFA treatment, and it was also beneficial for GGT, but it was not significant on ALT, AST, TC, and LDL. Conclusions. In this meta-analysis, omega-3 PUFAs improved liver fat, GGT, TG, and HDL in patients with NAFLD/NASH. Therefore, n-3 PUFAs may be a new treatment option for NAFLD.

  17. Platelet Counts and Liver Enzymes after Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Hans-Erik Johansson

    2013-01-01

    Full Text Available Background. Obesity is characterized by liver steatosis, chronic inflammation, and increased liver enzymes, that is, gamma-glutamyltransferase (GGT and alanine aminotransferase (ALT, markers for nonalcoholic fatty liver disease (NAFLD and liver fat content. Increased platelet counts (PCs are associated with inflammatory conditions and are a valuable biomarker of the degree of fibrosis in NAFLD. We investigated alterations in PC, GGT, and ALT after biliopancreatic diversion with duodenal switch (BPD-DS and Roux-en-Y gastric bypass (RYGBP. Methods. Ten morbidly obese patients (body mass index, BMI: 53.5±3.8 kg/m2 who underwent BPD-DS were evaluated preoperatively (baseline and 1 year (1st followup and 3 years (2nd followup after surgery and compared with 21 morbidly obese patients (BMI: 42.3±5.2 kg/m2 who underwent RYGBP. Results. Over the 3 years of followup, changes in BPD-DS and RYGBP patients (BPD-DS/RYGBP were as follows: BMI (−44%/−24%, GGT (−63%/−52%, and ALT (−48%/−62%. PC decreased (−21% statistically significantly only in BPD-DS patients. Conclusions. Morbidly obese patients treated by RYGBP or BPD-DS show sustained reductions in BMI, ALT, and GGT. The decrease in PC and liver enzymes after BPD-DS may reflect a more pronounced decrease of liver-fat-content-related inflammation and, as a result, a lowered secondary thrombocytosis.

  18. Comprehensive analysis of common serum liver enzymes as prospective predictors of hepatocellular carcinoma in HBV patients.

    Directory of Open Access Journals (Sweden)

    Hie-Won Hann

    Full Text Available Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC.We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT] in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during the first 1 or 2 years of follow-up were analyzed using multivariate Cox proportional hazards model. Patients were categorized into a normal or an elevated group based on the clinical cut-off of each enzyme. During a median follow-up of 7.5 years, 52 patients (incidence rate, 8.8% developed HCC. The incidence rates were higher in the elevated groups for all four enzymes. The most significant finding was for GGT, with the highest incidence rate of 16.4% in the elevated group compared to 4.6% in the normal group (P<0.001. Compared to patients with normal baseline GGT, those with elevated GGT exhibited a significantly increased HCC risk with a hazards ratio (HR of 2.60 (95% confidence interval [CI], 1.41-4.77, P = 0.002. Further analyses revealed a cumulative effect between baseline GGT and ALP (HR = 3.41, 95% CI 1.54-7.56, P = 0.003.Serum GGT might predict HCC risk in HBV patients individually or jointly with other enzymes.

  19. Reconstructive Effects of Percutaneous Electrical Stimulation Combined with GGT Composite on Large Bone Defect in Rats

    Directory of Open Access Journals (Sweden)

    Bo-Yin Yang

    2013-01-01

    Full Text Available Previous studies have shown the electromagnetic stimulation improves bone remodeling and bone healing. However, the effect of percutaneous electrical stimulation (ES was not directly explored. The purpose of this study was to evaluate effect of ES on improvement of bone repair. Twenty-four adult male Sprague-Dawley rats were used for cranial implantation. We used a composite comprising genipin cross-linked gelatin mixed with tricalcium phosphate (GGT. Bone defects of all rats were filled with the GGT composites, and the rats were assigned into six groups after operation. The first three groups underwent 4, 8, and 12 weeks of ES, and the anode was connected to the backward of the defect on the neck; the cathode was connected to the front of the defect on the head. Rats were under inhalation anesthesia during the stimulation. The other three groups only received inhalation anesthesia without ES, as control groups. All the rats were examined afterward at 4, 8, and 12 weeks. Radiographic examinations including X-ray and micro-CT showed the progressive bone regeneration in the both ES and non-ES groups. The amount of the newly formed bone increased with the time between implantation and examination in the ES and non-ES groups and was higher in the ES groups. Besides, the new bone growth trended on bilateral sides in ES groups and accumulated in U-shape in non-ES groups. The results indicated that ES could improve bone repair, and the effect is higher around the cathode.

  20. Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) Detection Techniques

    Science.gov (United States)

    Huang, Xing-Jiu; Choi, Yang-Kyu; Im, Hyung-Soon; Yarimaga, Oktay; Yoon, Euisik; Kim, Hak-Sung

    2006-01-01

    The levels of aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) in serum can help people diagnose body tissues especially the heart and the liver are injured or not. This article provides a comprehensive review of research activities that concentrate on AST/GOT and ALT/GPT detection techniques due to their clinical importance. The detection techniques include colorimetric, spectrophotometric, chemiluminescence, chromatography, fluorescence and UV absorbance, radiochemical, and electrochemical techniques. We devote the most attention on experimental principle. In some methods a few representative devices and important conclusions are presented.

  1. The redundant aminotransferases in lysine and arginine synthesis and the extent of aminotransferase redundancy in Escherichia coli.

    Science.gov (United States)

    Lal, Piyush Behari; Schneider, Barbara L; Vu, Khoan; Reitzer, Larry

    2014-11-01

    Aminotransferases can be redundant or promiscuous, but the extent and significance of these properties is not known in any organism, even in Escherichia coli. To determine the extent of redundancy, it was first necessary to identify the redundant aminotransferases in arginine and lysine synthesis, and then complement all aminotransferase-deficient mutants with genes for all aminotransferases. The enzymes with N-acetylornithine aminotransferase (ACOAT) activity in arginine synthesis were ArgD, AstC, GabT and PuuE; the major anaerobic ACOAT was ArgD. The major enzymes with N-succinyl-l,l-diaminopimelate aminotransferase (SDAP-AT) activity in lysine synthesis were ArgD, AstC, and SerC. Seven other aminotransferases, when overproduced, complemented the defect in a triple mutant. Lysine availability did not regulate synthesis of the major SDAP-ATs. Complementation analysis of mutants lacking aminotransferases showed that the SDAP-ATs and alanine aminotransferases were exceptionally redundant, and it is proposed that this redundancy may ensure peptidoglycan synthesis. An overview of all aminotransferase reactions indicates that redundancy and broad specificity are common properties of aminotransferases. © 2014 John Wiley & Sons Ltd.

  2. Effect of Orthodontic Tooth Movement on Salivary Aspartate Aminotransferase Activity

    Directory of Open Access Journals (Sweden)

    Steiven Adhitya

    2013-07-01

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

  3. Alanine aminotransferase controls seed dormancy in barley.

    Science.gov (United States)

    Sato, Kazuhiro; Yamane, Miki; Yamaji, Nami; Kanamori, Hiroyuki; Tagiri, Akemi; Schwerdt, Julian G; Fincher, Geoffrey B; Matsumoto, Takashi; Takeda, Kazuyoshi; Komatsuda, Takao

    2016-05-18

    Dormancy allows wild barley grains to survive dry summers in the Near East. After domestication, barley was selected for shorter dormancy periods. Here we isolate the major seed dormancy gene qsd1 from wild barley, which encodes an alanine aminotransferase (AlaAT). The seed dormancy gene is expressed specifically in the embryo. The AlaAT isoenzymes encoded by the long and short dormancy alleles differ in a single amino acid residue. The reduced dormancy allele Qsd1 evolved from barleys that were first domesticated in the southern Levant and had the long dormancy qsd1 allele that can be traced back to wild barleys. The reduced dormancy mutation likely contributed to the enhanced performance of barley in industrial applications such as beer and whisky production, which involve controlled germination. In contrast, the long dormancy allele might be used to control pre-harvest sprouting in higher rainfall areas to enhance global adaptation of barley.

  4. Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress.

    Science.gov (United States)

    Montonen, Jukka; Boeing, Heiner; Fritsche, Andreas; Schleicher, Erwin; Joost, Hans-Georg; Schulze, Matthias B; Steffen, Annika; Pischon, Tobias

    2013-02-01

    To examine the association of red meat and whole-grain bread consumption with plasma levels of biomarkers related to glucose metabolism, oxidative stress, inflammation and obesity. Our cross-sectional study was based on 2,198 men and women who were selected as a sub-cohort for an investigation of biological predictors of diabetes and cardiovascular diseases from the European Prospective Investigation into Cancer and Nutrition-Potsdam study. Circulating levels of glycated hemoglobin, adiponectin, hs-CRP, gamma-glutamyltransferase, alanine-aminotransferase, fetuin-A, HDL-cholesterol and triglycerides were measured from random blood samples. Diet and lifestyle data were assessed by questionnaires, and anthropometric data were measured. After multivariable adjustment, higher consumption of whole-grain bread was significantly (P trend consumption of red meat was significantly associated with higher levels of GGT and hs-CRP when adjusted for potential confounding factors related to lifestyle and diet. Further adjustment for body mass index and waist circumference attenuated the association between red meat and hs-CRP (P = 0.19). The results of this study suggest that high consumption of whole-grain bread is related to lower levels of GGT, ALT and hs-CRP, whereas high consumption of red meat is associated with higher circulating levels of GGT and hs-CRP.

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

    Directory of Open Access Journals (Sweden)

    Ricardo H. Rauber

    2013-09-01

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

  6. Crystal Structure of Human Kynurenine Aminotransferase ll*

    Energy Technology Data Exchange (ETDEWEB)

    Han,Q.; Robinson, H.; Li, J.

    2008-01-01

    Human kynurenine aminotransferase II (hKAT-II) efficiently catalyzes the transamination of knunrenine to kynurenic acid (KYNA). KYNA is the only known endogenous antagonist of N-methyl-d-aspartate (NMDA) receptors and is also an antagonist of 7-nicotinic acetylcholine receptors. Abnormal concentrations of brain KYNA have been implicated in the pathogenesis and development of several neurological and psychiatric diseases in humans. Consequently, enzymes involved in the production of brain KYNA have been considered potential regulatory targets. In this article, we report a 2.16 Angstroms crystal structure of hKAT-II and a 1.95 Angstroms structure of its complex with kynurenine. The protein architecture of hKAT-II reveals that it belongs to the fold-type I pyridoxal 5-phosphate (PLP)-dependent enzymes. In comparison with all subclasses of fold-type I-PLP-dependent enzymes, we propose that hKAT-II represents a novel subclass in the fold-type I enzymes because of the unique folding of its first 65 N-terminal residues. This study provides a molecular basis for future effort in maintaining physiological concentrations of KYNA through molecular and biochemical regulation of hKAT-II.

  7. Aspartate Aminotransferase (AST/GOT and Alanine Aminotransferase (ALT/GPT Detection Techniques

    Directory of Open Access Journals (Sweden)

    Hak-Sung Kim

    2006-07-01

    Full Text Available The levels of aspartate aminotransferase (AST/GOT and alanineaminotransferase (ALT/GPT in serum can help people diagnose body tissues especially theheart and the liver are injured or not. This article provides a comprehensive review ofresearch activities that concentrate on AST/GOT and ALT/GPT detection techniques due totheir clinical importance. The detection techniques include colorimetric, spectrophotometric,chemiluminescence, chromatography, fluorescence and UV absorbance, radiochemical, andelectrochemical techniques. We devote the most attention on experimental principle. Insome methods a few representative devices and important conclusions are presented.

  8. Kynurenine Aminotransferase Isozyme Inhibitors: A Review

    Directory of Open Access Journals (Sweden)

    Alireza Nematollahi

    2016-06-01

    Full Text Available Kynurenine aminotransferase isozymes (KATs 1–4 are members of the pyridoxal-5’-phosphate (PLP-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN to kynurenic acid (KYNA, a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS diseases, the KATs are prominent targets in the quest to treat neurodegenerative and cognitive impairment disorders. Recent studies suggest that inhibiting these enzymes would produce effects beneficial to patients with these conditions, as abnormally high levels of KYNA are observed. KAT-1 and KAT-3 share the highest sequence similarity of the isozymes in this family, and their active site pockets are also similar. Importantly, KAT-2 has the major role of kynurenic acid production (70% in the human brain, and it is considered therefore that suitable inhibition of this isozyme would be most effective in managing major aspects of CNS diseases. Human KAT-2 inhibitors have been developed, but the most potent of them, chosen for further investigations, did not proceed in clinical studies due to the cross toxicity caused by their irreversible interaction with PLP, the required cofactor of the KAT isozymes, and any other PLP-dependent enzymes. As a consequence of the possibility of extensive undesirable adverse effects, it is also important to pursue KAT inhibitors that reversibly inhibit KATs and to include a strategy that seeks compounds likely to achieve substantial interaction with regions of the active site other than the PLP. The main purpose of this treatise is to review the recent developments with the inhibitors of KAT isozymes. This treatise also includes analyses of their crystallographic structures in complex with this enzyme family, which provides further insight for researchers in this and related studies.

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

    OpenAIRE

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

    2010-01-01

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

  10. Ornithine aminotransferase deficiency: Diagnostic difficulties in neonatal presentation

    NARCIS (Netherlands)

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

    2005-01-01

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

  11. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci

    Directory of Open Access Journals (Sweden)

    Guillermo Hugo Peralta

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

  12. Evaluation of liver marker enzymes in diabetic subjects in the ...

    African Journals Online (AJOL)

    The activity levels of the liver marker enzymes; Aspartate and Alanine amino transferases (AST and ALT), Alkaline Phosphatase (ALP) and Gamma glutamyltransferase (GGT) in diabetic and non-diabetic subjects within the ages of 25 to 86 were assayed. This study was for two weeks. The results indicated that the plasma ...

  13. Mercury Exposure in Association With Decrease of Liver Function in Adults: A Longitudinal Study

    Directory of Open Access Journals (Sweden)

    Jonghyuk Choi

    2017-11-01

    Full Text Available Objectives Although mercury (Hg exposure is known to be neurotoxic in humans, its effects on liver function have been less often reported. The aim of this study was to investigate whether total Hg exposure in Korean adults was associated with elevated serum levels of the liver enzymes aspartate aminotransferase (AST, alanine transaminase (ALT, and gamma-glutamyltransferase (GGT. Methods We repeatedly examined the levels of total Hg and liver enzymes in the blood of 508 adults during 2010-2011 and 2014-2015. Cross-sectional associations between levels of blood Hg and liver enzymes were analyzed using a generalized linear model, and nonlinear relationships were analyzed using a generalized additive mixed model. Generalized estimating equations were applied to examine longitudinal associations, considering the correlations of individuals measured repeatedly. Results GGT increased by 11.0% (95% confidence interval [CI], 4.5 to 18.0% in women and 8.1% (95% CI, -0.5 to 17.4% in men per doubling of Hg levels, but AST and ALT were not significantly associated with Hg in either men or women. In women who drank more than 2 or 3 times per week, AST, ALT, and GGT levels increased by 10.6% (95% CI, 4.2 to 17.5%, 7.7% (95% CI, 1.1 to 14.7%, and 37.5% (95% CI,15.2 to 64.3% per doubling of Hg levels, respectively, showing an interaction between blood Hg levels and drinking. Conclusions Hg exposure was associated with an elevated serum concentration of GGT. Especially in women who were frequent drinkers, AST, ALT, and GGT showed a significant increase, with a significant synergistic effect of Hg and alcohol consumption.

  14. Structure of putrescine aminotransferase from Escherichia coli provides insights into the substrate specificity among class III aminotransferases.

    Science.gov (United States)

    Cha, Hyung Jin; Jeong, Jae-Hee; Rojviriya, Catleya; Kim, Yeon-Gil

    2014-01-01

    YgjG is a putrescine aminotransferase enzyme that transfers amino groups from compounds with terminal primary amines to compounds with an aldehyde group using pyridoxal-5'-phosphate (PLP) as a cofactor. Previous biochemical data show that the enzyme prefers primary diamines, such as putrescine, over ornithine as a substrate. To better understand the enzyme's substrate specificity, crystal structures of YgjG from Escherichia coli were determined at 2.3 and 2.1 Å resolutions for the free and putrescine-bound enzymes, respectively. Sequence and structural analyses revealed that YgjG forms a dimer that adopts a class III PLP-dependent aminotransferase fold. A structural comparison between YgjG and other class III aminotransferases revealed that their structures are similar. However, YgjG has an additional N-terminal helical structure that partially contributes to a dimeric interaction with the other subunit via a helix-helix interaction. Interestingly, the YgjG substrate-binding site entrance size and charge distribution are smaller and more hydrophobic than other class III aminotransferases, which suggest that YgjG has a unique substrate binding site that could accommodate primary aliphatic diamine substrates, including putrescine. The YgjG crystal structures provide structural clues to putrescine aminotransferase substrate specificity and binding.

  15. Hepatic lipidosis in llamas and alpacas: 31 cases (1991-1997).

    Science.gov (United States)

    Tornquist, S J; Van Saun, R J; Smith, B B; Cebra, C K; Snyder, S P

    1999-05-01

    To identify factors associated with hepatic lipidosis (HL) in llamas and alpacas. Retrospective case series. 30 llamas and 1 alpaca. Medical records were searched to identify llamas or alpacas in which a histologic diagnosis of HL was made. Information was retrieved on signalment, history, clinical and laboratory findings, and results of necropsy or examination of biopsy specimens. Data were analyzed using descriptive statistics and chi 2 analyses. Females were affected more often than males; however, the sex distribution was not different from that of the camelid population in the diagnostic laboratory's database. Fifty-four percent of the females were pregnant, and 46% were lactating. Most affected camelids were 6 to 10 years old. Anorexia and recent weight loss were common (51.6% of camelids). An infective agent was found in only one ilama, and toxins and mineral deficiencies were not identified. The most common abnormalities on serum biochemical analysis were a high concentration of bile acids, high activities of gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST), and hypoproteinemia. Concentrations of nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (beta-HB) were high in those camelids in which these compounds were assayed. Twenty-nine camelids did not survive. Sick camelids should be considered at risk for developing HL, especially those with anorexia or the metabolic demands of pregnancy and lactation. Other stresses also appear to contribute. High concentrations of NEFA, beta-HB, and bile acids; high activities of GGT and AST; and hypoproteinemia may indicate that HL has developed.

  16. Risk factors for incident type 2 diabetes in individuals with a BMI of Resistance Syndrome (DESIR).

    Science.gov (United States)

    Gautier, A; Balkau, B; Lange, C; Tichet, J; Bonnet, F

    2010-02-01

    Risk factors for incident type 2 diabetes, in particular, hepatic markers, have rarely been studied in leaner individuals. We aimed to identify the metabolic and hepatic markers associated with incident diabetes in men and women with a BMI of or=27 kg/m(2). Risk factors for 9 year incident diabetes were compared in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. Comparisons were made between the 2,947 participants with a BMI of or=27 kg/m(2). There were 92 incident cases of diabetes in individuals with a BMI of or=27 kg/m(2). Among those who were not markedly overweight, classical biological markers were associated with 9 year incident diabetes, glycaemia being the strongest predictor. gamma-Glutamyltransferase (GGT), either considered as a continuous variable or at levels >or=20 U/l, was associated with incident diabetes, with a stronger effect in the BMI or=27 kg/m(2) (results after adjustment for alcohol intake, alanine aminotransferase, waist circumference and the HOMA insulin resistance index). In individuals with a BMI of resistance, suggesting potential interactions between GGT, enhanced hepatic neoglucogenesis and/or early alterations of insulin secretion.

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

    Science.gov (United States)

    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 ×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.

  18. Serum aminotransferases and bilirubin levels in malaria patients ...

    African Journals Online (AJOL)

    ... (p<0.05) than those of the control samples. Serum aminotransferases and bilirubin levels should therefore be routinely monitored in malaria patients since Plasmodium parasites invasion could produce liver and blood complications, even when least suspected. International Journal of Natural and Applied Sciences Vol.

  19. Specific inhibition of the aspartate aminotransferase of Plasmodium falciparum

    NARCIS (Netherlands)

    Wrenger, Carsten; Mueller, Ingrid B.; Schifferdecker, Anna J.; Jain, Rishabh; Jordanova, Rositsa; Groves, Matthew R.

    2011-01-01

    Aspartate aminotransferases (AspATs; EC 2.6.1.1) catalyze the conversion of aspartate and α-ketoglutarate into oxaloacetate and glutamate and are key enzymes in the nitrogen metabolism of all organisms. Recent findings suggest that the plasmodial enzyme [Plasmodium falciparum aspartate

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

    African Journals Online (AJOL)

    Reham Al Swaff

    2012-04-04

    Apr 4, 2012 ... Abstract The relationship of serum alanine aminotransferase (ALT) level and viral replication to liver damage in chronic hepatitis C virus (HCV) patients remains unclear. The aim of the present study was to determine whether the stage of fibrosis correlates with HCV-. RNA titer and/or serum ALT level in ...

  1. Effect of thermoxidised groundnut oil on aminotransferase activity of ...

    African Journals Online (AJOL)

    The feeding experiment lasted for a period of twenty one days after which the animals were sacrificed and tissue homogenates analyzed for tissue enzymes using standard methods. The results indicated a significant increase (P<0.05) concentrations of alanine aminotransferase (ALT) in animals treated with the oils with ...

  2. Liver enzymes and psychological well-being response to aerobic exercise training in patients with chronic hepatitis C.

    Science.gov (United States)

    Abd El-Kader, Shehab M; Al-Jiffri, Osama H; Al-Shreef, Fadwa M

    2014-06-01

    Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person's physical and psychological health. The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic exercise training in patients with CHC. Fifty CHC patients were included in two equal groups. The first group (A) received aerobic exercise training in addition to their regular medical treatment. The second group (B) received no training and only has their regular medical treatment. The program consisted of three sessions per week for three months. There was a significant decrease in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT), Beck Depression Inventory (BDI ) & Profile of Mood States(POMS) and increase in Rosenberg Self-Esteem Scale (RSES) in group (A) after treatments, but the changes in group (B) were not significant. Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Aerobic exercise training improves hepatic enzymes and psychological well-being in patients with chronic hepatitis C.

  3. Targeting of human GGT in a renal cell carcinoma mouse model with 99mTc-HYNIC-mAb 138H11

    International Nuclear Information System (INIS)

    Kuenstler, J.U.; Seifert, S.; Zimmermann, J.; Fischer, P.; Invancevic, V.; Johannsen, B.

    2002-01-01

    The study shows that the specific tumor uptake of 99m Tc-HYNIC-mAb 138H11 in GGT positive tumours was 2 to 5 times as high as in the controls. A high unspecific background activity was observed in the blood and in all organs well supplied with blood. (orig.)

  4. Aspartate aminotransferase and tylosin biosynthesis in Streptomyces fradiae.

    Science.gov (United States)

    Lee, S H; Lee, K J

    1993-01-01

    Aspartate aminotransferase as well as valine dehydrogenase and threonine dehydratase was required for the biosynthesis of tylosin in Streptomyces fradiae NRRL 2702. The biosynthesis of these enzymes and tylosin production were repressed by high concentrations of ammonium ions. The change in specific tylosin production rates in batch cultures with different initial concentrations of ammonium ions showed patterns similar to those of the specific production rates of aspartate aminotransferase, valine dehydrogenase, and threonine dehydratase. Aspartate aminotransferase has been purified by acetone precipitation, DEAE-cellulose, hydroxyapatite, and preparative electrophoresis chromatographies. The purified enzyme (120 kDa) consisted of two subunits identical in molecular mass (54 kDa) and showed homogeneity, giving one band with a pI of 4.2 upon preparative isoelectric focusing. The enzyme was specific for L-aspartate in the forward reaction; the Km values were determined to be 2.7 mM for L-aspartate, 0.7 mM for 2-oxyglutarate, 12.8 mM for L-glutamate, and 0.15 mM for oxaloacetate. The enzyme was somewhat thermostable, having a maximum activity at 55 degrees C, and had a broad pH optimum that ranged from 5.5 to 8.0. The mode of action was a ping-pong-bi-bi mechanism. Images PMID:8481008

  5. Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and differentiation in astrocytic glioma cells in culture

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Lisá, Věra; Malík, Radek; Kozáková, Hana; Šedo, A.

    2003-01-01

    Roč. 18, č. 3 (2003), s. 687-693 ISSN 0213-3911 R&D Projects: GA ČR GA301/02/0962 Institutional research plan: CEZ:AV0Z5020903; CEZ:AV0Z5011922 Keywords : glioma * cisplatin * gamma-glutamytranspeptidase Subject RIV: FD - Oncology ; Hematology Impact factor: 1.830, year: 2003

  6. Molecular analysis of the role of two aromatic aminotransferases and a broad-specificity aspartate aminotransferase in the aromatic amino acid metabolism of Pyrococcus furiosus

    NARCIS (Netherlands)

    Ward, D.E.; Vos, de W.M.; Oost, van der J.

    2002-01-01

    The genes encoding aromatic aminotransferase II (AroAT II) and aspartate aminotransferase (AspAT) from Pyrococcus furiosus have been identified, expressed in Escherichia coli and the recombinant proteins characterized. The AroAT II enzyme was specific for the transamination reaction of the aromatic

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

    Directory of Open Access Journals (Sweden)

    Paulo César Ciarlini

    2011-10-01

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

  8. Aspartate aminotransferase – key enzyme in the human systemic metabolism

    Directory of Open Access Journals (Sweden)

    Dagmara Otto-Ślusarczyk

    2016-03-01

    Full Text Available Aspartate aminotransferase is an organ - nonspecific enzyme located in many tissues of the human body where it catalyzes reversible reaction of transamination. There are two aspartate aminotransferase isoforms - cytoplasmic (AST1 and mitochondrial (AST2, that usually occur together and interact with each other metabolically. Both isoforms are homodimers containing highly conservative regions responsible for catalytic properties of enzyme. The common feature of all aspartate aminotransfeses is Lys – 259 residue covalent binding with prosthetic group - pyridoxal phosphate. The differences in the primary structure of AST isoforms determine their physico-chemical, kinetic and immunological properties. Because of the low concentration of L-aspartate (L-Asp in the blood, AST is the only enzyme, which supply of this amino acid as a substrate for many metabolic processes, such as urea cycle or purine and pyrimidine nucleotides in the liver, synthesis of L-arginine in the kidney and purine nucleotide cycle in the brain and the skeletal muscle. AST is also involved in D-aspartate production that regulates the metabolic activity at the auto-, para- and endocrine level. Aspartate aminotransferase is a part of the malate-aspartate shuttle in the myocardium, is involved in gluconeogenesis in the liver and kidney, glyceroneogenesis in the adipose tissue, and synthesis of neurotransmitters and neuro-glial pathway in the brain. Recently, the significant role of AST in glutaminolysis - normal metabolic pathway in tumor cells, was demonstrated. The article is devoted the role of AST, known primarily as a diagnostic liver enzyme, in metabolism of various human tissues and organs.

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

    Directory of Open Access Journals (Sweden)

    Tušimová Eva

    2015-02-01

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

  10. Biocatalytic potential of vanillin aminotransferase from Capsicum chinense

    Science.gov (United States)

    2014-01-01

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

  11. Role of aminotransferases in glutamate metabolism of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger, James J. [University of Wisconsin-Madison, Department of Biochemistry (United States); Lewis, Ian A. [Princeton University, Lewis-Sigler Institute for Integrative Genomics (United States); Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, Department of Biochemistry (United States)

    2011-04-15

    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 {alpha}-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 {sup 1}H-{sup 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.

  12. Mediating effects of motor performance, cardiorespiratory fitness, physical activity, and sedentary behaviour on the associations of adiposity and other cardiometabolic risk factors with academic achievement in children.

    Science.gov (United States)

    Haapala, Eero A; Lintu, Niina; Eloranta, Aino-Maija; Venäläinen, Taisa; Poikkeus, Anna-Maija; Ahonen, Timo; Lindi, Virpi; Lakka, Timo A

    2018-03-09

    We investigated the associations of cardiometabolic risk factors with academic achievement and whether motor performance, cardiorespiratory fitness, physical activity, or sedentary behaviour mediated these associations. Altogether 175 children 6-8 years-of-age participated in the study. We assessed body fat percentage (BF%), waist circumference, insulin, glucose, triglycerides, HDL cholesterol, and systolic and diastolic blood pressure, leptin, alanine aminotransferase, and gamma-glutamyltransferase (GGT). Reading fluency, reading comprehension, and arithmetic skills were assessed using standardized tests. Speed/agility, balance, and manual dexterity test results were used to calculate motor performance score and physical activity was assessed by combined heart rate and movement sensor and cardiorespiratory fitness by maximal cycle ergometer test. In boys, BF% was inversely associated with reading fluency (β = -0.262, P = 0.007) and reading comprehension (β = -0.216, P = 0.025). Motor performance mediated these associations. Leptin was inversely related to reading fluency (β = -0.272, P = 0.006) and reading comprehension (β = -0.287, P = 0.003). The inverse association of leptin with reading fluency was mediated by motor performance. In girls, GGT was inversely associated with reading fluency independent of confounders (β = -0.325, P = 0.007). The inverse association of BF% with academic achievement among boys was largely explained by motor performance. Leptin in boys and GGT in girls were inversely associated with academic achievement independent of confounding factors.

  13. Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese

    Science.gov (United States)

    Zhang, Peng; Wang, Chun-Yan; Li, Yu-Xiang; Pan, Yu; Niu, Jun-Qi; He, Shu-Mei

    2015-01-01

    AIM: To determine the upper cut-off values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a Northern Chinese population. METHODS: A total of 3769 subjects in Jilin Province Northeast China were stratified to determine the potential factors affecting serum ALT and AST levels. The upper cut-off values of serum ALT and AST in these subjects were determined using receiver operating characteristic analysis and their sensitivity and specificity were evaluated. RESULTS: Stratification analysis revealed that serum ALT and AST levels were associated with gender, alcohol consumption, serum cholesterol and triglyceride levels, and body mass index. The upper cut-off values of serum ALT and AST were 22.15 U/L and 25.35 U/L for healthy men and 22.40 U/L and 24.25 U/L for healthy women, respectively. The new cut-off values had a higher sensitivity, but a slightly lower specificity than the current standards. CONCLUSION: Our results indicate that the new upper cut-off values of serum ALT and AST are markedly lower than current standards and may be valuable for the evaluation of liver function. PMID:25741150

  14. Aspartate Aminotransferase and Alanine Aminotransferase Detection on Paper-Based Analytical Devices with Inkjet Printer-Sprayed Reagents

    Directory of Open Access Journals (Sweden)

    Hsiang-Li Wang

    2016-01-01

    Full Text Available General biochemistry detection on paper-based microanalytical devices (PADs uses pipette titration. However, such an approach is extremely time-consuming for large-scale detection processes. Furthermore, while automated methods are available for increasing the efficiency of large-scale PAD production, the related equipment is very expensive. Accordingly, this study proposes a low-cost method for PAD manufacture, in which the reagent is applied using a modified inkjet printer. The optimal reaction times for the detection of aspartate aminotransferase (AST and alanine aminotransferase (ALT are shown to be 6 and 7 min, respectively, given AST and ALT concentrations in the range of 5.4 to 91.2 U/L (R2 = 0.9932 and 5.38 to 86.1 U/L (R2 = 0.9944. The experimental results obtained using the proposed PADs for the concentration detection of AST and ALT in real human blood serum samples are found to be in good agreement with those obtained using a traditional spectrophotometric detection method by National Cheng Kung University hospital.

  15. The effect of ammonium ions on the activity of glutamate dehydrogenase, alanine aminotransferase and aspartate aminotransferase in Cucumis sativus L. seedlings

    Directory of Open Access Journals (Sweden)

    Genowefa Kubiak-Dobosz

    2014-01-01

    Full Text Available Changes in the activity of glutamate dehydrogenase (GDH, alanine aminotransferase (GPT and aspartate aminotransferase (GOT were studied in various organs of Cucumis sativus L. seedlings in relation to the uptake of mineral nitrogen (in form of N03- or NH4+ from the medium. Activity of GDH, GPT, and GOT was higher in young leaves and roots of cucumber seedlings if the plants developed- in an ammonium medium. No similar changes of aminotransferases activity were noted in the cotyledons. Factors affecting varying effect of ammonium ions upon GPT and GOT activity are discussed for particular organs of cucumber seedlings.

  16. Crystal Structures of Aedes Aegypt Alanine Glyoxylate Aminotransferase

    Energy Technology Data Exchange (ETDEWEB)

    Han,Q.; Robinson, H.; Gao, Y.; Vogelaar, N.; Wilson, S.; Rizzi, M.; Li, J.

    2006-01-01

    Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75{angstrom} high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1{angstrom} resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.

  17. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases.

    Science.gov (United States)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura F; Sonnewald, Ursula; Waagepetersen, Helle S; Schousboe, Arne

    2016-12-01

    The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate-glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes oxidative degradation; thus, quantitative formation of glutamine from the glutamate taken up is not possible. Oxidation of glutamate is initiated by transamination catalyzed by an aminotransferase, or oxidative deamination catalyzed by glutamate dehydrogenase (GDH). We discuss methods available to elucidate the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [ 15 N]glutamate demonstrated activity of GDH in astrocytes in situ. These results, in conjunction with reports in the literature, support the conclusion that GDH is active in astrocytes both in culture and in vivo and that this enzyme plays a significant role in glutamate oxidation. Oxidative metabolism of glutamate, primarily mediated by GDH, but also by transamination by aspartate aminotransferase, provides considerably more energy than is required to maintain the activity of the high-affinity glutamate transporters needed for efficient removal of glutamate from the synaptic cleft. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Aminotransferases and Leucine Aminopeptidase Activity in Blood Plasma of Chickens

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  19. HPLC-PDA-MS/MS Characterization of Bioactive Secondary Metabolites from Turraea fischeri Bark Extract and Its Antioxidant and Hepatoprotective Activities In Vivo

    Directory of Open Access Journals (Sweden)

    Mansour Sobeh

    2017-11-01

    Full Text Available Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH and ferric reducing antioxidant power (FRAP assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST, total bilirubin, gamma-glutamyltransferase (GGT, and malondialdehyde (MDA and increase of glutathione (GSH was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications.

  20. HPLC-PDA-MS/MS Characterization of Bioactive Secondary Metabolites from Turraea fischeri Bark Extract and Its Antioxidant and Hepatoprotective Activities In Vivo.

    Science.gov (United States)

    Sobeh, Mansour; Mahmoud, Mona F; Sabry, Omar M; Adel, Rasha; Dmirieh, Malak; El-Shazly, Assem M; Wink, Michael

    2017-11-29

    Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans . Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications.

  1. Caspase-3 Expression and ALT, AST, and GGT Activity After 24 Hours of Porcine Liver Cold Storage, Depending on the Type of Transgenesis.

    Science.gov (United States)

    Roman, P; Budziński, G; Suszka-Świtek, A; Caban, A; Oczkowicz, G; Czech, E; Ryszka, F; Wiaderkiewicz, R; Smorąg, Z; Cierpka, L

    2016-06-01

    Because of an insufficient number of human organs for transplantation, xenotransplantation may become an effective alternative. We aimed to analyze if the type of transgenesis has an influence on the hepatic caspase-3 expression, the enzyme that executes apoptosis as well as ALT, AST, and GGT activity after 24 hours of cold storage. The experiment was carried out on the 24 livers of Polish White Landrace pigs carrying human α1,2-fucosyltransferase and/or α-galactosidase (GAL) genes and livers without this genetic modification (control). Livers were perfused, stored for 24 hours in solution, and subsequently re-flushed. Hepatic concentration of the caspase-3 protein and its mRNA expression were measured just after the animal was killed as well as after 30 minutes of perfusion and after 24 hours of cold storage followed by 30 minutes of reperfusion. Caspase-3 mRNA level was detected with the RT-PCR method. Protein concentration (capsase-3 active and inactive) was assessed with the Western blotting technique. Kinetic methods were applied for the analysis of the ALT, AST, and GGT activity. The highest increase of the ALT activity after cold storage was observed in the group with GAL transgenesis, whereas the GGT activity was highest in the unmodified livers. There was no difference in the caspase-3 expression and AST activity after cold storage as compared with the respective initial results (P = .57 and P = .97, respectively). It appears that transgenesis does not aggravate ischemic injury of the liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Inverse linear associations between liver aminotransferases and incident cardiovascular disease risk : The PREVEND study

    NARCIS (Netherlands)

    Kunutsor, Setor K.; Bakker, Stephan J. L.; Kootstra-Ros, Jenny E.; Blokzijl, Hans; Gansevoort, Ronald T.; Dullaart, Robin P. F.

    2015-01-01

    Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been linked with an increased risk of type 2 diabetes, but their relationships with cardiovascular disease (CVD) are uncertain. We aimed to assess the associations of ALT and AST with CVD risk and determine their

  3. Ambient Ionization Mass Spectrometry Measurement of Aminotransferase Activity

    Science.gov (United States)

    Yan, Xin; Li, Xin; Zhang, Chengsen; Xu, Yang; Cooks, R. Graham

    2017-06-01

    A change in enzyme activity has been used as a clinical biomarker for diagnosis and is useful in evaluating patient prognosis. Current laboratory measurements of enzyme activity involve multi-step derivatization of the reaction products followed by quantitative analysis of these derivatives. This study simplified the reaction systems by using only the target enzymatic reaction and directly detecting its product. A protocol using paper spray mass spectrometry for identifying and quantifying the reaction product has been developed. Evaluation of the activity of aspartate aminotransferase (AST) was chosen as a proof-of-principle. The volume of sample needed is greatly reduced compared with the traditional method. Paper spray has a desalting effect that avoids sprayer clogging problems seen when examining serum samples by nanoESI. This very simple method does not require sample pretreatment and additional derivatization reactions, yet it gives high quality kinetic data, excellent limits of detection (60 ppb from serum), and coefficients of variation <10% in quantitation. [Figure not available: see fulltext.

  4. Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate

    Directory of Open Access Journals (Sweden)

    Miguel Angel Moreno

    2014-12-01

    Full Text Available Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis in the Mediterranean basin. The disease is fatal without treatment, which has been based on antimonial pentavalents for more than 60 years. Due to resistances, relapses and toxicity to current treatment, the development of new drugs is required. The structure of the L. infantum tyrosine aminotransferase (LiTAT has been recently solved showing important differences with the mammalian orthologue. The characterization of LiTAT is reported herein. This enzyme is cytoplasmic and is over-expressed in the more infective stages and nitric oxide resistant parasites. Unlike the mammalian TAT, LiTAT is able to use ketomethiobutyrate as co-substrate. The pharmacophore model of LiTAT with this specific co-substrate is described herein. This may allow the identification of new inhibitors present in the databases. All the data obtained support that LiTAT is a good target candidate for the development of new anti-leishmanial drugs.

  5. Fragment Screening of Human Kynurenine Aminotransferase-II.

    Science.gov (United States)

    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.

  6. Valores de referência da atividade enzimática da aspartato-aminotransferase e da gama-glutamiltransferase em bovinos da raça Jersey. Influência dos fatores etários, sexuais e da infecção pelo vírus da leucose dos bovinos

    OpenAIRE

    Gregory L.; Birgel Junior E.H.; Mirandola R.M.S.; Araújo W.P.; Birgel E.H.

    1999-01-01

    Com o objetivo de estabelecer os valores de referência de parâmetros bioquímicos que avaliem a função hepática, por meio da determinação da atividade enzimática da aspartato-aminotransferase (AST) e da gama-glutamiltransferase (GGT), de bovinos da raça Jersey, criados no Estado de São Paulo, bem como avaliar a influência dos fatores etários, sexuais e da infecção pelo vírus da leucose dos bovinos sobre os referidos parâmetros bioquímicos, foram colhidas e examinadas amostras de soro sangüíneo...

  7. Alanine aminotransferase/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

    Science.gov (United States)

    2012-01-01

    Background The aim of the present study was to examine how liver markers are associated with insulin resistance in Japanese community-dwelling adults. Methods This cross-sectional study included 587 men aged 58 ± 14 (mean ± standard deviation; range, 20–89) years and 755 women aged 60 ± 12 (range, 21–88) years. The study sample consisted of 998 (74.4%) non-obese [body mass index (BMI) ALT)/aspartate aminotransferase (AST) ratio of 0.70 (95% confidence interval (CI), 0.63-0.77). In overweight subjects, AUC values for the ALT/AST ratio and ALT were 0.66 (0.59-0.72) and 0.66 (0.59-0.72), respectively. Multiple linear regression analyses for HOMA-IR showed that ALT/AST ratios were independently and significantly associated with HOMA-IR as well as other confounding factors in both non-obese and overweight subjects. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: ALT/AST ratio of ≥0.82 in non-obese subjects and ≥1.02 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for ALT/AST ratio. Conclusions In non-obese Japanese adults, ALT/AST ratio may be the best reliable marker of insulin resistance. PMID:23020992

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

    Science.gov (United States)

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

    2011-02-25

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

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

    Directory of Open Access Journals (Sweden)

    Edmundo Pessoa Lopes

    2009-01-01

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

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

    National Research Council Canada - National Science Library

    Berger, B

    2002-01-01

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

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

    Science.gov (United States)

    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.

  12. Biochemical and Structural Properties of Mouse Kynurenine Aminotransferase III

    Energy Technology Data Exchange (ETDEWEB)

    Han, Q.; Robinson, H; Cai, T; Tagle, D; Li, J

    2009-01-01

    Kynurenine aminotransferase III (KAT III) has been considered to be involved in the production of mammalian brain kynurenic acid (KYNA), which plays an important role in protecting neurons from overstimulation by excitatory neurotransmitters. The enzyme was identified based on its high sequence identity with mammalian KAT I, but its activity toward kynurenine and its structural characteristics have not been established. In this study, the biochemical and structural properties of mouse KAT III (mKAT III) were determined. Specifically, mKAT III cDNA was amplified from a mouse brain cDNA library, and its recombinant protein was expressed in an insect cell protein expression system. We established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60C. In addition, mKAT III is active toward a number of other amino acids. Its activity toward kynurenine is significantly decreased in the presence of methionine, histidine, glutamine, leucine, cysteine, and 3-hydroxykynurenine. Through macromolecular crystallography, we determined the mKAT III crystal structure and its structures in complex with kynurenine and glutamine. Structural analysis revealed the overall architecture of mKAT III and its cofactor binding site and active center residues. This is the first report concerning the biochemical characteristics and crystal structures of KAT III enzymes and provides a basis toward understanding the overall physiological role of mammalian KAT III in vivo and insight into regulating the levels of endogenous KYNA through modulation of the enzyme in the mouse brain.

  13. Alanine aminotransferase variants conferring diverse NUE phenotypes in Arabidopsis thaliana.

    Science.gov (United States)

    McAllister, Chandra H; Good, Allen G

    2015-01-01

    Alanine aminotransferase (AlaAT, E.C. 2.6.1.2), is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes the reversible transfer of an amino group from alanine to 2-oxoglutarate to produce glutamate and pyruvate, or vice versa. It has been well documented in both greenhouse and field studies that tissue-specific over-expression of AlaAT from barley (Hordeum vulgare, HvAlaAT) results in a significant increase in plant NUE in both canola and rice. While the physical phenotypes associated with over-expression of HvAlaAT have been well characterized, the role this enzyme plays in vivo to create a more N efficient plant remains unknown. Furthermore, the importance of HvAlaAT, in contrast to other AlaAT enzyme homologues in creating this phenotype has not yet been explored. To address the role of AlaAT in NUE, AlaAT variants from diverse sources and different subcellular locations, were expressed in the wild-type Arabidopsis thaliana Col-0 background and alaat1;2 (alaat1-1;alaat2-1) knockout background in various N environments. The analysis and comparison of both the physical and physiological properties of AlaAT over-expressing transgenic plants demonstrated significant differences between plants expressing the different AlaAT enzymes under different external conditions. This analysis indicates that the over-expression of AlaAT variants other than HvAlaAT in crop plants could further increase the NUE phenotype(s) previously observed.

  14. Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy.

    Science.gov (United States)

    Lee, Eun-Jeong; Facchini, Peter J

    2011-11-01

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

  15. Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Mehere, P.; Robinson, H.; Han, Q.; Lemkul, J. A.; Vavricka, C. J.; Bevan, D. R.; Li, J.

    2010-11-01

    Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using {alpha}-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 {angstrom} resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

  16. Tyrosine Aminotransferase: Biochemical and Structural Properties and Molecular Dynamics Simulations

    Energy Technology Data Exchange (ETDEWEB)

    P Mehere; Q Han; J Lemkul; C Vavricka; H Robinson; D Bevan; J Li

    2011-12-31

    Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using {alpha}-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 {angstrom} resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

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

    Directory of Open Access Journals (Sweden)

    Rozana Oliveira Gonçalves

    2005-10-01

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

  18. Níveis iônicos e enzimáticos de cutias (Dasyprocta sp. hígidas, criadas em cativeiro, influência do sexo e da idade Ion and enzymatic levels of healthy agouti (Dasyprocta sp. raised in captivit. Influence of gender and age

    Directory of Open Access Journals (Sweden)

    E.E.A. Ribeiro

    2008-06-01

    Full Text Available Determinou-se o perfil do ionograma e enzimas hepáticas de cutias (Dasyprocta sp. saudáveis, criadas em cativeiro, como também se avaliou a influência de sexo, idade e interação sexo-idade. Foi adotado um delineamento inteiramente ao acaso, em arranjo fatorial 2 x 4 (dois sexos e quatro faixas etárias, com três repetições, totalizando 24 cutias. Foram determinados os valores para o cálcio (Ca, fósforo (P, cloretos (Cl, aspartato aminotransferase (AST, alanina aminotransferase (ALT, fosfatase alcalina (FA e gama-glutamiltransferase (GGT. Os valores médios obtidos foram: Ca= 7,62+2,59mg/dl; P= 3,91+1,41mg/dl; Cl= 58,63+16,45mg/dl; AST= 119,54+79,35UI/ml; ALT= 28,08+15,53UI/ml; FA= 26,95+14,01UI/ml e GGT= 25,34+19,44UI/ml. O valor de P foi maior nas fêmeas e da FA nos machos. Os níveis de FA diminuíram com o aumento da idade.This research studied the profile of the ionogram and hepatic enzymes of healthy agoutis (Dasyprocta sp. raised in captivity as well as evaluated the influence of gender, age and interaction gender-age. It was used a completely randomized design, in a factorial arrangement of 2 x 4 (two genders and four age groups, with three repetitions, totaling 24 agoutis. The values were determined for calcium (Ca, phosphorus (P, chlorides (Cl, aspartate aminotransaminase (AST, alanine aminotransaminase (ALT, alkaline phosphatase (ALP, and gamma-glutamyltransferase (GGT. The mean values were: Ca= 7.62±2.59mg/dl; P= 3.91±1.41mg/dl; Cl= 58.63±16,45mg/dl; AST= 119.54±79.35UI/ml; ALT= 28.08±15.53UI/ml; ALP= 26.95±14.01UI/ml, and GGT= 25.34±19.44UI/ml. The value of P was larger in females and ALP in males. As the age increased, levels of ALP decreased.

  19. Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Music, Miralem; Dervisevic, Amela; Pepic, Esad; Lepara, Orhan; Fajkic, Almir; Ascic-Buturovic, Belma; Tuna, Enes

    2015-01-01

    Objectives: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. Methods: This cross-sectional study included 96 patients (age 47–83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG ≥ 6,1 mmol/L, TG ≥ 1,7 mmol/L and blood pressure ≥ 130/85 mm Hg. Results: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= -0,29, p<0,05) in T2DM-MS group of patients. Conclusion: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in

  20. Acute Effects of on Javdar Supplementation on Asparate Aminotransferase(AST and Alanine Aminotransferase(ALT after Exhaustive Incremental Exercise in Men’s Handball

    Directory of Open Access Journals (Sweden)

    Mojtaba Khansooz

    2017-03-01

    Full Text Available Abstract Background: The aim of this study was to investigate the acute effect of supplementation Jadvar on aspartate aminotransferase (AST and alanine aminotransferase (ALT enzymes after exhaustive incremental exercise in men's handball. Materials and Methods: In this semi-experimental double blinded study 12 handball players with at least 2 years record in league (with average age=21.42, height=186cm, weight=83.25, and body mass index=24.09kg/m2 divided into 2 groups (n=6 accidentally. Both groups performed maximum Bruce protocol until exhausting level. Before (fasting and after performing protocol ,blood samples were taken from middle forearm vein and transferred to lab then supplementation group consumed three 500 mg jadvar capsules and control group consumed three 500 mg maltodextrin for 7 days daily. 24 hours after eating last capsule ,they performed maximum Bruce protocol up to exhausting level and the samples were collected like primary protocol blood samples before (fastingand after performing protocol and were transferred to the laboratory. Results: The results of dependent and independent t-test showed that consuming jadvar supplements for 7days did not have significant effect on aspartate aminotransferase(AST and alanine aminotransferase(ALT(p≥0.05.But alanine aminotransferase in supplementation group (16.83 mg.dl-1 decreased in comparison to placebo group (20.5 mg.dl-1. Also, aspartate aminotransferase was increased from 28 mg.dl-1 to 35.17 mg.dl-1 , but neither decrease nor increase was not meaningful (p≥0.05. Conclusion: It seems that acute consuming of jadvar supplement and one session incremental exercise does not have meaningful effect on AST and ALT in man handball players.

  1. Gamma glutamyl transferase is an independent determinant for the association of insulin resistance with nonalcoholic fatty liver disease in Bangladeshi adults: Association of GGT and HOMA-IR with NAFLD.

    Science.gov (United States)

    Hossain, Israt Ara; Rahman Shah, Md Mijanur; Rahman, Mohammad Khalilur; Ali, Liaquat

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with insulin resistance (HOMA-IR) syndrome. Recently serum gamma glutamyl transferase (GGT) has been considered as surrogate marker of NAFLD leading to oxidative stress and hepatocellular damage. In the present study we examined the association of serum GGT and HOMA-IR with NAFLD in Bangladeshi adult subjects. Under a cross-sectional analytical design a total of 110 subjects were recruited who came for their routine health check up in the BIHS Hospital, Darussalam, Dhaka, Bangladesh. After whole abdomen ultrasonography, 62 were diagnosed as non-NAFLD and 48 were NAFLD subjects. Serum glucose was measured by glucose-oxidase method, lipid profile and liver enzymes by enzymatic colorimetric method, glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography (HPLC), serum insulin were measured by enzyme-linked immunosorbent assay. HOMA-IR was calculated by homeostasis model assessment (HOMA). NAFLD subjects had significantly higher levels of GGT and HOMA-IR as compared to their non-NAFLD counterparts. Multiple linear regression analysis showed a significant positive association of HOMA-IR with GGT after adjusting the effects of waist circumference (WC) and HbA1c. In binary logistic regression analysis, HOMA-IR and GGT were found to be significant determinants of NAFLD after adjusting the effects of WC and HbA1c. These results suggest that elevated levels of GGT and insulin resistance are more likely to develop NAFLD and thus support a role of these determinants in the pathogenesis of NAFLD in Bangladeshi adult subjects. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Gabriela Vasile

    2006-08-01

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

  3. Magnesium treatment in alcoholics: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Poikolainen Kari

    2008-01-01

    Full Text Available Abstract Background Magnesium (Mg deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. Methods The effect of Mg was studied in a randomized, parallel group, double-blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT activity; secondary outcomes included aspartate-aminotransferase (S-AST and alanine-aminotransferase (S-ALT activity. Results The number of randomized patients (completers was 64 (27 in the treatment and 54 (31 in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df = 53, p = 0.002. After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df = 49, p = 0.045. Conclusion Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. Trial Registration ClinicalTrials.gov ID NCT00325299

  4. The impact of dengue on liver function as evaluated by aminotransferase levels

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    Luiz José de Souza

    Full Text Available The objective of this study was to evaluate the impact of dengue virus infection on liver function by measuring aminotransferase in blood samples from patients serologically diagnosed by according to two MAC-ELISA protocols. Degrees of liver damage were classified according to aminotransferase levels: grade A - normal enzyme levels; grade B - increased levels of at least one of the enzymes; grade C - increased, with at least one of the enzymes being at levels higher than three times the upper reference values; grade D - acute hepatitis, with aminotransferase levels at least ten times their normal values. Of the 169 serologically confirmed cases of dengue at the dengue referral center in Campos dos Goytacazes in the state of Rio de Janeiro, Brazil, 65.1% had abnormal aminotransferase levels: 81 cases being classified as grade B, 25 as grade C and 3 as grade D. A further 34.9% of cases had normal enzyme levels and were classified as grade A. Liver damage is a common complication of dengue infection and aminotransferase levels are a valuable marker for monitoring these cases.

  5. The relationship of alanine aminotransferase to metabolic syndrome in a Korean population.

    Science.gov (United States)

    Lee, Seok Hoon; Cho, Doo Yeoun; Joo, Nam Seok; Kim, Kwang Min; Kim, Kyu Nam

    2018-01-01

    Although associations between serum alanine aminotransferase and metabolic syndrome are well-recognized in Western countries, only a limited number of prospective studies have been performed in Asian populations. The aim of the study was to cross-sectionally and longitudinally examine whether serum alanine aminotransferase levels are associated with metabolic syndrome and its associated components in a Korean population. A total of 31,832 subjects who received health screenings were included in cross-sectional analyses; a subgroup of 4.070 subjects without metabolic syndrome at baseline was included in the longitudinal analyses. The metabolic syndrome definition was based on the National Cholesterol Education Program Third Adult Treatment Panel criteria with modification on waist circumference cut-off to be more appropriate for an Asian population. In the cross-sectional analyses, serum alanine aminotransferase is positively associated with metabolic syndrome and its components. In the longitudinal analyses, the prevalence of metabolic syndrome increased across serum alanine aminotransferase quartiles in a dose-dependent manner after extensive adjustments (hazard ratios were 1.000, 1.609, 2.601, and 3.015 for quartiles, 1 through quartile 4; P for trendmetabolic syndrome and elevated serum alanine aminotransferase in a Korean population.

  6. Clinicopathological features of choledocholithiasis patients with high aminotransferase levels without cholangitis: Prospective comparative study.

    Science.gov (United States)

    Huh, Cheal Wung; Jang, Sung Ill; Lim, Beom Jin; Kim, Hee Wook; Kim, Jae Keun; Park, Jun Sung; Kim, Ja Kyung; Lee, Se Joon; Lee, Dong Ki

    2016-10-01

    Common bile duct (CBD) stones are generally associated with greater elevations of alkaline phosphatase and gamma-glutamyl transpeptidase levels than aspartate aminotransferase and alanine aminotransferase levels. However, some patients with CBD stones show markedly increased aminotransferase levels, sometimes leading to the misdiagnosis of liver disease. Therefore, the aim of this study was to investigate the clinicopathologic features of patients with CBD stones and high aminotransferase levels.This prospective cohort study included 882 patients diagnosed with CBD stones using endoscopic retrograde cholangiopancreatography (ERCP). Among these patients, 38 (4.3%) exhibited aminotransferase levels above 400 IU/L without cholangitis (gallstone hepatitis [GSH] group), and 116 (13.2%) exhibited normal aminotransferase levels (control group). We compared groups in terms of clinical features, laboratory test results, radiologic images, and ERCP findings such as CBD diameter, CBD stone diameter and number, and periampullary diverticulum. Liver biopsy was performed for patients in the GSH group.GSH patients were younger and more likely to have gallbladder stones than control patients, implying a higher incidence of gallbladder stone migration. Also, GSH patients experienced more severe, short-lasting abdominal pain. ERCP showed narrower CBDs in GSH patients than in control patients. Histological analysis of liver tissue from GSH patients showed no abnormalities except for mild inflammation.Compared with control patients, GSH patients were younger and showed more severe, short-lasting abdominal pain, which could be due to a sudden increase of CBD pressure resulting from the migration of gallstones through narrower CBDs. These clinical features could be helpful not only for the differential diagnosis of liver disease but also for investigating the underlying mechanisms of liver damage in obstructive jaundice. Moreover, we propose a new definition of "gallstone hepatitis

  7. Predictability of liver-related seromarkers for the risk of hepatocellular carcinoma in chronic hepatitis B patients.

    Directory of Open Access Journals (Sweden)

    Yu-Ju Lin

    Full Text Available BACKGROUND: Hepatitis B virus (HBV-related hepatocellular carcinoma (HCC is a major global health problem. A few risk calculators have been developed using mainly HBV seromarkers as predictors. However, serum HBV DNA level, HBV genotype, and mutants are not routinely checked in regular health examinations. This study aimed to assess the predictability of HCC risk in chronic hepatitis B patients, using a combination of liver-related seromarkers combined with or without HBV seromarkers. METHODS: A prospective cohort of 1,822 anti-HCV-seronegative chronic HBV carriers was included in this study. Liver-related seromarkers including aspartate aminotransferase (AST, alanine aminotransferase (ALT, alpha-fetoprotein (AFP, gamma-glutamyltransferase (GGT, total bilirubin, total protein, albumin, serum globulins, apolipoprotein A1, and apolipoprotein B were examined. Hazard ratios of HCC with 95% confidence intervals were estimated using Cox proportional hazards regression models. Regression coefficients of seromarkers significantly associated with HCC risk in multivariate analyses were used to create integer risk scores. The predictability of various risk models were assessed by area under receiver operating characteristic curves (AUROCs. RESULTS: During a median follow-up of 5.9 years, 48 newly-developed HCC cases were ascertained. Elevated serum levels of ALT (≥ 28 U/L, AFP (≥ 5 ng/mL, and GGT (≥ 41 U/L, an increased AST/ALT ratio (AAR, ≥ 1, and lowered serum levels of albumin (≤ 4.1 g/dL and alpha-1 globulin (≤ 0.2 g/dL were significantly associated with an increased HCC risk (P<0.05 in multivariate analysis. The risk model incorporating age, gender, AAR, and serum levels of ALT, AFP, GGT, albumin, and alpha-1 globulin had an AUROC of 0.89 for predicting 6-year HCC incidence. The AUROC was 0.91 after the addition of HBV seromarkers into the model, and 0.83 for the model without liver-related seromarkers, with the exception of ALT

  8. Fifteen-minute consultation: The child with an incidental finding of elevated aminotransferases.

    Science.gov (United States)

    Hegarty, Robert; Dhawan, Anil

    2018-02-06

    It is not unusual to encounter abnormal liver enzyme levels on routine blood tests. When the abnormal elevation in aminotransferases persist, they require prompt and appropriate investigations as liver diseases in children are often insidious in onset and clinically silent. This article aims to provide (1) an explanation to the aetiologies of elevated aminotransferases; (2) an investigational approach to these children and (3) an insight into further investigations performed at a liver centre. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Biochemical and Structural Characterization of a Ureidoglycine Aminotransferase in the Klebsiella pneumoniae Uric Acid Catabolic Pathway

    Energy Technology Data Exchange (ETDEWEB)

    French, Jarrod B.; Ealick, Steven E. (Cornell)

    2010-09-03

    Many plants, fungi, and bacteria catabolize allantoin as a mechanism for nitrogen assimilation. Recent reports have shown that in plants and some bacteria the product of hydrolysis of allantoin by allantoinase is the unstable intermediate ureidoglycine. While this molecule can spontaneously decay, genetic analysis of some bacterial genomes indicates that an aminotransferase may be present in the pathway. Here we present evidence that Klebsiella pneumoniae HpxJ is an aminotransferase that preferentially converts ureidoglycine and an {alpha}-keto acid into oxalurate and the corresponding amino acid. We determined the crystal structure of HpxJ, allowing us to present an explanation for substrate specificity.

  10. Where should the safe limits of alcohol consumption stand in light of liver enzyme abnormalities in alcohol consumers?

    Directory of Open Access Journals (Sweden)

    Onni Niemelä

    Full Text Available To estimate the prevalence and risk factors for abnormal liver enzymes in a large age- and gender stratified population-based sample of apparently healthy individuals with or without alcohol consumption and other health-related risk factors (adiposity, physical inactivity, smoking.Data on alcohol use, smoking, diet and physical activity were recorded using structured questionnaires from 13,976 subjects (6513 men, 7463 women, aged 25-74 years in the national FINRISK studies. Alcohol data was used to categorize the participants into abstainers, light drinkers, moderate drinkers and heavy drinkers. Serum gamma-glutamyltransferase (GGT and alanine aminotransferase (ALT activities were measured using standard kinetic methods.Male light drinkers, moderate drinkers and heavy drinkers showed significantly higher relative risks of abnormal GGT than abstainers: 1.37 (95% confidence interval 1.11 to 1.71, p < 0.01, 2.72 (2.08 to 3.56, p < 0.0005, and 6.10 (4.55 to 7.17, p < 0.0005, respectively. Corresponding values for women were 1.22 (0.99 to 1.51, p = 0.065, 1.90 (1.44 to 2.51, p < 0.0005, and 5.91 (3.80 to 9.17, p < 0.0005. Estimated threshold doses for a significant GGT elevation was 14 standard weekly alcohol doses for men and 7 for women. Excess body weight and age over 40 years modulated the thresholds towards smaller quantities of alcohol. The risk of abnormal GGT was also significantly influenced by physical inactivity and smoking. The relative risks of abnormal ALT activities were increased in male heavy drinkers, especially in those presenting with adiposity and sedentary lifestyle.Alcohol use markedly increases the risk for abnormal liver enzyme activities in those presenting with age over 40 years, obesity, smoking or sedentary lifestyle. The data should be considered in public health recommendations and in the definitions of safe limits of alcohol use.

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

    Energy Technology Data Exchange (ETDEWEB)

    Q Han; T Cai; D Tagle; J Li

    2011-12-31

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

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

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    Pranav R. Prabhu

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue...

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

    Science.gov (United States)

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

    2011-10-04

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

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

    Science.gov (United States)

    Jessen, Holly Jean; Liao, Hans H; Gort, Steven John; Selifonova, Olga V

    2014-11-18

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

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

    NARCIS (Netherlands)

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

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

  18. Follow-up of mild alanine aminotransferase elevation identifies hidden hepatitis C in primary care

    NARCIS (Netherlands)

    Helsper, C.W.|info:eu-repo/dai/nl/338910816; van Essen, G.A.|info:eu-repo/dai/nl/141200065; Frijling, B.D.; de Wit, N.J.|info:eu-repo/dai/nl/100525393

    2012-01-01

    BACKGROUND: Hepatitis C (HCV) and hepatitis B (HBV) virus infection can lead to serious complications if left untreated, but often remain undetected in primary care. Mild alanine aminotransferase (ALT) elevations (30-100 IU/l) are commonly found and could be associated with viral hepatitis;

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

    Science.gov (United States)

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

    2018-03-01

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

  20. Structural Determinants of the beta-Selectivity of a Bacterial Aminotransferase

    NARCIS (Netherlands)

    Wybenga, Gjalt G.; Crismaru, Ciprian G.; Janssen, Dick B.; Dijkstra, Bauke W

    2012-01-01

    Chiral beta-amino acids occur as constituents of various natural and synthetic compounds with potentially useful bioactivities. The pyridoxal 5'-phosphate (PLP)-dependent S-selective transaminase from Mesorhizobium sp. strain LUK (MesAT) is a fold type I aminotransferase that can be used for the

  1. Gender difference in the association between aminotransferase levels and hypertension in a Chinese elderly population.

    Science.gov (United States)

    Wu, Lei; He, Yao; Jiang, Bin; Liu, Miao; Yang, Shanshan; Wang, Yiyan; Zeng, Jing; Yao, Yao; Wang, Jianhua

    2017-05-01

    Few epidemiological studies have examined the association between serum aminotransferase levels and hypertension, and have yielded inconsistent results.A cross-sectional study was performed in a Chinese rural elderly population. A total of 2174 participants with normal range of aminotransferase levels and without excessive drinking were included in the present study. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured on fasting morning serum samples using the Kinetic method. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or receiving treatment for hypertension. Multiple logistic regression was used to estimate the association between gender-specific aminotransferase levels and hypertension.Increased serum ALT but not AST level was positively associated with hypertension. After adjusting for potential confounding variables, the association of hypertension and ALT level was only significant in women: for each 1 IU/L elevation of ALT level, the adjusted odds ratio (OR), and corresponding 95% confidence interval (CI) of hypertension was 1.04 (1.01, 1.07); the ORs of hypertension increased across tertiles of ALT, and the ORs (95% CIs) were 1.00, 1.17 (0.85, 1.60), and 1.63 (1.15, 2.31 (P value for trend = .021). Furthermore, the association was only significant in central obesity women or nondrinking women.ALT level was significantly associated with hypertension only in women in a Chinese rural elderly population. Further studies are warranted to explore the possible gender-related association and to extend them to different populations.

  2. New Concept of the Biosynthesis of 4-Alkyl-L-Proline Precursors of Lincomycin, Hormaomycin, and Pyrrolobenzodiazepines: Could a gamma-Glutamyltransferase Cleave the C-C Bond?

    Czech Academy of Sciences Publication Activity Database

    Jirásková, Petra; Gažák, Radek; Kameník, Zdeněk; Steiningerová, Lucie; Najmanová, Lucie; Kadlčík, Stanislav; Novotná, Jitka; Kuzma, Marek; Janata, Jiří

    2016-01-01

    Roč. 7, Mar 7 (2016), s. 276 ISSN 1664-302X R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) EE2.3.30.0003 Institutional support: RVO:61388971 Keywords : anticancer drug * antibiotics * natural product biosynthesis Subject RIV: EE - Microbiology, Virology Impact factor: 4.076, year: 2016

  3. Elevated Preoperative Serum Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) Ratio Is Associated with Better Prognosis in Patients Undergoing Curative Treatment for Gastric Adenocarcinoma.

    Science.gov (United States)

    Chen, Shu-Lin; Li, Jian-Pei; Li, Lin-Fang; Zeng, Tao; He, Xia

    2016-06-09

    The level of anine aminotransferase/aspartate aminotransferase (ALT/AST) ratio in the serum was often used to assess liver injury. Whether the ALT/AST ratio (LSR) was associated with prognosis for gastric adenocarcinoma (GA) has not been reported in the literature. Our aim was to investigate the prognostic value of the preoperative LSR in patients with GA. A retrospective study was performed in 231 patients with GA undergoing curative resection. The medical records collected include clinical information and laboratory results. We investigated the correlations between the preoperative LSR and overall survival (OS). Survival analysis was conducted with the Kaplan-Meier method, and Cox regression analysis was used to determine significant independent prognostic factors for predicting survival. A p value of 0.80. The LSR was independently associated with OS in patients with GA (hazard ratio: 0.610; 95% confidence interval: 0.388-0.958; p = 0.032), along with tumor stages (hazard ratio: 3.118; 95% confidence interval: 2.044-4.756; p < 0.001) and distant metastases (hazard ratio: 1.957; 95% confidence interval: 1.119-3.422; p = 0.019). Our study first established a connection between the preoperative LSR and patients undergoing curative resection for GA, suggesting that LSR was a simple, inexpensive, and easily measurable marker as a prognostic factor, and may help to identify high-risk patients for treatment decisions.

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

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    Yokoyama, Miyuki; Watanabe, Tetsu; Otaki, Yoichiro; Takahashi, Hiroki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Shibata, Yoko; Daimon, Makoto; Ueno, Yoshiyuki; Kato, Takeo; 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.

  5. Biochemical, anthropometric and body composition indicators as predictors of hepatic steatosis in obese adolescents

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    Amanda Oliva Gobato

    2014-06-01

    Full Text Available 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.

  6. Identification of aminotransferase genes for biosynthesis of aminoglycoside antibiotics from soil DNA.

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    Nagaya, Atsushi; Takeyama, Satoko; Tamegai, Hideyuki

    2005-07-01

    Aminoglycoside has been known as a clinically important antibiotic for a long time, but genetic information for the biosynthesis of aminoglycoside is still insufficient. In this study, we tried to clone aminoglycoside-biosynthetic genes from soil DNA for accumulation of genetic information. We chose the genes encoding L-glutamine:(2-deoxy-)scyllo-inosose aminotransferase as the target, because it is specific for all types of aminoglycoside biosynthesis. By degenerate PCR, we obtained 33 individual clones that were homologous with aminotransferase genes in aminoglycoside biosynthesis. Phylogenetic analysis and alignment of these genes showed that horizontal gene transfer has occurred in the soil. Among these, several quite interesting genes were obtained. Some genes probably originated from non-actinomycetes, and some were far from the known homologs. These genes can be useful markers for the isolation of entire gene clusters and originating organisms.

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

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    Chandra H McAllister

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

  8. Hepatic aminotransferases of normal and IUGR fetuses in cord blood at birth.

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    Kocylowski, Rafal; Dubiel, Mariusz; Gudmundsson, Saemundur; Fritzer, Elfriede; Kiserud, Torvid; von Kaisenberg, Constantin

    2012-07-01

    The accepted standard for assessing the wellbeing of the newborn is the Apgar score and blood gas analysis. However, the prediction of neonatal morbidity or mortality is limited. In small-for-gestation (SGA) fetuses at 18-38 weeks of gestation, pO(2) is normals. To test the hypothesis, that fetuses with intra uterine growth restriction (IUGR) have elevated AST (GOT) and ALT (GPT) aminotransferases as a result of hypoxic liver cell injury, and to establish references ranges. Prospective cohort study, serum of umbilical artery (n=156) and vein (n=180), 599 normal singletons at 37(+0)-42(+0)weeks, neonates with IUGR (n=41), analysis for pH, birthweight and maternal weight, spontaneous vs cesarean section, vein vs artery and for the sex. Aspartate aminotransferase (AST, GOT) and Alanine aminotransferase (ALT, GPT) were measured in normals and IUGR neonates. Neonates with IUGR (n=41) had AST values that were not different from the reference group, but had significantly lower ALT (-1.49, 95% CI -1.98 to -1.00 vs 0.14, 95% CI -0.42-0.13), (pblood were not elevated. Rather, a substantially reduced ALT suggests a down-regulated hepatic activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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    Pey, Angel L.; Albert, Armando; Salido, Eduardo

    2013-01-01

    Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP) as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis. PMID:23956997

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

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    Angel L. Pey

    2013-01-01

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

  11. Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1 gene and metabolic risk factors in the EPIC-Potsdam study.

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    Maria Arregui

    Full Text Available BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1 is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1 could potentially modify metabolic risk factors, but few human studies have addressed this question. METHODS: In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384 and 5 inferred haplotypes with frequency >5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI, waist circumference (WC, glycated haemoglobin (HbA1c, high-sensitivity C-reactive protein (hs-CRP, gamma-glutamyltransferase (GGT, alanine aminotransferase (ALT and fetuin-A. RESULTS: No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction. CONCLUSION: These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors

  12. Elevated Preoperative Serum Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST Ratio Is Associated with Better Prognosis in Patients Undergoing Curative Treatment for Gastric Adenocarcinoma

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    Shu-Lin Chen

    2016-06-01

    Full Text Available The level of anine aminotransferase/aspartate aminotransferase (ALT/AST ratio in the serum was often used to assess liver injury. Whether the ALT/AST ratio (LSR was associated with prognosis for gastric adenocarcinoma (GA has not been reported in the literature. Our aim was to investigate the prognostic value of the preoperative LSR in patients with GA. A retrospective study was performed in 231 patients with GA undergoing curative resection. The medical records collected include clinical information and laboratory results. We investigated the correlations between the preoperative LSR and overall survival (OS. Survival analysis was conducted with the Kaplan–Meier method, and Cox regression analysis was used to determine significant independent prognostic factors for predicting survival. A p value of <0.05 was considered to be statistically significant. A total of 231 patients were finally enrolled. The median overall survival was 47 months. Multivariate analysis indicated that preoperative LSR was an independent prognostic factor in GA. Patients with LSR ≤ 0.80 had a greater risk of death than those with LSR > 0.80. The LSR was independently associated with OS in patients with GA (hazard ratio: 0.610; 95% confidence interval: 0.388–0.958; p = 0.032, along with tumor stages (hazard ratio: 3.118; 95% confidence interval: 2.044–4.756; p < 0.001 and distant metastases (hazard ratio: 1.957; 95% confidence interval: 1.119–3.422; p = 0.019. Our study first established a connection between the preoperative LSR and patients undergoing curative resection for GA, suggesting that LSR was a simple, inexpensive, and easily measurable marker as a prognostic factor, and may help to identify high-risk patients for treatment decisions.

  13. Influence of gender on the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) in patients with and without hyperbilirubinemia.

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    Mera, Jorge R; Dickson, Beverly; Feldman, Mark

    2008-03-01

    The serum asparate aminotransferase (AST)/alanine aminotransferase (ALT) ratio is widely used in the differential diagnosis of icteric and non-icteric hepatic disorders. Our objective was to determine whether there are gender related-differences in the serum AST/ALT ratio. We used sera from 3,618 unselected patients sent to our laboratory for an automated chemistry panel, which included measurements of AST, ALT, alkaline phosphatase, and total bilirubin. Effects of gender on serum AST, ALT, and AST/ALT were examined in different age groups. Among patients with normal total serum bilirubin concentrations, serum AST and ALT concentrations were significantly lower in the females than in the males (P < 0.0001). However, the serum AST/ALT ratio was higher in the females than the males (median values of 0.90 and 0.81, respectively; P < 0.0001). AST and ALT were also lower in the 54 hyperbilirubinemic females than in the 102 hyperbilirubinemic males. Serum AST/ALT ratios were considerably higher in these 156 hyperbilirubinemic patients than in the normobilirubinemic group, with median ratios of 1.09 in females and 0.92 in males (P = 0.02). Significantly higher serum AST/ALT ratios in females were first evident in the 3rd age decade and remained significantly higher than ratios in males through the 8th decade. We conclude that serum AST/ALT ratios are higher in women than men. When clinicians utilize serum AST/ALT ratios to assess the etiology or chronicity of liver disease, the patient's gender also should be taken into consideration.

  14. The Antioxidant Activity and the Effects of Convolvulus Aucheri (Convolvulaceae Extract on Biochemical Indices in Rats

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    R. MAMMADOV

    2014-06-01

    Full Text Available Convolvulus L., the second largest genus of the family Convolvulaceae, has about 250 species distributed mainly in the temperate and tropical regions of the world, with a cosmopolitan distribution. According to recent studies, this genus is represented in Turkey by 33 species, 9 of which are endemic. Convolvulus species are extensively used in traditional medicine for various purposes as in ulcer treatment, diabetes, and tension. The aim of this study was to investigate the antioxidant activity and the effects of Convolvulus aucheri extract on biochemical indices in rats.The antioxidant activities of various solvent extracts (methanol, ethanol, acetone and benzene obtained from C. aucheri were evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH and β-carotene-linoleic acid assays. In addition, total phenolic contents in all the extracts of C. aucheri were determined as gallic acid equivalents. As for the biochemical assay, the extracts of the plant at the concentrations of 0.5 and 1 ml/100 g body weight/day were administered orally to the experimental groups for 36 days. Blood samples were taken by cardiac venipuncture on the 2nd and 4th weeks after the initial treatment. Aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma-glutamyltransferase (GGT and blood urea nitrogen (BUN were measured for the determination of liver function.Among all the extracts, the ethanolic extracts of C. aucheri showed the highest antioxidant activity (66.88 ± 0.8%. The highest free radical scavenging activity (59.50 ± 1.2% was recorded on the ethanolic extracts. The phenolic contents of the ethanolic extracts are higher than the other types of extracts (23.03 mg/g GAE. In biochemical assay, it was found a significant increase in the levels of serum ALT, AST and decrease the serum GGT levels in the experimental groups when compared to the controls (p<0.05. On the other hand, we found significant increase in the level of BUN.

  15. Hepatoprotective and hypoglycemic effects of a tannin rich extract from Ximenia americana var. caffra root.

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    Sobeh, Mansour; Mahmoud, Mona F; Abdelfattah, Mohamed A O; El-Beshbishy, Hesham A; El-Shazly, Assem M; Wink, Michael

    2017-09-15

    Liver diseases and diabetes are serious health disorders associated with oxidative stress and ageing. Some plant polyphenols can lower the risk of these diseases. We investigated the phytochemical profiling of a root extract from Ximenia americana var. caffra using HPLC-PDA-ESI-MS/MS. The antioxidant activities in vitro were investigated. The hepatoprotective activities were studied in rat models with d-galactosamine (d-GaIN)-induced hepatotoxicity and the antidiabetic activities in STZ-diabetic rats were also investigated. HPLC-PDA-ESI-MS/MS was used to identify plant phenolics. The antioxidant activities in vitro were determined using DPPH and FRAP assays. The in vivo hepatoprotective activities were determined for d-GaIN-induced hepatotoxicity in rats. We determined the liver markers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), liver peroxidation product malondialdehyde (MDA), glutathione content (GSH), albumin and total bilirubin concentration. The histopathological changes in rat liver were also studied. The antidiabetic activities were also investigated in STZ-diabetic rats and serum glucose, serum insulin hormone, and lipid peroxides were determined. The root extract is rich in tannins with 20 compounds including a series of stereoisomers of (epi)catechin, (epi)catechin-(epi)catechin, (epi)catechin-(epi)catechin-(epi)catechin, and their galloyl esters. Promising antioxidant potential was observed in vitro in DPPH assay with EC 50 of 6.5 µg extract / 26 µg raw material and in FRAP assay with 19.54 mM FeSO 4 compared with ascorbic acid (EC 50 of 2.92 µg/ml) and quercetin (FeSO 4 24.04 mM/mg), respectively. Significant reduction of serologic enzymatic markers and hepatic oxidative stress markers such as ALT, AST, MDA, GGT, and total bilirubin, as well as elevation of GSH and albumin were observed in rats with d-galactosamine-induced liver damage treated with the extract. These findings agree

  16. Effect of bullfrog (Rana catesbeiana oil administered by gavage on the fatty acid composition and oxidative stress of mouse liver

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    L.P. Silva

    2004-10-01

    Full Text Available The aim of the present study was to investigate the effects of daily intragastric administration of bullfrog oil (oleic, linoleic and palmitoleic acid-rich oil, corresponding to 0.4% of body weight for four weeks, on fatty acid composition and oxidative stress (lipid peroxidation and catalase activity in mouse liver. The activities of aspartate aminotransferase (AST, alkaline phosphatase (ALP, alanine aminotransferase (ALT, and gamma-glutamyltransferase (GGT, biomarkers of tissue injury, were determined in liver homogenates and serum. The proportions of 18:2n-6, 20:4n-6, 20:5n-3, and 22:6n-3 (polyunsaturated fatty acids, from 37 to 60% in the total fatty acid content were increased in the liver of the bullfrog oil-treated group (P < 0.05 compared to control. At the same time, a significant decrease in the relative abundance of 14:0, 16:0, and 18:0 (saturated fatty acids, from 49 to 25% was observed. The hepatic content of thiobarbituric acid reactive substances (TBARS was increased from 2.3 ± 0.2 to 12.3 ± 0.3 nmol TBA-MDA/mg protein and catalase activity was increased from 840 ± 32 to 1110 ± 45 µmol reduced H2O2 min-1 mg protein-1 in the treated group. Bullfrog oil administration increased AST and ALP activities in the liver (from 234.10 ± 0.12 to 342.84 ± 0.13 and 9.38 ± 0.60 to 20.06 ± 0.27 U/g, respectively and in serum (from 95.41 ± 6.13 to 120.32 ± 3.15 and 234.75 ± 11.5 to 254.41 ± 2.73 U/l, respectively, suggesting that this treatment induced tissue damage. ALT activity was increased from 287.28 ± 0.29 to 315.98 ± 0.34 U/g in the liver but remained unchanged in serum, whereas the GGT activity was not affected by bullfrog oil treatment. Therefore, despite the interesting modulation of fatty acids by bullfrog oil, a possible therapeutic use requires care since some adverse effects were observed in liver.

  17. Antitumoral and antioxidant effects of a hydroalcoholic extract of cat's claw (Uncaria tomentosa) (Willd. Ex Roem. & Schult) in an in vivo carcinosarcoma model.

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    Dreifuss, Arturo Alejandro; Bastos-Pereira, Amanda Leite; Avila, Thiago Vinicius; Soley, Bruna da Silva; Rivero, Armando J; Aguilar, José Luis; Acco, Alexandra

    2010-07-06

    The present work intended to study the antitumoral and antioxidant effects of Uncaria tomentosa (UT) hydroalcoholic extract in the Walker-256 cancer model. Walker-256 cells were subcutaneously inoculated in the pelvic limb of male Wistar rats. Daily gavage with UT extract (10, 50 or 100 mg kg(-1), Groups UT) or saline solution (Control, Group C) was subsequently initiated, until 14 days afterwards. For some parameters, a group of healthy rats (Baseline, Group B) was added. At the end of treatment the following parameters were evaluated: (a) tumor volume and mass; (b) plasmatic concentration of urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) and lactate dehydrogenase (LDH); (c) hepatic and tumoral activity of catalase (CAT) and superoxide dismutase (SOD), as well as the rate of lipid peroxidation (LPO) and gluthatione (GSH); and (d) hepatic glutathione-S-transferase (GST) activity. The reactivity of UT extract with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) was assessed in parallel. UT hydroalcoholic extract successfully reduced the tumor growth. In addition, treatment with UT reduced the activity of AST, which had been increased as a result of tumor inoculation, thus attempting to return it to normal levels. UT did not reverse the increase of LDH and GGT plasma levels, although all doses were remarkably effective in reducing urea plasma levels. An important in vitro free radical-scavenging activity was detected at various concentrations of UT extract (1-300 microg mL(-1)). Treatment also resulted in increased CAT activity in liver, while decreasing it in tumor tissue. SOD activity was reduced in liver as well as in tumor, compared to Group C. No statistical significance concerning ALT, GST, LPO or GSH were observed. This data represent an in vivo demonstration of both antitumoral and antioxidant effects of UT hydroalcoholic extract. The antineoplastic activity may result, partially at least

  18. Prevalence of hepatitis and its correlation with serum ferritin and aminotransferase levels among thalassemia major patients in Indonesia

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    Pustika Amalia Wahidiyat

    2017-08-01

    Full Text Available Background Thalassemia major patients who undergo routine transfusion have an increased risk of acquiring transfusion-transmitted infections (TTI, including hepatitis B and C. These diseases have serious implications and may affect the serum ferritin and aminotransferase levels of thalassemia major patients. Objectives To identify the prevalence of hepatitis B and/or C infections among thalassemia major patients and to evaluate its correlation with serum ferritin and aminotransferase levels. Methods This was across-sectional study conducted at the Thalassemia Center of Dr. Cipto Mangunkusumo Hospital in Jakarta, Indonesia. The subjects were screened for hepatitis B and C infections, and their serum ferritin and aminotransferase levels were also measured. Results In total, 621 subjects were included in the study, among which 5 subjects tested positive for hepatitis B surface antigen (HBsAg (0.8%, 111 subjects tested positive for anti-HCV (17.8%, and 5 subjects tested positive for both HBsAg and anti-HCV (0.8%. The subjects who tested positive for hepatitis B, hepatitis C, or both showed significantly higher values of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and serum ferritin compared to their negative counterparts. Moreover, serum ferritin showed a positive, moderate correlation with both AST and ALT. Conclusion This study shows a significant association between hepatitis and serum ferritin as well as aminotransferase levels. Early detection and early management of hepatitis B and C infections is warranted to minimize the occurrence of liver damage in thalassemia major patients.

  19. Clinical Relevance and Discriminatory Value of Elevated Liver Aminotransferase Levels for Dengue Severity

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

    2012-01-01

    Background Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT≥1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. Methodology/Principal Findings We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT≥1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve = 0.62; 95% confidence interval [CI]: 0.57–0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve = 0.56; 95% CI: 0.52–0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Conclusions Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue. PMID:22679523

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

    Science.gov (United States)

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

    2012-01-01

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

  1. Branched-chain amino acid aminotransferase activity in the tissues of lake trout

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    Hughes, S.G.; Rumsey, G.L.; Nesheim, M.C.

    1983-01-01

    1. The enzyme branched-chain amino acid aminotransferase (BCAT) was found in five tissues of fingerling lake trout, Salvelinus namaycush, (listed in order of decreasing tissue specific activity): posterior kidney, skeletal muscle, gill, liver, and anterior kidney.2. This pattern is consistent with that found in other animals.3. The results of this study seem to indicate that BCAT in the liver of lake trout has a higher specific activity than that of the rat and that the specific activity is higher in both the liver and skeletal muscle than it is in these organs of the chick.

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

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    Liu, Lina; Chen, Yuanfang; Yang, Li

    2014-12-15

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

  3. A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose.

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    Curtis, R Mason; Sivilotti, Marco L A

    2015-11-01

    Risk prediction following acetaminophen (paracetamol, APAP) overdose is based on serum APAP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. One recently proposed risk stratification tool, the APAPxAT multiplication product, uses either AST or ALT, whichever is higher, yet their interrelation is not well known following APAP-induced hepatic injury. To describe the kinetics of AST and ALT release into and disappearance from the circulation following APAP overdose. An observational case series of adult patients with peak AST or ALT > 100 IU/L attributable to APAP toxicity. Cases were identified by electronic search of hospital laboratory database and by discharge diagnosis corroborated by structured explicit medical record review. Of 68 cases identified (mean age (SD): 39 (18) years, 63% female, and 21% ethanol co-ingested), 28 (41%) developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy (international normalized ratio or INR > 2), and 21 (31%) both. Three patients (4%) were transferred for liver transplantation and ultimately six (8.8%) died. Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell at distinctly different rates: AST activity fell with a half-life (interquartile range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using an aminotransferase falling to below 50% of peak as the basis for discontinuing acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR: 9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration; of these six, four died and one survivor developed coagulopathy. AST and ALT release into the circulation appears tightly linked and numerically similar, except in the sickest patients. Once the aminotransferases peak, AST returns to baseline more quickly. Either AST or ALT can be used for early risk

  4. An LL-diaminopimelate aminotransferase defines a novel variant of the lysine biosynthesis pathway in plants.

    Science.gov (United States)

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

    2006-01-01

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

  5. Structural Insight into the Mechanism of Substrate Specificity of Aedes Kynurenine Aminotransferase

    Energy Technology Data Exchange (ETDEWEB)

    Han,Q.; Gao, Y.; Robinson, H.; Li, J.

    2008-01-01

    Aedes aegypti kynurenine aminotransferase (AeKAT) is a multifunctional aminotransferase. It catalyzes the transamination of a number of amino acids and uses many biologically relevant a-keto acids as amino group acceptors. AeKAT also is a cysteine S-conjugate {beta}-lyase. The most important function of AeKAT is the biosynthesis of kynurenic acid, a natural antagonist of NMDA and {alpha}7-nicotinic acetylcholine receptors. Here, we report the crystal structures of AeKAT in complex with its best amino acid substrates, glutamine and cysteine. Glutamine is found in both subunits of the biological dimer, and cysteine is found in one of the two subunits. Both substrates form external aldemines with pyridoxal 5-phosphate in the structures. This is the first instance in which one pyridoxal 5-phosphate enzyme has been crystallized with cysteine or glutamine forming external aldimine complexes, cysteinyl aldimine and glutaminyl aldimine. All the units with substrate are in the closed conformation form, and the unit without substrate is in the open form, which suggests that the binding of substrate induces the conformation change of AeKAT. By comparing the active site residues of the AeKAT-cysteine structure with those of the human KAT I-phenylalanine structure, we determined that Tyr286 in AeKAT is changed to Phe278 in human KAT I, which may explain why AeKAT transaminates hydrophilic amino acids more efficiently than human KAT I does.

  6. Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total hepatic perfusion and liver functions.

    Science.gov (United States)

    Nasr, Ahmed; Nafeh, Hanan

    2009-11-01

    In this prospective longitudinal clinical trial, 87 postmenopausal women receiving for 12 consecutive months a daily dose of 40 mg of a dry extract preparation of Cimicifuga racemosa (Klimadynon) for relief of vasomotor symptoms were followed up by evaluation of total hepatic blood flow, assessed by color Doppler ultrasound, as well as prothrombin time and concentration, serum albumin, bilirubin, gamma-glutamyltransferase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Because no significant changes in total hepatic blood flow or any of the liver functions tested were reported, we concluded that use of C. racemosa for 1 year by healthy postmenopausal women without evidence of liver disease does not seem to influence the liver.

  7. Bioanalysis for biocatalysis: multiplexed capillary electrophoresis-mass spectrometry assay for aminotransferase substrate discovery and specificity profiling.

    Science.gov (United States)

    Mironov, Gleb G; St-Jacques, Antony D; Mungham, Alexander; Eason, Matthew G; Chica, Roberto A; Berezovski, Maxim V

    2013-09-18

    In this work, we introduce an entirely automated enzyme assay based on capillary electrophoresis coupled to electrospray ionization mass spectrometry termed MINISEP-MS for multiple interfluent nanoinjections-incubation-separation-enzyme profiling using mass spectrometry. MINISEP-MS requires only nanoliters of reagent solutions and uses the separation capillary as a microreactor, allowing multiple substrates to be assayed simultaneously. The method can be used to rapidly profile the substrate specificity of any enzyme and to measure steady-state kinetics in an automated fashion. We used the MINISEP-MS assay to profile the substrate specificity of three aminotransferases (E. coli aspartate aminotransferase, E. coli branched-chain amino acid aminotransferase, and Bacillus sp. YM-1 D-amino acid aminotransferase) for 33 potential amino acid substrates and to measure steady-state kinetics. Using MINISEP-MS, we were able to recapitulate the known substrate specificities and to discover new amino acid substrates for these industrially relevant enzymes. Additionally, we were able to measure the apparent K(M) and k(cat) parameters for amino acid donor substrates of these aminotransferases. Because of its many advantages, the MINISEP-MS assay has the potential of becoming a useful tool for researchers aiming to identify or create novel enzymes for specific biocatalytic applications.

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

    Directory of Open Access Journals (Sweden)

    J. N. Ribeiro

    2009-01-01

    Full Text Available

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

  9. The role of glutamine oxoglutarate aminotransferase and glutamate dehydrogenase in nitrogen metabolism in Mycobacterium bovis BCG.

    Science.gov (United States)

    Viljoen, Albertus J; Kirsten, Catriona J; Baker, Bienyameen; van Helden, Paul D; Wiid, Ian J F

    2013-01-01

    Recent evidence suggests that the regulation of intracellular glutamate levels could play an important role in the ability of pathogenic slow-growing mycobacteria to grow in vivo. However, little is known about the in vitro requirement for the enzymes which catalyse glutamate production and degradation in the slow-growing mycobacteria, namely; glutamine oxoglutarate aminotransferase (GOGAT) and glutamate dehydrogenase (GDH), respectively. We report that allelic replacement of the Mycobacterium bovis BCG gltBD-operon encoding for the large (gltB) and small (gltD) subunits of GOGAT with a hygromycin resistance cassette resulted in glutamate auxotrophy and that deletion of the GDH encoding-gene (gdh) led to a marked growth deficiency in the presence of L-glutamate as a sole nitrogen source as well as reduction in growth when cultured in an excess of L-asparagine.

  10. Effect of Carboxyl-Terminal Truncation on the Catalytic Performance of D-Phenylglycine Aminotransferase

    Directory of Open Access Journals (Sweden)

    Aiya Chantarasiri

    2016-01-01

    Full Text Available The D-phenylglycine aminotransferase (D-PhgAT is a novel enzyme that can be used to synthesize precursors of antibiotics. This research addressed the function of the carboxyl-terminal (C-terminal of DPhgAT. Its C-terminal amino acid sequence was compared to other related proteins using bioinformatics tools. The analyzed amino acid sequence was used to produce a genetically modified enzyme having a truncation of the 10 amino acid residues at the C-terminal region. The truncated D-PhgAT was purified and analyzed for catalytic performance. The results revealed that the truncated enzyme had better catalytic performance than the full-length enzyme by 37.49%. This research is a preliminary study for improving the enzymatic performance of D-PhgAT by structure-guided engineering and can be applied in the development of other enzymes.

  11. Abdominal obesity validates the association between elevated alanine aminotransferase and newly diagnosed diabetes mellitus.

    Science.gov (United States)

    Yueh, Chen-Yu; Yang, Yao-Hsu; Sung, Yi-Ting; Lee, Li-Wen

    2014-01-01

    To examine how elevated alanine aminotransferase (ALT) could be associated with newly diagnosed diabetes mellitus. We conducted a cross-sectional analysis on a mass health examination. The odds ratios (ORs) for diabetes mellitus and newly diagnosed diabetes mellitus were compared between people with and without abdominal obesity, together with and without elevated ALT levels. 5499 people were included in this study. Two hundred fifty two (4.6%) fulfilled the diagnosis of diabetes mellitus with 178 (3.2%) undiagnosed before. Metabolic syndrome was vigorously associated with diabetes mellitus and newly diagnosed diabetes mellitus (12.4% vs. 1.4% and 9.0% vs. 0.9%), but elevated ALT alone was not. However, coexisting with obesity, elevated ALTs were robustly associated with diabetes mellitus and newly diagnosed diabetes mellitus. For the incidence of newly diagnosed diabetes mellitus, in comparison to non-obese people with normal ALT (1.7%, OR = 1), obese people especially with elevated ALT levels had significantly higher ORs (obese with ALT ≤ 40 U/L: 4.7%, OR 1.73, 95% CI 1.08-2.77, P 0.023; ALT 41-80 U/L: 6.8%, OR 2.06, 95% CI 1.20-3.55, P 0.009; ALT 81-120 U/L: 8.8%, OR 3.07, 95% CI 1.38-6.84, P 0.006; ALT > 120 U/L: 18.2%, OR 7.44, 95% CI 3.04-18.18, P obesity validates the association between elevated alanine aminotransferase and diabetes mellitus and newly diagnosed diabetes mellitus. People with abdominal obesity, especially with coexisting elevated ALT levels should be screened for undiagnosed diabetes mellitus.

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

    Directory of Open Access Journals (Sweden)

    Janaína Luz Narciso-Schiavon

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

  13. A heterozygous mutation in GOT1 is associated with familial macro-aspartate aminotransferase.

    Science.gov (United States)

    Kulecka, Maria; Wierzbicka, Aldona; Paziewska, Agnieszka; Mikula, Michal; Habior, Andrzej; Janczyk, Wojciech; Dabrowska, Michalina; Karczmarski, Jakub; Lazniewski, Michal; Ginalski, Krzysztof; Czlonkowska, Anna; Socha, Piotr; Ostrowski, Jerzy

    2017-11-01

    Macro-aspartate aminotransferase (macro-AST) manifests as a persistent elevation of AST levels, because of association of the protein with immunoglobulins in the circulation. Macro-AST is a rare, benign condition without a previously confirmed genetic basis. Whole exome sequencing (WES)-based screening was performed on 32 participants with suspected familial macro-AST, while validation of variants was performed on an extended cohort of 92 probands and 1,644 healthy controls using Taqman genotyping. A missense variant (p.Gln208Glu, rs374966349) in glutamate oxaloacetate transaminase 1 (GOT1) was found, as a putative causal variant predisposing to familial macro-AST. The GOT1 p.Gln208Glu mutation was detected in 50 (54.3%) of 92 probands from 20 of 29 (69%) families, while its prevalence in healthy controls was only 0.18%. In silico analysis demonstrated that the amino acid at this position is not conserved among different species and that, functionally, a negatively charged glutamate on the GOT1 surface could strongly anchor serum immunoglobulins. Our data highlight that testing for the p.Gln208Glu genetic variant may be useful in diagnosis of macro-AST. Higher than normal levels of aspartate aminotransferase (AST) in the bloodstream may be a sign of a health problem. Individuals with macro-AST have elevated blood AST levels, without ongoing disease and often undergo unnecessary medical tests before the diagnosis of macro-AST is established. We found a genetic variant in the GOT1 gene associated with macro-AST. Genetic testing for this variant may aid diagnosis of macro-AST. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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.

  16. Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A]: An Unstable Hemoglobin Newly Detected as a De Novo Mutation in a Mauritanian Patient.

    Science.gov (United States)

    Ghaber, Sidi M; Trabelsi, Nawel; Salem, Mohamed L; Haddad, Faten; Abba, Aminetou; Darragi, Imen; Abbes, Salem

    2018-01-01

    Unstable hemoglobins (Hbs) are a group of Hb disorders that could be the origin of chronic hemolytic anemia. Most of these disorders are caused by point mutations taking place in the globin genes and affecting the stability of the Hb molecule. They are inherited as autosomal dominant diseases and described worldwide. Herein we report a new observation of an unstable variant in the Mauritanian population. The patient was a young girl of Mauritanian origin. She presented with chronic hemolytic anemia with an unknown etiology after being referred to several medical centers. Laboratory investigations based on routine analyses, capillary electrophoresis (CE), cation exchange high performance liquid chromatography (HPLC) and DNA sequencing revealed an abnormal unstable Hb known as Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A] that occurred as a de novo mutation newly detected in an African girl of Mauritanian origin.

  17. Alanine aminotransferase and the 6-year risk of the metabolic syndrome in Caucasian men and women : The Hoorn Study

    NARCIS (Netherlands)

    Schindhelm, R. K.; Dekker, J. M.; Nijpels, G.; Stehouwer, C. D A; Bouter, L. M.; Heine, R. J.; Diamant, M.

    Aims: To study the association between alanine aminotransferase (ALT) and the 6-year risk of the metabolic syndrome in a population-based study in Caucasian men and women. Methods: The association of ALT with the 6-year risk of the metabolic syndrome in 1097 subjects, aged 50-75 years, was assessed

  18. Increased alanine aminotransferase levels and associated characteristics among newly diagnosed type 2 diabetes patients: Results from the DD2 study

    DEFF Research Database (Denmark)

    Mor, Anil; Thomsen, Reimar W.; Rungby, Jørgen

    Objectives: Elevated levels of serum alanine aminotransferase (ALAT) have been linked with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), insulin resistance and the metabolic syndrome in type 2 diabetes (T2D) patients. We examined ALAT levels in newly diagnosed T2D...

  19. Expression of Aryl Hydrocarbon Hydroxylase Induction and Suppression of Tyrosine Aminotransferase Induction in Somatic-Cell Hybrids

    Science.gov (United States)

    Benedict, W. F.; Nebert, D. W.; Thompson, E. B.

    1972-01-01

    Aryl hydrocarbon hydroxylase activity is inducible in mouse 3T3 fibroblasts by benz[α]anthracene, whereas no detectable basal or inducible levels of this enzyme occur in rat-hepatoma tissue culture cells. Conversely, tyrosine aminotransferase activity is inducible in hepatoma cells by dexamethasone, whereas only low noninducible levels of this enzyme exist in 3T3 cells. In hybrids formed by fusion of these two parent lines, levels of inducible hydroxylase activity range from the same as, to more than 20-fold greater than, that in the 3T3 parent; aminotransferase levels remain very low and noninducible in all of these same hybrids. A majority of the 1S-chromosomal complement from each parent is retained in most of these hybrids. The kinetics of hydroxylase induction and degradation, responses of hydroxylase induction to actinomycin D and cycloheximide, and the relative thermolability of the control and induced activities are similar in the 3T3 parent and in the hybrids. Failure to inactivate any of the aminotransferase activity in the hybrids with antibody specific for the rat enzyme indicates that all of the basal noninducible aminotransferase activity is derived from the mouse 3T3 parent. Images PMID:4403306

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

    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 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 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 level of ALT ( r =-0.044, P >0.05) , and that the serum level of AST was positively correlated with that of ALT ( r =0.736, P stress was positively correlated with the serum level of AST ( r =0.069, P level of ALT ( r =-0.042, P >0.05) , and the serum level

  2. L-lysine epsilon-aminotransferase involved in cephamycin C synthesis in Streptomyces lactamdurans.

    Science.gov (United States)

    Kern, B A; Hendlin, D; Inamine, E

    1980-01-01

    In Streptomyces lactamdurans, the precursor of the alpha-aminoadipoyl side-chain of cephamycin C is L-lysine. In this regard, streptomycetes differ strikingly from the fungi, which produce alpha-aminoadipic acid during the synthesis, rather than the breakdown, of L-lysine. Studies using a cell-free system showed that an aminoadipic acid. The product of this reaction was trapped and subsequently purified by ion-exchange chromatography. Thin-layer chromatography, spectrophotometry, and amino acid oxidase digestion studies identified the reaction product as L-1-piperideine-6-carboxylate, implying enzymatic removal of the epsilon amino group of L-lysine. This enzymatic activity (E.C. 2.6.1.36; L-lysine: 2-oxoglutarate 6-aminotransferase) is highly unusual and was previously conclusively demonstrated only in the genus Flavobacterium. In S. lactamdurans, the specific activity of this enzyme reaches a peak early in the fermentation (approximately 20 h) and decreases as the antibiotic begins to appear. PMID:6772093

  3. Progesterone causes metabolic changes involving aminotransferases and creatine kinase in cryopreserved bovine spermatozoa.

    Science.gov (United States)

    Fernández, Silvina; Córdoba, Mariana

    2016-01-01

    Progesterone (P4) is capable of inducing acrosome reaction in many species. The objective of this study was to determine the activity of enzymes involved in metabolism that contribute to the redox state and supply energy for acrosome reaction in cryopreserved bull spermatozoa. To accomplish this aim, acrosome reaction was induced by P4 in capacitated and non-capacitated samples. Alanine and aspartate aminotransferases (ALT, AST) and creatine kinase (CK) activities were measured spectrophotometrically at 340 nm after acrosome reaction with P4. Oxygen consumption was measured polarographically. ALT and AST activities increased by the addition of P4 capacitated and non-capacitated samples. P4 addition provoked an increase in CK activity in non-capacitated spermatozoa compared to heparin capacitated spermatozoa with or without P4 addition. P4 increased oxygen consumption, the percentage of acrosome reacted spermatozoa as well as the absence of acrosome integrity in both capacitated and non-capacitated bovine spermatozoa, but oxygen consumption in P4 samples was significantly lower than in heparin capacitated spermatozoa (Pspermatozoa, compared to heparin induced capacitation process. Copyright © 2015. Published by Elsevier B.V.

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

    Science.gov (United States)

    Thuy, Tran Nguyen Thanh; Tseng, Tina T-C

    2016-05-26

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

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

    Science.gov (United States)

    Sandorf, Iris; Holländer-Czytko, Heike

    2002-11-01

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

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

    Science.gov (United States)

    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.

  7. Cadmium affects the activity of rat liver tyrosine aminotransferase and its induction by dexamethasone

    Energy Technology Data Exchange (ETDEWEB)

    Dundjerski, J. [Department of Ecology, Institute for Biological Research, 29. Novembra 142, Yu-11060 Belgrade (Yugoslavia); Butorovic, B. [Department of Molecular Biology and Biochemistry, Institute for Biological Research, 29. Novembra 142, YU-11060 Belgrade (Yugoslavia); Kipic, J. [Department of Molecular Biology and Biochemistry, Institute for Biological Research, 29. Novembra 142, YU-11060 Belgrade (Yugoslavia); Trajkovic, D. [Department of Molecular Biology and Biochemistry, Institute for Biological Research, 29. Novembra 142, YU-11060 Belgrade (Yugoslavia); Matic, G. [Department of Molecular Biology and Biochemistry, Institute for Biological Research, 29. Novembra 142, YU-11060 Belgrade (Yugoslavia)

    1996-03-01

    The effects of cadmium (Cd) administration to intact rats on hepatic glucocorticoid receptor (GR) steroid binding capacity and DNA-binding ability were examined and correlated with the influence of the metal on rat liver tyrosine aminotransferase (TAT) activity and its induction by dexamethasone. It was found that 24 h after i.p. administration of Cd doses ranging from 0.5 to 4 mg/kg, the GR steroid- and DNA-binding activities were significantly reduced in a dose-dependent manner. The same doses of Cd also affected the basal and dexamethasone-induced level of TAT activity, as well as the concentration of metallothionein in rat liver. The decrease in TAT activity and in its induction by dexamethasone observed in response to low Cd doses was proportional to the alterations of the GR functional properties. Higher doses of Cd, which were more effective in reducing both the GR binding of the hormone and to DNA, however, stimulated TAT activity and potentiated dexamethasone induction of the enzyme. The results led to the conclusion that Cd may alter physiological response of rat liver cells to glucocorticoids interfering with the GR-dependent transcriptional regulation of the TAT gene. (orig.). With 6 figs.

  8. High aspartate aminotransferase level predicts poor neurodevelopmental outcome in infants with meconium aspiration syndrome.

    Science.gov (United States)

    Chen, I-Lun; Ou-Yang, Mei-Chen; Chen, Feng-Shun; Chung, Mei-Yung; Chen, Chih-Cheng; Huang, Hsin-Chun

    2014-11-01

    The aim of our study is to clarify the perinatal predictive factors of meconium aspiration syndrome (MAS) with neurodevelopmental delay (ND) in infants. In this retrospective study, data were collected from the infants born between 1990 and 2008. They all had primary diagnosis of MAS. Multivariable analyzed perinatal predictive factors of MAS with ND. The developmental status of these infants was followed at least 2 years with the Wechsler Intelligence Scale for Children. A total of 114 surviving babies met the criteria of MAS. Six babies were defined as ND group. Lower 5-minute Apgar score and diastolic blood pressure were significantly related to the ND group. Elevated asparatate aminotransferase (AST), nucleated red blood cells, and white blood cells at the time of admission were significantly high in ND group. Furthermore, AST had area under the receiver operating characteristic curve of 0.879, (95% confidence interval: 0.801, 0.934), p < 0.0001. At 96 mg/dL, it had 83.33% sensitivity, 80.81% specificity, and negative predictive value of 98.8. Multivariable logistic regression analysis revealed AST was the only significant predictive factor for MAS with ND. Early intervention should be recommended in infants having MAS with high AST level at birth for improving their neurodevelopmental outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Design and Mechanism of Tetrahydrothiophene-Based γ-Aminobutyric Acid Aminotransferase Inactivators

    Energy Technology Data Exchange (ETDEWEB)

    Le, Hoang V. [Departments; Hawker, Dustin D. [Departments; Wu, Rui [Department; Doud, Emma [Departments; Widom, Julia [Departments; Sanishvili, Ruslan [X-ray; Liu, Dali [Department; Kelleher, Neil L. [Departments; Silverman, Richard B. [Departments

    2015-03-25

    Low levels of gamma-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinsons disease, Alzheimers disease, Huntingtons 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 bloodbrain barrier and inhibit the activity of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues 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 8 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-bonding interactions with Arg-192, a pi-pi interaction with Phe-189, and a weak nonbonded (SO)-O-...=C interaction with Glu-270, thereby inactivating the enzyme.

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

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    Tran Nguyen Thanh Thuy

    2016-05-01

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

  11. Regional variation of alanine aminotransferase serum levels in the People's Republic of China

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    Peng Li

    2017-11-01

    Full Text Available The regional variation of the blood concentration of alanine aminotransferase (ALT, a sensitive predictor of liver damage, was studied in the People’s Republic of China with reference to its potential association with environmental variables and geographic location. The research results presented are based on 121,977 blood samples from healthy adults in 93 cities in the country using correlation analysis, ridge regression estimation and trend surface analysis that were applied to explore if there was any tendency of spatial variation. A regression formula using a simulation equation under the condition of known local geographic factors was used. Statistical significance was set at P<0.05. A positive correlation between ALT concentration altitude and sunshine hours and a negative correlation between ALT concentration and temperature, humidity and precipitation were found. With respect to geographical location, there was a negative correlation between ALT concentration and longitude. Higher ALT values were found in western China compared to eastern regions, dividing the country into three different regions with respect to serum ALT levels.

  12. Measurement and purification of Alanine aminotransferase (ALT enzyme activity in patients with celiac disease

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    Taghreed U. Mohammed

    2017-09-01

    Full Text Available Celiac disease (CD is the most common genetically - based disease in correlation with food intolerance. The aim of this study is to measure the activity of ALT enzyme and purify enzyme from sera women with celiac disease. Alanine aminotransferase (ALT activity has been assayed in (30 women serum samples with celiac disease, age range between (20-40 year and (30 serum of healthy women as control group, age range between (22-38 year. In the present study, the mean value of ALT activity was significantly higher in patients with celiac disease than healthy group (p<0.01. The ALT enzyme was partial purified from sera women with celiac disease by dialysis, gel filtration using Sephadex G- 50 and ion exchange chromatography using DEAE- cellulose A-50 . The results showed a single peak by using gel filtration and the activity reached 31-15 U/L .Two isoenzymes were obtained by using ion exchange chromatography and the purity degree of isoenzymse (I, II were (5.7 and (5.53 fold respectively

  13. [Reestimation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio based on JSCC consensus method--changes of criteria for a differential diagnosis of hepatic disorders following the alteration from Karmen method to JSCC method].

    Science.gov (United States)

    Kotani, K; Maekawa, M; Kanno, T

    1994-02-01

    We estimated clinical criteria of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio that is measured by the consensus method of JSCC (Japan Society of Clinical Chemistry) for serum AST and ALT. The JSCC consensus method is closely correlated with both IFCC (International Federation of Clinical Chemistry) recommended method without pyridoxal phosphate and Karmen method recommended by the expert panel of liver function tests in Japanese Society of Gastroenterology. The slopes of the regression line is estimated to be 1.00 and 0.87 respectively. We propose that the decision making value of AST/ALT ratio to differentiate several types of liver diseases should be set to 0.87 measured by JSCC consensus method, instead of 1.0 measured by Karmen method.

  14. Prevalence of viral hepatitis (B and C serological markers in healthy working population

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    José Luis Calleja-Panero

    2013-06-01

    Full Text Available Introduction and objectives: prevalence of viral hepatitis (B and C changes geographically. Our aim was to determinate the prevalence of hepatitis B (HBV and hepatitis C virus (HCV serological markers in healthy working population and to describe the epidemiological characteristics associated to its presence. Methods: blood samples and epidemiological data of 5,017 healthy workers from Murcia and Madrid were recorded prospectively. Results: a total of 5,017 healthy volunteers participated. Mean age 39 ± 11 years, men predominance (73 %. Prevalence of serological markers of HCV and HBV was 0.6 % and 0.7 %. Age of patients with HCV antibody was significantly higher (43 ± 9 years vs. 39 ± 11 years; p = 0.03. We observed significant differences in liver test values (alanine aminotransferase [ALT] 64 ± 56 IU/L vs. 28 ± 20 IU/L; p < 0.001; aspartate aminotransferase [AST] (51 ± 45 IU/L vs. 23 ± 12 IU/L; p < 0.001 and in gamma-glutamyltransferase (GGT value (104 ± 122 IU/L vs. 37 ± 46 IU/L; p < 0.001. The presence of HCV antibody was related significantly to previous transfusion (13 % vs. 5 %; p = 0.03, tattoos (29 % vs. 13 %; p < 0.01, intravenous drug addiction (13 % vs. 0.2 %; p < 0.001 and coexistence with people with positive HCV antibody (16 % vs. 4 %; p < 0.001. In HBV no differences in basal characteristics were observed with exception in AST values (29 ± 15 IU/L vs. 23 ± 12 IU/L; p < 0.01. Hepatitis B surface antigen (HBsAg was related significantly to previous transfusion (15 % vs. 5 %; p < 0.01, tattoos (26 % vs. 14 %; p = 0.04 and coexistence with people with positive HBsAg (17 % vs. 4 %; p < 0.001. Conclusions: prevalence of serological markers in healthy working population is low. Risk factors for infection were previous transfusion and tattoos. Intravenous drug addiction was only a risk factor in HCV.

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

    Science.gov (United States)

    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

  16. PLATELET COUNT SQUARED/SPLEEN DIAMETER-ASPARTATE AMINOTRANSFERASE RATIO: NON-INVASIVE METHOD TO PREDICT ESOPHAGEAL VARICES

    OpenAIRE

    MATTOS, Ângelo Zambam de; DAROS, Larissa Faraco; MATTOS, Angelo Alves de

    2017-01-01

    ABSTRACT BACKGROUND - Variceal bleeding has a high mortality among cirrhotics, and screening with endoscopy is indicated at the diagnosis of cirrhosis. Screening with endoscopy implies discomfort, risks and considerable costs. OBJECTIVE - To evaluate platelet count squared/spleen diameter-aspartate aminotransferase ratio (PS/SA), as a non-invasive predictor of esophageal varices in cirrhotics. METHODS - This cross-sectional study evaluated cirrhotics for PS/SA and presence of esophageal...

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

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    B Sabayan

    2010-06-01

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

  18. Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

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    Fábio Heleno de Lima Pace

    2012-08-01

    Full Text Available INTRODUCTION: Approximately 30% of hepatitis C virus (HCV monoinfected patients present persistently normal alanine aminotransferase (ALT levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive with known time of HCV infection (intravenous drugs users were selected. Patients with hepatitis B surface antigen (HBsAg positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80% were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26% patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001 periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001 and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

  19. L,L-diaminopimelate aminotransferase from Chlamydomonas reinhardtii: a target for algaecide development.

    Science.gov (United States)

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

    2011-01-01

    In some bacterial species and photosynthetic cohorts, including algae, the enzyme L,L-diaminopimelate aminotransferase (DapL) (E.C. 2.6.1.83) is involved in the anabolism of the essential amino acid L-lysine. DapL catalyzes the conversion of tetrahydrodipicolinate (THDPA) to L,L-diaminopimelate (L,L-DAP), in one step bypassing the DapD, DapC and DapE enzymatic reactions present in the acyl DAP pathways. Here we present an in vivo and in vitro characterization of the DapL ortholog from the alga Chlamydomonas reinhardtii (Cr-DapL). The in vivo analysis illustrated that the enzyme is able to functionally complement the E. coli dap auxotrophs and was essential for plant development in Arabidopsis. In vitro, the enzyme was able to inter-convert THDPA and L,L-DAP, showing strong substrate specificity. Cr-DapL was dimeric in both solution and when crystallized. The structure of Cr-DapL was solved in its apo form, showing an overall architecture of a α/β protein with each monomer in the dimer adopting a pyridoxal phosphate-dependent transferase-like fold in a V-shaped conformation. The active site comprises residues from both monomers in the dimer and shows some rearrangement when compared to the apo-DapL structure from Arabidopsis. Since animals do not possess the enzymatic machinery necessary for the de novo synthesis of the amino acid L-lysine, enzymes involved in this pathway are attractive targets for the development of antibiotics, herbicides and algaecides.

  20. L,L-diaminopimelate aminotransferase from Chlamydomonas reinhardtii: a target for algaecide development.

    Directory of Open Access Journals (Sweden)

    Renwick C J Dobson

    Full Text Available In some bacterial species and photosynthetic cohorts, including algae, the enzyme L,L-diaminopimelate aminotransferase (DapL (E.C. 2.6.1.83 is involved in the anabolism of the essential amino acid L-lysine. DapL catalyzes the conversion of tetrahydrodipicolinate (THDPA to L,L-diaminopimelate (L,L-DAP, in one step bypassing the DapD, DapC and DapE enzymatic reactions present in the acyl DAP pathways. Here we present an in vivo and in vitro characterization of the DapL ortholog from the alga Chlamydomonas reinhardtii (Cr-DapL. The in vivo analysis illustrated that the enzyme is able to functionally complement the E. coli dap auxotrophs and was essential for plant development in Arabidopsis. In vitro, the enzyme was able to inter-convert THDPA and L,L-DAP, showing strong substrate specificity. Cr-DapL was dimeric in both solution and when crystallized. The structure of Cr-DapL was solved in its apo form, showing an overall architecture of a α/β protein with each monomer in the dimer adopting a pyridoxal phosphate-dependent transferase-like fold in a V-shaped conformation. The active site comprises residues from both monomers in the dimer and shows some rearrangement when compared to the apo-DapL structure from Arabidopsis. Since animals do not possess the enzymatic machinery necessary for the de novo synthesis of the amino acid L-lysine, enzymes involved in this pathway are attractive targets for the development of antibiotics, herbicides and algaecides.

  1. Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

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    Setor K Kunutsor

    Full Text Available BACKGROUND: Elevated baseline circulating alanine aminotransferase (ALT level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS, but the nature of the dose-response relationship is uncertain. METHODS: We performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines. RESULTS: Of the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38 between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%. Evidence was lacking of heterogeneity and publication bias among the contributing studies. CONCLUSIONS: Baseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-08-24

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

  4. Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.

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    Joanne M Kingsbury

    2015-12-01

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

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

    Science.gov (United States)

    Lee, Eun-Jeong; Facchini, Peter J.

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bin Shen

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

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

    Science.gov (United States)

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

    2016-04-01

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

  8. A prospective study on the causes of notably raised alanine aminotransferase (ALT).

    Science.gov (United States)

    Björnsson, Helgi Kristinn; Olafsson, Sigurdur; Bergmann, Ottar M; Björnsson, Einar S

    2016-01-01

    High levels of alanine aminotransferase (ALT) can be a marker of severe liver disease with variable aetiologies and prognosis. Very few prospective studies have been undertaken on the aetiology and prognosis of patients with high ALT levels. No population-based prospective study has systematically evaluated drug-induced liver injury (DILI) among these patients. The objective was to determine the aetiology and prognosis of patients with high ALT. In a catchment area of 160,000 inhabitants, a population-based prospective study identified all adult patients with serum level of ALT >500 U/L during a 12-month period. All underwent thorough diagnostic work-up and follow-up. In suspected DILI, causality was assessed with Roussel Uclaf Causality Assessment Method. A total of 155 patients were identified with ALT >500 U/L, 12 children and one with ALT of non-liver-related origin, leaving 142 patients for the analysis: 73 (51%) males, median age 52 (IQR 36-68, range 19-89 years). The most common causes were choledocholithiasis 48/142 (34%), ischaemic hepatitis 26 (18%), viral hepatitis 16 (11%) and DILI 15 (11%), hepatobiliary malignancy (n = 6), surgery/interventions (n = 8) and other aetiologies (n = 23). No specific aetiology was found in 6% of cases. In the total study cohort 99 (70%) required hospitalisation, 78 (55%) had jaundice and 22 (16%) died, liver-related death in 10%, 35% in IH and 7% in DILI. The most common cause of notably high ALT was choledocholithiasis. Ischaemic hepatitis was a common aetiology with approximately 35% liver-related mortality. Viral hepatitis and DILI were important aetiologies among these patients.

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

    Science.gov (United States)

    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.

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

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    Mehrnaz Shirmohammadi*

    2017-06-01

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

  11. The role of liver fat and insulin resistance as determinants of plasma aminotransferase elevation in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Maximos, Maryann; Bril, Fernando; Portillo Sanchez, Paola; Lomonaco, Romina; Orsak, Beverly; Biernacki, Diane; Suman, Amitabh; Weber, Michelle; Cusi, Kenneth

    2015-01-01

    Plasma aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are usually increased in patients with nonalcoholic fatty liver disease (NAFLD). However, the factors behind their elevation remain unclear. The aim of this study was to assess the role of insulin resistance (IR) and liver triglyceride content in relation to histology in patients with NAFLD/nonalcoholic steatohepatitis (NASH) with normal or elevated ALT levels. To this end, we enrolled 440 patients, divided into three groups: no NAFLD (n = 60); NAFLD with normal ALT (n = 165); and NAFLD with elevated ALT (n = 215). We measured: (1) liver fat by proton magnetic resonance spectroscopy ((1)H-MRS); (2) severity of liver disease by biopsy (n = 293); and (3) insulin sensitivity in liver, muscle, and adipose tissue by a euglycemic hyperinsulinemic clamp with 3-(3)H-glucose. Patients with NAFLD and elevated ALT, even when well matched for body mass index to those with normal ALT, had worse adipose tissue insulin resistance (ATIR; P insulin resistance. Similar results were found when only patients with NASH were compared: both ATIR (P management. © 2014 by the American Association for the Study of Liver Diseases.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    for colorectal cancer metastases. Methods: Patients undergoing liver resection for colorectal cancer metastases in a European institution during 2003–2010 were retrospectively enrolled. Relevant data, such as neoadjuvant chemotherapy, preoperative liver function tests, and perioperative complications, were.......175) or steatosis (p = 0.173) in the nontumorous liver in surgical specimens. Conclusion: The preoperative aspartate aminotransferase-to-platelet ratio index, but not the aspartate-to-alanine aminotransferase ratio, predicts perioperative liver-related complications following hepatectomy due to colorectal cancer...... with neoadjuvant chemotherapy (odds ratio: 1.157, p = 0.004) but not in those without such therapy (p = 0.062). The aspartate-to-alanine aminotransferase ratio was not related to liver-related complications (p = 0.929). The area under the receiver operating characteristics curve for the aspartate aminotransferase...

  13. Association of vitamin E intake at early childhood with alanine aminotransferase levels at mid-childhood.

    Science.gov (United States)

    Woo Baidal, Jennifer A; Cheng, Erika R; Rifas-Shiman, Sheryl L; Oken, Emily; Gillman, Matthew W; Taveras, Elsie M

    2018-04-01

    The extent to which vitamin E (alpha-tocopherol) intake early in childhood is associated with alanine aminotransferase (ALT) level later in childhood is unknown. The objective of this research is to test the hypothesis that higher alpha-tocopherol intake during early childhood is associated with lower odds of elevated ALT levels during mid-childhood and to examine how body mass index (BMI) influences these relationships. We studied 528 children in Project Viva. Mothers reported child dietary intake at early childhood visits (median 3.1 years) using a validated food frequency questionnaire. At mid-childhood (median 7.6 years), we collected child blood and anthropometric data. The main outcome was elevated sex-specific mid-childhood ALT level (≥22.1 U/L for female children and ≥25.8 U/L for male children). In multivariable logistic regression models, we assessed the association of energy-adjusted alpha-tocopherol intake with ALT levels, adjusting for child age, sex, race/ethnicity, diet, and age-adjusted sex-specific BMI z-score at mid-childhood. Among children in this study, 48% were female, 63% were non-Hispanic white, 19% were non-Hispanic black, and 4% were Hispanic/Latino. Mean alpha-tocopherol intake was 3.7 ± 1.0 mg/day (range, 1.4-9.2) at early childhood. At mid-childhood, mean BMI z-score was 0.41 ± 1.0 units and 22% had an elevated ALT level. In multivariable-adjusted logistic regression models, children with higher early childhood vitamin E intake had lower odds of elevated mid-childhood ALT (adjusted odds ratio [AOR], 0.62; 95% confidence interval [CI], 0.39, 0.99) for quartiles 2-4 compared with the lowest quartile of intake. Findings persisted after accounting for early childhood diet (AOR, 0.62; 95% CI, 0.36, 1.08) and were strengthened after additionally accounting for mid-childhood BMI z-score (AOR, 0.56; 95% CI, 0.32, 0.99). In this cohort, higher early childhood intake of alpha-tocopherol was associated with lower odds of elevated mid

  14. Alanine aminotransferase catalyses the breakdown of alanine after hypoxia in Arabidopsis thaliana.

    Science.gov (United States)

    Miyashita, Yo; Dolferus, Rudy; Ismond, Kathleen P; Good, Allen G

    2007-03-01

    Alanine aminotransferase (AlaAT) catalyses the reversible transfer of an amino group from glutamate to pyruvate to form 2-oxoglutarate and alanine. The regulation of AlaAT in several plant species has been studied in response to low-oxygen stress, light and nitrogen application. In this study, induction of Arabidopsis AlaAT1 and AlaAT2 during hypoxia was observed at the transcriptional level, and an increase in enzyme activity was detected in hypoxically treated roots. In addition, the tissue-specific expression of AlaAT1 and AlaAT2 was analysed using promoter:GUS fusions. The GUS staining patterns indicated that both AlaAT genes are expressed predominantly in vascular tissues. We manipulated AlaAT expression to determine the relative importance of this enzyme in low-oxygen stress tolerance and nitrogen metabolism. This was done by analysing T-DNA mutants and over-expressing barley AlaAT in Arabidopsis. The AlaAT1 knockout mutant (alaat1-1) showed a dramatic reduction in AlaAT activity, suggesting that AlaAT1 is the major AlaAT isozyme in Arabidopsis. Over-expression of barley AlaAT significantly increased the AlaAT activity in the transgenic plants. These plants were analysed for metabolic changes over a period of hypoxic stress and during their subsequent recovery. The results showed that alaat1-1 plants accumulate more alanine than wild-type plants during the early phase of hypoxia, and the decline in accumulated alanine was delayed in the alaat1-1 line during the post-hypoxia recovery period. When alanine was supplied as the nitrogen source, alaat1-1 plants utilized alanine less efficiently than wild-type plants did. These results indicate that the primary role of AlaAT1 is to break down alanine when it is in excess. Therefore, AlaAT appears to be crucial for the rapid conversion of alanine to pyruvate during recovery from low-oxygen stress.

  15. External validation of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity from paracetamol overdose.

    Science.gov (United States)

    Wong, Anselm; Sivilotti, Marco L A; Dargan, Paul I; Wood, David M; Greene, Shaun L

    2015-01-01

    Risk prediction in paracetamol (acetaminophen, or APAP) poisoning treated with acetylcysteine helps guide initial patient management and disposition. The paracetamol-aminotransferase multiplication product may be a useful and less time-sensitive risk predictor. The aim of this study was to validate this multiplication product in an independent cohort of patients with paracetamol overdose. Using an existing toxicology dataset of poisoned patients from two large inner-city United Kingdom teaching hospitals, we retrospectively identified by electronic search all paracetamol overdoses from February 2005 to March 2013. We assessed the diagnostic accuracy of the multiplication product (serum APAP concentration × alanine transaminase [ALT] activity), especially at the pre-specified cut-off points of 1 500 mg/L × IU/L (10 000 micromol/L × IU/L) and 10 000 mg/L × IU/L (66 000 micromol/L × IU/L). The primary outcome was hepatotoxicity defined by a peak ALT > 1000 IU/L. Of 3823 total paracetamol overdose presentations, there were 2743 acute single, 452 delayed single (> 24 h post overdose), 426 staggered (ingestion over > 1 h), and 202 supratherapeutic ingestions. Altogether, 34 patients developed hepatotoxicity. Among the acute single-ingestion patients, a multiplication product > 10 000 mg/L × IU/L had a sensitivity of 80% (95% confidence interval [CI]: 44%, 96%) and specificity of 99.6% [99.3%, 99.8%], while a product > 1 500 mg/L × IU/L had a sensitivity of 100% [66%, 100%] and specificity of 92% [91%, 93%]. Overall, 16 patients with a multiplication product > 10 000 mg/L × IU/L developed hepatotoxicity (likelihood ratio: 250, 95% CI: 130, 480), and 4 patients with a multiplication product between 1 500 and 10 000 (likelihood ratio: 2.5, 95% CI: 1.0, 6.0). No patient with a product 10 000 mg/L × IU/L was associated with a very high likelihood, and < 1 500 mg/L × IU/L with a very low likelihood, of developing hepatotoxicity in patients treated with acetylcysteine.

  16. Validity of aspartate aminotransferase to platelet ratio index as predictor of early viral response in patients with hepatitis C treated by interferon-based therapy.

    Science.gov (United States)

    Samiullah, Shaikh; Bikharam, Devrajai; Musarat, Kalhoro

    2012-10-01

    To observe any change in value of aspartate aminotransferase to platelet ratio index from the baseline and to compare it with the Hepatitis C virus ribonucleic acid at 12 weeks after the start of interferon-based treatment in patients with Hepatitis C. The prospective study, conducted at the Department of Medicine, Liaquat University of Medical and Health Sciences Hospital, Jamshoro, Pakistan, from September 2009 to March 2010, included 158 consecutive, chronic patients of Hepatitis C with grade > or = 2 fibrosis on liver biopsy, or having aspartate aminotransferase/Platelet ratio index of > 1. The aspartate aminotransferase to platelet ratio index was determined as aspartate aminotransferase level (upper normal limit)/platelets counts (10(9)/L) x 100. Eligible patients were assigned to receive thrice weekly subcutaneous injection of 3MIU standard interferon > or = -2b and weight-base dosage of ribavirin. The early virological response was defined as undetectable Hepatitis C virus ribonucleic acid test at week 12 of the study. APRI virus ribonucleic acid after 12 weeks of treatment was non-detectable (early viral response achieved) in 72 (80%) patients. A strong relation was found between aspartate aminotransferase to platelet ratio index and Negative polymerase chain reaction with early virological response as only 2 (4.5%) patients with negative polymerase chain reaction at 12 weeks had aspartate aminotransferase to platelet ratio index > 1 (p = 0.001). APRI can act as a predictor of early viral response in patients with Hepatits C.

  17. Padre Pio Rest Home, Cappoquin, Waterford.

    LENUS (Irish Health Repository)

    Elshorbagy, Amany K

    2009-07-01

    We recently reported a strong positive association of plasma total cysteine (tCys) with fat mass in over 5,000 subjects. As gamma-glutamyltransferase (GGT) enzyme increases cysteine availability by catalyzing glutathione breakdown and is positively associated with BMI and adiposity, we hypothesized that GGT might explain the association of tCys with adiposity. To study whether the associations of tCys and serum GGT with BMI and obesity were interrelated we conducted a cross-sectional study using data from 1,550 subjects recruited from nine European countries in the COMAC project. Multiple linear and logistic regression models and concentration-response curves were used. In age and sex-adjusted analyses, tCys showed strong positive associations with BMI (partial r = 0.19, P < 0.001), and obesity (odds ratio (OR) for 4th vs. 1st tCys quartile: 2.8; 95% confidence interval: 1.6-5.0, P < 0.001), both of which remained robust after adjustment for GGT and other metabolic and lifestyle confounders. Serum GGT was also a positive predictor of BMI (partial r = 0.17, P < 0.001) and obesity (OR for 4th vs. 1st GGT quartile: 4.8; 95% confidence interval: 2.5-9.2, P < 0.001), independent of tCys. However, the associations of GGT with BMI and obesity were weakened by adjustment for obesity-related factors such as serum lipids and blood pressure. These results indicate that tCys is a strong positive predictor of BMI and obesity, independent of GGT and other obesity-related factors. We also suggest that the association of serum GGT with BMI and obesity is unrelated to the role of GGT in cysteine turnover. The potential link between cysteine and fat metabolism should be further evaluated.

  18. GGT (Gamma-Glutamyl Transferase) Test

    Science.gov (United States)

    ... Culture Blood Gases Blood Ketones Blood Smear Blood Typing Blood Urea Nitrogen (BUN) BNP and NT-proBNP ... Luteinizing Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, Second Trimester Measles and Mumps Tests Mercury ...

  19. Reconfiguration of N Metabolism upon Hypoxia Stress and Recovery: Roles of Alanine Aminotransferase (AlaAT and Glutamate Dehydrogenase (GDH

    Directory of Open Access Journals (Sweden)

    Houssein Diab

    2016-05-01

    Full Text Available In the context of climatic change, more heavy precipitation and more frequent flooding and waterlogging events threaten the productivity of arable farmland. Furthermore, crops were not selected to cope with flooding- and waterlogging-induced oxygen limitation. In general, low oxygen stress, unlike other abiotic stresses (e.g., cold, high temperature, drought and saline stress, received little interest from the scientific community and less financial support from stakeholders. Accordingly, breeding programs should be developed and agronomical practices should be adapted in order to save plants’ growth and yield—even under conditions of low oxygen availability (e.g., submergence and waterlogging. The prerequisite to the success of such breeding programs and changes in agronomical practices is a good knowledge of how plants adapt to low oxygen stress at the cellular and the whole plant level. In the present paper, we summarized the recent knowledge on metabolic adjustment in general under low oxygen stress and highlighted thereafter the major changes pertaining to the reconfiguration of amino acids syntheses. We propose a model showing (i how pyruvate derived from active glycolysis upon hypoxia is competitively used by the alanine aminotransferase/glutamate synthase cycle, leading to alanine accumulation and NAD+ regeneration. Carbon is then saved in a nitrogen store instead of being lost through ethanol fermentative pathway. (ii During the post-hypoxia recovery period, the alanine aminotransferase/glutamate dehydrogenase cycle mobilizes this carbon from alanine store. Pyruvate produced by the reverse reaction of alanine aminotransferase is funneled to the TCA cycle, while deaminating glutamate dehydrogenase regenerates, reducing equivalent (NADH and 2-oxoglutarate to maintain the cycle function.

  20. Reconfiguration of N Metabolism upon Hypoxia Stress and Recovery: Roles of Alanine Aminotransferase (AlaAT) and Glutamate Dehydrogenase (GDH)

    Science.gov (United States)

    Diab, Houssein; Limami, Anis M.

    2016-01-01

    In the context of climatic change, more heavy precipitation and more frequent flooding and waterlogging events threaten the productivity of arable farmland. Furthermore, crops were not selected to cope with flooding- and waterlogging-induced oxygen limitation. In general, low oxygen stress, unlike other abiotic stresses (e.g., cold, high temperature, drought and saline stress), received little interest from the scientific community and less financial support from stakeholders. Accordingly, breeding programs should be developed and agronomical practices should be adapted in order to save plants’ growth and yield—even under conditions of low oxygen availability (e.g., submergence and waterlogging). The prerequisite to the success of such breeding programs and changes in agronomical practices is a good knowledge of how plants adapt to low oxygen stress at the cellular and the whole plant level. In the present paper, we summarized the recent knowledge on metabolic adjustment in general under low oxygen stress and highlighted thereafter the major changes pertaining to the reconfiguration of amino acids syntheses. We propose a model showing (i) how pyruvate derived from active glycolysis upon hypoxia is competitively used by the alanine aminotransferase/glutamate synthase cycle, leading to alanine accumulation and NAD+ regeneration. Carbon is then saved in a nitrogen store instead of being lost through ethanol fermentative pathway. (ii) During the post-hypoxia recovery period, the alanine aminotransferase/glutamate dehydrogenase cycle mobilizes this carbon from alanine store. Pyruvate produced by the reverse reaction of alanine aminotransferase is funneled to the TCA cycle, while deaminating glutamate dehydrogenase regenerates, reducing equivalent (NADH) and 2-oxoglutarate to maintain the cycle function. PMID:27258319

  1. Correlation between Aminotransferase Ratio (AST/ALT and Other Biochemical Parameters in Chronic Liver Disease of Viral Origin

    Directory of Open Access Journals (Sweden)

    Shah Md Fazlul Karim

    2015-03-01

    Full Text Available Background: In recent years the ratio of aspartate aminotransferase (AST to alanine aminotransferase (ALT in patients of chronic liver disease (CLD of various origins has gained much attention. This variable is readily available, easy to interpret, and inexpensive and the clinical utility of the AST/ALT ratio in the diagnostic workup of patients with CLD is quite promising. Objective: The present study was designed to find out the link between aminotransferase (AST/ALT ratio with commonly measured biochemical parameters of liver function tests in CLD of viral origin. Materials and method: This cross sectional study was carried out in the department of Biochemistry, Sir Salimullah Medical College, Dhaka, Bangladesh. Forty four biopsy proven diagnosed subjects of chronic viral hepatitis without cirrhosis of both sex were selected purposively. With aseptic precaution 5 mL venous blood was collected from each subject and common liver function tests (serum AST, ALT, AST/ALT ratio, alkaline phosphatase, total bilirubin, serum total protein, serum albumin, serum globulin, serum albumin/globulin ratio, prothrombin time and viral serology (HBsAg, Anti HDV antibody, Anti HCV antibody were performed. Data were analyzed by SPSS version 19 for Windows. Pearson’s correlation test was done to determine association between AST/ALT with other biochemical parameters. Results: Mean(±SD age of the study subjects was 32.55±10.55 years (range 20-50 years with 48 (77.7% male and 14 (22.6% female subjects. Pearson’s correlation test was done between AST to ALT ratio with other biochemical parameters and prothrombin time showed significant positive correlation (p <0.01. Conclusion: In our study we found significant positive correlation between AST/ALT with prothrombin time in CLD subjects without cirrhosis.

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

    Science.gov (United States)

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

    2017-06-01

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

  3. Tratamento homeopático da hepatotoxicose aguda induzida por tetracloreto de carbono em coelhos Homeopatic treatment of acute carbon tetrachloride induced hepatotoxicity in rabbits

    Directory of Open Access Journals (Sweden)

    Maria Cecília Ribeiro Moncorvo

    1998-09-01

    Full Text Available Quinze (15 coelhos (Oryctolagus cuniculus foram submetidos à intoxicação pelo tetracloreto de carbono na dosagem de 0,5 ml/kg de peso corporal, dose única, administrado por sonda gástrica. Foram realizadas as dosagens de alanina amino transferase (ALT, aspartato amino transferase (AST, fosfatase alcalina (FA e gama glutamil transferase (GGT antes e durante o experimento. Vinte e quatro (24 horas após a intoxicação, os coelhos foram divididos aleatoriamente em três grupos de 5 animais. Cada grupo recebeu um tratamento diferente durante 13 dias. O grupo I foi tratado com tetracloreto de carbono diluído na 30ª centesimal hahnemanniana (30 CH, uma vez ao dia. O grupo II recebeu Phosphorus 30 CH, também uma vez ao dia. O grupo III desempenhou o papel de controle, recebendo diariamente uma dose de placebo, pelo mesmo período de tempo que os grupos anteriores. Os resultados das concentrações séricas de ALT, AST, GGT e FA foram submetidos à análise estatística. A variação da concentração de todas as enzimas foi significativa entre os dias, mas nem todas variaram significativamente entre os grupos considerados. O tetracloreto de carbono 30 CH foi capaz de acelerar a recuperação do quadro de hepatite tóxica aguda determinada pela redução dos níveis de ALT. O tratamento com Phosphorus 30 CH mostrou-se incapaz seja de reverter o quadro de hepatite tóxica, seja de acelerar a regeneração hepática.Fithteen (15 New Zeland and Californian rabbits (Oryctolagus cuniculus were submitted to intoxication with carbon tethracloride in a dose 0/0.5 ml/kg, once a day, administred by orogastric sonde. Enzimatic parameters: alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase and gamma-glutamyltransferase of those rabbits were tested before and during the experiment. After the intoxication, the rabbits were divided in three groups of five animals. Each group received differents treatments during 13 days. The

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

    Science.gov (United States)

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

    2006-01-01

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

  5. AKTIVITAS ASPARTAT AMINOTRANSFERASE (AST DAN ALANIN TRANSAMINASE (ALT PADA MONYET EKOR PANJANG (Macaca fascicularis OBESITAS DI PURA LUHUR ULUWATU, BALI

    Directory of Open Access Journals (Sweden)

    Ayu Paramita Lestari

    2016-08-01

    Full Text Available Penelitian obsevasional-deskriptif dengan pendekatan cross-sectional telah dilakukan untuk mengetahui aktivitas aspartat aminotransferase (AST dan alanin transaminase (ALT pada monyet ekor panjang (Macaca fascicularis obesitas yang hidup liar di kawasan Pura Luhur Uluwatu, Bali. Sebanyak 16 ekor monyet ekor panjang berhasil dibius menggunakan ketamine dosis 10 mg/kg berat badan dicampur dengan premedikasi xylasin dosis 1-2 mg/kg berat badan. Sampel yang digunakan adalah serum darah monyet obesitas yang diambil dari monyet dalam keadaan terbius. Dari 16 ekor monyet, 12 ekor tergolong obesitas berdasarkan Indeks Massa Tubuh dan Berat Badan. Aktivitas aspartat aminotransferase (AST dan alanin transaminase (ALT ditentukan menggunakan mesin automatic chemistry analyzer (Indiko-Thermo Scientific. Hasil penelitian menunjukkan nilai AST bervariasi dari 43-88 U/L dan ALT 26-77 U/L dengan rataan 69,4 ± 14,9 U/L. Dari hasil penelitian dapat disimpulkan bahwa nilai AST dan ALT monyet obesitas cenderung lebih tinggi dari nilai AST dan ALT normal.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  7. Homology of 1-aminocyclopropane-1-carboxylate synthase, 8-amino-7-oxononanoate synthase, 2-amino-6-caprolactam racemase, 2,2-dialkylglycine decarboxylase, glutamate-1-semialdehyde 2,1-aminomutase and isopenicillin-N-epimerase with aminotransferases.

    Science.gov (United States)

    Mehta, P K; Christen, P

    1994-01-14

    Profile analysis showed the title enzymes to be homologous with the aminotransferases. 1-Aminocyclopropane-1-carboxylate synthase is closely related to subgroup I of aminotransferases which includes aspartate, alanine, histidinol-phosphate, tyrosine and phenylalanine aminotransferase. 2,2-Dialkylglycine decarboxylase, glutamate-1-semialdehyde 2,1-aminomutase and 2-amino-6-caprolactam racemase are most similar to subgroup II which comprises aminotransferases with omega-amino acids as substrates. 8-Amino-7-oxononanoate synthase is closely related to both subgroup I and II, and isopenicillin-N-epimerase to subgroup IV with serine and phosphoserine aminotransferase. Aminotransferases and the title enzymes belong to a regio-specific family of evolutionarily related pyridoxal-5'-phosphate-dependent enzymes.

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

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    Hartinger Doris

    2010-08-01

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

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

    Science.gov (United States)

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

    2016-01-25

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

  10. Aminotransferase elevation in HIV/hepatitis B virus co-infected patients treated with two active hepatitis B virus drugs.

    Science.gov (United States)

    Jain, Mamta K; Parekh, Nimisha K; Hester, Jill; Lee, William M

    2006-12-01

    Discerning drug hepatotoxicity from viral hepatitis flares remains an ongoing problem unique to patients coinfected with HIV and hepatitis B (HBV). We present three such coinfected patients who have been on two anti-HBV agents, lamivudine and tenofovir disoproxil fumarate simultaneously, as part of highly active antiretroviral therapy (HAART). All three developed significant aminotransferase elevations 6-12 weeks after initiation of HAART despite being on two active HBV drugs. Two of the three patients were initially thought to have drug-related hepatotoxicity from HIV medications. It seems more likely that all three patients demonstrated hepatitis B reactivation of differing severity as the result of varying degrees of immune recovery. Distinguishing clearly between drug-related hepatotoxicity and hepatitis reactivation may be difficult but is important as their clinical management differs.

  11. The Discovery of in Vivo Active Mitochondrial Branched-Chain Aminotransferase (BCATm) Inhibitors by Hybridizing Fragment and HTS Hits.

    Science.gov (United States)

    Bertrand, Sophie M; Ancellin, Nicolas; Beaufils, Benjamin; Bingham, Ryan P; Borthwick, Jennifer A; Boullay, Anne-Bénédicte; Boursier, Eric; Carter, Paul S; Chung, Chun-wa; Churcher, Ian; Dodic, Nerina; Fouchet, Marie-Hélène; Fournier, Charlène; Francis, Peter L; Gummer, Laura A; Herry, Kenny; Hobbs, Andrew; Hobbs, Clare I; Homes, Paul; Jamieson, Craig; Nicodeme, Edwige; Pickett, Stephen D; Reid, Iain H; Simpson, Graham L; Sloan, Lisa A; Smith, Sarah E; Somers, Donald O'N; Spitzfaden, Claus; Suckling, Colin J; Valko, Klara; Washio, Yoshiaki; Young, Robert J

    2015-09-24

    The hybridization of hits, identified by complementary fragment and high throughput screens, enabled the discovery of the first series of potent inhibitors of mitochondrial branched-chain aminotransferase (BCATm) based on a 2-benzylamino-pyrazolo[1,5-a]pyrimidinone-3-carbonitrile template. Structure-guided growth enabled rapid optimization of potency with maintenance of ligand efficiency, while the focus on physicochemical properties delivered compounds with excellent pharmacokinetic exposure that enabled a proof of concept experiment in mice. Oral administration of 2-((4-chloro-2,6-difluorobenzyl)amino)-7-oxo-5-propyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile 61 significantly raised the circulating levels of the branched-chain amino acids leucine, isoleucine, and valine in this acute study.

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

    Science.gov (United States)

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

    2018-04-10

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

  13. The efficacy of aspartate aminotransferase-toplatelet ratio index for assessing hepatic fibrosis in childhood nonalcoholic steatohepatitis for medical practice

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    Earl Kim

    2013-01-01

    Full Text Available Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD, and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST-to-platelet ratio index (APRI have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement &gt;5.9 kPa Fibroscan were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (&gt;5.9 kPa. In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875 presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.

  14. Lactococcal aminotransferases AraT and BcaT are key enzymes for the formation of aroma compounds from amino acids in cheese

    NARCIS (Netherlands)

    Rijnen, L.; Yvon, M.; Kranenburg, van R.; Courtin, P.; Verheul, A.; Chambellon, E.; Smit, G.

    2003-01-01

    Amino acid catabolism plays a major role in cheese aroma development. Previously, we showed that the lactococcal aminotransferases AraT and BcaT initiate the conversion of aromatic amino acids, branched-chain amino acids and methionine to aroma compounds. In this study, we evaluated the importance

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

    Science.gov (United States)

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

    2016-12-01

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

  16. Prospective association of liver function biomarkers with development of hepatobiliary cancers

    NARCIS (Netherlands)

    Stepien, Magdalena; Fedirko, Veronika; Duarte-Salles, Talita; Ferrari, Pietro; Freisling, Heinz; Trepo, Elisabeth; Trichopoulou, Antonia; Bamia, Christina; Weiderpass, Elisabete; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; Racine, Antoine; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Lagiou, Pagona; Benetou, Vassiliki; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H. Bas|info:eu-repo/dai/nl/06929528X; Peeters, Petra H.|info:eu-repo/dai/nl/074099655; Lund, Eiliv; Quirós, J. Ramón; Nápoles, Osmel Companioni; Sánchez, María José; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Nystrom, Hanna; Khaw, Kay Tee; Key, Timothy J.; Gunter, Marc; Cross, Amanda; Riboli, Elio; Romieu, Isabelle; Jenab, Mazda

    2016-01-01

    Introduction: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of

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

    Science.gov (United States)

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

    2016-02-01

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

  18. SERUM ACTIVITIES OF ASPARTATE AMINOTRANSFERASE, CREATINE KINASE AND LACTATE DEHYDROGENASE IN HORSES WITH COLIC ATIVIDADE SÉRICA DAS ENZIMAS ASPARTATO AMINOTRANSFERASE, CREATINA QUINASE E LACTATO DESIDROGENASE EM EQÜINOS COM CÓLICA

    Directory of Open Access Journals (Sweden)

    Aureo Evangelista Santana

    2008-12-01

    Full Text Available Seventy equines distributed in two experimental groups were used, G1 (20 healthy equines, and G2 (50 equines with colic. Blood samples were obtained by jugular vein puncture in ten different moments. The variables aspartate aminotransferase (AST, creatine kinase (CK, and lactate dehydrogenase (LDH were determined by spectrophotometric assay using specific reagents. The average values presented by the animals of the G2 for variables CK, AST, and LDH were higher (P<0.05 than the values presented by the animals of the G1 in all the evaluation moments. The results showed for G2 animals suggest the existence of acute muscle injury. The muscle injuries in equines with colic were attributed to the tissue hypoperfusion, and the muscular damage.

    KEY WORDS: Acute abdomen, horses, muscles enzyme. De setenta eqüinos, distribuídos em dois grupos experimentais – G1 (vinte eqüinos hígidos e G2 (cinqüenta eqüinos com cólica –, colheram-se amostras de sangue em dez diferentes momentos, mediante punção da jugular, para a determinação da atividade sérica das enzimas aspartato aminotransferase (AST, creatina quinase (CK e lactato desidrogenase (LDH. Os valores médios apresentados pelos animais do G2, para as variáveis CK, AST e LDH, foram superiores (P<0,05 aos valores médios apresentados pelos animais do G1 em todos os momentos de avaliação. Os resultados apresentados pelos animais com cólica (G2 sugerem a existência de lesão muscular aguda, porém com tendência a cura, e foram atribuídos a hipoperfusão tecidual e a traumas musculares. A análise seriada das enzimas CK, AST e LDH auxilia tanto no diagnóstico de lesões musculares em eqüinos com cólica como no acompanhamento da evolução do processo de cura.

    PALAVRAS-CHAVES: Abdômen agudo, cavalos, enzimas musculares.

  19. Monitoramento de parâmetros laboratoriais em gatos sem raça definida durante o período neonatal Monitoring of laboratory parameters during neonatal period in mixed-bred cats

    Directory of Open Access Journals (Sweden)

    Maria Lucia G. Lourenço

    2012-12-01

    Full Text Available O objetivo do presente estudo foi à monitoração dos parâmetros laboratoriais como hemograma, enzimas hepáticas alanina aminotransferase (ALT e gama-glutamiltransferase (GGT, glicemia e proteinograma sérico, e avaliar o efeito da idade em gatos sem raça definida durante a fase neonatal. Vinte gatos machos e fêmeas foram utilizados a partir do terceiro dia de vida até o 38º dia de idade. As amostras de sangue foram colhidas semanalmente e as análises laboratoriais (hemograma, enzimas hepáticas, glicemia e proteinograma sérico realizadas no 3º, 10º, 17º, 24º, 31º e 38º dia de idade. Os resultados exibiram efeito significativo da idade sobre a contagem total de eritrócitos, concentração de hemoglobina, volume globular, volume corpuscular médio, concentração de hemoglobina corpuscular média, leucócitos totais, neutrófilos, eosinófilos e basófilos. Nenhum efeito foi observado em células como linfócitos, monócitos ou na concentração sérica de glicose. A análise das modificações ocorridas nos parâmetros laboratoriais durante a fase neonatal reflete o desenvolvimento fisiológico do filhote e contribui para o conhecimento do processo adaptativo em gatos neonatos durante o primeiro mês de vida, sendo útil para a avaliação clínica, diagnóstico e tratamento das doenças neonatais.The purpose of the study was to evaluate the effects of age on blood count, liver enzymes alanine aminotransferase (ALT and gamma-glutamyltransferase (GGT, glycemia and on protein profile in mixed-breed cats during the neonatal phase. Twenty male and female cats were used from 3 to 38 days after birth. Weekly blood samples were obtained and laboratory analyses (blood count, liver enzymes, glycemia and protein profile were performed on the 3rd, 10th, 17th, 24th, 31st and 38th day of age. The results exhibited significant effect of age on total red blood cell count, hemoglobin concentration, packed cell volume, mean cell volume, mean cell

  20. Hubungan Kadar Trigliserida dan Kolesterol-HDL Terhadap Kadar Alanine Aminotransferase pada Pasien Non Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Bayu Gemilang

    2016-01-01

    Full Text Available AbstrakTrigliserida dan Kolesterol HDL (c-HDL merupakan beberapa dari komponen Sindroma Metabolik (SM. SM dipercaya merupakan faktor utama penyebab Non Alcoholic Fatty Liver Disease (NAFLD. NAFLD merupakan penyakit hati kronik yang nantinya dapat menyebabkan fibrosis sel-sel hepar dan juga keganasan. NAFLD tidak menunjukkan manifestasi klinis yang khas, sehingga diperlukan pemeriksaan penunjang seperti pemeriksaan enzim hati untuk menegakkan diagnosis. Alanine Aminotransferase (ALT menjadi pilihan sebagai marker pada penyakit NAFLD. Tujuan penelitian ini adalah menentukan hubungan antara trigliserida dan c-HDL dengan ALT pada penderita NAFLD. Ini merupakan penelitian analitik deskriptif dengan desain retrospektif menggunakan data pasien NAFLD di instalasi rekam medik RSUP dr.M.Djamil Padang. Sampel penelitian ini adalah 51 pasien NAFLD. Hasil penelitian didapatkan dari uji korelasi pearson terdapat derajat hubungan yang kuat (r=0,512 dan hubungan yang bermakna (p<0,001 antara kadar trigliserida dengan kadar ALT serum dan derajat hubungan yang sedang (r=0,26 dan hubungan yang tidak bermakna (p=0,065 antara c-HDL dengan ALT serum. Kesimpulan penelitian ini adalah kadar ALT berhubungan dengan kadar trigliserida pada penderita NAFLD, namun tidak dengan c-HDLKata kunci: NAFLD, trigliserida, HDL, ALT, sindroma metabolik AbstractTriglyceride and HDL Cholesterol (HDL-C are some of the Metabolic Syndrome (MS components. MS is believed as the main factor for the Non Alcoholic Fatty Liver Disease (NAFLD. NAFLD is a chronic liver disease, which later can cause hepatocyte fibrosis and also malignancy. NAFLD does not show a typical clinical appearance, so it is important to do workups such as liver enzyme test to make the diagnosis. Alanine Aminotransferase (ALT is considered as the marker of NAFLD.The objective of this study was to determine the relationship between triglycerides and HDL-C to ALT level in NAFLD patients.This  was a descriptive analytical

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

    Science.gov (United States)

    Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

    2015-09-01

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

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

    Science.gov (United States)

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

    2011-01-01

    In the anabolic synthesis of diaminopimelate and lysine in plants and in some bacteria, the enzyme L,L-diaminopimelate aminotransferase (DapL; EC 2.6.1.83) catalyzes the conversion of tetrahydrodipicolinic acid (THDPA) to L,L-diaminopimelate, bypassing the DapD, DapC and DapE enzymatic steps in the bacterial acyl pathways. Here, the cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DapL from the alga Chlamydomonas reinhardtii are presented. Protein crystals were grown in conditions containing 25% (w/v) PEG 3350 and 200 mM lithium sulfate and initially diffracted to ∼1.35 Å resolution. They belonged to space group P2(1)2(1)2(1), with unit-cell parameters a=58.9, b=91.8, c=162.9 Å. The data were processed to 1.55 Å resolution with an Rmerge of 0.081, an Rp.i.m. of 0.044, an Rr.i.m of 0.093 and a VM of 2.28 Å3 Da(-1).

  3. Delirium tremens: some clinico-chemical features. A study of alanine-aminotransferase, alcaline phosphatase, prothrombine and enolase.

    Science.gov (United States)

    Hemmingsen, R; Kramp, P; Dissing, J

    1980-11-01

    The relationship between variables reflecting liver disease (serum-alanine-aminotransferase (SGPT), serum alcaline phosphatase and plasma prothrombine) and the clinical signs and symptoms during delirium tremens (DT; grade 3) and related clinical states (grade 2) was studied. Furthermore, it was investigated whether the two isoenzymes of enolase which predominante in brain tissue were present in plasma or cerebrospinal fluid (CSF) in DT patients. A correlation between SGPT and clinical state was not observed, which indicates that a causal relationship does not exist between acute liver cell damage and clinical state during DT of grade 3 or 2. In grade 2 patients, but not in grade 3 patients, both SGPT and serum alcaline phosphatase decreased between admission and recovery. This difference between the groups may be due to a higher alcohol consumption and a shorter interval between last drink and admission in grade 3. The difference in recent drinking history may also account for the finding of a higher plasma prothrombine index in grade 3 compared with grade 2, because chronic ethanol intoxication may be accompanied by enhanced hepatic protein synthesis. "Brain-enolase" was not present in detectable amounts in blood or CSF during DT thus suggesting that brain cell damage resulting in leakage of this enzyme from the cells did not prevail during DT.

  4. Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans)

    Energy Technology Data Exchange (ETDEWEB)

    Gozalo, Alfonso S.; Chavera, Alfonso; Montoya, Enrique J.; Takano, Juan; Weller, Richard E.

    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 had 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.

  5. Aspartate aminotransferase-to-platelet ratio index for fibrosis and cirrhosis prediction in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Roberto Gomes da Silva Junior

    Full Text Available In chronic hepatitis C (CHC, liver biopsy is the gold standard method for assessing liver histology, however it is invasive and can have complications. Non-invasive markers have been proposed and aspartate aminotransferase (AST-to-platelet ratio index (APRI has been shown as an easy and inexpensive marker of liver fibrosis. This study evaluated the diagnostic performance of APRI for significant fibrosis and cirrhosis prediction in CHC patients. This study included treatment-naive CHC patients who had undergone liver biopsy from January 2000 to August 2006. All histological slides were reviewed according to the METAVIR system. APRI was calculated based on laboratory results performed within four months from the biopsy. Twenty-eight (56% patients had significant fibrosis (F2-F4 and 13 (26% had cirrhosis (F4. The area under ROC curves of APRI for predicting significant fibrosis and cirrhosis were 0.92 (0.83-1.00 and 0.92 (0.85-1.00, respectively. Using cut-off values recommended by prior studies, significant fibrosis could be identified, in accordance with liver biopsy, in 44% and cirrhosis in 66% of patients. APRI could identify significant fibrosis and cirrhosis at a high degree of accuracy in studied patients.

  6. Molecular cloning and expression of phosphoglycerate dehydrogenase and phosphoserine aminotransferase in the serine biosynthetic pathway from Acanthamoeba castellanii.

    Science.gov (United States)

    Deng, Yihong; Wu, Duo; Tachibana, Hiroshi; Cheng, Xunjia

    2015-04-01

    Free-living amoebae of the genus Acanthamoeba are widespread protozoans that can cause serious infectious diseases. This study characterised phosphoglycerate dehydrogenase (PGDH) and phosphoserine aminotransferase (PSAT) in the phosphorylated serine biosynthetic pathway of Acanthamoeba castellanii. The PGDH gene encodes a protein of 442 amino acids with a calculated molecular weight of 47.7 kDa and an isoelectric point (pI) of 7.64. Meanwhile, the PSAT gene encodes a protein of 394 amino acids with a calculated molecular weight of 43.8 kDa and a pI of 5.80. Confocal microscopy suggests that PGDH is mainly diffused in the cytoplasm, whereas PSAT is located in the inner part of the cell membrane. The messenger RNA (mRNA) expression levels of PGDH and PSAT vary depending on growth state under consecutive culture conditions. No significant changes in the mRNA expression levels of both PGDH and PSAT occur after the incubation of L-serine with Acanthamoeba. This result indicates that exogenous serine exerts no influence on the expression of these genes and that the so-called feedback inhibition of both PGDH and PSAT in Acanthamoeba differs from that in bacteria or other organisms. We propose that the enzymes in the phosphorylated serine biosynthetic pathway function in amoeba growth and proliferation.

  7. Metagenomic profiling of the viromes of plasma collected from blood donors with elevated serum alanine aminotransferase levels.

    Science.gov (United States)

    Furuta, Rika A; Sakamoto, Hirotaka; Kuroishi, Ayumu; Yasiui, Kazuta; Matsukura, Harumichi; Hirayama, Fumiya

    2015-08-01

    In Japanese Red Cross (JRC) blood centers, blood collected from donors with serum alanine aminotransferase (ALT) levels of more than 60 U/L are disqualified even if serologically negative for transfusion-transmitted infections (TTIs). To assess potential risks of TTIs in plasma with elevated serum ALT levels in the current donor screening program of the JRC, we conducted a metagenomic analysis (MGA) of virome profiles in the plasma of blood donors with or without elevated serum ALT levels. Based on serum ALT levels, donors were classified into three groups: "high," more than 79 U/L; "middle," 61 to 79 U/L; and "low," less than 61 U/L. We individually analyzed 100 plasma samples from each group by MGA, employing shotgun sequencing. Viral sequences detected using MGA were partly confirmed using real-time polymerase chain reaction (PCR). Donors with high and middle ALT levels were significantly younger than those with low ALT levels, and more than 90% were males. Herpesviridae, Anelloviridae, Picornaviridae, and Flaviviridae sequences were identified in plasma samples, and their distribution and frequency were not significantly different among the three groups. The serum ALT test may be unsuitable for monitoring for additional risks of TTIs in blood donors who were negative for typical TTIs using serologic and nucleic acid tests. Although MGA is less sensitive than PCR, it remains the best technology to detect known viruses in these donors. © 2015 AABB.

  8. Intoxicação experimental por Brachiaria decumbens em ovinos confinados Experimental poisoning by Brachiaria decumbens in feedlot sheep

    Directory of Open Access Journals (Sweden)

    Klaus C. Saturnino

    2010-03-01

    and in the periportal space and also optically active refringent crystal in the lumen of bile tubules. These finds are characteristic of hepatogenous photosensitization, mainly by presence of photophobia, even when the sheep did not present photodermatitis. The results of serum biochemistry activity, during the course of poisoning with strong relation between increased gamma glutamyltransferase activity, and lethality. Onset of arising gama glutamyltransferase activity was 11 days, in average, before beginning of clinical signs. Aspartate aminotransferase had increased activity only close to the beginning of clinical signs. Serum biochemistry results of GGT suggest that they are useful for a precocious diagnosis preventing deaths caused by ingestion of B. decumbens. Thirteen sheep didn't show clinical signs despite significant increases on serum enzyme activity, suggesting the existence of tolerant/resistant individuals. The experimental model of feedlot was adequate to study B. decumbens toxicosis in sheep.

  9. Dietary freshwater clam (Corbicula fluminea) extract suppresses accumulation of hepatic lipids and increases in serum cholesterol and aminotransferase activities induced by dietary chloretone in rats.

    Science.gov (United States)

    Chijimatsu, Takeshi; Umeki, Miki; Kobayashi, Satoru; Kataoka, Yutaro; Yamada, Koji; Oda, Hiroaki; Mochizuki, Satoshi

    2015-01-01

    We investigated the ameliorative effect of freshwater clam extract (FCE) on fatty liver, hypercholesterolemia, and liver injury in rats exposed to chloretone. Furthermore, we examined the effects of major FCE components (fat and protein fractions) to determine the active components in FCE. Chloretone increased serum aminotransferase activities and led to hepatic lipid accumulation. Serum aminotransferase activities and hepatic lipid content were lower in rats fed total FCE or fat/protein fractions of FCE. Expression of fatty acid synthase and fatty acid desaturase genes was upregulated by chloretone. Total FCE and fat/protein fractions of FCE suppressed the increase in gene expression involved in fatty acid synthesis. Serum cholesterol levels increased twofold upon chloretone exposure. Total FCE or fat/protein fractions of FCE showed hypocholesterolemic effects in rats with hypercholesterolemia induced by chloretone. These suggest that FCE contains at least two active components against fatty liver, hypercholesterolemia, and liver injury in rats exposed to chloretone.

  10. Hematologic and plasma biochemical reference values in Indian peafowl (Pavo cristatus).

    Science.gov (United States)

    Samour, Jaime; Naldo, Jesus; Rahman, Habeeb; Sakkir, Mohammed

    2010-06-01

    Blood samples were collected from captive, adult, clinically normal Indian peafowl (Pavo cristatus) for hematologic and plasma biochemical analyses. Hematologic parameters investigated were total red blood cell count, hemoglobin, packed cell volume, fibrinogen, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, total white blood cell count, differential white blood cell count, and thrombocyte count. Plasma biochemical parameters investigated were alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bile acids, total bilirubin, blood urea nitrogen, calcium, cholesterol, creatinine, creatine kinase, gamma glutamyltransferase, lactate dehydrogenase, glucose, iron, phosphorus, and uric acid, as well as plasma protein electrophoresis. Results were compared with values from studies done in houbara bustards (Chlamydotis undulata), kori bustards (Ardeotis kori), stone curlews (Burhinus oedicnemus), and taxonomically related species, including ring-necked pheasants (Phasianus colchicus), red-legged partridges (Alectoris rufa), Kashmir native fowl (Kashmirfavorella), and Bangladesh native, Fayoumi, and Assil fowl (Gallus domesticus).

  11. Evaluation of the risk of liver damage from the use of 5-aminolevulinic acid for intra-operative identification and resection in patients with malignant gliomas

    DEFF Research Database (Denmark)

    Offersen, Cecilie Mørck; Skjoeth-Rasmussen, Jane

    2017-01-01

    BACKGROUND: The clinical efficacy of 5-aminolevulinic acid (5-ALA) for fluorescence-guided surgery of malignant gliomas is evident from several studies; however, as post-operative elevations of liver enzymes have been seen, there is a potential risk of liver damage upon administration. The aim...... (September 2012-September 2014) at the University Hospital of Copenhagen, Rigshospitalet, was conducted. All patients received a pre-operative dose of 20 mg/kg bodyweight 5-ALA. The pre- and post-operative enzyme levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase...... and amylase of both men and women, respectively, were evaluated. RESULTS: Ninety-nine adults met the inclusion criteria. Fifty patients had one or multiple temporary post-operative elevations of their liver enzymes. The mean post-operative values were not increased, except for a brief elevation of gamma...

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

    Directory of Open Access Journals (Sweden)

    Maritrini Colón

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

  13. L,L-diaminopimelate aminotransferase (DapL: A putative target for the development of narrow-spectrum antibacterial compounds

    Directory of Open Access Journals (Sweden)

    Alexander J Triassi

    2014-09-01

    Full Text Available Despite the urgent need for sustained development of novel antibacterial compounds to combat the drastic rise in antibiotic resistant and emerging bacterial infections, only a few clinically relevant antibacterial drugs have been recently developed. One of the bottlenecks impeding the development of novel antibacterial compounds is the identification of new enzymatic targets. The nutritionally essential amino acid anabolic pathways, for example lysine biosynthesis, provide an opportunity to explore the development of antibacterial compounds, since human genomes do not possess the genes necessary to synthesize these amino acids de novo. The diaminopimelate (DAP/lysine (lys anabolic pathways are attractive targets for antibacterial development since the penultimate lys precursor meso-DAP (m-DAP is a cross-linking amino acid in the peptidoglycan (PG cell wall of most Gram-negative bacteria and lys plays a similar role in the PG of most Gram-positive bacteria, in addition to its role as one of the 20 proteogenic amino acids. The L,L-diaminopimelate aminotransferase (DapL pathway was recently identified as a novel variant of the DAP/lys anabolic pathways. The DapL pathway has been identified in the pathogenic bacteria belonging to the genus; Chlamydia, Leptospira and Treponema. The dapL gene has been identified in the genomes of 381 or approximately 13% of the 2,771 bacteria that have been sequenced, annotated and reposited in the NCBI database, as of May 23, 2014. The narrow distribution of the DapL pathway in the bacterial domain provides an opportunity for the development and or discovery of narrow spectrum antibacterial compounds.

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

    Science.gov (United States)

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

    2008-05-01

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

  15. Pre-steady-state kinetics of Escherichia coli aspartate aminotransferase catalyzed reactions and thermodynamic aspects of its substrate specificity

    International Nuclear Information System (INIS)

    Kuramitsu, Seiki; Hiromi, Keitaro; Hayashi, Hideyuki; Morino, Yoshimasa; Kagamiyama, Hiroyuki

    1990-01-01

    The four half-transamination reactions [the pyridoxal form of Escherichia coli aspartate aminotransferase (AspAT) with aspartate or glutamate and the pyridoxamine form of the enzyme with oxalacetate or 2-oxoglutarate] were followed in a stopped-flow spectrometer by monitoring the absorbance change at either 333 or 358 nm. The reaction progress curves in all cases gave fits to a monophasic exponential process. Kinetic analyses of these reactions showed that each half-reaction is composed of the following three processes: (1) the rapid binding of an amino acid substrate to the pyridoxal form of the enzyme; (2) the rapid binding of the corresponding keto acid to the pyridoxamine form of the enzyme; (3) the rate-determining interconversion between the two complexes. This mechanism was supported by the findings that the equilibrium constants for half- and overall-transamination reactions and the steady-state kinetic constants agreed well with the predicted values on the basis of the above mechanism using pre-steady-state kinetic parameters. The significant primary kinetic isotope effect observed in the reaction with deuterated amino acid suggests that the withdrawal of the α-proton of the substrates is rate determining. The pyridoxal form of E. coli AspAT reacted with a variety of amino acids as substrates. The substrate specificity of the E. coli enzyme was much broader than that of pig isoenzymes, reflecting some subtle but distinct difference in microenvironment accommodating the side chain of the substrate between e. coli and mammalian AspATs

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

    Directory of Open Access Journals (Sweden)

    Vijai Bhadauria

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

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

    Science.gov (United States)

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

    2016-06-06

    Alanine aminotransferase (ALT) predicts type 2 diabetes but it is uncertain whether it also predicts gestational diabetes mellitus (GDM). We recruited 17359 Chinese women with ALT measured in their first trimester. At 24-28 weeks of gestation, all women underwent a 50-gram 1-hour glucose challenge test (GCT) followed by a 75-gram 2-hour oral glucose tolerance test if GCT result was ≥7.8 mmol/L. Restricted cubic spline analysis was used to examine full-range risk associations of ALT levels with GDM. Relative excess risk due to interaction, attributable proportion due to interaction and synergy index were used to estimate additive interaction between high ALT and overweight/obesity for GDM. Finally, 1332 (7.7%) women had GDM. ALT levels were positively associated with GDM risk without a clear threshold. Using ALT levels <22 U/L as the referent, the middle ALT levels (≥22 to <40 U/L) [odds ratio (OR) (95% confidence intervals): 1.41(1.21-1.65)] and high ALT levels (≥40 U/L) [1.62 (1.31-2.00)] were associated with increased GDM risk. Maternal overweight/obesity greatly enhanced the OR of ALT ≥22 U/L from 1.44 (1.23-1.69) to 3.46 (2.79-4.29) with significant additive interactions. In conclusion, elevated ALT levels in the first trimester even within normal range predicted GDM risk, further enhanced by overweight/obesity.

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

    Science.gov (United States)

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

    2014-06-01

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

  19. Two mechanisms for putrescine-dependent transcriptional expression of the putrescine aminotransferase gene, ygjG, in Escherichia coli.

    Science.gov (United States)

    Kim, Young-Sik; Shin, Hyun-Chul; Lee, Jong-Ho

    2014-09-01

    In this study, on evaluating the physiological function and mechanism of putrescine, we found that putrescine supplementation (1 mM) increases transcription of the putrescine aminotransferase gene, ygjG. Putrescine-dependent expression was confirmed by measuring β-galactosidase activity and with reverse transcription-polymerase chain reaction. To understand the role of putrescine in ygjG expression, we genetically characterized and found that a knockout mutation in an alternative sigma factor, rpoS, abolished putrescine-dependent ygjG-lacZ expression. In the rpoS mutant, RpoS overexpression complemented the mutant phenotype. However, RpoS overexpression induced ygjG-lacZ expression with putrescine supplementation but not without supplementation. We also found that the loss of putrescine-dependent ygjG-lacZ expression induced by rpoS was completely restored under nitrogen-starvation conditions. The putrescine-dependent expression of ygjG-lacZ under this condition was clearly dependent on another alternative sigma factor, rpoN, and its cognate activator ntrC. These results show that rpoS is required for putrescine-dependent ygjG-lacZ expression, but the effect of putrescine on this expression is not caused by simple modulation of RpoS synthesis. Putrescine-dependent expression of ygjG-lacZ was controlled by at least two sigma factors: rpoS under excess nitrogen conditions and rpoN under nitrogen-starvation conditions. These results suggest that putrescine plays an important role in the nitrogen regulation system.

  20. Aspartate aminotransferase and free thyroid hormones in vaginal washing fluid as markers for preterm pre-labor rupture of membranes.

    Science.gov (United States)

    Farag, Amr H; Elghetany, Sherif S; Elkashif, Mohamed S

    2015-09-01

    To evaluate the diagnostic value of vaginal fluid aspartate aminotransferase (AST), free triiodothyronine (T3) and free thyroxine (T4 ) in women with preterm pre-labor rupture of membranes (PPROM). A case-control study was carried out of 100 women: 50 with PPROM (study group) and 50 age-, gestational age- and weight-matched women with intact membranes (control group). All women underwent sterile speculum vaginal examination. The vaginal posterior fornix was irrigated and the retrieved fluid was sent for AST, free T3 and free T4 assays. Median vaginal fluid free T3, free T4 and AST were significantly higher in the PPROM group compared with the control group, with vaginal fluid free T4 having the largest area under the curve on receiver operating characteristic curve analysis (P<0.001). Sensitivity, specificity, positive and negative predictive values for free T3 (cut-off, 1.06 pg/mL) were 88%, 70%, 74.6% and 85.4%, respectively, while those for free T4 (cut-off 0.063 ng/dL) were 86%, 72%, 75.4% and 83.7%, and those for AST (4.5 IU/L) were 56%, 70%, 65.1% and 61.4%, respectively. Vaginal fluid AST had less diagnostic accuracy when compared with either free T3 or free T4. Vaginal fluid AST, free T3 and free T4 seem to be useful and simple markers in diagnosis of PPROM. © 2015 Japan Society of Obstetrics and Gynecology.

  1. Saccharomyces cerevisiae Bat1 and Bat2 Aminotransferases Have Functionally Diverged from the Ancestral-Like Kluyveromyces lactis Orthologous Enzyme

    Science.gov (United States)

    Colón, Maritrini; Hernández, Fabiola; López, Karla; Quezada, Héctor; González, James; López, Geovani; Aranda, Cristina; González, Alicia

    2011-01-01

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

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

    Science.gov (United States)

    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.

  3. Relationships between alanine aminotransferase (ALT), visceral adipose tissue (AT) and metabolic risk factors in a middle-aged Japanese population.

    Science.gov (United States)

    Oka, Rie; Yagi, Kunimasa; Nakanishi, Chiaki; Konno, Tetsuo; Kawashiri, Masa-aki; Hayashi, Kenshi; Nohara, Atsushi; Inazu, Akihiro; Yamagishi, Masakazu

    2014-01-01

    The commonly observed relationship between increased visceral adiposity and metabolic abnormalities may be partly mediated by a concomitant increase in liver fat content. We evaluated the independent association between the level of alanine aminotransferase (ALT) as a surrogate marker of the liver fat content and the incidence of metabolic abnormalities after adjusting for the amount of visceral adipose tissue (AT). The subjects included 1,118 Japanese individuals (44% women) who underwent computed tomography to assess the amount of visceral AT on medical checkups. Cross-sectional associations between the serum ALT, visceral AT and metabolic risk factors were examined. The ALT level and visceral AT were found to show a significant correlation(r=0.41 in men and r=0.36 in women, p<0.001). In a multivariable linear regression analysis, the ALT level and visceral AT were found to be independently associated with blood pressure in men and triglycerides and 2-hour post-challenge glucose in both genders(p<0.01), whereas only visceral AT was found to be associated with HDL-cholesterol(p<0.01). When the participants were classified into four subgroups based on the 75th percentiles of ALT and visceral AT, the low ALT/high-visceral AT group, but not the high-ALT/low-visceral AT group, had a significantly higher odds ratio for low HDL-cholesterol among both genders(p<0.05) and for hypertriglyceridemia in men only(p<0.05). Meanwhile, the high-ALT/low-visceral AT group, but ot the low-ALT/high-visceral AT group, had a significantly higher odds ratio for IGT among women(p<0.05). Although the ALT level and visceral AT were found to be independently associated with most metabolic risk factors, visceral AT had a dominant association with dyslipidemia in both genders, while the ALT level appeared to have a closer association with IGT in women.

  4. [Serum levels of alanine aminotransferase in Chilean population: analysis of results of the national health survey 2009-2010].

    Science.gov (United States)

    Tejos, Rodrigo; Padilla, Oslando; Pizarro, Margarita; Solís, Nancy; Arab, Juan Pablo; Margozzini, Paula; Miquel, Juan Francisco; Riquelme, Arnoldo; Arrese, Marco

    2013-07-01

    Determination of Alanine aminotransferase serum levels ([ALT]s) is a sensitive ana reliable test for liver diseases. To report the prevalence of abnormal [ALT]s in Chilean population and to identify associated variables. We analyzed data from a random sub-sample of 2,794 adults surveyed during the second Chilean National Health Survey. Abnormal [ALT]s were defined by using three different cut-off values (COV), two fixed COV (COV1: > 30 IU/L in men and > 19 IU/L in women and COV2 pre-defined by the performing laboratory) and a COV adjusted by age, weight and sex (COV3 > 31 IU/L for women and > 44 IU/L and men > 42 IU/L and > 66 IU/L with a BMI > 23). Logistic regression analysis was performed to determine risk factors for elevated [ALT]s. Mean [ALT]s values were 30.14 I U/L in men and 22.03 IU/L in women. The observed prevalence of abnormal [ALT]s defined by different COV were 38%, 11.5%, and 8.1% for COV1, COV2 and COV3 respectively. Variables independently associated to abnormal [ALT]s in a multivariate analysis were the following: serum gamma-glutamyl-transpeptidase (OR: 1.055 [95% CI 1.033-1.078]) and body mass index (OR:1.13 [95% CI 1.09-1.17]). Variables inversely associated with abnormal [ALT]s (COV1) were mole gender (OR-.0.976 [95% CI 0.96-0.99) and HDL-cholesterol (OR:0979 [95% CI 0.96-0.99]). Independently of the COV used, Chilean population exhibits a high prevalence of abnormal [ALT]s which may reflect a significant burden of liver disease. Non-alcoholic fatty liver disease could be a major contributor to elevated [ALT]s considering the association of abnormal [ALT]s and metabolic variables.

  5. An evaluation on the activity level of Aspartate aminotransferase and Alkaline phosphatase nzymes in peri-implant sulcus fluid

    Directory of Open Access Journals (Sweden)

    Paknegad M. Assistant Professor

    2003-07-01

    Full Text Available Statement of Problem: The correlation between the activity of aspartate aminotransferase (AST and alkaline phosphatase (ALP enzymes in gingival sulcular fluid (GCF with inflammation and periodontal attachment loss has been proved, however there are not adequate studies about dental implants. Purpose: The aim of present study was to investigate the presence and activity level of AST & ALP and their correlation with pocket depth (PD and bleeding of peri-implant slcular fluid (PISF, and to evaluate the possibility of using these assessments as a diagnostic index in oral implantology. Material and Methods: In this study, 41 implants as test group and 41 contralateral teeth as control group, in 21 patients were evaluated. At first visit, the general information about implants and the values of pocket probing depth (PPD, modified sulcus bleeding index (mSBl and modified plaque index (mPI were recorded. At the second visit, samples of GCF/PISF were collected. AST & ALP activity was determined spectrophotometrically and data were analyzed by "t", "Mann-Whitney" tests and Pearson Spearman correlation coefficient."nResults: The results showed that there was a significant difference in the activity of AST between two study groups (P<0.0001. The average activity of ALP in test group was more than control group but the difference was not significant. After elimination of the confounding variables, the average AST in test group was 54.6 (S£=2.3 and in control groups was 44.8 (SE=2.3 (P=0.004. The average ALP in test group (SE=2.2 and in control (SE=2.2 were 36.6 and 35.4, respectively. Values of AST and ALP were positively correlated with other clinical parameters such as PD and mSBI which was significant in test group."nConclusion: The present study suggests that PISF analysis could be considered as a proper diagnostic strategy in the evaluation of dental implant success.

  6. Mechanism of Substrate Recognition And PLP-Induced Conformational Changes in II-Diaminopimelate Aminotransferase From Arabidopsis Thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, N.; Clay, M.D.; Belkum, M.J.van; Cherney, M.M.; Vederas, J.C.; James, M.N.G.

    2009-05-26

    LL-Diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal phosphate (PLP)-dependent enzyme in the lysine biosynthetic pathways of plants and Chlamydia, is a potential target for the development of herbicides or antibiotics. This homodimeric enzyme converts L-tetrahydrodipicolinic acid (THDP) directly to LL-DAP using L-glutamate as the source of the amino group. Earlier, we described the 3D structures of native and malate-bound LL-DAP-AT from Arabidopsis thaliana (AtDAP-AT). Seven additional crystal structures of AtDAP-AT and its variants are reported here as part of an investigation into the mechanism of substrate recognition and catalysis. Two structures are of AtDAP-AT with reduced external aldimine analogues: N-(5'-phosphopyridoxyl)-L-glutamate (PLP-Glu) and N-(5'-phosphopyridoxyl)- LL-Diaminopimelate (PLP-DAP) bound in the active site. Surprisingly, they reveal that both L-glutamate and LL-DAP are recognized in a very similar fashion by the same sets of amino acid residues; both molecules adopt twisted V-shaped conformations. With both substrates, the {alpha}-carboxylates are bound in a salt bridge with Arg404, whereas the distal carboxylates are recognized via hydrogen bonds to the well-conserved side chains of Tyr37, Tyr125 and Lys129. The distal C{sup {var_epsilon}} amino group of LL-DAP is specifically recognized by several non-covalent interactions with residues from the other subunit (Asn309*, Tyr94*, Gly95*, and Glu97* (Amino acid designators followed by an asterisk (*) indicate that the residues originate in the other subunit of the dimer)) and by three bound water molecules. Two catalytically inactive variants of AtDAP-AT were created via site-directed mutagenesis of the active site lysine (K270N and K270Q). The structures of these variants permitted the observation of the unreduced external aldimines of PLP with L-glutamate and with LL-DAP in the active site, and revealed differences in the torsion angle about the PLP-substrate bond

  7. Interaction between obesity and the Hypoxia Inducible Factor 3 Alpha Subunit rs3826795 polymorphism in relation with plasma alanine aminotransferase.

    Science.gov (United States)

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Chawla, Nitesh V; Ma, Jun; Wang, Haijun

    2017-07-28

    Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been demonstrated to be associated with obesity in the methylation level, and it also has a Body Mass Index (BMI)-independent association with plasma alanine aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A polymorphism and methylation remains unclear. This study aims to identify the association between HIF3A polymorphism and plasma ALT, and further to determine whether the effect of HIF3A polymorphism on ALT could be modified by obesity or mediated by DNA methylation. The HIF3A rs3826795 polymorphism was genotyped in a case-control study including 2030 Chinese children aged 7-18 years (705 obese cases and 1325 non-obese controls). Furthermore, the HIF3A DNA methylation of the peripheral blood was measured in 110 severely obese children and 110 age- and gender- matched normal-weight controls. There was no overall association between the HIF3A rs3826795 polymorphism and ALT. A significant interaction between obesity and rs3826795 in relation with ALT was found (P inter  = 0.042), with rs3826795 G-allele number elevating ALT significantly only in obese children (β' = 0.075, P = 0.037), but not in non-obese children (β' = -0.009, P = 0.741). Additionally, a mediation effect of HIF3A methylation was found in the association between the HIF3A rs3826795 polymorphism and ALT among obese children (β' = 0.242, P = 0.014). This is the first study to report the interaction between obesity and HIF3A gene in relation with ALT, and also to reveal a mediation effect among the HIF3A polymorphism, methylation and ALT. This study provides new evidence to the function of HIF3A gene, which would be helpful for future risk assessment and personalized treatment of liver diseases.

  8. Development of monoclonal antibodies and immunochromatographic lateral flow device for rapid test of alanine aminotransferase isoenzyme 1.

    Science.gov (United States)

    Hu, Xiaomei; Cheng, Shiliang; Liu, Xinfeng; Li, Jie; Zheng, Wen; Lu, Gang; Zhang, Jun; Zheng, Jian; Zhang, Juan

    2016-03-01

    Alanine aminotransferase (ALT) has been used as a sensitive marker for liver injury in people and in preclinical toxicity studies. But measurement of ALT isoenzymes, ALT1 and ALT2, was reported to be of more diagnostic value. The aim of this study is to develop an ideal pair of anti-ALT1 monoclonal antibodies (MAbs) of high specificity and affinity, and subsequently prepare a Immunochromatographic lateral flow device (LFD) for rapid test of ALT1 in human serums. The complete coding sequence of ALT1 gene (1500 bp) was cloned from human hepatoma G2 cells (HepG2) and inserted into the expression vector pET-32a(+). ALT1 recombinant protein was routinely prepared by E. coli BL21 (DE3) expression and Ni(2+) affinity purification. Balb/c mice were immunized with purified ALT1 and the splenocytes were fused with Sp2/0 myeloma cells. The positive clones, verified by indirect enzyme-linked immunosorbent assay (ELISA) using purified ALT1, were subcloned to single clones by limiting dilution process. A MAb pair was selected from the obtained MAbs according the sandwich ELISA pairing results and then used for lateral flow device (LFD) production. After evaluation of the sensitivity and specificity, the LFD strips were employed to test human serum samples with known ALT activity levels. ALT1 recombinant protein was expectedly prepared by expression and purification. A total of 8 stable clones that produced antibodies specifically recognizing ALT1 protein were developed. After sandwich ELISA pairing, an ideal pair of anti-ALT1 MAbs, designated as BD7 and DG3, were selected and proved to be of high specificity, titer and affinity. Based on the MAb pair, LFD strips specifically for ALT1 rapid test were subsequently prepared. The detection threshold of the LFD strips was 12 U/L. No cross reaction was found. The ALT1 LFD with high sensitivity and specificity was successfully developed. It is valuable for testing ALT1 protein in human sera and can be a beneficial complement for

  9. AST/ALT ratio is not an index of liver fibrosis in chronic hepatitis C when aminotransferase activities are determinate according to the international recommendations.

    Science.gov (United States)

    Guéchot, Jérôme; Boisson, Renée Claude; Zarski, Jean-Pierre; Sturm, Nathalie; Calès, Paul; Lasnier, Elisabeth

    2013-11-01

    The aspartate aminotransferase activity (AST)/alanine aminotransferase activity (ALT) ratio is used as liver fibrosis index whereas the reported data are conflicting. In chronic hepatitis C (CHC), reported diagnostic accuracies range from none to good for significant fibrosis and to excellent for cirrhosis. Assuming that AST/ALT increases are mainly due to vitamin B6 defects since pyridoxal phosphate (PLP), active form of B6, acts as coenzyme in transamination reactions, we evaluated the diagnostic accuracy of the AST/ALT ratio using standardized methods for AST and ALT activities, with PLP addition as recommended, in a prospective multicenter cohort of CHC patients. ALT and AST activities were measured using the recommended IFCC methods with addition of pyridoxal 5'-phosphate. We evaluated the AST/ALT ratio for the diagnosis of liver fibrosis or cirrhosis in a cohort of CHC patients included in a multicenter prospective study. A liver biopsy was performed in each patient and reviewed by two independent pathologists in order to determine the fibrosis stage according to Metavir classification which was the reference standard. AST/ALT ratio significantly increased with histological stage of liver fibrosis and there was a significant correlation between Metavir fibrosis stage and AST/ALT ratio (r=0.129, PALT ratio does not discriminate significant fibrosis (F≥2) (AUROC=0.531) and had only very poor diagnostic accuracies for severe fibrosis (F≥3) (AUROC=0.584) or cirrhosis (F4) (AUROC=0.626). AST/ALT ratio is not a good and discriminative index of liver fibrosis in CHC when aminotransferase activities are determinate according to the international recommendations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Biochemical liver function test parameter levels in relation to treatment response in liver metastatic colorectal patients treated with FOLFOX4 with or without bevacizumab

    Directory of Open Access Journals (Sweden)

    Denić Kristina

    2016-01-01

    Full Text Available Introduction. Combined use of bevacizumab and conventional anticancer drugs leads to a significant improvement of treatment response in patients with metastatic colorectal carcinoma (CRC. Conventional treatment protocols exert undesired effects on the liver tissue. Hepatotoxic effects are manifested as a disturbance of liver function test parameters. The relation between clinical outcome and disorder of biochemical parameters has not been completely evaluated. Objective. The objective of our study was to examine whether clinical outcome in patients with liver metastatic CRC correlates with the level of liver function test parameters. Methods. The study included 96 patients with untreated liver metastatic CRC who received FOLFOX4 protocol with or without bevacizumab. Biochemical liver parameters were performed before and after the treatment completion. Treatment response was evaluated as disease regression, stable disease, and disease progression. The patients were divided into three groups according to the accomplished treatment response. Results. In the group of patients with disease regression the post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin were statistically significantly increased. In contrast to this, gamma-glutamyltransferase and protein post-treatment values were significantly lower in relation to initial values. In patients with stable disease, difference was found only in the level of proteins being lower after the treatment. In patients with disease progression, values of aspartate aminotransferase and bilirubin were significantly increased after completed treatment. Conclusion. Treatment responses are not completely associated with the level of liver function test parameters. The only parameter which correlated with treatment response is gamma-glutamyltransferase. Its decrease is accompanied with disease regression.

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

    Science.gov (United States)

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

    2000-07-01

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

  12. Characterization of tryptophan aminotransferase 1 of Malassezia furfur, the key enzyme in the production of indolic compounds by M. furfur.

    Science.gov (United States)

    Preuss, Janina; Hort, Wiebke; Lang, Sarah; Netsch, Anette; Rahlfs, Stefan; Lochnit, Günter; Jortzik, Esther; Becker, Katja; Mayser, Peter A

    2013-11-01

    Malassezia yeasts are responsible for the widely distributed skin disease Pityriasis versicolor (PV), which is characterized by a hyper- or hypopigmentation of affected skin areas. For Malassezia furfur, it has been shown that pigment production relies on tryptophan metabolism. A tryptophan aminotransferase was found to catalyse the initial catalytic step in pigment formation in the model organism Ustilago maydis. Here, we describe the sequence determination, recombinant production and biochemical characterization of tryptophan aminotransferase MfTam1 from M. furfur. The enzyme catalyses the transamination from l-tryptophan to keto acids such as α-ketoglutarate with Km values for both substrates in the low millimolar range. Furthermore, MfTam1 presents a temperature optimum at 40°C and a pH optimum at 8.0. MfTam1 activity is highly dependent on pyridoxal phosphate (PLP), whereas compounds interfering with PLP, such as cycloserine (CS) and aminooxyacetate, inhibit the MfTam1 reaction. CS is known to reverse hyperpigmentation in PV. Thus, the results of the present study give a deeper insight into the role of MfTam1 in PV pathogenesis and as potential target for the development of novel PV therapeutics. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. A comparative research on obesity hypertension by the comparisons and associations between waist circumference, body mass index with systolic and diastolic blood pressure, and the clinical laboratory data between four special Chinese adult groups.

    Science.gov (United States)

    Wu, Ou; Leng, Jian-Hang; Yang, Fen-Fang; Yang, Hai-Ming; Zhang, Hu; Li, Zeng-Fang; Zhang, Xing-Yu; Yuan, Cheng-Da; Li, Jia-Jia; Pan, Qi; Liu, Wei; Ren, Yan-Jun; Liu, Bing; Liu, Qing-Min; Cao, Cheng-Jian

    2018-01-01

    was statistically significantly positively related to ALT, Ua, LDLC, WC, and TC/HDLC, and negatively to ALB, HDLC, and CB. DB statistically significantly positively correlated with ALP, BMI, and WC. SB was statistically significantly positively related to LDLC, GLU, serum levels of fructosamine (FA), serum levels of the total protein (TC), BMI, and WC. The negative body effects of obesity are comprehensive. Obesity may lead to hypertension through multiple ways by different percents. GGT, serum levels of gamma glutamyltransferase; ALB, serum levels of albumin; ALT, serum levels of alanine aminotransferase; LDLC, serum levels of low density lipoprotein cholesterol; TG, serum levels of triglyceride; HDLC, serum levels of high density lipoprotein cholesterol; FA, serum levels of fructosamine; S.C.R, serum levels of creatinine; IB, serum levels of indirect bilirubin; ALP, serum levels of alkaline phosphatase; CB, serum levels of conjugated bilirubin; UREA, Urea; Ua, serum levels of uric acid; GLU, serum levels of glucose; TC, serum levels of the total cholesterol; TB, serum levels of the total bilirubin; TP, serum levels of the total protein; TC/HDLC, TC/HDLC ratio.

  14. Short report: elevated levels of alanine aminotransferase and hepatitis A in the context of a pediatric malaria vaccine trial in a village in Mali.

    Science.gov (United States)

    Ellis, Ruth D; Dicko, Alassane; Sagara, Issaka; Kamate, Beh; Guindo, Ousmane; Niambele, Mohamed Balla; Sogoba, Moussa; Doumbo, Ogobara

    2008-12-01

    A Phase 1 study of the apical membrane antigen malaria vaccine AMA1-C1/Alhydrogel was conducted in 2-3-year-old children in a village in Mali. A high frequency of elevated levels of alanine aminotransferase (ALT) caused by hepatitis A was seen, with 8 of 36 children diagnosed by specific IgM antibody over the course of the study. Hepatitis A is a common cause of asymptomatic elevations of ALT levels in children, particularly in less-developed settings. Investigators should be aware of the frequency of hepatitis A in this age group to guard against inadvertently facilitating transmission at study facilities and to properly evaluate symptomatic or asymptomatic elevations of ALT levels.

  15. (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

    DEFF Research Database (Denmark)

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

    2012-01-01

    Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off...... at 1/300-1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20-40 times higher than those needed to treat addiction in rats, exhibited...... reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction...

  16. Effect of single and three months treatment with Ukrain on aminotransferases (ALT and AST) and on the serum protein level in rodents.

    Science.gov (United States)

    Jagiełło-Wójtowicz, E; Kleinrok, Z; Surmaczyńska, B; Baran, E; Feldo, M; Nowicky, J W

    1992-01-01

    The influence of Ukrain on the activity of aminotransferases (ALT and AST) and on the serum total protein content was estimated in mice and rats of both sexes receiving single or repeated doses of the drug. It was found that one hour after intraperitoneal (i.p.) administration of Ukrain no characteristic changes were recorded in the activity of the investigated enzymes, or in the serum protein content of animals of either sex. Similar effects were observed after three months treatment with Ukrain in rats of either sex. Only in mice receiving Ukrain for three months was a rise in ALT and AST activity found. No particular changes were observed in the total serum protein level, except for a small decreases in the sera of male mice.

  17. [Effect of alpha-tocopherol on the activity of the liver glutathione antioxidative system and the activity of serum aminotransferase in rats during tetrachloromethane poisoning].

    Science.gov (United States)

    Gubskiĭ, Iu I; Khmelevskiĭ, Iu V; Sil'chenko, N A

    1983-01-01

    The activities of glutathione peroxidase, glutathione reductase in the liver as well as of glutamate-pyruvate, and glutamate-oxaloacetate transaminase in blood serum were studied in rats which were injected tetrachloromethane in a dose of 1.04 mmol per 100 g mass for seven days. Tetrachloromethane poisoning is accompanied by a considerable decrease in the glutathione peroxidase activity in the liver and an increase in the aminotransferase activity in the blood serum. Additional administration of 20 and 30 mg of L-tocopherol per 100 g of mass prevents a tetrachloromethane-induced decrease in the activity of glutathione peroxidase in the liver and somewhat normalizes the activity of glutamate-pyruvate and glutamate-oxaloacetate transaminase in the blood serum. Possible mechanisms of the alpha-tocoferol protective action are under discussion.

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

    Science.gov (United States)

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

    2006-11-21

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

  19. Genetic and bibliographic information: Ggt1 [GenLibi

    Lifescience Database Archive (English)

    Full Text Available Cell Lymphoblastic Leukemia-Lymphoma (C04.557.337.428.600.600) Hemic and Lymphatic Diseases... (C15) > Lymphatic Diseases (C15.604) > Lymphoproliferative Disorders (C15.604.515) > Leukemia, Ly...B-Cell Lymphoblastic Leukemia-Lymphoma (C15.604.515.560.600.600) Immune System Diseases

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

    Directory of Open Access Journals (Sweden)

    Elisiane Lourdes Da Cás

    2001-12-01

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

  1. Liver synthesis function in chronic asymptomatic or oligosymptomatic alcoholics: correlation with other liver tests A função de síntese hepática em alcoolistas crônicos assintomáticos ou oligossintomáticos. Correlações com outros testes hepáticos

    Directory of Open Access Journals (Sweden)

    Paulo Borini

    1999-06-01

    Full Text Available Liver function and its correlation with bilirubin and hepatic enzymes were evaluated in 30 male chronic asymptomatic or oligosymptomatic alcoholics admitted into the psychiatric hospital for detoxification and treatment of alcoholism. Hypoalbuminemia, lowered prothrombin activity, hypotransferrinemia and hypofibrinogenemia were detected in 32 %, 32 %, 28 %, and 24 % of patients, respectively. Transferrin was elevated in 8 %. Greater prevalence of hyperbilirubinemia was found in patients with lowered prothrombin activity, hypofibrinogenemia, or hypotransferrinemia. No correlation was found between serum bilirubin or aminotransferase levels and normal or elevated albumin levels, time or activity of prothrombin, and fibrinogen levels. Serum alkaline phosphatase was elevated in normoalbuminemics and gamma-glutamyltransferase in patients with lowered prothrombin activity. Hypoalbuminemia was associated with hypofibrinogenemia, hypotransferrinemia with elevated aspartate aminotransferase or gamma-glutamyltransferase, and hypertransferrinemia with elevation of alanine aminotransferase. These data indicated the occurrence of hepatic dysfunction due to liver damage caused directly by alcohol or by alcoholism-associated nutritional deficiencies.A função hepática e suas correlações com a bilirrubina e as enzimas hepáticas foram avaliados em 30 alcoolistas crônicos do sexo masculino, assintomáticos ou oligossintomáticos, internados em hospital psiquiátrico para desintoxicação e tratamento do alcoolismo. Hipoalbuminemia, hipoatividade da protrombina, hipofibrinogenemia e hipotransferrinemia ocorreram em 32%, 32%, 24% e 28% dos pacientes, respectivamente. A transferrina estava elevada em 8%. Maior prevalência de hiperbilirrubinemia foi encontrada em pacientes com hipoatividade da protrombina, hipofibrinogemia e hipotransferrinemia. Não observou-se correlações entre os níveis séricos da bilirrubina e das aminotransferases e os níveis normais

  2. Enzymes in intestinal juice from patients with liver diseases and colon polyps: measurement of bilirubin, alkaline phosphatase, aspartate aminotransferase and lactate dehydrogenase.

    Science.gov (United States)

    Uno, Y; Saitoh, H; Ying, H; Tamai, Y; Ono, F; Yoshiike, M; Munakata, A; Yoshida, Y

    1996-02-01

    Since the amounts of hepatogenous enzymes discharged into the intestinal tract remain unknown, this study was initiated to evaluate the amounts of the enzymes in the intestinal tract. Whole gut lavage fluid (polyethyleneglycol electrolyte solution) was administered orally to 42 subjects, consisting of 5 patients with hepatoma, 10 with chronic hepatitis, 10 with colon polyps, and 17 control subjects without liver disease. Two hr after the large intestinal lavage, the digestive tract juice was aspirated by colonoscopy, and the bilirubin (Bil), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the aspirates were measured. A positive correlation between the AST and LDH values was found, and a significant difference in these values between the hepatic disorders and the normal controls was noticed. A significant positive correlation between the ALP and Bil values was found, and a statistical difference in these values between the group of colon polyps and the controls and other groups was observed. This lavage fluid technique enables to estimate the amounts of hepatic enzymes discharged into the intestinal tract, thereby opening a new avenue for future enzyme research.

  3. Evaluation of Milk Trace Elements, Lactate Dehydrogenase, Alkaline Phosphatase and Aspartate Aminotransferase Activity of Subclinical Mastitis as and Indicator of Subclinical Mastitis in Riverine Buffalo (Bubalus bubalis)

    Science.gov (United States)

    Guha, Anirban; Gera, Sandeep; Sharma, Anshu

    2012-01-01

    Mastitis is a highly morbid disease that requires detection at the subclinical stage. Tropical countries like India mainly depend on milch buffaloes for milk. The present study was conducted to investigate whether the trace minerals viz. copper (Cu), iron (Fe), zinc (Zn), cobalt (Co) and manganese (Mn) and enzyme activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in riverine buffalo milk can be used as an indicator of subclinical mastitis (SCM) with the aim of developing suitable diagnostic kit for SCM. Trace elements and enzyme activity in milk were estimated with Atomic absorption Spectrophotometer, GBC 932 plus and biochemical methods, respectively. Somatic cell count (SCC) was done microscopically. The cultural examination revealed Gram positive bacteria as the most prevalent etiological agent. A statistically significant (p<0.01) increase in SCC, Fe, Zn, Co and LDH occurred in SCM milk containing gram positive bacterial agents only. ALP was found to be elevated in milk infected by both gram positive and negative bacteria. The percent sensitivity, specificity and accuracy, predictive values and likelihood ratios were calculated taking bacterial culture examination and SCC≥2×105 cells/ml of milk as the benchmark. Only ALP and Zn, the former being superior, were found to be suitable for diagnosis of SCM irrespective of etiological agents. LDH, Co and Fe can be introduced in the screening programs where Gram positive bacteria are omnipresent. It is recommended that both ALP and Zn be measured together in milk to diagnose buffalo SCM, irrespective of etiology. PMID:25049573

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

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

    2008-05-01

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

  7. Molecular cloning of the cDNA encoding aspartate aminotransferase from bean root nodules and determination of its role in nodule nitrogen metabolism.

    Science.gov (United States)

    Silvente, Sonia; Camas, Alberto; Lara, Miguel

    2003-06-01

    A cDNA clone encoding aspartate aminotransferase (PVAAT-2) (EC 2.6.1.1) was isolated from the common bean Phaseolus vulgaris nodule cDNA library. The nucleotide sequence analysis of the full-length cDNA allowed its identification by comparison with sequence databases. The amino acid sequence of the bean PvAAT-2 showed high similarity with the AAT-2 isoforms described in other leguminous plants. The amino-terminal region of the PvAAT-2 contains a sequence, which shares common features of plastid transit peptides. Southern blot analysis showed that the PvAAT-2 clone is encoded by a single gene in the P. vulgaris genome. Analysis of the PvAAT-2 mRNA levels suggests that the expression of this gene is nodule enhanced. The PvAAT-2 transcript is more abundant in nodules with increased synthesis of amides and is down-regulated in conditions where ureides accumulate. When plants were supplemented with ureides or with amides, PvAAT-2 expression was reduced, while it was not affected when plants were treated with allopurinol, an inhibitor of ureide synthesis. On the other hand, the expression of asparagine synthetase (another enzyme involved in the synthesis of amides) is not affected either by ureides or amides. These data suggest a role for AAT-2 in the mechanism involved in the synthesis of nitrogen compounds in bean nodules.

  8. Peginterferon alpha-2a and ribavirin in patients with hepatitis C virus genotype 1 infection with persistently normal alanine aminotransferase levels.

    Science.gov (United States)

    Calleja, José-Luis; García-Samaniego, Javier; Ruiz-Antorán, Belén; Trapero, María; Morillas, Rosa; de la Revilla, Juan; Erdozaín, José Carlos; Espinosa, María-Dolores; Suárez, Dolores; Solá, Ricard; Romero-Gómez, Manuel; Baños, Fernando; Alvarez, Marco-Antonio

    2012-11-01

    To evaluate the efficacy and safety of peginterferon α-2a plus ribavirin at standard doses in patients with hepatitis C virus (HVC) genotype 1 infection with persistently normal alanine aminotransferase (ALT) levels. Patients aged 18 to 65 years were included in this observational, prospective study if they had evidence of a HCV genotype 1 infection. The serum HCV RNA concentration was determined at baseline and week 12. A qualitative HCV RNA test was performed at baseline and at weeks 48 and 72. Liver function tests were performed at each study visit. The primary efficacy measure was the sustained virological response in the intention-to-treat population. Logistic regression analyses were also performed to explore predictors of virological response. A sustained virological response was observed in 100 of the 175 patients (57%). An early virological response and end-of-treatment response were seen in 159 patients (91%) and 133 patients (76%), respectively. Thirty-seven of the 122 evaluable patients for this outcome (30%) showed a rapid virological response. A higher viral load was a significant predictor for a lack of rapid virological response and lack of sustained virological response. There were not any unexpected safety or tolerability findings. Our study suggests that the efficacy of the combination of peginterferon α-2a and ribavirin in patients with HCV genotype 1 infection and normal ALT levels is at least similar to that reported in patients with elevated ALT levels. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure-Associated Liver Disease in Pediatric Patients.

    Science.gov (United States)

    Rumbo, Carolina; Martinez, María Inés; Cabanne, Ana; Trentadue, Julio; Fernández, Adriana; Gondolesi, Gabriel

    2017-07-01

    Intestinal failure-associated liver disease (IFALD) is a frequent indication for intestinal transplantation. Liver biopsy (LBX) is the gold standard test for its diagnosis. Identifying noninvasive markers of fibrosis progression would be of considerable clinical use. Aspartate aminotransferase/platelet ratio index (APRI) has a good correlation in adult patients with chronic liver disease; few studies have been performed in children with IFALD. To evaluate APRI in a cohort of children with IFALD. Retrospective analysis of a prospective database of patients failure and at least 1 LBX, registered in our unit from March 2006 to December 2014. Forty-nine LBX were done on 36 patients: 20 were male, and 31 had short gut. Fibrosis was found in 71% of LBX. Biopsies were grouped according to the fibrosis stage (METAVIR [M]): (1) group 1 (G1) LBX with M 0, 1, 2 (n = 33) and (2) group 2 (G2) LBX with M 3, 4 (n = 16). The median APRI score was 0.92 (interquartile range [IQR] 0.63-1.50) for G1 and 2.50 (IQR 1.81-5.82) for G2 ( P = .001) The c statistic of the receiving operating characteristic curve was 0.79 (95% CI 0.64-0.94; P 1.6 correlates with advanced fibrosis.

  10. PsAAT3, an oomycete-specific aspartate aminotransferase, is required for full pathogenicity of the oomycete pathogen Phytophthora sojae.

    Science.gov (United States)

    Wang, Rongbo; Zhang, Meixiang; Liu, Hong; Xu, Jing; Yu, Jia; He, Feng; Zhang, Xiong; Dong, Suomeng; Dou, Daolong

    2016-04-01

    Pathogen nutrient acquisition and metabolism are critical for successful infection and colonization. However, the nutrient requirements and metabolic pathways related to pathogenesis in oomycete pathogens are unknown. In this study, we bioinformatically identified Phytophthora sojae aspartate aminotransferases (AATs), which are key enzymes that coordinate carbon and nitrogen metabolism. We demonstrated that P. sojae encodes more AATs than the analysed fungi. Some of the AATs contained additional prephenate dehydratase and/or prephenate dehydrogenase domains in their N-termini, which are unique to oomycetes. Silencing of PsAAT3, an infection-inducible expression gene, reduced P. sojae pathogenicity on soybean plants and affected the growth under N-starving condition, suggesting that PsAAT3 is involved in pathogen pathogenicity and nitrogen utilisation during infection. Our results suggest that P. sojae and other oomycete pathogens may have distinct amino acid metabolism pathways and that PsAAT3 is important for its full pathogenicity. Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  11. Risk factors associated with hepatitis B or C markers or elevated alanine aminotransferase level among blood donors on a tropical island: the Guadeloupe experience.

    Science.gov (United States)

    Fest, T; Viel, J F; Agis, F; Coffe, C; Dupond, J L; Hervé, P

    1992-10-01

    Donated blood is currently screened for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV), and alanine aminotransferase (ALT) levels to prevent posttransfusion hepatitis. A prospective study of 2368 blood donors was carried out in Guadeloupe (French West Indies) with a view to determining the risk factors associated with serologic abnormalities. Blood donors included in the study had to complete a questionnaire. Statistical analysis was performed on the data thus obtained: 571 donations (24%) were positive for at least one of the four analyzed markers. The results were that 3.2 percent were positive for HBsAg, 22 percent for anti-HBc, and 0.8 percent for anti-HCV, and 1.4 percent had ALT > or = 45 IU per L. A good correlation was found between anti-HCV and elevated ALT. Transfusion history and two socioeconomic categories (working class, military personnel) were found to be risk factors. Other risk factors were lifelong residence in Guadeloupe (with risk increasing with the number of years), birthplace and current residence in the southern part of the island, and the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.98). The results of this study illustrate the difficulty of implementing a preventive policy against posttransfusion hepatitis in a tropical area. The unique epidemiologic situation of Guadeloupe as regards hepatitis B virus has led to more restrictive criteria for the acceptance of blood donors.

  12. Hair Trace Elements in Overweight and Obese Adults in Association with Metabolic Parameters.

    Science.gov (United States)

    Skalnaya, Margarita G; Skalny, Anatoly V; Grabeklis, Andrey R; Serebryansky, Eugeny P; Demidov, Vasily A; Tinkov, Alexey A

    2018-03-01

    The objective of the present study was to investigate the level of toxic and essential trace elements in hair of adult overweight and obese persons as well as its association with metabolic parameters. Hair trace element levels were assessed using inductively coupled plasma mass-spectrometry in 112 overweight and obese patients and 106 lean controls. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, uric acid (UA) levels, and cholinesterase (CE) and gamma-glutamyltransferase (GGT) activity were also assessed. Excessive body weight significantly affected hair trace element levels. In particular, hair Co (33%), Cu (13%), I (30%), Mg (2-fold), Mn (25%), Zn (17%), and Ni (21%) levels were lower, whereas Al (14%) and As levels were higher in comparison to those in the control group. Correlation analysis demonstrated the most significant correlations for hair Mg with body weight, BMI, systolic and diastolic blood pressure, and UA, and for hair Al with body weight, BMI, TC, glucose, TG, CE, GGT, and UA. Multiple regression analysis demonstrated that trace elements were not associated with TC and LDL-C levels neither in crude nor in adjusted models. In turn, crude and adjusted models accounted for 25 and 43% of serum TG variance. The most significant associations were observed for hair Al, Fe, Si, and V in adjusted model. The obtained data demonstrate that obesity-related metabolic disorders may be at least partially mediated by altered trace element and mineral levels.

  13. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen

    2000-01-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT activity, whereas in PFIC type 3, the serum GGT activity is elevated. PFIC types 1 and 2 occur due to mutations in loci at chromosome 18 and chromosome 2, respectively. The pathophysiology of PFIC type 1 is not well understood. PFIC types 2 and 3 are caused by transport defects in the liver affecting the hepatobiliary secretion of bile acids and phospholipids, respectively. Benign recurrent intrahepatic cholestasis (BRIC is linked to a mutation in the same familial intrahepatic cholestasis 1 locus at chromosome 18. Defects of bile acid synthesis may be difficult to differentiate from these transport defects.Intrahepatic cholestasis of pregnancy (ICP appears to be related to these cholestatic diseases. For example, heterozygosity in families with PFIC type 3 is associated with ICP, but ICP has also been reported in families with BRIC.In Dubin-Johnson syndrome there is no cholestasis; only the hepatobiliary transport of conjugated bilirubin is affected. This, therefore, is a mild disease, and patients have a normal lifespan.

  14. Efeito da pimenta rosa associada a diversas dosagens de antibióticos em frangos de corte Effect of Brazilian red pepper meal associated with different levels of antibiotics on broilers chickens

    Directory of Open Access Journals (Sweden)

    Fabiano Gomes Gonçalves

    2012-08-01

    diet; T2: Positive Control (PC: basal diet with 1,2% BRPM; T3: PC+11ppm zinc bacitracin and 17ppm salinomycin, T4: PC + 22ppm zinc bacitracin and 34ppm salinomycin; T5: PC+33ppm zinc bacitracin and 51ppm salinomycin; T6: PC+45ppm zinc bacitracin and 67ppm salinomycin. BRPM contains tannins thus its use in animal feed needs to evaluate by liver function and animal performance. The dosage of the enzymes ALT (alanine aminotransferase, AST (aspartate aminotransferase and GGT (gamma glutamyltransferase is a tool in the diagnosis of liver damage. For this, were randomly collected blood samples from 10 animals per treatment between 21 and 41 days age. At 21 days of age it was observed elevated values of AST and decreased of ALT in broilers fed diet BRPM associated with higher levels of antibiotics compared to the others (P0.05. There was no effect (P>0.05 of treatments on broilers weight and relative liver weight at 43 days of age. The supplementation of Brazilian red pepper with or without antibiotics improved feed conversion at 43 days of age. It was concluded that the inclusion of 1.2% BRPM did not affect liver function but the addition of high levels of antibiotics associated with the BRPM resulted in alteration of hepatic enzymes.

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

    Directory of Open Access Journals (Sweden)

    Ericson Cavalcanti Gouveia

    2004-02-01

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

  16. Molecular and functional analyses support a role of Ornithine-{delta}-aminotransferase in the provision of glutamate for glutamine biosynthesis during pine germination.

    Science.gov (United States)

    Cañas, Rafael A; Villalobos, David P; Díaz-Moreno, Sara M; Cánovas, Francisco M; Cantón, Francisco R

    2008-09-01

    We report the molecular characterization and functional analysis of a gene (PsdeltaOAT) from Scots pine (Pinus sylvestris) encoding Orn-delta-aminotransferase (delta-OAT; EC 2.6.1.13), an enzyme of arginine metabolism. The deduced amino acid sequence contains a putative N-terminal signal peptide for mitochondrial targeting. The polypeptide is similar to other delta-OATs from plants, yeast, and mammals and encoded by a single-copy gene in pine. PsdeltaOAT encodes a functional delta-OAT as determined by expression of the recombinant protein in Escherichia coli and analysis of the active enzyme. The expression of PsdeltaOAT was undetectable in the embryo, but highly induced at early stages of germination and seedling development in all different organs. Transcript levels decreased in later developmental stages, although an increase was observed in lignified stems of 90-d-old plants. An increase of delta-OAT activity was observed in germinating embryos and seedlings and appears to mirror the observed alterations in PsdeltaOAT transcript levels. Similar expression patterns were also observed for genes encoding arginase and isocitrate dehydrogenase. Transcripts of PsdeltaOAT and the arginase gene were found widely distributed in different cell types of pine organs. Consistent with these results a metabolic pathway is proposed for the nitrogen flow from the megagametophyte to the developing seedling, which is also supported by the relative abundance of free amino acids in embryos and seedlings. Taken together, our data support that delta-OAT plays an important role in this process providing glutamate for glutamine biosynthesis during early pine growth.

  17. Molecular and Functional Analyses Support a Role of Ornithine-δ-Aminotransferase in the Provision of Glutamate for Glutamine Biosynthesis during Pine Germination1[W

    Science.gov (United States)

    Cañas, Rafael A.; Villalobos, David P.; Díaz-Moreno, Sara M.; Cánovas, Francisco M.; Cantón, Francisco R.

    2008-01-01

    We report the molecular characterization and functional analysis of a gene (PsδOAT) from Scots pine (Pinus sylvestris) encoding Orn-δ-aminotransferase (δ-OAT; EC 2.6.1.13), an enzyme of arginine metabolism. The deduced amino acid sequence contains a putative N-terminal signal peptide for mitochondrial targeting. The polypeptide is similar to other δ-OATs from plants, yeast, and mammals and encoded by a single-copy gene in pine. PsδOAT encodes a functional δ-OAT as determined by expression of the recombinant protein in Escherichia coli and analysis of the active enzyme. The expression of PsδOAT was undetectable in the embryo, but highly induced at early stages of germination and seedling development in all different organs. Transcript levels decreased in later developmental stages, although an increase was observed in lignified stems of 90-d-old plants. An increase of δ-OAT activity was observed in germinating embryos and seedlings and appears to mirror the observed alterations in PsδOAT transcript levels. Similar expression patterns were also observed for genes encoding arginase and isocitrate dehydrogenase. Transcripts of PsδOAT and the arginase gene were found widely distributed in different cell types of pine organs. Consistent with these results a metabolic pathway is proposed for the nitrogen flow from the megagametophyte to the developing seedling, which is also supported by the relative abundance of free amino acids in embryos and seedlings. Taken together, our data support that δ-OAT plays an important role in this process providing glutamate for glutamine biosynthesis during early pine growth. PMID:18621980

  18. Contributions of the substrate-binding arginine residues to maleate-induced closure of the active site of Escherichia coli aspartate aminotransferase.

    Science.gov (United States)

    Matharu, A; Hayashi, H; Kagamiyama, H; Maras, B; John, R A

    2001-03-01

    Crystallography shows that aspartate aminotransferase binds dicarboxylate substrate analogues by bonds to Arg292 and Arg386, respectively [Jager, J, Moser, M. Sauder, U. & Jansonius, J. N. (1994) J. Mol. Biol., 239, 285-305]. The contribution of each interaction to the conformational change that the enzyme undergoes when it binds ligands via these residues, is assessed by probing mutant forms of the enzyme lacking either or both arginines. The probes used are NaH(3)BCN which reduces the cofactor imine, the reactive substrate analogue, cysteine sulfinate and proteolysis by trypsin. The unreactive substrate analogue, maleate, is used to induce closure. Each single mutant reacted only 2.5-fold more slowly with NaH(3)BCN than the wild-type indicating that charge repulsion by the arginines contributes little to maintaining the open conformation. Maleate lowered the rate of reduction of the wild-type enzyme more than 300-fold but had little effect on the reaction of the mutant enzymes indicating that the ability of this dicarboxylate analogue to bridge the arginines precisely makes the major contribution to closure. The R292L mutant reacted 20 times more rapidly with cysteine sulfinate than R386L but 5 x 10(4) times more slowly than the wild-type enzyme, consistent with the proposal that enzyme's catalytic abilities are not developed unless closure is induced by bridging of the arginines. Proteolysis of the mutants with trypsin showed that, in the wild-type enzyme, the bonds most susceptible to trypsin are those contributed by Arg292 and Arg386. Proteolysis of the next most susceptible bond, at Arg25 in the double mutant, was protected by maleate demonstrating the presence of an additional site on the enzyme for binding dicarboxylates.

  19. Evaluation of Milk Trace Elements, Lactate Dehydrogenase, Alkaline Phosphatase and Aspartate Aminotransferase Activity of Subclinical Mastitis as and Indicator of Subclinical Mastitis in Riverine Buffalo (

    Directory of Open Access Journals (Sweden)

    Anirban Guha

    2012-03-01

    Full Text Available Mastitis is a highly morbid disease that requires detection at the subclinical stage. Tropical countries like India mainly depend on milch buffaloes for milk. The present study was conducted to investigate whether the trace minerals viz. copper (Cu, iron (Fe, zinc (Zn, cobalt (Co and manganese (Mn and enzyme activity of lactate dehydrogenase (LDH, alkaline phosphatase (ALP and aspartate aminotransferase (AST in riverine buffalo milk can be used as an indicator of subclinical mastitis (SCM with the aim of developing suitable diagnostic kit for SCM. Trace elements and enzyme activity in milk were estimated with Atomic absorption Spectrophotometer, GBC 932 plus and biochemical methods, respectively. Somatic cell count (SCC was done microscopically. The cultural examination revealed Gram positive bacteria as the most prevalent etiological agent. A statistically significant (p<0.01 increase in SCC, Fe, Zn, Co and LDH occurred in SCM milk containing gram positive bacterial agents only. ALP was found to be elevated in milk infected by both gram positive and negative bacteria. The percent sensitivity, specificity and accuracy, predictive values and likelihood ratios were calculated taking bacterial culture examination and SCC≥2×105 cells/ml of milk as the benchmark. Only ALP and Zn, the former being superior, were found to be suitable for diagnosis of SCM irrespective of etiological agents. LDH, Co and Fe can be introduced in the screening programs where Gram positive bacteria are omnipresent. It is recommended that both ALP and Zn be measured together in milk to diagnose buffalo SCM, irrespective of etiology.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  2. Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase.

    Science.gov (United States)

    Nandi, Shyam Sundar; Zheng, Hong; Sharma, Neeru M; Shahshahan, Hamid R; Patel, Kaushik P; Mishra, Paras K

    2016-10-01

    MicroRNAs (miRNAs) have a fundamental role in diabetic heart failure. The cardioprotective miRNA-133a (miR-133a) is downregulated, and contractility is decreased in diabetic hearts. Norepinephrine (NE) is a key catecholamine that stimulates contractility by activating β-adrenergic receptors (β-AR). NE is synthesized from tyrosine by the rate-limiting enzyme, tyrosine hydroxylase (TH), and tyrosine is catabolized by tyrosine aminotransferase (TAT). However, the cross talk/link between TAT and TH in the heart is unclear. To determine whether miR-133a plays a role in the cross talk between TH and TAT and regulates contractility by influencing NE biosynthesis and/or β-AR levels in diabetic hearts, Sprague-Dawley rats and miR-133a transgenic (miR-133aTg) mice were injected with streptozotocin to induce diabetes. The diabetic rats were then treated with miR-133a mimic or scrambled miRNA. Our results revealed that miR-133a mimic treatment improved the contractility of the diabetic rat's heart concomitant with upregulation of TH, cardiac NE, β-AR, and downregulation of TAT and plasma levels of NE. In miR-133aTg mice, cardiac-specific miR-133a overexpression prevented upregulation of TAT and suppression of TH in the heart after streptozotocin was administered. Moreover, miR-133a overexpression in CATH.a neuronal cells suppressed TAT with concomitant upregulation of TH, whereas knockdown and overexpression of TAT demonstrated that TAT inhibited TH. Luciferase reporter assay confirmed that miR-133a targets TAT. In conclusion, miR-133a controls the contractility of diabetic hearts by targeting TAT, regulating NE biosynthesis, and consequently, β-AR and cardiac function. © 2016 by the American Diabetes Association.

  3. Estimation of free energy barriers in the cytoplasmic and mitochondrial aspartate aminotransferase reactions probed by hydrogen-exchange kinetics of C alpha-labeled amino acids with solvent

    International Nuclear Information System (INIS)

    Julin, D.A.; Wiesinger, H.; Toney, M.D.; Kirsch, J.F.

    1989-01-01

    The existence of the postulated quinonoid intermediate in the cytoplasmic aspartate amino-transferase catalyzed transamination of aspartate to oxaloacetate was probed by determining the extent of transfer of tritium from the C alpha position of tritiated L-aspartate to pyridoxamine 5'-phosphate in single turnover experiments in which washout from the back-reaction was obviated by product trapping. The maximum amount of transferred tritium observed was 0.7%, consistent either with a mechanism in which a fraction of the net transamination reaction proceeds through a quinonoid intermediate or with a mechanism in which this intermediate is formed off the main reaction pathway. It is shown that transfer of labeled hydrogen from the amino acid to cofactor cannot be used to differentiate a stepwise from a concerted transamination mechanism. The amount of tritium transferred is a function of the rate constant for torsional equilibration about the epsilon-amino group of Lys-258, the presumptive abstractor of the C alpha proton; the relative rate constants for hydrogen exchange with solvent versus cofactor protonation; and the tritium isotope effect on this ratio. The free energy barriers facing the covalent intermediate between aldimine and keto acid product (i.e., ketimine and possibly quinonoid) were evaluated relatively by comparing the rates of C alpha-hydrogen exchange in starting amino acid with the rates of keto acid formation. The value of theta (= kexge/kprod) was found to be 2.6 for the reaction of cytoplasmic isozyme with aspartate and ca. 0.5 for that of the mitochondrial form with glutamate

  4. Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet.

    Science.gov (United States)

    Koppe, Sean W P; Elias, Marc; Moseley, Richard H; Green, Richard M

    2009-08-01

    Diets high in trans fats are associated with an increased risk of cardiovascular disease and components of the metabolic syndrome. The influence of these toxic fatty acids on the development of nonalcoholic fatty liver disease has not been significantly examined. Therefore, we sought to compare the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats. Male AKR/J mice were fed a calorically identical trans fat diet or standard high-fat diet for 10 days, 4 wk, and 8 wk. Serum alanine aminotransferase (ALT), lipid, insulin, and leptin levels were determined and the quantitative insulin-sensitivity check index (QUICKI) was calculated as a measure of insulin resistance. Additionally, hepatic triglyceride content and gene expression of several proinflammatory genes were assessed. By 8 wk, trans fat-fed mice exhibited higher ALT values than standard high-fat-fed mice (126 +/- 16 vs. 71 +/- 7 U/l, P Trans fat-fed mice also had increased insulin resistance compared with high-fat-fed mice at 4 and 8 wk with significantly higher insulin levels and lower QUICKI values. Additionally, hepatic interleukin-1beta (IL-1beta) gene expression was 3.6-fold higher at 4 wk (P trans fat-fed mice compared with standard high-fat-fed mice. Trans fat feeding results in higher ALT values, increased insulin resistance, and elevated IL-1beta levels compared with standard high-fat feeding.

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

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    Naoya Murao

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

  6. Elevated preoperative aspartate aminotransferase to lymphocyte ratio index as an independent prognostic factor for patients with hepatocellular carcinoma after hepatic resection

    Science.gov (United States)

    Liao, Yan; Li, Jun; Liao, Weijia; He, Songqing

    2015-01-01

    Few studies have elucidated the relationship between preoperative aspartate aminotransferase (AST) to lymphocyte ratio and high incidence of hepatocellular carcinoma (HCC). In search of a simple non-invasive prognostic marker, we investigated the prognostic significance of AST to lymphocyte ratio index (ALRI) in HCC. We reviewed retrospectively clinical parameters of 371 HCC patients who were treated with hepatectomy. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of preoperative ALRI. The predictive value of preoperative ALRI in HCC was evaluated by univariate and multivariate analyses using Cox proportional hazards regression modeling, and the survival probability of HCC patients was acquired by the Kaplan-Meier plots. In addition, stratified analysis was used to investigate the impact of preoperative ALRI on survival in different HCC subgroups. The results showed that preoperative ALRI was closely correlated with age (p = 0.007), median size (p = 0.004), clinical tumor-node-metastasis (TNM) stage (p 25.2 have a poorer disease-free survival (DFS) and overall survival (OS) after tumor resection. Multivariate analysis further identified preoperative ALRI > 25.2 (p = 0.002), III-IV of TNM stage (p = 0.011), PVTT (p = 0.035), size of tumor > 5 cm (p 25.2 (p = 0.001), III-IV of TNM stage (p = 0.005), PVTT (p = 0.012), size of tumor > 5 cm (p < 0.001), recurrence (p < 0.001) as independent prognostic factors for OS in HCC patients. Additionally, preoperative ALRI also showed different prognostic value in various subgroups of HCC. Elevated preoperative ALRI as a noninvasive, simple, and easily assessable parameter is an independent effective predictor of prognosis for patients with HCC. PMID:26057470

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

  9. Alanine-glyoxylate aminotransferase 2 (AGXT2 polymorphisms have considerable impact on methylarginine and β-aminoisobutyrate metabolism in healthy volunteers.

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    Anja Kittel

    Full Text Available Elevated plasma concentrations of asymmetric (ADMA and symmetric (SDMA dimethylarginine have repeatedly been linked to adverse clinical outcomes. Both methylarginines are substrates of alanine-glyoxylate aminotransferase 2 (AGXT2. It was the aim of the present study to simultaneously investigate the functional relevance and relative contributions of common AGXT2 single nucleotide polymorphisms (SNPs to plasma and urinary concentrations of methylarginines as well as β-aminoisobutyrate (BAIB, a prototypic substrate of AGXT2. In a cohort of 400 healthy volunteers ADMA, SDMA and BAIB concentrations were determined in plasma and urine using HPLC-MS/MS and were related to the coding AGXT2 SNPs rs37369 (p.Val140Ile and rs16899974 (p.Val498Leu. Volunteers heterozygous or homozygous for the AGXT2 SNP rs37369 had higher SDMA plasma concentrations by 5% and 20% (p = 0.002 as well as higher BAIB concentrations by 54% and 146%, respectively, in plasma and 237% and 1661%, respectively, in urine (both p<0.001. ADMA concentrations were not affected by both SNPs. A haplotype analysis revealed that the second investigated AGXT2 SNP rs16899974, which was not significantly linked to the other AGXT2 SNP, further aggravates the effect of rs37369 with respect to BAIB concentrations in plasma and urine. To investigate the impact of the amino acid exchange p.Val140Ile, we established human embryonic kidney cell lines stably overexpressing wild-type or mutant (p.Val140Ile AGXT2 protein and assessed enzyme activity using BAIB and stable-isotope labeled [²H₆]-SDMA as substrate. In vitro, the amino acid exchange of the mutant protein resulted in a significantly lower enzyme activity compared to wild-type AGXT2 (p<0.05. In silico modeling of the SNPs indicated reduced enzyme stability and substrate binding. In conclusion, SNPs of AGXT2 affect plasma as well as urinary BAIB and SDMA concentrations linking methylarginine metabolism to the common genetic trait of hyper

  10. Performance of an Optimized Paper-Based Test for Rapid Visual Measurement of Alanine Aminotransferase (ALT in Fingerstick and Venipuncture Samples.

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    Sidhartha Jain

    Full Text Available A paper-based, multiplexed, microfluidic assay has been developed to visually measure alanine aminotransferase (ALT in a fingerstick sample, generating rapid, semi-quantitative results. Prior studies indicated a need for improved accuracy; the device was subsequently optimized using an FDA-approved automated platform (Abaxis Piccolo Xpress as a comparator. Here, we evaluated the performance of the optimized paper test for measurement of ALT in fingerstick blood and serum, as compared to Abaxis and Roche/Hitachi platforms. To evaluate feasibility of remote results interpretation, we also compared reading cell phone camera images of completed tests to reading the device in real time.96 ambulatory patients with varied baseline ALT concentration underwent fingerstick testing using the paper device; cell phone images of completed devices were taken and texted to a blinded off-site reader. Venipuncture serum was obtained from 93/96 participants for routine clinical testing (Roche/Hitachi; subsequently, 88/93 serum samples were captured and applied to paper and Abaxis platforms. Paper test and reference standard results were compared by Bland-Altman analysis.For serum, there was excellent agreement between paper test and Abaxis results, with negligible bias (+4.5 U/L. Abaxis results were systematically 8.6% lower than Roche/Hitachi results. ALT values in fingerstick samples tested on paper were systematically lower than values in paired serum tested on paper (bias -23.6 U/L or Abaxis (bias -18.4 U/L; a correction factor was developed for the paper device to match fingerstick blood to serum. Visual reads of cell phone images closely matched reads made in real time (bias +5.5 U/L.The paper ALT test is highly accurate for serum testing, matching the reference method against which it was optimized better than the reference methods matched each other. A systematic difference exists between ALT values in fingerstick and paired serum samples, and can be

  11. From Genotype to Phenotype: Nonsense Variants in SLC13A1 Are Associated with Decreased Serum Sulfate and Increased Serum Aminotransferases

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    Christina G. Tise

    2016-09-01

    Full Text Available Using genomic applications to glean insights into human biology, we systematically searched for nonsense single nucleotide variants (SNVs that are rare in the general population but enriched in the Old Order Amish (Amish due to founder effect. We identified two nonlinked, nonsense SNVs (R12X and W48X in SLC13A1 (allele frequencies 0.29% and 0.74% in the Amish; enriched 1.2-fold and 3.7-fold, compared to the outbred Caucasian population, respectively. SLC13A1 encodes the apical sodium-sulfate cotransporter (NaS1 responsible for sulfate (reabsorption in the kidneys and intestine. SLC13A1 R12X and W48X were independently associated with a 27.6% (P = 2.7 × 10−8 and 27.3% (P = 6.9 × 10−14 decrease in serum sulfate, respectively (P = 8.8 × 10-20 for carriers of either SLC13A1 nonsense SNV. We further performed the first exome- and genome-wide association study (ExWAS/GWAS of serum sulfate and identified a missense variant (L348P in SLC26A1, which encodes the basolateral sulfate-anion transporter (Sat1, that was associated with decreased serum sulfate (P = 4.4 × 10−12. Consistent with sulfate’s role in xenobiotic detoxification and protection against acetaminophen-induced hepatotoxicity, SLC13A1 nonsense SNV carriers had higher aminotransferase levels compared to noncarriers. Furthermore, SLC26A1 L348P was associated with lower whole-body bone mineral density (BMD and higher serum calcium, consistent with the osteochondrodysplasia exhibited by dogs and sheep with naturally occurring, homozygous, loss-of-function mutations in Slc13a1. This study demonstrates the power and translational potential of systematic identification and characterization of rare, loss-of-function variants and warrants additional studies to better understand the importance of sulfate in human physiology, disease, and drug toxicity.

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

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    O. M. Vasilyuk

    2015-06-01

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

  13. Performance of an Optimized Paper-Based Test for Rapid Visual Measurement of Alanine Aminotransferase (ALT) in Fingerstick and Venipuncture Samples.

    Science.gov (United States)

    Jain, Sidhartha; Rajasingham, Radha; Noubary, Farzad; Coonahan, Erin; Schoeplein, Ryan; Baden, Rachel; Curry, Michael; Afdhal, Nezam; Kumar, Shailendra; Pollock, Nira R

    2015-01-01

    A paper-based, multiplexed, microfluidic assay has been developed to visually measure alanine aminotransferase (ALT) in a fingerstick sample, generating rapid, semi-quantitative results. Prior studies indicated a need for improved accuracy; the device was subsequently optimized using an FDA-approved automated platform (Abaxis Piccolo Xpress) as a comparator. Here, we evaluated the performance of the optimized paper test for measurement of ALT in fingerstick blood and serum, as compared to Abaxis and Roche/Hitachi platforms. To evaluate feasibility of remote results interpretation, we also compared reading cell phone camera images of completed tests to reading the device in real time. 96 ambulatory patients with varied baseline ALT concentration underwent fingerstick testing using the paper device; cell phone images of completed devices were taken and texted to a blinded off-site reader. Venipuncture serum was obtained from 93/96 participants for routine clinical testing (Roche/Hitachi); subsequently, 88/93 serum samples were captured and applied to paper and Abaxis platforms. Paper test and reference standard results were compared by Bland-Altman analysis. For serum, there was excellent agreement between paper test and Abaxis results, with negligible bias (+4.5 U/L). Abaxis results were systematically 8.6% lower than Roche/Hitachi results. ALT values in fingerstick samples tested on paper were systematically lower than values in paired serum tested on paper (bias -23.6 U/L) or Abaxis (bias -18.4 U/L); a correction factor was developed for the paper device to match fingerstick blood to serum. Visual reads of cell phone images closely matched reads made in real time (bias +5.5 U/L). The paper ALT test is highly accurate for serum testing, matching the reference method against which it was optimized better than the reference methods matched each other. A systematic difference exists between ALT values in fingerstick and paired serum samples, and can be addressed by

  14. Fotossensibilização primária em eqüídeos e ruminantes no semi-árido causada por Froelichia humboldtiana (Amaranthaceae Primary photosensitization in equidae and ruminants in the Brazilian semi-arid caused by Froelichia humboldtiana (Amaranthaceae

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    Luciano A. Pimentel

    2007-01-01

    colocados na mesma pastagem com F. humboldtiana por um período de 44 dias. A égua, que não tinha áreas de pele despigmentadas não apresentou lesões, no entanto o potro desenvolveu dermatite nas áreas brancas de pele 25 dias após o início do pastejo. Após serem retirados da pastagem o potro recuperou-se totalmente em 15 dias. Estes experimentos indicam que F. humboldtiana causa fotossensibilização primária em animais domésticos. A ausência de lesões nos animais que ingeriram a planta após ser coletada e mantida em geladeira sugere que a planta perde sua toxicidade depois da coleta. A ausência de lesões oculares características da intoxicação por furocumarinas sugere que F. humboldtiana contém derivados da naftodiantrona, similares aos encontrados em Fagopyrum esculentum e Hypericum perforatum que não causam lesões oculares.Photosensitization is common in the Brazilian semiarid, affecting mainly horses, but also donkeys, mules, sheep and cattle. The dermatitis affects mainly non pigmented skin, and the animals recover after being withdrawn from the pastures. To demonstrate the etiology of the disease, Froelichia humboldtiana (Roem. et Schult. Seub., collected in the field one or two times a week and kept in the refrigerator for 1-4 days, was administered for 30 or more days as the only food ad libitum to 2 donkeys and one white sheep, and as the only forage ad libitum, to one white horse. No clinical signs were observed in those animals, and serum activities of aspartate-aminotransferase (AST, alanine-aminotransferase (AST, and gamma-glutamyltransferase (GGT were within normal ranges. In another experiment, one sheep was tied by a rope, during the day, in a pasture of exclusively F. humboldtiana for a 26 days period. Skin lesions characteristic of photosensitization appeared 4-5 days after the start of the experiment and became severe until day 26. After the withdrawal of the animal from the pasture on day 26 it fully recovered within 30 days. In

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

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    Andreia Salezze Vieira

    2012-06-01

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

  16. BALANÇO ELETROLÍTICO E PROTÉICO DIETÉTICOS SOBRE AS AMINOTRANSFERASES HEPÁTICAS, RENAIS E SÉRICAS E TEORES SÉRICOS DE MAGNÉSIO E CLORO DE FRANGOS DE CORTE ELETROLÍCTIC AND PROTEIN DIET BALANCE ON AMINOTRANSFERASES ON LIVER, KIDNEY AND SERUM AND SERIC MAGNESIUM AND CHOLRIDE LEVELS IN BROILERS

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    Cíntia Silva Minafra Rezende

    2009-07-01

    Full Text Available

    Desenvolveu-se um experimento com pintos de corte machos para o estudo dos efeitos dos níveis de 20% e 23% de proteína bruta (PB combinados com 0, 50, 100, 150, 200, 250, 300 e 350 mEq/kg de balanço eletrolítico (BE sobre o perfil da atividade das aminotransferases (AST e ALT no tecido hepático, tecido renal e no soro, além dos níveis séricos do cloro (Cl e magnésio (Mg de frangos de corte de sete, quatorze e vinte e um dias de idade. O delineamento utilizado foi fatorial 2x8. Forneceram-se dietas e água ad libitum. Coletou-se o sangue, de quatro aves de cada tratamento, por punção cardíaca para separação do soro, o qual foi congelado a -200C. Após, sacrificaram-se as aves por deslocamento cervical, para remoção do tecido hepático e renal, material esse pesado e congelado em nitrogênio líquido e posteriormente homogeneizado. Centrifugou-se uma alíquota de cada amostra homogeneizada a 7.000rpm por três minutos a 4oC, para determinação das atividades das aminotransferases no sobrenadante. Níveis de PB e BE na dieta afetaram a atividade enzimática da AST no tecido renal aos sete e vinte e um dias de idade, e no soro aos sete e quatorze dias. A atividade da ALT foi alterada, aos quatorze dias no tecido renal, e aos sete e quatorze dias no soro. A concentração do íon cloro, no soro, aos quatorze dias de idade sofreu alteração pela interação dos níveis de BE e PB. A concentração do íon magnésio não foi alterada pelos níveis de PB e BE. Mostra-se, neste trabalho, um perfil dos resultados, uma vez que não há dados disponíveis na literatura. Com os resultados obtidos não se pôde correlacionar as modificações dos níveis de PB e BE com as alterações nas concentrações das enzimas ALT e AST no tecido hepático e renal, consequentemente, com as alterações metabólicas.

    PALAVRAS-CHAVES: Balanço eletrolítico, fígado, frangos, proteína dietética, frangos, soro, rim.

    An experiment was

  17. Determinação das atividades séricas de creatina quinase, lactato desidrogenase e aspartato aminotransferase em eqüinos de diferentes categorias de atividade Determination of serum activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase in horses of different activities classes

    Directory of Open Access Journals (Sweden)

    I.A. Câmara e Silva

    2007-02-01

    Full Text Available The creatine kinase (CK, lactate dehydrogenase (LDH, and aspartate aminotransferase (AST seric activities in horses of different activity classes (athlete, traction, and reproduction, were compared. Fifty-eight horses were alloted into three groups - group 1 with 20 athletes, "vaquejada" competitors; group 2 with 20 breeding horses; and group 3 with 18 draft horses, averaging 10 working hours daily. The average values for CK serum activity were 80.2, 83.9, and 94.4 U/l in groups 1, 2, and 3, respectively. Result of group 3 was significantly different from the other groups. The averages values for LDH were 102.5, 98.6, and 112.8 U/l in groups 1, 2, and 3, respectively, with no statistical difference between groups. The AST averages were 56.8, 33.0, and 50.1 U/l in groups 1, 2, and 3, respectively, with group 2 significantly differing from the others. Clinical biochemistry values of muscular function in horses varied according to activity category.

  18. Albuminuria and its associated biomedical factors among indigenous adults in Far North Queensland: a 7-year follow up study.

    Science.gov (United States)

    Li, Ming; McDermott, Robyn

    2015-12-10

    To document albuminuria prevalence and its associated factors in Aboriginal and Torres Strait Islander (TSI) adults with high renal and metabolic risks from 19 rural and remote north Queensland communities. One thousand nine hundred seventy-one indigenous adults were enrolled in 1998 and 566 completed follow up in 2007 in this population-based study. Measurements included weight, waist circumference (WC), blood pressure (BP), fasting glucose, lipids, gamma-glutamyltransferase (GGT), urinary albumin creatinine ratio (UACR), smoking, alcohol intake and physical activity (PA). Albuminuria was defined as an UACR > =2.5 g/mol in males and > =3.5 g/mol in females. The association between albuminuria and biomedical factors was assessed with generalised linear modelling. Baseline albuminuria prevalence was 19.7 % (95 % CI: 18.0-21.6 %). Follow up prevalence was 42.4 % (95 % CI: 38.4-46.5 %) among the 566 adults having the 2(nd) UACR measurements. Follow-up albuminuria was associated with fasting glucose of 5.4 mmol/L (OR 2.5, 95 % CI 1.5-4.2), GGT tertiles in a dose-response manner (OR 2.0 for 2(nd) and 3.7 for 3(rd) tertile, p for trend albuminuria compared to TSI counterparts, while TSI smokers had twice the likelihood (95 % CI 1.2-3.2). At both baseline and follow up, albuminuria was more prevalent among older participants. Indigenous Australians in north Queensland are at high risk of albuminuria. Overweight and obesity, glycaemia, increased GGT, and smoking were associated with albuminuria at baseline and/or follow up.

  19. Value of ethyl glucuronide in plasma as a biomarker for recent alcohol consumption in the emergency room.

    Science.gov (United States)

    Neumann, Tim; Helander, Anders; Dahl, Helen; Holzmann, Tilly; Neuner, Bruno; Weiss-Gerlach, Edith; Müller, Christian; Spies, Claudia

    2008-01-01

    This emergency department (ED) study compared the value of plasma ethyl glucuronide (EtG) testing with the information about alcohol consumption obtained using the standard alcohol biomarkers gamma-glutamyltransferase (GGT) and carbohydrate-deficient transferring (CDT) and the AUDIT questionnaire. Minimally injured and clinically non-intoxicated male patients (n = 81) admitted to an ED were screened regarding their alcohol consumption, using the computerized AUDIT questionnaire and a paper-and-pencil assessment including the type, amount and time of alcohol intake. Blood samples were collected for determination of ethanol, EtG (LC-MS) and GGT in plasma and %CDT in serum (Axis-Shield %CDT immunoassay). Out of the 81 patients, 23 (28%) were positive (>/=8 points) on the AUDIT questionnaire. Only 3 (4%) showed a detectable ethanol concentration (range 0.01-0.07 g/L) but 31 (38%) showed a detectable EtG (0.16-39.5 mg/L). In four patients, EtG was detectable in plasma for >48 h after estimated completed elimination of ethanol. EtG was not correlated with the long-term biomarkers %CDT or GGT, or the AUDIT results, but with the time since estimated completed ethanol elimination. EtG testing in blood was found useful in the ED as a way to detect recent drinking, even in cases of a negative ethanol test, and to confirm abstinence from alcohol. This sensitive and specific short-term biomarker provides valuable additional information about individual drinking habits and might also be helpful to identify an alcohol hangover.

  20. Evaluation of cardiac risk by oxidative stress and inflammatory markers in diabetic patients

    International Nuclear Information System (INIS)

    Khan, D.A.; Qayyum, S.

    2010-01-01

    Objectives: To evaluate the diabetic patients for cardiac risk by measuring oxidative stress and inflammatory markers in relation with glycaemic control. Methodology: A total of 140 subjects were included in this case-control study, comprising of 70 diabetic patients with coronary heart disease (CHD) and an equal number, age and sex matched controls. The patients were non-alcoholic and had age >40 years, BMI < 30 kg/m/sup 2/ and glycated hemoglobin (HbA1c) 7-10%. Serum total cholesterol (TC) and gamma glutamyltransferase (GGT) were analyzed on selectra-E auto analyzer. Serum nitrate was measured at 540 nm on ELISA. HbA1c on was analyzed by using Human kit. Serum high sensitivity C-reactive protein (hS-CRP) was analyzed on immulite 1000. Results: Patients mean age was 51 (range 40-73) years. Diabetic patients had significantly elevated median of HbA1c (7.9 vs 4.9), hS CRP (6.0 vs 2.12), TC (5.95 vs 4.45), nitrate (19.20vs 10.70) and GGT (29.50 vs 22.50) as compared to controls (p< 0.001). HbA1c showed a positive correlation (p <0.001) with hS-CRP (r=0.49), TC (r=0.69), nitrate (r=0.41) and GGT (r=0.30). Conclusion: Oxidative stress and inflammatory markers should be used in addition to HbA1c for assessment of increased cardiac risk in un-controlled diabetic patients because of accelerated atherosclerosis due to free radical injury. (author)

  1. Liver enzymes and psychological well-being response to aerobic ...

    African Journals Online (AJOL)

    Liver enzymes and psychological well-being response to aerobic exercise training in patients with chronic hepatitis C. ... Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma – Glutamyltransferase (GGT) , Beck Depression Inventory (BDI ) & Profile of Mood States(POMS) and increase in Rosenberg ...

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

    African Journals Online (AJOL)

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

  3. Biochemical assessement of liver enzymes in immunocompromised ...

    African Journals Online (AJOL)

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

  4. Alterações hepáticas em trabalhadores de uma refinaria de petróleo e em uma população de referência no Estado da Bahia, Brasil Liver changes in workers at an oil refinery and in a reference population in the state of Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    João Luiz Barberino

    2005-01-01

    workers at an oil refinery located in the state of Bahia, Brazil, as compared to a reference population with no occupational exposure to chemical products, and to describe the factors associated with the observed differences in prevalence. METHODS: We studied workers at the refinery and at the company's central management office located in the city of Salvador, which is the state capital. Blood samples of 692 refinery workers and 377 workers from the reference population were analyzed. Cases were defined as individuals presenting high serum levels of both gamma-glutamyltransferase (GGT and alanine aminotransferase (ALT (GGT > 50 U/L for males and > 32 U/L for females; ALT > 50 U/L. Data were collected on age, sex, weight, height, years working for the company, use of alcohol, smoking habits, physical exercise, occupational exposure to chemical products, use of personal safety equipment, and medical history of hepatitis, jaundice, and obesity. RESULTS: The prevalence of liver changes among refinery workers was 15.3% (95% CI: 12.5 to 18.1, vs. 3.8% (95% CI: 1,8 to 5,8 in the reference population. According to multiple logistic regression analysis, the prevalence of liver changes among refinery workers was 3.56 times greater (95% CI: 1,99 to 6,38 than in the reference population, regardless of the presence of other relevant co-variables, such as obesity, exercise, smoking, and alcohol consumption. CONCLUSIONS: These results suggest that occupational exposure may play a major role in the development of liver changes among workers at the oil refinery where the study was carried out.

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

    Directory of Open Access Journals (Sweden)

    Martín R. Salazar

    2007-04-01

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

  6. Crystal Structure of Ll-Diaminopimelate Aminotransferase From 'Arabidopsis Thaliana': a Recently-Discovered Enzyme in the Biosynthesis of L-Lysine By Plants And 'Chlamydia'

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, N.; Cherney, M.M.; van Belkum, M.J.; Marcus, S.L.; Flegel, M.D.; Clay, M.D.; Deyholos, M.K.; Vederas, J.C.; James, M.N.G.

    2007-07-13

    The essential biosynthetic pathway to l-Lysine in bacteria and plants is an attractive target for the development of new antibiotics or herbicides because it is absent in humans, who must acquire this amino acid in their diet. Plants use a shortcut of a bacterial pathway to l-Lysine in which the pyridoxal-5-phosphate (PLP)-dependent enzyme ll-diaminopimelate aminotransferase (LL-DAP-AT) transforms l-tetrahydrodipicolinic acid (L-THDP) directly to LL-DAP. In addition, LL-DAP-AT was recently found in Chlamydia sp., suggesting that inhibitors of this enzyme may also be effective against such organisms. In order to understand the mechanism of this enzyme and to assist in the design of inhibitors, the three-dimensional crystal structure of LL-DAP-AT was determined at 1.95 Angstroms resolution. The cDNA sequence of LL-DAP-AT from Arabidopsis thaliana (AtDAP-AT) was optimized for expression in bacteria and cloned in Escherichia coli without its leader sequence but with a C-terminal hexahistidine affinity tag to aid protein purification. The structure of AtDAP-AT was determined using the multiple-wavelength anomalous dispersion (MAD) method with a seleno-methionine derivative. AtDAP-AT is active as a homodimer with each subunit having PLP in the active site. It belongs to the family of type I fold PLP-dependent enzymes. Comparison of the active site residues of AtDAP-AT and aspartate aminotransferases revealed that the PLP binding residues in AtDAP-AT are well conserved in both enzymes. However, Glu97* and Asn309* in the active site of AtDAP-AT are not found at similar positions in aspartate aminotransferases, suggesting that specific substrate recognition may require these residues from the other monomer. A malate-bound structure of AtDAP-AT allowed LL-DAP and L-glutamate to be modeled into the active site. These initial three-dimensional structures of LL-DAP-AT provide insight into its substrate specificity and catalytic mechanism.

  7. Expression, purification, crystallization, data collection and preliminary biochemical characterization of methicillin-resistant Staphylococcus aureus Sar2028, an aspartate/tyrosine/phenylalanine pyridoxal-5′-phosphate-dependent aminotransferase

    Energy Technology Data Exchange (ETDEWEB)

    Seetharamappa, Jaldappagari [Scottish Structural Facility and Centre for Biomolecular Sciences, The University, St Andrews KY16 9ST,Scotland (United Kingdom); Department of Chemistry, Karnatak University, Pavate Nagar, Dharwad 580 003, Karnataka State (India); Oke, Muse; Liu, Huanting; McMahon, Stephen A.; Johnson, Kenneth A.; Carter, Lester; Dorward, Mark; Zawadzki, Michal [Scottish Structural Facility and Centre for Biomolecular Sciences, The University, St Andrews KY16 9ST,Scotland (United Kingdom); Overton, Ian M.; Niekirk, C. A. Johannes van [Scottish Structural Facility and School of Life Sciences Research, University of Dundee, Dow Street, Dundee DD1 5EH,Scotland (United Kingdom); Graham, Shirley; Botting, Catherine H.; Taylor, Garry L.; White, Malcolm F. [Scottish Structural Facility and Centre for Biomolecular Sciences, The University, St Andrews KY16 9ST,Scotland (United Kingdom); Barton, Geoffrey J. [Scottish Structural Facility and School of Life Sciences Research, University of Dundee, Dow Street, Dundee DD1 5EH,Scotland (United Kingdom); Coote, Peter J.; Naismith, James H., E-mail: naismith@st-andrews.ac.uk [Scottish Structural Facility and Centre for Biomolecular Sciences, The University, St Andrews KY16 9ST,Scotland (United Kingdom)

    2007-05-01

    As part of work on S. aureus, the crystallization of Sar2028, a protein that is upregulated in MRSA, is reported. Sar2028, an aspartate/tyrosine/phenylalanine pyridoxal-5′-phosphate-dependent aminotransferase with a molecular weight of 48 168 Da, was overexpressed in methicillin-resistant Staphylococcus aureus compared with a methicillin-sensitive strain. The protein was expressed in Escherichia coli, purified and crystallized. The protein crystallized in a primitive orthorhombic Laue group with unit-cell parameters a = 83.6, b = 91.3, c = 106.0 Å, α = β = γ = 90°. Analysis of the systematic absences along the three principal axes indicated the space group to be P2{sub 1}2{sub 1}2{sub 1}. A complete data set was collected to 2.5 Å resolution.

  8. Glicemia, proteinograma e perfil de alguns componentes bioquímicos séricos de cabritos da raça Bôer

    Directory of Open Access Journals (Sweden)

    Rodrigo Yanaka

    2012-02-01

    Full Text Available The newborn goat kids suffer several adjustments to life outside the uterus that affect different body functions that they need to produce heat, muscle activity and start searching for food. All these events lead to changes in several blood constituents such as proteins and serum biochemical parameters. Other studies have shown these variations, but not extend beyond the neonatal period to phase in young animals. The aim was to test the hypothesis that there is variation of the protein profile, and biochemical components of blood glucose in goat kids from birth to 75 days of life in terms of adaptation to extra uterine life. To achieve these objectives have been collected blood samples from 25 goats born by normal delivery, regardless of their sex. The variables serum total protein (TP, albumin, α-globulin, β-globulin, γ-globulin, which includes the immunoglobulin G (IgG, aspartate (AST, alkaline phosphatase (ALP, gamma-glutamyltransferase (GGT, creatinine and urea, and glucose were determined at times zero (immediately after birth, two, seven, 15, 30 and 75 days old. We observed significant differences in all variables between times, but only the creatinine concentration was higher than those of other moments in time zero and two days old, probably due to immaturity of renal function in newborn animals. The blood constituents of the kids had variations in the study period, related to physiological and nutritional causes.

  9. Thiamethoxam Actara® induced alterations in kidney liver cerebellum and hippocampus of male rats

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun-Oularbi

    2017-12-01

    Full Text Available Thiamethoxam (TMX, a second-generation neonicotinoid insecticide, is one of the most widely used insecticides in Algeria. The present study assessed the effects of repeated subchronic exposure to the commercial formulation of thiamethoxam (Actara®, 25% WG in albino male rats. The toxic effects of thiamethoxam (TMX were studied biochemically and histopathologically. Twenty-eight male albino rats weighing between 226 and 243 g were randomly assigned to four groups. One group served as control, and the other three were served as experimental groups administered a neonicotinoid thiamethoxam (TMX; 26, 39 and 78 mg/kg/day for 6 weeks. The effects of the insecticide on various biochemical parameters were evaluated at 2, 4 and 6 weeks. Histopathological studies were carried out in the liver, kidney, cerebellum and hippocampus at the end of the experiment. Changes in biochemical parameters glucose, ALT (alanine aminotransferase, AST (aspartate aminotransferase, γGT (gamma-glutamyltransferase ALP (alkaline phosphatase urea and creatinine were observed in treated-groups in a dose dependent manner when compared to the control. Histopathological alterations were more intense in male rats from the TMX high dose group than those from group 2 and 3. Based on these results, subchronic oral administration of thiamethoxam altered the biochemical parameters, which correlated with histopathological changes in the liver kidney and brain.

  10. Chronic effects of fumonisin B1 on ducks.

    Science.gov (United States)

    Tran, S T; Auvergne, A; Benard, G; Bailly, J D; Tardieu, D; Babilé, R; Guerre, P

    2005-01-01

    Partially purified fumonisin B1 (FB1) was orally administrated for 77 d to 5 groups of 8 mule ducks starting at 7 d of age; the concentrations corresponded to 5 diets containing 0, 2, 8, 32, and 128 mg of FB1/kg of feed. No mortality was observed, and no effects on feed consumption and body weight gain were observed at the end of the treatment period. But, surprisingly, FB1 ingested at 32 and 128 mg/kg led to decreased body weight from d 28 to 63 and from d 7 to 63, respectively. FB1 had no effect on the relative weight of heart and breast muscle, whereas a significant increases in the relative weights of gizzard, spleen, and liver were measured in ducks receiving 32 and 128 mg of FB1/kg of feed without evidence of detectable microscopic modification of these organs. FB1 had no significant effect of the serum aspartate aminotransferase and gamma-glutamyltransferase levels but increased serum total protein, cholesterol, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase levels when 128 mg of FB1/kg of feed was given. Serum, liver, and kidney sphinganine to sphingosine ratio was significantly increased in ducks fed 8 to 128 mg of FB1/kg of feed. The biggest increase was observed in kidneys, suggesting that this organ is the most sensitive to detect FB1-induced disruption of sphingolipid metabolism.

  11. Impact of coffee on liver diseases: a systematic review.

    Science.gov (United States)

    Saab, Sammy; Mallam, Divya; Cox, Gerald A; Tong, Myron J

    2014-04-01

    Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed. Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase and alanine aminotransferase values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. Moreover, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Resolution of persistent pneumothorax by use of blood pleurodesis in a dog after surgical correction of a diaphragmatic hernia.

    Science.gov (United States)

    Merbl, Yael; Kelmer, Efrat; Shipov, Anna; Golani, Yael; Segev, Gilad; Yudelevitch, Sigal; Klainbart, Sigal

    2010-08-01

    A 15-kg (33-lb) pregnant female mixed-breed dog of unknown age was referred because of a 10-day history of difficulty breathing. Physical examination findings were dyspnea, tachypnea, decreased bronchovesicular sounds (bilateral), muffled heart sounds, and abdominal distention with palpable fetuses. Hematologic abnormalities included anemia, leukocytosis, and thrombocytosis. Abnormalities detected during serum biochemical analysis included decreases in concentrations of albumin, sodium, triglycerides, and total calcium and increases in activities of alkaline phosphatase, alanine aminotransferase, gamma-glutamyltransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. Thoracic radiography revealed a diaphragmatic hernia with fetuses and a soft tissue or fluid opacity within the thoracic cavity. Exploratory celiotomy, ovariohysterectomy, partial sternotomy, placement of a right-sided thoracostomy tube, and herniorrhaphy were performed. After surgery, pneumothorax developed, and the thoracostomy tube was used to remove pleural effusion and free air. The pneumothorax did not resolve after continuous drainage of the thoracic cavity for 4 days. Autologous blood pleurodesis was performed by infusion of 80 mL (6 mL/kg [2.73 mL/lb]) of whole blood. The pneumothorax resolved immediately after injection of the blood. Blood pleurodesis was used for resolution of pneumothorax in a dog after correction of a diaphragmatic hernia. Blood pleurodesis may provide a simple, safe, and inexpensive medical treatment for resolution of persistent (duration>5 days) pneumothorax when surgery is not an option.

  13. [Inhibitory effects of Scutellaria barbate extracts on diethylnitrosamine-induced hepatocarcinoma in rats].

    Science.gov (United States)

    Dai, Zhi-Jun; Wang, Xi-Jing; Ji, Zong-Zheng; Liu, Xiao-Xu; Kang, Hua-Feng; Diao, Yan; Ma, Xiao-Bin; Liu, Lei; Ren, Hong-Tao

    2009-04-01

    To investigate the inhibitory effects of Scutellaria barbate extracts on diethylnitrosamine-induced hepatocarcinoma in rats. Hepatocarcinoma model rats were induced by diethylnitrosamine (DEN). Sixty SD male rats were randomly divided into 4 groups: normal control group, hepatocarcinoma model group, ESB of high dose group and ESB of low dose group. All rats were killed in the 18th week, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), gamma-glutamyltransferase (gamma-GT) and alpha-L-fucosidase (AFU) in serum were measured by biochemical examinations; Hematoxy and eosin (HE) methods were used to examine the changes of liver pathology. The levels of ALT, AST, TBIL, ALP, gamma-GT, AFU in hepatocarcinoma model group and ESB groups were higher than that of control group (P < 0.05). ESB could relieve hepatic injures. The levels of liver function indexes in ESB groups were lower than that of model group. Histological examination demonstrated that the number of liver cancer nodus in ESB groups were lower than that of model group. Furthermore, ESB could attenuate the grade of cancer cell differentiation. ESB could inhibit experimental hepatocarcinoma and relieve hepatic injures in rats.

  14. Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

    Directory of Open Access Journals (Sweden)

    B. O. Chekh

    2017-08-01

    Full Text Available The aim of our work was to study biological properties of the polymer based on pseudo-polyamino acids GluLa-DPG-PEG600, its ability to bind albumin, as well as its localization in rat body and influence on physio­logical and functional state of rat kidneys and liver. We have found the ability of GluLa-DPG-PEG600 to bind bovine serum albumin (BSA using electrophoresis in 5% polyacrylamide gel. Structural and functional state of the liver and kidneys of rats after injections of polymer were investigated by histological analysis of organs and determination the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and content of cholesterol and creatinine in blood. Our results showed little toxic effect of GluLa-DPG-PEG600 on rat body. Using fluorescent microscopy we have studied polymer in complex with BSA distribution in rat body: after intravenous injection polymer are localized in kidneys and spleen, and after intramuscular – in liver and brain. It has been shown that polymer passed through the blood-brain barrier and are localized in the immune organ – spleen, indicating GluLa-DPG-PEG600 as a potential drug transporter.

  15. Rangelia vitalii: changes in the enzymes ALT, CK and AST during the acute phase of experimental infection in dogs.

    Science.gov (United States)

    Costa, Márcio Machado; França, Raqueli Teresinha; Da Silva, Aleksandro Schafer; Paim, Carlos Breno; Paim, Francine; do Amaral, Carlos Henrique; Dornelles, Guilherme Lopes; da Cunha, João Paulo Monteiro Carvalho Mori; Soares, João Fabio; Labruna, Marcelo Bahia; Mazzanti, Cinthia Melazzo Andrade; Monteiro, Silvia Gonzalez; Lopes, Sonia Terezinha Dos Anjos

    2012-01-01

    Rangelia vitalii is a protozoon that causes diseases in dogs, and anemia is the most common laboratory finding. However, few studies on the biochemical changes in dogs infected with this protozoon exist. Thus, this study aimed to investigate the biochemical changes in dogs experimentally infected with R. vitalii, during the acute phase of the infection. For this study, 12 female dogs (aged 6-12 months and weighing between 4 and 7 kg) were used, divided in two groups. Group A was composed of healthy dogs (n = 5); and group B consisted of infected animals (n = 7). Blood samples were collected on days 0, 10, 20 and 30 after infection, using tubes without anticoagulant to obtain serum and analyze the biochemical parameters. An increase in alanine aminotransferase (ALT) on day 20 (P < 0.05) was observed. Also, increased creatine kinase (CK) and aspartate aminotransferase (AST) levels were observed throughout the experimental period (P < 0.05). No changes in the serum gamma-glutamyltransferase, urea and creatinine levels were observed. Thus, is possible to conclude that experimental infection with R. vitalii in dogs causes changes to the biochemical profile, with increased ALT, AST and CK enzyme levels.

  16. Coffee Intake and Liver Enzyme Association in Korean Immigrants and Japanese: A Comprehensive Cross-Sectional Study.

    Science.gov (United States)

    Kim, Soo Ki; Shin, Myung-Hee; Sugimoto, Kayo; Kim, Soo Ryang; Imoto, Susumu; Kim, Ke Ih; Taniguchi, Miyuki; Oh, Hyun-Kyung; Yano, Yoshihiko; Hayashi, Yoshitake; Kudo, Masatoshi

    Significant inverse association between coffee intake and the levels of liver enzymes has been reported. We demonstrated higher prevalence of metabolic syndrome in Korean immigrants (KIs) than in indigenous Japanese (IJs). The aim of this study was to investigate whether the association between coffee intake and liver enzyme levels was different between the 2 ethnic groups. This study is a cross-sectional study including a total of 966 subjects comprising KIs and IJs. The association between the quintiles of coffee intake and dichotomous values of liver enzymes was evaluated by logistic regression analysis in KIs, IJs, a high-risk group (current smokers or alcohol drinkers ≥45 g/day), and a low-risk group (non-smokers and alcohol drinkers coffee intake and serum aspartate aminotransferase (AST) levels was observed. In the IJs, a significant inverse association between coffee intake and serum alanine aminotransferase levels was observed. In the high-risk group, a significant inverse association between coffee intake and serum AST and gamma-glutamyltransferase levels was observed. No difference was observed between KIs and IJs regarding the association between coffee and liver enzymes. Coffee might inhibit hepatic damage by alcohol drinking and smoking. © 2016 S. Karger AG, Basel.

  17. [Proposal for early detection of ethanol consumption in students of the Universidad Autónoma del Estado de Morelos].

    Science.gov (United States)

    García-Jiménez, Sara; Erazo-Mijares, Miguel; Toledano-Jaimes, Cairo D; Monroy-Noyola, Antonio; Bilbao-Marcos, Fernando; Sánchez-Alemán, Miguel A; Déciga-Campos, Myrna

    2016-01-01

    The present study determined through analytic techniques the quantification of some biomarkers that have been useful to detect early ethanol consumption in a college population. A group of 117 students of recent entry to the Universidad Autónoma del Estado de Morelos was analyzed. The enzyme determination of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyltransferase as metabolic markers of ethanol, as well as the carbohydrate-deficient transferrin (CDT) detected by high chromatographic liquid (up to 1.8% of CDT), allowed us to identify that 6% of the college population presented a potential risk of alcohol consumption. The use of the biochemical-analytical method overall with the psychological drug and a risk factor instrument established by the Universidad Autónoma del Estado de Morelos permit us to identify students whose substance abuse consumption puts their terminal efficiency at risk as well as their academic level. The timely detection on admission to college can monitor and support a student consumer's substance abuse.

  18. Fotossensibilização em ovinos associada à ingestão de Brachiaria brizantha no estado do Pará Photosensitization of sheep kept on Brachiaria brizantha pasture in the state of Pará

    Directory of Open Access Journals (Sweden)

    Tatiane Teles Albernaz

    2010-09-01

    que não receberam foram semelhantes, já os valores de creatinina, AST e bilirrubinas foram menores nos animais que receberam fluido ruminal em comparação aos que não receberam. Foram determinados dois tipos de saponinas nas amostras de B. brizantha dos surtos e do experimento, a metilprotodioscina e a protodioscina. O nível de saponina no surto 01 e 02 foi 0,92% e 0,88%, respectivamente. Os níveis de saponinas no experimento variaram de 1,13% a 1,62%. A quantidade de Pithomyces chartarum, tanto nos surtos quanto no experimento, foi insignificante. Na necropsia foi verificada icterícia generalizada, fígado com consistência aumentada de coloração amarelada e com padrão lobular acentuado. Nos rins foi observada coloração amarelo-esverdeado e aumento de tamanho. As alterações histológicas ocorreram principalmente no fígado e consistiram de leve proliferação das vias biliares nos espaços porta, presença de hepatócitos binucleados, presença de macrófagos espumosos, necrose incipiente de hepatócitos isolados, colangite, presença de cristais em macrófagos e hepatócitos.Two outbreaks of photosensitization by Brachiaria brizantha were studied and an experiment was performed in Santa Inês and Dorper crossbred sheep, two to three months old, on a farm in Santa Luzia do Pará municipality. These animals were kept from birth until about two months of age in a suspended stall floor, fed purple elephant grass (Pennisetum purpureum cv. purple, and had minerals and water ad libitum. After this period they were placed into a paddock of B. brizantha. At the time of the outbreaks and the experimental studies, the farm was visited for epidemiological assessment and clinical examination of the sheep, collection of blood samples for measurement of gamma glutamyltransferase, aspartate aminotransferase, conjugated bilirubin, unconjugated bilirubin, urea, and creatinine. Pasture samples were collected for saponin determination and count of Pithomyces chartarum

  19. Effectiveness of Melatonin, as a Radiation Damage-Mitigating Drug in Modulating Liver Biochemical disorders in γ-Irradiated Rats

    International Nuclear Information System (INIS)

    El-Fatih, N.M.; Elshamy, E.

    2011-01-01

    Melatonin has an anti per oxidative effect on several tissues as well as a scavenger effect on reactive oxygen species (ROS). Whilst radiation-hazards due to free radical generation, present enormous challenges for biological and medical safety. Therefore, rats were classified into four groups; control (n= 8), (received 0.5 ml of alcoholic saline as a vehicle for 5 days). Melatonin-treated rats received 10 mg/ kg body wt, for 5 days (given to the animals in the morning via stomach tube). gamma-irradiated rats received 0.5 ml of the melatonin vehicle followed by one shot dose of 3 Gy gamma-rays. Each of these groups was compared with a further group, which-received melatonin for 5 days after 3 Gy gamma-irradiation exposure. The results revealed that all considered biochemical parameters were not changed significantly in melatonin-treated group as compared with control one. In the liver tissue of the gamma-irradiated animals (3 Gy), the oxidative stress markers malondialdehyde (MDA) and protein carbonyl (PC) were significantly increased, while a marked decrease occurred in the contents of deoxy- and ribo-nucleic acids (DNA and RNA) and glutathione (GSH) as well as activity of glutathione-S-transferase (GST). In addition, catalase (CAT) and myeloperoxidase (MPO) activities were increased. Activities of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) were significantly increased in sera of the irradiated rats. Treatment with melatonin for 5 days after gamma-rays exposure significantly modulated the radiation-induced elevations in MDA and PC levels in the liver tissue and significantly restored hepatic GSH content, GST, CAT and MPO activities. Post-irradiation treatment with melatonin showed significant higher hepatic DNA and RNA contents than irradiated rats. The activities of AST, ALP, and GGT in serum were significantly ameliorated when melatonin was administrated after irradiation. Conclusion: Melatonin has effective

  20. Effects of structural injure in the bile bacterial contamination after balloon transduodenal sphincteroplasty (papillary dilation in dogs

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    Zavadinack Netto Martin

    2006-01-01

    Full Text Available PURPOSE: To evaluate, in dogs, the biliary sphincter subjected to dilation by hydrostatic balloon by the point of view of structural alterations of the papilla and the biochemestry and bacterial contamination of the bile. METHODS: Twenty dogs were submitted to laparotomy, duodenotomy, and enlargement of the major duodenal papilla- GA(n=10 - with balloon of 8mm inflated with pressure of 0,5atm, during 2 minutes or to the sham procedure - GB(n=10. Blood samples collected on times t(0day, t(7days and t(28days were subjected to dosages of alkaline phosphatase (ALP and gamma-glutamyltransferase (GGT for cholestasis evaluation. The collected material from the gall bladder at the same times were registered and numbered to be submitted to culture in BHI, blood agar (rich, non-selective element and Mac Conkey (selective element for Gram-negative bacillus. On the 28th day three fragments of the papilla were tranversally cut by the choledoc axis 3mm from the duodenal papilla and the cuts, stained with hematoxylin-eosin and Masson's tricome, were evaluated according to their inflammatory reaction. RESULTS: The GGT and ALP averages on the three periods in the groups A and B did not show significant differences, not being characterizes the cholestasis. The bacterian contamination was significantly higher in GA (2,19 than in GB (1,96; the contamination was lower in the initial time compared with 7 and 28 days (t0

  1. Effects of structural injure in the bile bacterial contamination after balloon transduodenal sphincteroplasty (papillary dilation) in dogs.

    Science.gov (United States)

    Zavadinack Netto, Martin; Fagundes, Djalma José; Bandeira, César Orlando Peralta

    2006-01-01

    To evaluate, in dogs, the biliary sphincter subjected to dilation by hydrostatic balloon by the point of view of structural alterations of the papilla and the biochemestry and bacterial contamination of the bile. Twenty dogs were submitted to laparotomy, duodenotomy, and enlargement of the major duodenal papilla- GA(n=10) - with balloon of 8mm inflated with pressure of 0,5 atm, during 2 minutes or to the sham procedure - GB(n=10). Blood samples collected on times t(0 day), t(7 days) and t(28 days) were subjected to dosages of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) for cholestasis evaluation. The collected material from the gall bladder at the same times were registered and numbered to be submitted to culture in BHI, blood agar (rich, non-selective element) and Mac Conkey (selective element for Gram-negative bacillus. On the 28th day three fragments of the papilla were tranversally cut by the choledoc axis 3mm from the duodenal papilla and the cuts, stained with hematoxylin-eosin and Masson's tricome, were evaluated according to their inflammatory reaction. The GGT and ALP averages on the three periods in the groups A and B did not show significant differences, not being characterizes the cholestasis. The bacterian contamination was significantly higher in GA (2,19) than in GB (1,96); the contamination was lower in the initial time compared with 7 and 28 days (t0

  2. Aspects of fetal physiology from 18 to 37 weeks' gestation as assessed by blood sampling.

    Science.gov (United States)

    Nava, S; Bocconi, L; Zuliani, G; Kustermann, A; Nicolini, U

    1996-06-01

    To construct reference ranges for fetal pH, oxygen pressure (PO2), and hematologic and biochemical blood constituents, which can be used to analyze changes with gestation and differences with maternal values, thus elucidating some aspects of fetal biology and the effects of the maternal and placental environments. We assayed venous pH, PO2, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatine kinase, triglycerides, and cholesterol concentrations in 157 fetuses and 134 mothers who underwent fetal blood sampling from 18 to 37 weeks' gestation. None of the fetuses was infected or had chromosomal, hematologic, or hormonal abnormalities. All the variables analyzed were similar in fetuses sampled at the placental cord insertion (n = 125) or at the intrahepatic vein (n = 32). Maternal and fetal concentrations of glucose (r = 0.79, P PO2 decreased with gestational age, whereas hematocrit increased, similar to what has been described previously. All of the other variables, with the exception of amylase and cholesterol, changed significantly during the investigated period of pregnancy. Gestational age explained at least 40% of the variance in values of fetal total protein, pseudocholinesterase, alanine aminotransferase, creatine kinase, and triglycerides, but only 3-25% of the variation in the remainder. Most enzymes were higher in the fetus than in the maternal circulation, and all except alkaline phosphatase increased with gestational age. The maternal-fetal glucose difference correlated significantly with hematocrit, pH, and PO2, independent of gestational age and independent of each other. With the exception of aspartate aminotransferase, all of the analyzed fetal variables were different from the maternal values, and most changed with gestational age. The mechanisms

  3. High predictability of a sustained virological response (87%) in chronic hepatitis C virus genotype 1 infection treatment by combined IL28B genotype analysis and γ-glutamyltransferase/alanine aminotransferase ratio: a retrospective single-center study.

    Science.gov (United States)

    Amanzada, A; Goralczyk, A D; Schneider, S; Moriconi, F; Lindhorst, A; Mihm, S; Van Thiel, D H; Ramadori, G

    2012-01-01

    Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-α and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low γ-glutamyltransferase (γ-GT) serum activities, a low pretreatment γ-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1-16.7, p ratio (OR = 2.5, CI: 1.7-3.3, p ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10-71.1, p ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-α-based combination therapy in a nontriaged ordinary setting. Copyright © 2012 S. Karger AG, Basel.

  4. Acompanhamento laboratorial da função renal de cães sadios tratados experimentalmente com doses terapêuticas de anfotericina B Laboratorial accompaniment of kidney funtion of health dogs experimentally treated with therapeutic dosages of amphotericin B

    Directory of Open Access Journals (Sweden)

    Flávia Santin

    2006-12-01

    Full Text Available O presente trabalho objetivou avaliar a função renal de dez cães adultos saudáveis submetidos à administração de doses terapêuticas do antifúngico anfotericina B, cuja utilização tem sido limitada pelo seu elevado potencial nefrotóxico, e avaliar o método laboratorial mais sensível e precoce de diagnóstico de lesão renal. Foram realizadas, diariamente, urinálise, excreção fracionada de sódio e potássio, dosagem sérica de creatinina e uréia e atividade urinária de gama-glutamiltransferase (GGT. Concluiu-se que a anfotericina B provoca lesões nos túbulos proximal e distal, induzindo acidose tubular renal do tipo I e Diabetes insipidus nefrogênico em cães. Avaliação da função renal, preferencialmente por dosagens de creatinina, uréia e potássio séricos, é recomendada antes de cada aplicação do fármaco. A densidade urinária foi o parâmetro mais precocemente alterado pela lesão renal. A GGT urinária não foi eficaz para o diagnóstico precoce de lesão induzida por anfotericina B.The objective of this experiment was to assess the renal function of ten healthy male adult dogs submitted to therapeutic doses of amphotericin B, whose use has been limited due to its high nephrotoxic potential, as well as to evaluate the more sensitive and early method to diagnose kidney lesions. The renal function was evaluated through daily urinalysis, fractioned excretion of sodium and potassium, serum concentration of creatinine and blood urea nitrogen (BUN and urinary activity of gamma-glutamyltransferase (GGT. It was concluded that amphotericin b provokes lesions in both proximal and distal tubules, inducing type I renal tubular acidosis and nephrogenic Diabetes insipidus in dogs. Renal function evaluation, preferably by serum creatinine, BUN and potassium dosage is recommended before each drug application. Urinalysis proved to diagnose kidney lesions in its earliest stage through a modification of the density parameters

  5. Association between markers of fatty liver disease and impaired glucose regulation in men and women from the general population: the KORA-F4-study.

    Directory of Open Access Journals (Sweden)

    Ina-Maria Rückert

    Full Text Available OBJECTIVE: To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT, glutamate-pyruvate transaminase (GPT, glutamate-oxalacetate transaminase (GOT and alkaline phosphatase (AP and non-alcoholic fatty liver disease (NAFLD respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG and impaired glucose tolerance (IGT or known and newly diagnosed diabetes (NDD, in men and women from the general German population. METHODS: The study was based on 3009 subjects (1556 females, 1453 males aged 32 to 81 years who participated in the KORA-F4-Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants underwent an oral glucose tolerance test to assess disturbances in glucose metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni Fatty Liver Index (FLI. RESULTS: 229 participants (7.6% reported known diabetes, 106 had NDD (3.5%, 107 (3.6% had IFG, 309 (10.3% had IGT, 69 (2.3% were affected with both metabolic disorders (IFG/IGT and 74 (2.5% could not be classified. GGT and GPT were significantly elevated in persons with pre-diabetes and diabetes (GGT in diabetic persons OR = 1.76, [1.47-2.09], in IFG OR = 1.79 [1.50-2.13], GPT in diabetic persons OR = 1.51, [1.30-1.74], in NDD OR = 1.77 [1.52-2.06], GOT and AP only inconsistently in some pre-diabetes groups. The effects were sharpened in models using an increase of two or three out of three enzymes as an estimate of fatty liver and especially in models using the FLI. Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men: 53.2%. In participants with fatty liver disease, the OR for NDD adjusted for sex and age was 8.48 [5.13-14.00], 6.70 [3.74-12.01] for combined IFG and IGT and 4.78 [3.47-6.59] for known diabetes respectively. CONCLUSIONS: Elevated GGT and GPT-values as well as estimates of fatty liver disease are significantly associated with pre

  6. Quantitative measurement of hepatic fibrosis with gadoxetic acid-enhanced magnetic resonance imaging in patients with chronic hepatitis B infection: A comparative study on aspartate aminotransferase to platelet ratio index and fibrosis-4 index

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Guy Mok; Kim, Youe Ree; Cho, Eun Young; Lee, Young Hwan; Yoon, Kwon Ha [Wonkwang University School of Medicine, Iksan (Korea, Republic of); Ryu, Jong Hyun; Kim, Tae Hoon [Imaging Science Research Center, Wonkwang University, Iksan (Korea, Republic of)

    2017-06-15

    To quantitatively measure hepatic fibrosis on gadoxetic acid-enhanced magnetic resonance (MR) in chronic hepatitis B (CHB) patients and identify the correlations with aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) values. This study on gadoxetic acid-enhanced 3T MR imaging included 81 patients with CHB infection. To quantitatively measure hepatic fibrosis, MR images were analyzed with an aim to identify inhomogeneous signal intensities calculated from a coefficient of variation (CV) map in the liver parenchyma. We also carried out a comparative analysis between APRI and FIB-4 based on metaregression results. The diagnostic performance of the CV map was evaluated using a receiver-operating characteristic (ROC) curve. In the MR images, the mean CV values in control, groups I, II, and III based on APRI were 4.08 ± 0.92, 4.24 ± 0.80, 5.64 ± 1.11, and 5.73 ± 1.28, respectively (p < 0.001). In CHB patients grouped by FIB-4, the mean CV values of groups A, B, and C were 4.22 ± 0.95, 5.40 ± 1.19, and 5.71 ± 1.17, respectively (p < 0.001). The mean CV values correlated well with APRI (r = 0.392, p < 0.001) and FIB-4 (r = 0.294, p < 0.001). In significant fibrosis group, ROC curve analysis yielded an area under the curve of 0.875 using APRI and 0.831 using FIB-4 in HB, respectively. Gadoxetic acid-enhanced MR imaging for calculating a CV map showed moderate correlation with APRI and FIB-4 values and could be employed to quantitatively measure hepatic fibrosis in patients with CHB.

  7. Intact Protein Analysis at 21 Tesla and X-Ray Crystallography Define Structural Differences in Single Amino Acid Variants of Human Mitochondrial Branched-Chain Amino Acid Aminotransferase 2 (BCAT2)

    Science.gov (United States)

    Anderson, Lissa C.; Håkansson, Maria; Walse, Björn; Nilsson, Carol L.

    2017-09-01

    Structural technologies are an essential component in the design of precision therapeutics. Precision medicine entails the development of therapeutics directed toward a designated target protein, with the goal to deliver the right drug to the right patient at the right time. In the field of oncology, protein structural variants are often associated with oncogenic potential. In a previous proteogenomic screen of patient-derived glioblastoma (GBM) tumor materials, we identified a sequence variant of human mitochondrial branched-chain amino acid aminotransferase 2 as a putative factor of resistance of GBM to standard-of-care-treatments. The enzyme generates glutamate, which is neurotoxic. To elucidate structural coordinates that may confer altered substrate binding or activity of the variant BCAT2 T186R, a 45 kDa protein, we applied combined ETD and CID top-down mass spectrometry in a LC-FT-ICR MS at 21 T, and X-Ray crystallography in the study of both the variant and non-variant intact proteins. The combined ETD/CID fragmentation pattern allowed for not only extensive sequence coverage but also confident localization of the amino acid variant to its position in the sequence. The crystallographic experiments confirmed the hypothesis generated by in silico structural homology modeling, that the Lys59 side-chain of BCAT2 may repulse the Arg186 in the variant protein (PDB code: 5MPR), leading to destabilization of the protein dimer and altered enzyme kinetics. Taken together, the MS and novel 3D structural data give us reason to further pursue BCAT2 T186R as a precision drug target in GBM. [Figure not available: see fulltext.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

  9. Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1 S ,3 S )-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyunbeom [Department; Doud, Emma H. [Department; Department; Wu, Rui [Department; Sanishvili, Ruslan [X-ray; Juncosa, Jose I. [Department; Liu, Dali [Department; Kelleher, Neil L. [Department; Department; Silverman, Richard B. [Department; Department

    2015-02-10

    gamma-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.

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

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Zhu

    2013-01-01

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

  11. Influence of serum levels of alkaline phosphatase and gamma-glutamyl transpeptidase on the prognosis of patients with primary liver cancer undergoing radiofrequency ablation

    Directory of Open Access Journals (Sweden)

    ZHU Ge

    2016-12-01

    Full Text Available ObjectiveTo investigate the influence of serum levels of alkaline phosphatase (ALP and gamma-glutamyltransferase (GGT before treatment on the prognosis of patients with primary liver cancer undergoing radiofrequency ablation. MethodsA total of 165 patients with pathologically or clinically confirmed primary liver cancer who were admitted to Cancer Center of The First Hospital of Jilin University from October 2010 to June 2015 and treated with radiofrequency ablation were enrolled, and their preoperative clinical data were collected. The chi-square test was used for comparison of categorical data between groups, and the Kaplan-Meier method and Cox regression analysis were used to analyze the association of serum ALP and GGT levels before treatment with overall survival, progression-free survival, and clinical features. ResultsThere were significant differences in the 1-, 2-, and 5-year survival rates between the patients with normal (≤135 U/L or abnormal (>135 U/L serum ALP before treatment (91%/90%/35% vs 79%/68%/18%, P=0.01. There were also significant differences in the 1-, 2-, and 5-year survival rates between the patients with normal (≤45 U/L or abnormal (>45 U/L serum GGT before treatment (95%/85%/37% vs 87%/71%/21%, P<0.001. The serum levels of ALP (HR=1.766, 95%CI:1.068-2.921,P=0.027 and GGT (HR=2.312, 95%CI:1.367-3.912,P=0.002 before treatment were closely associated with the overall survival of patients with primary liver cancer after radiofrequency ablation and were independent prognostic factors. There were significant differences in the 1-, 2-, and 5-year progression-free survival rates between the patients with normal (≤135 U/L or abnormal (>135 U/L serum ALP before treatment (72%/52%/14% vs 50%/21%/3%, P<0.001; there were also significant differences in the 1-, 2-, and 5-year progression-free survival rates between the patients with normal (≤45 U/L or abnormal (>45 U/L serum GGT before treatment (81%/62%/18% vs

  12. Clinical, biochemical and haemathological effects in Rhamdia quelen exposed to cypermethrin

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    F.P. Montanha

    2014-06-01

    Full Text Available The acute intoxication of Cypermethrin in Silver Catfish (Rhamdia quelen was evaluated. Animals weighing 56.67±4.43g and measuring 18.92±1.16cm were exposed to sublethal concentrations of Cypermethrin for the species in hydrological conditions during 96 hours. A total of 52 fish divided into three groups were used and received the following concentrations of Cypermethrin: 0 (n=12; 1.5 (n=20 and 2.5 (n=20mg/L. The intoxicated animals suffered behavioral changes such as loss of balance, swimming alteration, dyspnea, upright swimming and sudden spiral swimming movements. As soon as the 96-hour period was over, a blood collection for hematological and biochemical analyses was performed. A complete haemogram test, plasmatic protein test, albumin, alanine transaminase (ALT, aspartate aminotransferase (AST, gamma glutamyltransferase and alkaline phosphatase (ALP were studied. The values of erythrocytes, hematocrits, haemoglobin, total number of leukocytes, thrombocyte, ALT, AST and ALP changed according to the groups. The results have shown that the environmental contamination by Cypermethrin is toxic to the species.

  13. Serum uric acid and its association with metabolic syndrome and carotid atherosclerosis in obese children.

    Science.gov (United States)

    Pacifico, Lucia; Cantisani, Vito; Anania, Caterina; Bonaiuto, Elisabetta; Martino, Francesco; Pascone, Roberto; Chiesa, Claudio

    2009-01-01

    The association between hyperuricemia, metabolic syndrome (MS), and atherosclerotic vascular disease has been reported in adults, but very little is known about this association in children. The aims of our study were to ascertain the correlates of uric acid (UA) in a sample of obese children, and to investigate whether UA is associated with carotid intima-media thickness (IMT) independently from classical risk factors including MS. We analyzed carotid IMT along with serum triglycerides, total and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), alanine aminotransferase, gamma-glutamyltransferase, creatinine, and UA in 120 obese children and 50 healthy control children. UA concentrations were significantly higher in obese children compared with controls; moreover, they correlated with the most established cardiovascular risk factors. In the group of obese children, after adjustment for age, sex, pubertal stage, and creatinine, an independent association between UA levels and the presence of MS syndrome was observed (unstandardized coefficient, 0.044 (95% confidence intervals (CI) 0.015-0.072); Pcreatinine, and MS (considered as a single clinical entity), or the individual components of MS simultaneously included, the association between UA and carotid IMT was significant (P<0.01). In obese children and adolescents, increased UA levels are associated with carotid atherosclerosis.

  14. Assessment of Hematological and Biochemical parameters with extended D-Ribose ingestion

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    Frelich Angela

    2008-09-01

    Full Text Available Abstract D-ribose, a naturally occurring pentose carbohydrate, has been shown to replenish high- energy phosphates following myocardial ischemia and high intensity, repetitive exercise. Human studies have mainly involved short-term assessment, including potential toxicity. Reports describing adverse effects of D-ribose with prolonged ingestion have been lacking. Therefore, this study assessed the toxicity of extended consumption of D-ribose in healthy adults. Nineteen subjects ingested 20 grams/Day (10 grams, twice a Day of ribose with serial measurements of biochemical and hematological parameters at Days 0, 7, and 14. No significant toxic changes over the 14-day assessment period occurred in complete blood count, albumin, alkaline phosphatase, gamma glutamyltransferase, alanine amiotransferase, and aspartate aminotransferase. However, D-ribose did produce an asymptomatic, mild hypoglycemia of short duration. Uric acid levels increased at Day 7, but decreased to baseline values by Day 14. D-ribose consumption for 14 days appears not to produce significant toxic changes in both hematological and biochemical parameters in healthy human volunteers.

  15. Effect of the leafy vegetable Solanum nigrum on the activities of some liver drug-metabolizing enzymes after aflatoxin B1 treatment in female rats.

    Science.gov (United States)

    Moundipa, P F; Domngang, F M

    1991-01-01

    Wistar albino female rats were maintained for 10 d on diets containing various levels of the vegetable Solanum nigrum. Simultaneously, they received daily intraperitoneal injections of aflatoxin B1 (AFB1) (either 0.2 or 0.4 mg/kg body-weight) diluted in propylene glycol. At the end of the experiment, all animals were killed and their serum and hepatic microsomes were prepared for assay of enzymes. Results showed that aminopyrine N-demethylase activity increased 2.5-fold with 200 (S200) and 600 (S600) g S. nigrum/kg diets. Activity of uridine diphosphate glucuronyltransferase (UDPGT) (EC 2.4.1.17) also increased twofold. Similar results were obtained with glutathione S-transferase (EC 2.5.1.18) activity which increased by 60% with diet S600. After AFB1 treatment, a general increase in the activities of the above enzymes was found, except for UDPGT in the group fed on diet S600. When rats were fed on the diet without S. nigrum, AFB1 induced an increase in alkaline phosphatase (ALP) (EC 3.1.3.1), aspartate aminotransferase (AST) (EC 2.6.1.1) and gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) levels in the serum. AFB1 also induced increases in serum ALP and gamma-GT levels when rats were fed on diet S600.

  16. Toxicological evaluation of long-term intravenous administration of amitraz in horses

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    Queiroz-Neto A.

    2002-01-01

    Full Text Available With the aim of determining the possible toxicity of amitraz after its prolonged use in horses, six English Thoroughbred horses received intravenous injections of amitraz (0.05, 0.10 or 0.15 mg/kg weekly for four months, constituting the experimental group. Eight other animals (control group, via the same route following the same drug administration schedule and period of time, received the vehicle, dimethylformamide. At the end of this period, blood was collected from all the animals, and a comparison was made of the means of the values obtained for the various blood analyses: complete hemogram, alkaline phosphatase, gamma-glutamyltransferase, blood urea nitrogen, lactate dehydrogenase, aspartate aminotransferase, creatine phosphokinase, glucose, albumin, total protein, creatinine, Na+ , K+, Cl- and CO2. The results for the biochemical characteristics showed that only the mean value for urea of the animals submitted to treatment with amitraz was significantly different than the mean value obtained for the control group. The analyses of the hematological characteristics showed that no significant differences between groups were observed. Similarly, the measurement of blood electrolyte levels demonstrated that long-term treatment with amitraz did not cause significant changes in the variables analyzed. The results indicate that amitraz, given in the doses employed in this study, did not show signs of inducing toxic effects in vital organs, even after prolonged administration.

  17. Effects of carprofen or meloxicam on selected haemostatic variables in miniature pigs after orthopaedic surgery

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    Petr Raušer

    2011-01-01

    Full Text Available The aim of the study was to detect and compare the haemostatic variables and bleeding after 7‑days administration of carprofen or meloxicam in clinically healthy miniature pigs. Twenty-one clinically healthy Göttingen miniature pigs were divided into 3 groups. Selected haemostatic variables such as platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, serum biochemical variables such as total protein, bilirubin, urea, creatinine, alkaline phosphatase, alanine aminotransferase and gamma-glutamyltransferase and haemoglobin, haematocrit, red blood cells, white blood cells and buccal mucosal bleeding time were assessed before and 7 days after daily intramuscular administration of saline (1.5 ml per animal, control group, carprofen (2 mg·kg-1 or meloxicam (0.1 mg·kg-1. In pigs receiving carprofen or meloxicam, the thrombin time was significantly increased (p p p p < 0.05 compared to the control group. Significant differences were not detected in other haemostatic, biochemical variables or bleeding time compared to other groups or to the pretreatment values. Intramuscular administration of carprofen or meloxicam in healthy miniature pigs for 7 days causes sporadic, but not clinically important changes of selected haemostatic variables. Therefore, we can recommend them for perioperative use, e.g. for their analgesic effects, in orthopaedic or other surgical procedures without increased bleeding.

  18. The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population.

    Science.gov (United States)

    Yu, Rong-Bin; Hong, Xin; Ding, Wei-Liang; Tan, Yong-Fei; Zhang, Yong-Xiang; Sun, Nan-Xiong; Wu, Guan-Ling; Zhan, Sheng-Wei; Ge, Da-Fang

    2008-09-01

    To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C. A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction-sequencing based typing (PCR-SBT). Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse. These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.

  19. 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.

    Science.gov (United States)

    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

  20. Up-regulation of gamma-glutamyl transpeptidase (GGT) activity in growth perturbed C6 astrocytes

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Malík, Radek; Lisá, Věra; Šedo, Aleksi

    2005-01-01

    Roč. 136, č. 1-2 (2005), s. 75-80 ISSN 0169-328X R&D Projects: GA ČR(CZ) GA301/02/0962; GA MZd(CZ) NR8105 Institutional research plan: CEZ:AV0Z50110509 Keywords : gamma-glutamyl transpeptidase * reactive C6 astrocytes * oxidative stress Subject RIV: FH - Neurology Impact factor: 1.585, year: 2005

  1. First-line therapy and mitochondrial damage: different nucleosides, different findings.

    Science.gov (United States)

    Blanco, Francisco; García-Benayas, Teresa; José de la Cruz, Juan; González-Lahoz, Juan; Soriano, Vincent

    2003-01-01

    Antiretroviral therapy has been associated with the development of morphologic body-shape changes and metabolic abnormalities, including dislipemia, insulin resistance, and hyperlactatemia. Mitochondrial damage secondary to the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been related to some of these complications, although the role of different NRTIs in their development is not well established. To assess the incidence of hyperlactatemia and lipodystrophy body-shape changes in drug-naïve HIV-infected patients who began highly active antiretroviral therapy (HAART) based on a backbone of two different NRTI combinations. Prospective, longitudinal, observational study of all consecutive drug-naïve HIV-infected individuals who started HAART with zidovudine (AZT) plus lamivudine (3TC) or didanosine (ddI) plus stavudine (d4T) between June 2000 and June 2001 at one single institution. Serum lactate levels and lipodystrophy body-shape changes were monitored periodically during 12 months. At 1 year, mean lactate values remained or=2 mmol/L) steadily increased in those on ddI+d4T (from 30% at 3 months to 71% at 12 months), whereas it remained below 10% in patients treated with AZT+3TC. Two patients on ddI+d4T developed lactic acidosis. Mean serum lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and amylase significantly increased in patients treated with ddI+d4T, whereas they remained unaltered in patients under AZT+3TC. Significant correlations were found between lactate and LDH, alkaline phosphatase (AP), and GGT. In the multivariate analysis, treatment with ddI+d4T, LDH, and AP was significantly associated with lactate levels. At 12 months, subcutaneous lipoatrophy was significantly more frequent in patients treated with ddI+d4T than in those on AZT+3TC (35% vs. 8%; p =.01). In drug-naïve HIV-infected patients who start antiretroviral therapy, ddI+d4T-based combinations produce a greater increase in serum lactate and lipoatrophy

  2. Effect of etonogestrel contraceptive implant (Implanon) on portal blood flow and liver functions.

    Science.gov (United States)

    Nasr, Ahmed; Nafeh, Hanan M

    2009-03-01

    This study was conducted to evaluate changes in portal blood flow and liver functions among women using Implanon for 2 years. Fifty healthy Implanon users were enrolled in this longitudinal study and followed up for 24 months. Portal blood flow, assessed by color Doppler; prothrombin time and concentration; serum albumin; bilirubin; gamma-glutamyl transferase (GGT); alanine aminotransferase (ALT); and aspartate aminotransferase (AST) were measured before and 24 months after insertion. After 24 months of Implanon insertion, there were no significant changes in portal blood flow, serum albumin, prothrombin time or concentration. However, there was a significant increase in serum levels of total and unconjugated bilirubin and GGT and a significant decrease in ALT and AST levels. All levels, however, remained within the normal range of values. Implanon use for 2 years does not seem to influence portal hemodynamics. Changes in serum levels of bilirubin, GGT, ALT and AST are unlikely to be of clinical significance.

  3. [Design of a preoperative predictive score for choledocholithiasis].

    Science.gov (United States)

    Bueno Lledó, Jose; Ibáñez Cirión, Jose Luis; Torregrosa Gallud, Antonio; López Andújar, Rafael

    2014-11-01

    Choledocholithiasis is the most common cause of obstructive jaundice and occurs in 5-10% of patients with cholelithiasis. To design a preoperative predictive score for choledocholithiasis. A prospective study was carried out in 556 patients admitted to our department for biliary disease. Preoperative clinical, laboratory, and ultrasound variables were compared between patients without choledocholithiasis and 65 patients with this diagnosis. A multivariate logistic analysis was performed to obtain a predictive model of choledocholithiasis, determining sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Predictors of choledocholithiasis were the presence of a prior history of biliary disease (history of biliary colic, acute cholecystitis, choledocholithiasis or acute biliary pancreatitis) (p=0.021, OR=2.225, 95% CI: 1.130-4.381), total bilirubin values >4mg/dl (p=0.046, OR=2.403, 95% CI: 1.106-5.685), alkaline phosphatase values >150mg/dl (p=0.022 income, OR=2.631, 95%: 1.386-6.231), gamma-glutamyltransferase (GGT) values >100mg/dl (p=0.035, OR=2.10, 95% CI: 1.345-5.850), and an ultrasound finding of biliary duct >8mm (p=0.034, OR=3.063 95% CI: 1086-8649). A score superior to 5 had a specificity and PPV of 100% for detecting choledocholithiasis and a score less than 3 had a sensitivity and NPV of 100% for excluding this diagnosis. The preoperative score can exclude or confirm the presence of choledocholithiasis and allows patients to directly benefit from laparoscopic cholecystectomy (LC) or prior endoscopic retrograde cholangiopancreatography (ERCP). Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  4. Effect of Nigella sativa Linn oil on tramadol-induced hepato- and nephrotoxicity in adult male albino rats

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    A. Elkhateeb

    2015-01-01

    Full Text Available The present study was carried out to evaluate the role of Nigella sativa Linn (NsL oil against subacute tramadol-induced hepatotoxicity, nephrotoxicity as well as oxidative stress in adult male albino rats. Sixty adult male albino rats were divided into four groups. Group I: control group; 30 rats equally subdivided into: Ia; −ve control group, Ib; +ve control group received saline, Ic; +ve control group received corn oil. Group II: 10 rats received NsL oil; 1 mg/kg in 1 ml corn oil/day, group III: 10 rats received tramadol; 30 mg/kg/day, group IV: 10 rats received tramadol + NsL oil in the previous doses. Treatments were given by gavage for 30 days. Then rats were sacrificed and specimens from the livers and kidneys were taken for biochemical and histopathological study. Biochemical data showed elevated liver enzymes; alanine transaminase (ALT, aspartate transaminase (AST, gamma glutamyltransferase (GGT, bilirubin as well as urea and creatinine in tramadol group. A significant increase in hepatic and renal malondialdehyde (MDA and a decrease in glutathione peroxidase (GPx levels were also noticed. Histological analysis of the liver showed vacuolated hepatocyte cytoplasm indicating hydropic degeneration with binucleated cells, apoptotic nuclei, congested central veins, cellular infiltration and hemorrhage. Kidney sections revealed atrophied glomeruli with collapsed tufts and wide Bowman's space, degenerated tubules, hemorrhage and mononuclear cellular infiltration. There was also an increase in area % of collagen fibers in both organs. Concomitant use of NsL oil with tramadol induced partial improvement in the hepato- and nephrotoxic effects. In conclusion, this study suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadol-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.

  5. Clinicopathologic evaluation of hepatic lipidosis in periparturient dairy cattle.

    Science.gov (United States)

    Kalaitzakis, Emmanouil; Roubies, Nikolaos; Panousis, Nikolaos; Pourliotis, Konstantinos; Kaldrymidou, Eleni; Karatzias, Harilaos

    2007-01-01

    Fatty change of the liver (FCL) is very common in dairy cattle periparturiently. Many laboratory methods have been implicated in order to assist the diagnosis. To investigate whether FCL in dairy cattle could be evaluated by assessment of ornithine carbamoyl transferase (OCT) by means of an assay modified for bovine serum, other enzyme activity, serum bile acids (SBA) concentration, or other biochemical constituents. A total of 187 dairy cattle were included: 106 were suspected to have liver dysfunction and were examined after referral by veterinarians; 70 were clinically healthy with mild FCL; and 11 were clinically healthy without FCL. Blood and liver biopsy samples were obtained after clinical examination. Histologic examination by light microscopy and classification of samples according to the severity of FCL was done, and total lipid and triglyceride concentration was measured. In serum, OCT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), alkaline phosphatase (ALP), and gamma-glutamyltransferase (gamma-GT) activity as well as SBA, glucose, ketones, total bilirubin (tBIL), and nonesterified fatty acids (NEFA) concentration were measured. OCT and AST activity and tBIL concentration correlate well with the degree of FCL. SBA concentration does not contribute well to FCL diagnosis. The majority of FCL cases appeared within the first 21 days-in-milk (DIM). The majority of moderate-to-severe and severe FCL cases arose in the first 7 DIM. Except for OCT, AST, and tBIL, none of the biochemical tests used, including SBA, had sufficient discriminatory power to differentiate reliably between mild and severe FCL because of poor sensitivity. A weak correlation between clinical signs and the extent of FCL was evident.

  6. Clinical biochemistry in healthy manatees (Trichechus manatus latirostris)

    Science.gov (United States)

    Harvey, J.W.; Harr, K.E.; Murphy, D.; Walsh, M.T.; Chittick, E.J.; Bonde, R.K.; Pate, M.G.; Deutsch, C.J.; Edwards, H.H.; Haubold, E.M.

    2007-01-01

    Florida manatees (Trichechus manatus latirostris) are endangered aquatic mammals living in coastal and riverine waterways of Florida and adjacent states. Serum or plasma biochemical analyses are important tools in evaluating the health of free-ranging and captive manatees. The purpose of this study was to measure diagnostically important analytes in the plasma of healthy manatees and to determine whether there was significant variation with respect to location (free-ranging versus captive), age class (small calves, large calves, subadults, adults), and gender. No significant differences in plasma sodium, potassium, bilirubin, glucose, alanine aminotransferase, or creatine kinase were found among these classes of animals. Compared to free-ranging manatees, captive animals had significantly lower mean concentrations of plasma chloride, phosphate, magnesium, triglycerides, anion gap, and lactate. Captive manatees had significantly higher mean values of total CO2, calcium, urea, creatinine, alkaline phosphatase, gamma-glutamyltransferase, total protein, albumin, and albumin/globulin ratio than did free-ranging animals. Differences in the environments of these two groups, including diet, temperature, salinity, and stress, might account for some of these results. The higher plasma lactate and anion gap concentrations and lower total CO2 concentrations of free-ranging manatees were probably due to greater exertion during capture, but the lack of elevated plasma creatine kinase activity relative to captive animals indicates that there was no serious muscle injury associated with capture. Plasma phosphate decreased and total globulins increased with age. Plasma cholesterol and triglyceride concentrations were highest in small calves. Plasma aspartate aminotransferase was higher in large calves than in adults and subadults, and the albumin/ globulin ratio was higher in subadults than in adults. Plasma total CO2 was higher and chloride was slightly lower in females than in

  7. Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats.

    Science.gov (United States)

    Khamphaya, Tanaporn; Chansela, Piyachat; Piyachaturawat, Pawinee; Suksamrarn, Apichart; Nathanson, Michael H; Weerachayaphorn, Jittima

    2016-10-15

    Cholestasis is a cardinal manifestation of liver diseases but effective therapeutic approaches are limited. Therefore, alternative therapy for treating and preventing cholestatic liver diseases is necessary. Andrographolide, a promising anticancer drug derived from the medicinal plant Andrographis paniculata, has diverse pharmacological properties and multi-spectrum therapeutic applications. However, it is unknown whether andrographolide has a hepatoprotective effect on intrahepatic cholestasis. The aims of this study were to investigate the protective effect and possible mechanisms of andrographolide in a rat model of acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). Andrographolide was administered intragastrically for four consecutive days, with a single intraperitoneal injection of ANIT on the second day. Liver injury was evaluated biochemically and histologically together with hepatic gene and protein expression analysis. Rats pretreated with andrographolide prior to ANIT injection demonstrated lower levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, as well as bilirubin and bile acids as compared to rats treated with ANIT alone. Andrographolide also decreased the incidence and extent of periductular fibrosis and bile duct proliferation. Analysis of protein expression in livers from andrographolide-treated cholestatic rats revealed markedly decreased expression of alpha-smooth muscle actin and nuclear factor kappa-B (NF-κB). In conclusion, andrographolide has a potent protective property against ANIT-induced cholestatic liver injury. The mechanisms that underlie this protective effect are mediated through down-regulation of NF-κB expression and inhibition of hepatic stellate cell activation. These findings suggest that andrographolide could be a promising therapeutic option in prevention and slowing down the progression of cholestatic liver diseases. Copyright

  8. Possible hepatotoxicity of chronic marijuana usage

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    Paulo Borini

    Full Text Available CONTEXT: Hepatotoxicity is a potential complication from the usage of various illicit drugs, possibly consequent to their liver metabolism, but information on this is scarce in the medical literature. OBJECTIVE: To study the occurrence of clinical and laboratory hepatic alterations in chronic marijuana users, from the use of marijuana on its own or in association with other legal or illicit drugs. TYPE OF STUDY: transversal study SETTING: Hospital Espírita de Marília, Marília, São Paulo, Brazil PARTICIPANTS: The study was made among 123 patients interned in the Hospital Espírita de Marília from October 1996 to December 1998, divided into 3 groups: 26 (21% using only marijuana, 83 (67.5% using marijuana and crack, and 14 (11.4% consuming marijuana and alcohol. PROCEDURES AND MAIN MEASUREMENTS: Patients were examined clinically with special emphasis on types of drugs used, drug intake route, age when consumption began, length and pattern of usage, presence of tattooing, jaundice, hepatomegaly and splenomegaly. Serum determinations of total proteins, albumin, globulin, total and fractions of bilirubin, aspartate (AST and alanine (ALT aminotransferases, alkaline phosphatase (AP, gamma-glutamyltransferase and prothrombin activity were performed. RESULTS: Among users of only marijuana, hepatomegaly was observed in 57.7% and splenomegaly in 73.1%, and slightly elevated AST (42.3%, ALT (34.6% and AP (53.8%. The three groups did not differ significantly in the prevalence of hepatomegaly, splenomegaly and hepatosplenomegaly. The group using both marijuana and alcohol showed the highest prevalence of alterations and highest levels of aminotransferases. Mean AP levels were above normal in all groups. CONCLUSIONS: Chronic marijuana usage, on its own or in association with other drugs, was associated with hepatic morphologic and enzymatic alterations. This indicates that cannabinoids are possible hepatotoxic substances.

  9. Differential effects of two indigenous broilers exposed to cold stress and characters of follicle density and diameter

    Directory of Open Access Journals (Sweden)

    Xing Y. Chen

    2011-02-01

    Full Text Available digenous chickens from various part of China, due to different feather characters, always performed differently when countered with cold stress. In this study, the effects of long term hypothermia on serum hormones (triiodothyronine, thyroxine and insulin and activity of plasma enzymes (Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, creatine kinase and lactic dehydrogenase were studied in two indigenous broiler breeds, Huainan partridge (H and Wenchang (W chickens. Chickens in 20°C±2°C were compared with those subjected to moderate (15°C±2°C and severe low temperature (10°C±2°C for one week. Long-term hypothermia elevated plasma insulin and reduced T4 in W, decelerated insulin and increased T4 in H, while T3 did not change in the two breeds. Plasma enzymes AST, LDH and CK decreased in the two breeds and ALT only decreased in W exposed to cold stress. A significantly decreased body weight gain of H and no variations in W at low temperature were observed. However, a trend of decreased weight gain in W was observed when bred under low temperature condition. Follicle density and diameter were compared in the two breeds with back density in H significantly higher than W and diameter from back of H significantly smaller than W, while much larger than the latter at latero-abdominal part. We investigated the pattern of serum biological change, follicle diameter and density under cold stress condition in two indigenous broiler breeds from different areas of China to provide informative guidance for broiler production and indications in breeding of cold resistant breed.

  10. The effect of a multidisciplinary intervention program on hepatic adiposity in overweight-obese children: protocol of the EFIGRO study.

    Science.gov (United States)

    Medrano, M; Maiz, E; Maldonado-Martín, S; Arenaza, L; Rodríguez-Vigil, B; Ortega, F B; Ruiz, J R; Larrarte, E; Diez-López, I; Sarasúa-Miranda, A; Tobalina, I; Barrenechea, L; Pérez-Asenjo, J; Kannengiesser, S; Manhães-Savio, A; Echaniz, O; Labayen, I

    2015-11-01

    Non-alcoholic fatty liver disease is the most frequent liver abnormality observed in overweight or obese children and is strongly associated with metabolic syndrome and insulin resistance. (i) To evaluate the effect of a 22-week multidisciplinary intervention program on hepatic fat fraction in overweight or obese children and (ii) to examine the effect of the intervention on cardiometabolic risk factors, self-esteem and well-being. A total of 160 children, 9-11 years, will be recruited by pediatricians and randomly assigned to control (N = 80) or intervention (N = 80) groups. The control group will receive a family-based lifestyle and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week). The duration of training sessions will be 90 min of exercise, including warm-up, moderate to vigorous aerobic activities, and strength exercises. The primary outcome is the change in hepatic fat fraction (magnetic resonance imaging, MRI). Secondary outcomes include cardiometabolic risk factors such as total adiposity (dual Xray absorptiometry), visceral adiposity (MRI), functional peak aerobic capacity (cardiopulmonary exercise testing), blood pressure, muscular fitness, speed–agility, and fasting blood insulin, glucose, C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, lipid profile and psychological measurements (questionnaires). All the measurements will be evaluated at baseline prior to randomization and after the intervention. This study will provide insight in the efficacy of a multidisciplinary intervention program including healthy lifestyle education, psycho-education and supervised exercise to reduce hepatic fat and cardiometabolic risk in overweight children.

  11. Morphological and biochemical effects of weekend alcohol consumption in rats: Role of concentration and gender.

    Science.gov (United States)

    Morales-González, José A; Sernas-Morales, María de Lourdes; Morales-González, Ángel; González-López, Laura Ligía; Madrigal-Santillán, Eduardo Osiris; Vargas-Mendoza, Nancy; Fregoso-Aguilar, Tomás Alejandro; Anguiano-Robledo, Liliana; Madrigal-Bujaidar, Eduardo; Álvarez-González, Isela; Chamorro-Cevallos, Germán

    2018-02-27

    To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats. Wistar rats weighing 170-200 g were divided into groups as follows: (1) Control groups; and (2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations: (1) Group of males or females with a consumption of a solution of alcohol at 40%; and (2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy. In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocellular disorganization. The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.

  12. The effects of serial intravascular transfusions in ascitic/hydropic RhD-alloimmunized fetuses.

    Science.gov (United States)

    Craparo, F J; Bonati, F; Gementi, P; Nicolini, U

    2005-02-01

    To evaluate the effects of serial intravascular transfusions on RhD-alloimmunized fetuses with ascites/hydrops at the time of the first transfusion by measuring multiple hematological/biochemical blood variables. Thirty-one singleton pregnancies were referred for management of RhD alloimmunization. Seven fetuses had hydrops on presentation and were transfused immediately. The remainder underwent weekly ultrasound examinations, and fetal blood sampling and transfusion were performed on development of ascites. In the 104 samples collected overall from the 31 fetuses, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase (PCHE), creatine kinase, triglycerides and cholesterol were measured and compared with a reference range for non-anemic fetuses. The median gestational age at first transfusion was 26 (range, 18-34) weeks. There were three fetal losses after the first transfusion, two of which were due to procedure-related complications; one further loss occurred. At the first transfusion fetal hematocrit, pO2, total protein, PCHE, creatinine and urea concentrations were significantly decreased compared to reference data, while total and direct bilirubin, AST, ALT, amylase, triglyceride and uric acid concentrations were increased. In all surviving fetuses ascites/hydrops had disappeared by the second transfusion. Fetal pO2, total protein, AST, ALT and PCHE concentrations had normalized by the third transfusion. Correction of fetal anemia did not affect the other variables. RhD-alloimmunized fetuses with ascites/hydrops at the time of the first transfusion had a survival rate of 87%. Alterations of several biochemical fetal blood indices are present at the first sampling/transfusion, but most variables normalize with intravascular transfusions. Copyright 2005 ISUOG.

  13. Effect of Indigenous Herbs on Growth, Blood Metabolites and Carcass Characteristics in the Late Fattening Period of Hanwoo Steers

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    D. H. Kim

    2013-11-01

    Full Text Available This study was conducted to evaluate the effects of indigenous herbal supplements on growth, blood metabolites and carcass characteristics in the late fattening period of Hanwoo steers. In a 6 month feeding trial, thirty Hanwoo steers (647±32 kg were allotted to one of 5 treatment groups, control (basal diet contained lasalocid, licorice, clove, turmeric and silymarin, with six steers per pen. All groups received ad libitum concentrate and 1 kg rice straw/animal/d throughout the feeding trial. Blood samples were collected at the beginning, middle, and the end of the experiment and the steers were slaughtered at the end. Blood glucose, triglyceride, total protein, and albumin concentrations were higher in the turmeric treatment compared with other treatments. Blood urea nitrogen and creatinine concentrations were highest (p<0.003 and p = 0.071, respectively in steers treated with silymarin. Alanine aminotransferase activity was lower (p<0.06 for licorice and silymarin compared with the control group. There were no alterations in serum aspartate aminotransferase and gamma glutamyltransferase activities as a consequence of herb treatments (p = 0.203 and 0.135, respectively. Final body weight, body weight gain, average dairy gain and dry matter intake were not significantly different among treatments. Yield grade, marbling score and quality grade were higher for silymarin group than those of the control group (p<0.05. Therefore, the results suggest that silymarin can be used an effective dietary supplement as an alternative to antibiotic feed additive and a productivity enhancer, providing safe and more consumer acceptable alternative to synthetic compounds during the late fattening period of steers.

  14. Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.

    Science.gov (United States)

    Leonard, T B; Neptun, D A; Popp, J A

    1984-08-01

    Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bile duct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bile duct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bile duct hyperplasia.

  15. High levels of both serum gamma-glutamyl transferase and alkaline phosphatase are independent preictors of mortality in patients with stage 4-5 chronic kidney disease.

    Science.gov (United States)

    Caravaca-Fontán, Fernando; Azevedo, Lilia; Bayo, Miguel Ángel; Gonzales-Candia, Boris; Luna, Enrique; Caravaca, Francisco

    High serum gamma-glutamyl transferase (GGT) levels are associated with increased mortality in the general population. However, this association has scarcely been investigated in patients with chronic kidney disease (CKD). This study aims to investigate the clinical characteristics of CKD patients with abnormally elevated serum GGT, and its value for predicting mortality. Retrospective observational study in a population cohort of adults with stage 4-5 CKD not yet on dialysis. Demographic, clinical, and biochemical parameters of prognostic interest were recorded and used to characterise CKD patients with high levels of GGT (>36 IU/l). Cox proportional hazard regression models were used to analyse the influence of baseline serum GGT and alkaline phosphatase (ALP) levels on mortality for whatever reason. The study group consisted of 909 patients (mean age 65±15 years). Abnormally elevated GGT or ALP levels at baseline were observed in 209 (23%) and 172 (19%) patients, respectively, and concomitant elevations of GGT and ALP in 68 (7%). High GGT levels were associated with higher comorbidity burden, and a biochemical profile characterised by higher serum concentration of uric acid, triglycerides, alanine aminotransferase, ferritin, and C-reactive. During the study period, 365 patients (40%) died (median survival time=74 months). In adjusted Cox regression models, high levels of GGT (hazard ratio [HR]=1.39;CI 95%: 1.09-1.78, P=.009) and ALP (HR=1.31; CI95%: 1.02-1.68, P=.038) were independently associated with mortality. High serum levels of GGT are independent predictors of mortality in CKD patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Prediction of liver injury using the BP-ANN model with metabolic parameters in overweight and obese Chinese subjects.

    Science.gov (United States)

    Hu, Lufeng; Wang, Fan; Xu, Jinzhong; Wang, Xiaofang; Lin, Hong; Zhang, Yi; Yu, Yang; Wang, Youpei; Pang, Lingxia; Zhang, Xi; Liu, Qi; Qiu, Guoshi; Jiang, Yongsheng; Xie, Longteng; Liu, Yanlong

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is often associated with dyslipidemia. Metabolic disequilibrium, resulting from being overweight and obesity, increases risk to cardiovascular system and chronic liver disease. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) are standard clinical markers for liver injury. In this study, we examined association of body mass index (BMI) and metabolic markers with serum ALT, AST and GGT activity in an overweight and obese Chinese population. A total of 421 overweight and obese Chinese adults (211 males and 210 females) from The First Affiliated Hospital of Wenzhou Medical University were recruited in this study in 2014. All participants underwent anthropometric measures and phlebotomy after an overnight fast. Elevated ALT, AST and GGT levels were found in 17%, 5% and 24%, respectively. There were significant correlations between ALT and BMI, plasma triglycerides (TG), cholesterol, HDL and glucose, and between AST and plasma TG and cholesterol. GGT also correlated with plasma TG, cholesterol and glucose. The levels of ALT, AST and GGT could be predicted by BMI, plasma TG, cholesterol, HDL and glucose using the back propagation artificial neural network model (BP-ANN). These data suggest that abnormal metabolic markers could be used to monitor liver function to determine whether liver damage has occurred in overweight and obese individuals. This approach has clinical utility with respect to early scanning of liver injury or NAFLD based on routinely available metabolic data in overweight and obese population.

  17. High-Dose Micafungin for Preterm Neonates and Infants with Invasive and Central Nervous System Candidiasis.

    Science.gov (United States)

    Auriti, Cinzia; Falcone, Marco; Ronchetti, Maria Paola; Goffredo, Bianca Maria; Cairoli, Sara; Crisafulli, Rosamaria; Piersigilli, Fiammetta; Corsetti, Tiziana; Dotta, Andrea; Pai, Manjunath P

    2016-12-01

    High doses of micafungin are advocated in neonates with systemic candidiasis, but limited pharmacokinetic (PK) and safety data are available to support their use. Eighteen preterm neonates and infants with systemic candidiasis, three of whom had meningitis, were treated for at least 14 days with 8 to 15 mg/kg of body weight/day of intravenous micafungin. Plasma micafungin concentrations (four measurements for each patient) were determined after the third dose, and the cerebrospinal fluid (CSF) micafungin concentrations in three patients were also obtained. Population PK analyses were used to identify the optimal model, and the model was further validated using external data (n = 5). The safety of micafungin was assessed by measurement of the levels of liver and kidney function biomarkers. The mean age and weight at the initiation of treatment were 2.33 months (standard deviation [SD], 1.98 months) and 3.24 kg (SD, 1.61 kg), respectively. The optimal PK model was one that scaled plasma clearance to weight and the transaminase concentration ratio. The CSF of three patients was sampled, and the observed concentrations were between 0.80 and 1.80 mg/liter. The model-predicted mean micafungin area under the concentration-time curve over 24 h was 336 mg · h/liter (SD, 165 mg · h/liter) with the 10-mg/kg/day dosage. Eighteen of the 23 subjects (78.2%) had clinical resolution of their infection, but 5 had neurologic impairments. Among the transaminases, alkaline phosphatase measurements were significantly higher posttreatment, with a geometric mean ratio of 1.17 (90% confidence interval, 1.01, 1.37). Furthermore, marked elevations in the gamma-glutamyltransferase (GGT) level were observed in three patients treated with 10- to 15-mg/kg/day doses, and improvement of the GGT level was noted after a dose reduction. Higher weight-based doses of micafungin were generally well tolerated in neonates and infants and achieved pharmacokinetic profiles predictive of an effect

  18. Motivational interviewing with hazardous drinkers.

    Science.gov (United States)

    Beckham, Nancy

    2007-02-01

    To test the effectiveness of motivational interviewing in a population of hazardous drinkers utilizing community health care centers in rural southeastern Idaho. This study targeted rural people at risk for alcohol dependence utilizing low-income community health care centers in rural southeastern Idaho. The Alcohol Use Disorders Identification Test (AUDIT) was used to screen interested clients' alcohol use. Clients achieving an AUDIT score indicating hazardous alcohol use were recruited into the study and randomized into a control or treatment group. Twenty-six hazardous drinkers attending five low-income community health centers participated in the study. The experimental group participated in one motivational interviewing session with the investigator, a family nurse practitioner (NP). The comparison group received no treatment. Alcohol use was tracked for 6 weeks after successful recruitment into the program. Participants in the study significantly decreased their average number of drinks per day. At time 1 (pretreatment), the control group drank 4.37 drinks per day and the treatment group drank 4.65 drinks per day. At time 2 (posttest), the control group drank 3.77 drinks per day and the treatment group drank 1.95 drinks per day. The effects of the motivational interviewing treatment on hazardous drinking also were measured by serum gamma-glutamyltransferase (GGT), a liver function test. There was also a significant decrease in the GGT from pretest to posttest in the treatment group. The results of this investigation found that motivational interviewing shows promise as an effective intervention for hazardous drinkers attending low-income community clinics. Although other possible explanations could be postulated for the positive changes in sample participants, the data indicate that the motivational interviewing approach was responsible for a significant portion of the positive changes within the current sample. The information collected from the study adds

  19. Investigation of the tolerability of oral stevioside in Brazilian hyperlipidemic patients

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    Gisleine Elisa Cavalcante da Silva

    2006-07-01

    Full Text Available The tolerability of stevioside (2.75 mg/kg/day obtained from leaves of Stevia rebaudiana (Bert Bertoni (Compositae was investigated in hyperlipidemic patients. For this purpose a placebo controlled double blind study was performed. The patients were randomized in two groups: the first group received capsules containing placebo and the second group received capsules containing stevioside (50 mg during 90 days. All capsules were ingested twice daily, i.e., 2 capsules before lunch and 2 capsules before dinner. After the selection of the patients and each 30 days body mass index and laboratory tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, total cholesterol, high density lipoprotein, low density lipoprotein, very low density lipoprotein, triglycerides and glucose were performed. Stevioside did not show any clinical relevant modification in all parameters investigated. Moreover the patients did not report severe adverse effect. Thus, we can concluded that stevioside, at least in the doses employed in this study was safe.A tolerabilidade do esteviosideo (2.75 mg/kg/dia obtido a partir de folhas de Stevia rebaudiana (Bert Bertoni (Compositae foi investigada em pacientes hiperlipidêmicos. Para alcançar este objetivo realizamos estudo clínico do tipo duplo cego. Os pacientes foram randomizados em 2 grupos: o primeiro recebeu cápsulas contendo placebo e o segundo recebeu cápsulas contendo esteviosídeo (50 mg. Foram ingeridas duas cápsulas antes do almoço e duas cápsulas antes do jantar durante 90 dias. Após a seleção dos pacientes e a cada 30 dias o índice de massa corpórea e exames laboratoriais (alanina aminotransferase, aspartato aminotransferase, gama-glutamiltransferase, colesterol total, lipoproteína de alta densidade, lipoproteína de baixa densidade, lipoproteína de muito baixa densidade, trigliceridemia e glicemia foram realizados. O esteviosídeo não acarretou qualquer altera

  20. Serum chemistry comparisons between captive and free-ranging giraffes (Giraffa camelopardalis).

    Science.gov (United States)

    Schmidt, Debra A; Barbiers, Robyn B; Ellersieck, Mark R; Ball, Ray L; Koutsos, Elizabeth A; Griffin, Mark E; Grobler, Douw; Citino, Scott B; Bush, Mitchell

    2011-03-01

    Serum chemistry analyses were compared between captive and free-ranging giraffes (Giraffa camelopardalis) in an attempt to better understand some of the medical issues seen with captive giraffes. Illnesses, including peracute mortality, energy malnutrition, pancreatic disease, urolithiasis, hoof disease, and severe intestinal parasitism, may be related to zoo nutrition and management issues. Serum samples were collected from 20 captive giraffes at 10 United States institutions. Thirteen of the captive animal samples were collected from animals trained for blood collection; seven were banked samples obtained from a previous serum collection. These samples were compared with serum samples collected from 24 free-ranging giraffes in South Africa. Differences between captive and free-ranging giraffes, males and females, and adults and subadults were analyzed by using a 2 x 2 x 2 factorial and Fisher's least significant difference for mean separation; when necessary variables were ranked and analyzed via analysis of variance. Potassium and bilirubin concentrations and alanine aminotransferase (ALT) activities were different between captive and free-ranging giraffes, but all fell within normal bovid reference ranges. The average glucose concentration was significantly elevated in free-ranging giraffes (161 mg/dl) compared with captive giraffes (113 mg/dl). All giraffes in this study had glucose concentrations higher than bovine (42-75 mg/ dl) and caprine (48-76 mg/dl) reference ranges. Differences were also seen in lipase, chloride, and magnesium though these findings are likely not clinically significant. There were no differences detected between sexes. Adults had higher concentrations of potassium, total protein, globulins, and chloride and higher gamma glutamyltransferase activities, whereas subadults had higher concentrations of phosphorus. Within the captive group, nonimmobilized animals had higher concentrations of total protein and globulins. Captive giraffe diets

  1. Is it possible a new definition of metabolic syndrome in childhood?

    Science.gov (United States)

    Martino, F; Pannarale, G; Puddu, P E; Colantoni, C; Zanoni, C; Martino, E; Torromeo, C; Paravati, V; Perla, F M; Barillà, F

    2015-11-01

    To investigate whether a group of Italian children and adolescents who were diagnosed to have metabolic syndrome (MS) according to a new ethnic age and gender specific definition had, in comparison with a control group, other signs and metabolic risk factors which are commonly associated with MS. The cross-sectional study population included 300 subjects (51% boys, age range 6-14 years), who were divided into 2 groups according to the presence of MS, diagnosed on the basis of 3/5 factors derived from the age and gender specific quantile distribution of MS components in a large regional Italian population survey (Calabrian Sierras Community Study, CSCS). In all subjects the following data were collected: anthropometric measures, blood pressure, liver function, C-reactive protein (hsCRP), uric acid blood levels, lipid and glucose profile. Triglycerides/HDL-cholesterol (TG/HDL-C) ratio was calculated. There were 38 subjects (13%) with MS, who had higher indices of growth and fat distribution and higher blood levels of uric acid, alanine aminotransferase and gamma-glutamyltransferase. TG/HDL ratio was higher (median 3.11 vs. 1.14, p = 0.00001) in MS subjects who had lower apolipoprotein A and higher apolipoprotein B and non-HDL-C levels. hsCRP was not different between groups. Our ethnic age and gender specific definition of MS in Italian children and adolescents was able to identify in a youth group different cardiometabolic risk factors related to insulin resistance, endothelial damage and nonalcoholic fatty liver disease, which are commonly associated with MS diagnosis.

  2. Tepoxalin on renal function and liver enzymes in cats exposed to hypotension with isoflurane

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    Gabrielle Coelho Freitas

    2014-06-01

    Full Text Available This study aimed to evaluate the possible renal and hepatic toxicity of tepoxalin administered before or after isoflurane-induced hypotension, as well as for five consecutive days. Twelve healthy mixed-breed cats, adult males, weighing 4.0±0.8kg were allocated into two groups. They received 25mgkg-1 of tepoxalin orally, two hours before the anesthetic procedure (PRE or after the procedure (POST and daily for five days. Cats were anesthetized with isoflurane and the concentration was increased until mean arterial pressure reached 40-60mmHg and kept at this level for 60 minutes. During hypotension, the physiological variables were measured at time 0 and every 10 minutes until 60 minutes, and bleeding time was measured at time 0, 30 and 60 minutes. Blood samples were drawn for a hemogram and determination of concentrations of alanine aminotransferase, alkaline phosphatase, urea, creatinine and Na+ at baseline, 24 hours, 48 hours and 7 days post-hypotension. Urine was collected at baseline, 24 hours, 48 hours and 7 days post-hypotension for determination of concentrations of creatinine, gamma-glutamyltransferase, urine specific gravity, protein, albumin and Na+. During the anesthetic procedure there were no important variations in physiological variables and bleeding time. There were differences only in fractional excretion of Na+, which was elevated at 7 days of evaluation in PRE and in the urine protein/creatinine ratio in PRE, which was higher than in POST at 24 and 48 hours post-hypotension. We conclude that tepoxalin does not cause alterations in hepatic enzymes but can cause discrete renal injury, resulting in proteinuria, in cats subjected to 60min of hypotension.

  3. Salivary exoglycosidases as markers of alcohol dependence.

    Science.gov (United States)

    Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zalewska, Anna; Zwierz, Krzysztof; Szulc, Agata; Szajda, Sławomir Dariusz

    2014-01-01

    Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β-glucuronidase (GLU), and their applicability as markers of alcohol dependence. The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence). © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  4. Neapolis (CD 126 beta+ GGT->GGG): a result of a screening in Campania, a region in Southern Italy.

    Science.gov (United States)

    Pagano, Leonilde; Viola, Assunta; Fioretti, Gennaro; Ammirabile, Massimiliano; Ricchi, Paolo; Prossomariti, Luciano

    2007-07-01

    Between January 1995 and December 2005, we conducted a screening program for the presence of Hb Neapolis, a rare abnormal Hb variant, in Campania, a region in Southern Italy. Nineteen patients with Hb Neapolis in heterozygosis and six patients with a genetic compound (Hb Neapolis/beta-thalassemia) were identified. Patients with Hb Neapolis in heterozygosis showed a slight alteration in HbA2 levels while compounds showed typical characteristics of thalassemia intermedia ranging from a non transfusion-dependent form for five patients to a transfusion-dependent form for one adult patient.

  5. Enhanced erythropoietin and suppression of γ-glutamyl trans-peptidase (GGT) activity in murine lymphoma following administration of vanadium

    International Nuclear Information System (INIS)

    Chakraborty, A.; Chatterje, M.

    1994-01-01

    Administration of vanadium as ammonium mono-vanadate (0.005 μg/0.1 ml/mouse/day) was found to reduce the tumor cell proliferation in the host mice bearing Dalton's lymphoma. The high activity of γ-glutamyl trans-peptidase (CCT), a neoplastic marker, was seen in the host cells bearing lymphoma. Vanadium effectively prevented an increase in activity of γ-glutamyl trans-peptidase and maintained a sustained low activity of this enzyme. In addition, an improvement of the hematological aspects of the mice and almost fourfold elevation of erythropoietin (Epo) was obtained following vanadium treatment. This in Epo activity may play a vital role in regulating the growth of cellular neoplasia. The present study further confirms the anti-tumorigenic potential of vanadium in the control of tumor progression in lymphoma via modulating several factors involving erythropoiesis and may emerge as a new chemo-preventive agent for the future. (author)

  6. Prevalence of cardiometabolic risk factors and metabolic syndrome in obese Kuwaiti adolescents

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    Boodai SA

    2014-10-01

    Full Text Available Shurooq A Boodai,1 Lynne M Cherry,2 Naveed A Sattar,2 John J Reilly3 1University of Glasgow School of Medicine, Yorkhill Hospitals, Glasgow, Scotland; 2Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland; 3University of Strathclyde Physical Activity for Health Group, School of Psychological Sciences and Health, Glasgow, Scotland Background: Childhood and adolescent obesity is associated with insulin resistance, abnormal glucose metabolism, hypertension, dyslipidemia, inflammation, liver disease, and compromised vascular function. The purpose of this pilot study was to determine the prevalence of cardiometabolic risk factor abnormalities and metabolic syndrome (MetS in a sample of obese Kuwaiti adolescents, as prevalence data might be helpful in improving engagement with obesity treatment in future. Methods: Eighty obese Kuwaiti adolescents (40 males with a mean (standard deviation age of 12.3 years (1.1 years participated in the present study. All participants had a detailed clinical examination and anthropometry, blood pressure taken, and assessment of fasting levels of C-reactive protein, intracellular adhesion molecule, interleukin-6, fasting blood glucose, insulin, liver function tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, lipid profile (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin resistance by homeostasis model assessment, and adiponectin. MetS was assessed using two recognized criteria modified for use in younger individuals. Results: The cardiometabolic risk factors with highest prevalence of abnormal values included aspartate aminotransferase (88.7% of the sample and insulin resistance by homeostasis model assessment (67.5%, intracellular adhesion molecule (66.5%, fasting insulin (43.5%, C-reactive protein (42.5%, low

  7. Which liver enzymes are better indicators of metabolic syndrome in adolescents: the Fifth Korea National Health and Nutrition Examination Survey, 2010.

    Science.gov (United States)

    Lee, Kayoung; Yang, Jin Hyang

    2013-08-01

    This study aimed to examine the relationships of liver enzyme levels with metabolic syndrome in adolescents. A total of 808 adolescents (430 males and 378 females, aged 10-19 years) participated in the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1) in 2010, the relationships between liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), ratio of AST to ALT (AST/ALT), and γ-glutamyltransferase (GGT)] and metabolic syndrome defined by the International Diabetes Federation criteria were assessed using logistic regression and receiver operating characteristic (ROC) curve analyses. After adjusting for age, higher ALT and GGT levels and a lower AST/ALT level were associated with clustering of metabolic syndrome components, whereas AST level was not associated with it in both sexes. The strength of association between the liver enzymes and clustering of metabolic syndrome components was higher in females than in males. In the non-overweight group, higher AST, ALT, and GGT levels and a lower AST/ALT level were associated with clustering of metabolic syndrome components, whereas none of the liver enzymes was associated with metabolic syndrome in the overweight group. The area under the ROC curve (AUC) of AST to determine metabolic syndrome was not significant and was significantly lower than AUCs of ALT, AST/ALT, and GGT in both sexes. The cutoff values of ALT, AST/ALT, and GGT to determine metabolic syndrome were higher in males than in females. ALT, AST/ALT, and GGT were found to be associated with clustering of metabolic syndrome components, and the relationships appear to be sex- and weight group-specific.

  8. Efeito do óleo de copaíba nas aminotransferases de ratos submetidos à isquemia e reperfusão hepática com e sem pré-condicionamento isquêmico Copaiba oil effect in rats aminotrasnferases submitted to hepatic ischemic and reperfusion with and without preconditioning

    Directory of Open Access Journals (Sweden)

    Francisco Alves de Araújo Júnior

    2005-02-01

    Full Text Available OBJETIVO: Estudar o efeito do óleo de copaíba nas aminotransferases de ratos submetidos à isquemia e reperfusão (IR hepática, com e sem pré-condicionamento isquêmico (PCI. MÉTODOS: Foram utilizados 24 Rattus norvegicus albinus machos distribuídos em: Grupo padrão (GP, Grupo copaíba (GC, Grupo isquemia-reperfusão (GIR, Grupo isquemia-reperfusão + copaíba (GIRC, Grupo pré-condicionamento isquêmico (GPCI e Grupo pré-condicionamento isquêmico + copaíba (GPCIC. Foi administrado 0,63ml/kg/dia de copaíba, durante sete dias, por meio de gavagem nos animais do GC, GIRC e GPCIC. A isquemia hepática foi de 30 minutos e, nos animais submetidos ao PCI, realizou-se isquemia de 10 minutos, seguida de reperfusão de 5 minutos e isquemia de 30 minutos com posterior reperfusão. Os animais foram anestesiados via inalatória com éter etílico. O período de reperfusão foi de 24 horas. No 1° DPO foi realizada coleta de sangue venoso e dosagem das aminotransferases. RESULTADOS: Os níveis de AST não se alteraram nos animais submetidos à administração do óleo de copaíba. O óleo estudado não alterou os valores de ALT no GIRC quando comparado com o GIR, entretanto, houve aumento do nível sérico dessa enzima no GPCIC em comparação com o GPCI. CONCLUSÃO: O óleo de copaíba não alterou os níveis de AST nos grupos estudados. Ao se avaliar a ALT, esse óleo não influenciou os valores séricos nos animais submetidos somente à IR hepática, entretanto houve aumento dos níveis dessa enzima no GPCIC em relação ao seu controle. Os valores de ALT não foram diferentes estatisticamente entre os grupos IRC e PCIC.PURPOSE: To study the copaiba oil effect in rats' aminotrasnferases submited to hepatic ischemic and reperfusion with and without preconditioning. METHODS: 24 male and adults rats (Rattus norvegicus albinus,Wistar were distributed into six groups: Standard Group (SG; Copaiba Group (CG, Ischemic-reperfusion Group (IRG, Ischemic

  9. Efeito da adição de cloreto de cálcio sobre a qualidade espermática e atividade da aspartato amino transferase no sêmen resfriado de suíno Effect of adding calcium chloride on the spermatic quality and aminotransferase aspartate in cool swine semen

    Directory of Open Access Journals (Sweden)

    Fernanda Pinheiro Lima

    2007-10-01

    Full Text Available O experimento foi realizado com o objetivo de testar dois processos de resfriamento de sêmen suíno, analisar o efeito da adição de CaCl2 ao diluidor BTS e testar o método de avaliação do perfil enzimático da Aspartato Aminotransferase (AAT sobre a qualidade espermática. Foram utilizados 12 ejaculados suínos de animais procedentes do setor de Suinocultura - DZO/UFLA. Estes ejaculados foram diluídos e receberam diferentes concentrações de CaCl2 (A: 0,0; B: 2,5; C: 5,0 e D: 7,5 mM. As amostras dos ejaculados foram submetidas a três processos de resfriamento (1: convencional - 15º C ; 2: lento - 15º C/5º C; 3: rápido - 5º C, sendo que cada ejaculado ficou armazenado por um período de 72 horas para avaliações da qualidade espermática, constituindo os tratamentos experimentais. Os parâmetros seminais avaliados foram motilidade e vigor espermáticos e perfil enzimático da AAT. Houve diferença significativa (P0,05. Conclui-se que a adição de CaCl2 melhora a motilidade espermática das amostras dos ejaculados suínos e que o processo de resfriamento lento substitui o processo convencional sem afetar a qualidade espermática do sêmen submetido à refrigeração. A avaliação da AAT não é válida para sêmen resfriado.The study was carried out with objective to test two swine semen cooling processes and verify the effects of adding chloride of calcium (CaCl2 on semen dilutor BTS and also to test the evaluation method of Aspartate Aminotransferase (AAT enzymatic profile on the cooled swine semen spermatic quality. Were used twelve samples of ejaculation of breeders supplied by the Swine Breeding section at the DZO/UFLA. The samples were diluted and received different concentrations of CaCl2 (A: 0.0; B: 2.5; C 5.0; D 7.5mM. The samples of ejaculation were submitted to three processes of cooling: 1 - standard cooling (15º C; 2 - slow cooling (15º C/ 5º C; 3 - fast cooling (5º C, and each sample of ejaculation was stored for

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

    African Journals Online (AJOL)

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

  11. Place des alanine-aminotransferases dans la securite ...

    African Journals Online (AJOL)

    The serological assays' performance seems to deny all interest to the ALAT determination in the blood safety. Nous avons mené une étude sur 164 donneurs de sang bénévoles au Centre National de Transfusion Sanguine (CNTS) de Lomé pour évaluer la place de la mesure de l'activité des transaminases de type

  12. effect of thermoxidised groundnut oil on aminotransferase activity of ...

    African Journals Online (AJOL)

    PROF. BARTH EKWEME

    age of globalization. Makurdi, Nigeria. 82. Osim, E. E., Owu, D. U., Isong, E. U and Umoh, I. B.,. 1994. Influence of chronic consumption of thermoxidised palm oil diet on basal metabolic rate, body weight and morphology of tissues in rats. Discovery and Innovation (6): 389- 396. Owu, D. U., Osim, E. E and Ebong, P. E., 1998.

  13. effect of thermoxidised groundnut oil on aminotransferase activity of ...

    African Journals Online (AJOL)

    PROF. BARTH EKWEME

    goal of enhancing palatability as well as facilitating quick digestion (Sanders 1993).Prominent amongst these processing methods is hydrogenation process especially .... lipidperoxidation in modulation of cellular signallying pathways, cell dysfunction and death in nervous system. Rev. Neuroscience (9): 105-. 116. National ...

  14. Homology modeling of ɣ-aminobutyrate- aminotransferase, a ...

    African Journals Online (AJOL)

    Jane

    2011-06-29

    Jun 29, 2011 ... of GABA-AT is not experimentally known, and we thus resorted to homology modelling to build a model based on x-ray crystal ... MUSCLE programs. The model was further checked for its correctness by predicting the .... is an important step for the prediction of protein's tertiary structure. Secondary structure ...

  15. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases

    DEFF Research Database (Denmark)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura Frendrup

    2016-01-01

    to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes...... the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [15N]glutamate demonstrated activity of GDH......The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate–glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back...

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

    African Journals Online (AJOL)

    Reham Al Swaff

    2012-04-04

    Apr 4, 2012 ... Department of Internal Medicine, Faculty of Medicine, Ain Shams University, 30 Manshiet Al Bakry Street, Heliopolis, Cairo, Egypt. Received 26 February 2012; ... Egypt has the highest prevalence of HCV worldwide (15%). [2] and the highest .... antitrypsin deficiency. 8. Current intravenous drug abuse. 9.

  17. [Aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in health surveillance of workers exposed to vinyl chloride monomer: preliminary results].

    Science.gov (United States)

    Di Lorenzo, L; Corfiati, M; Bulfaro, D; Liuzzi, G; Zenzola, M; Soleo, L

    2003-01-01

    An AST/ALT ratio > 1 is predictive of liver fibrosis and cirrhosis in patients with chronic hepatitis C virus infection. The aim of this case-control study is to assess AST/ALT ratio in 150 workers exposed to VCM (E) from the beginning of the 1960s to the end of the 1990s. The non-exposed group (NE) consists in 150 male workers employed in the production of a food industry. At least since 1983 exposed subjects worked at VCM environmental concentrations 1 significantly higher than non-exposed. The mean AST/ALT ratio results significantly higher in the exposed group, also after stratification for alcohol consumption. In exposed workers who consume alcoholic beverages and are operating since before 1983 AST/ALT ratio is significantly and positively influenced only by the working age until 1983. If these results will be confirmed, AST/ALT ratio could be proposed to be included in the periodic medical surveillance of VCM workers.

  18. [Aspartate aminotransferase (AST) more than alanine aminotransferase (ALT) levels predict the progression of liver fibrosis in chronic HCV infection].

    Science.gov (United States)

    Stránský, J; Ryzlová, M; Striteský, J; Horák, J

    2002-10-01

    The development and severity of liver fibrosis in patients with chronic HCV infection can be evaluated best according to the staging of fibrosis in blind liver biopsy. So far there is however no biochemical indicator suggesting advanced fibrosis or progression of fibrosis in chronic HCV infection. In 1997 - 1999 60 adult out-patients (32 women) with chronic HCV infection were examined by blind liver biopsy. The grading of hepatitis was scored according to Knodell and staging of fibrosis according to Desmet. All patients were anti-HCV positive, assessed by the ELISA-3 method and 48/60 had positive HCV RNA in serum. The main risk factor of HCV infection was blood transfusion (67%). Of 27 examined patients 20 (74%) had serotype HCV 1. Staging of fibrosis: histologically confirmed fibrosis was not recorded in 11 patients (18.3%), mild and medium fibrosis was recorded in 25 (42%), severe fibrosis in 14 (23%) and cirrhosis in 10 (17%). With confirmed fibrosis correlated more closely AST serum activity (p < 0.002) than ALT activity (p < 0.03). Steatosis of the liver was found in 25 (42%) patients. The mean age of patients with steatosis was significantly higher than that of patients without steatosis (p < 0.0008). Steatosis was more frequent in patients with fibrosis (p < 0.04), in particularin the age group above 60 years. The development of fibrosis in patients with chronic HCV infection is suggested by permanently elevated activity of both transaminases whereby AST has a higher predictive value than ALT activity. A total of 40% histologically tested patients had the highest staging of fibrosis (3 - 4). Steatosis is in chronic HCV infection a very frequent finding (42%), in particular in patients above 60 years and those with serious fibrosis. The finding of fibrosis should stimulate the initiation of antiviral treatment which can lead to regression of fibrosis and improvement of the histological finding.

  19. Efeitos do metronidazol sobre a atividade enzimática da ALT (alanina aminotransferase) e AST (aspartato aminotransferase), em ratos

    OpenAIRE

    Souza, Patrícia Medeiros de

    2013-01-01

    Este trabalho teve por objetivo avaliar os efeitos do metronidazol sobre a função hepática, um medicamento comumente empregado no tratamento da tticommúase vaginal e outras parasitoses, alem de infecções anaeróbias bacterianas. Para tal, empregaram-se 72 ratos albinos Wistar, machos, tratados com metronidazol 7,5 mg/kg, 15 mglkg e 30 mg/kg ou com solução de NaCl 0,9% (controle), em duas aplicações diárias, por 4 dias, via ip. Após 48, 72 e 96 horas do inicio dos tratamentos, co...

  20. Efeitos do metronidazol sobre a atividade enzimatica da ALT (Alamina aminotransferase) e AST (aspartato aminotransferase), em ratos

    OpenAIRE

    Patricia Medeiros de Souza Pena Barbosa

    1997-01-01

    Resumo:Este trabalho teve por objetivo avaliar os efeitos do metronidazol sobre a função hepática, um medicamento comumente empregado no tratamento da tricomoníase vaginal e outras parasitoses, alem de infecções anaeróbias bacterianas. Para tal, empregaram-se 72 ratos albinos Wistar, machos, tratados com metronidazol 7,5 mg/kg, 15 mg/kg e 30 mg/kg ou com solução de NaCI 0,9% (controle), em duas aplicações diárias, por 4 dias, via ip. Após 48, 72 e 96 horas do início dos tratamentos, colheram-...

  1. Effect of Eight Weeks Forced Swimming Training with Methadone Supplementation on Aspartate Aminotransferase, Alanine Aminotransferase, and Alkaline Phosphatase of Rats

    Directory of Open Access Journals (Sweden)

    Seyed Ali Hoseini

    2016-12-01

    Full Text Available Background & Objective: Narcotics abuse can induce liver disorders; nevertheless, exercises improve liver disorders. The present research aimed to review the effect of eight weeks forced swimming training with methadone supplementation on liver enzymes of rats. Material & Method: In this experimental research, 48 rats were selected, and after one week adaptation to lab environment, they were randomly divided into four groups of 12 rats including (1 forced swimming training, (2 methadone supplementation, (3 forced swimming training with methadone supplementation, and (4 control. Groups 2 and 3 used 2 mg/kg methadone daily for 8 weeks. Also, groups 1 and 3 swam for 8 weeks, three sessions per week and each session for 30 minutes. For statistical analysis of data, one way ANOVA and Tukey post hoc tests were used (α≤0.05. Results: Findings showed that forced swimming training, methadone supplementation, and forced swimming training with methadone supplementation had no significant effect on AST (P=0.90 and ALT (P=0.99 enzymes; forced swimming training had significant effect on increase of ALP (P=0.001; also, forced swimming training, compared with methadone supplementation and combination of forced swimming training with methadone supplementation, had significant effect on increase of ALP (P=0.001. Conclusion: Accordingly, 8 weeks of forced swimming training with methadone has possibly no significant effect on liver enzymes.

  2. ASSOCIATION OF GAMMA-GLUTAMYL TRANSFERASE WITH METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Masilamani

    2016-12-01

    Full Text Available BACKGROUND Metabolic Syndrome (MeS is associated with an increased risk of cardiovascular morbidity and mortality. Elevation of liver enzymes particularly alterations in Gamma-Glutamyl transferase (GGT levels are observed in metabolic syndrome in response to oxidative stress. MATERIALS AND METHODS In this case-sectional study, 100 cases of metabolic syndrome and 100 apparently normal healthy subjects in the age group between 25-65 years were included. Anthropometric measurements such as height, weight, waist/hip ratio and BMI were measured for both the study groups and serum levels of blood glucose, total cholesterol, triglycerides, HDL, LDL, ALT, AST and Gamma-Glutamyl transferase (GGT were measured using enzymatic methods. Patients with hypothyroidism, malignant disease, severe renal insufficiency, cirrhosis, active liver disease and alcohol consumption were excluded. RESULTS Among the various biochemical parameters, fasting blood glucose, serum triglycerides, total cholesterol and HDL showed statistically significant elevation among the MeS subjects when compared to healthy controls with p value <0.05. The mean values of GGT and Alanine Aminotransferase (ALT levels were statistically significantly higher in MeS group. The mean values of liver enzymes in MeS group, GGT, AST and ALT respectively were 74.77±15.36, 27.3±10.25 and 37.6±6.5. CONCLUSION Patients with MeS have more significantly elevated levels of GGT showing a significant association of GGT with metabolic syndrome. Moreover, GGT may play a role in early diagnosis of metabolic syndrome and risk for cardiovascular disease.

  3. The biosynthesis of UDP-d-FucNAc-4N-(2)-oxoglutarate (UDP-Yelosamine) in Bacillus cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp protein that ligates 2-oxoglutarate to UDP-4-amino-sugars.

    Science.gov (United States)

    Hwang, Soyoun; Li, Zi; Bar-Peled, Yael; Aronov, Avi; Ericson, Jaime; Bar-Peled, Maor

    2014-12-19

    Surface glycan switching is often observed when micro-organisms transition between different biotic and abiotic niches, including biofilms, although the advantages of this switching to the organism are not well understood. Bacillus cereus grown in a biofilm-inducing medium has been shown to synthesize an unusual cell wall polysaccharide composed of the repeating subunit →6)Gal(α1-2)(2-R-hydroxyglutar-5-ylamido)Fuc2NAc4N(α1-6)GlcNAc(β1→, where galactose is linked to the hydroxyglutarate moiety of FucNAc-4-amido-(2)-hydroxyglutarate. The molecular mechanism involved in attaching 2-hydroxyglutarate to 4-amino-FucNAc has not been determined. Here, we show two genes in B. cereus ATCC 14579 encoding enzymes involved in the synthesis of UDP-FucNAc-4-amido-(2)-oxoglutarate (UDP-Yelosamine), a modified UDP-sugar not previously reported to exist. Using mass spectrometry and real time NMR spectroscopy, we show that Bc5273 encodes a C4″-aminotransferase (herein referred to as Pat) that, in the presence of pyridoxal phosphate, transfers the primary amino group of l-Glu to C-4″ of UDP-4-keto-6-deoxy-d-GlcNAc to form UDP-4-amino-FucNAc and 2-oxoglutarate. Pat also converts 4-keto-xylose, 4-keto-glucose, and 4-keto-2-acetamido-altrose to their corresponding UDP-4-amino-sugars. Bc5272 encodes a carboxylate-amine ligase (herein referred as Pyl) that, in the presence of ATP and Mg(II), adds 2-oxoglutarate to the 4-amino moiety of UDP-4-amino-FucNAc to form UDP-Yelosamine and ADP. Pyl is also able to ligate 2-oxoglutarate to other 4-amino-sugar derivatives to form UDP-Yelose, UDP-Solosamine, and UDP-Aravonose. Characterizing the metabolic pathways involved in the formation of modified nucleotide sugars provides a basis for understanding some of the mechanisms used by bacteria to modify or alter their cell surface polysaccharides in response to changing growth and environmental challenges. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Detection of TTV in peripheral blood cells from patients with altered ALT and AST levels.

    Science.gov (United States)

    de Oliveira, Jaqueline Carvalho; Nasser, Thiago Franco; Oda, Julie Massayo Maeda; Aoki, Mateus Nóbrega; Carneiro, Juliana Laino do Val; Barbosa, Décio Sabbatini; Reiche, Edna Maria Vissoci; Watanabe, Maria Angelica Ehara

    2008-04-01

    This work analyzes the prevalence of TTV DNA in peripheral blood cells from patients with hepatic alterations and healthy blood donors and measures levels of sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in certain randomly selected patients. DNA samples from 111 individuals were evaluated. They were divided into two groups, "A" (study) and "B" (control), including 54 patients with liver enzyme alterations (ALT/AST) presenting non-B-non-C hepatitis and 57 blood donors, respectively. TTV DNA was determined by nested PCR. Certain products of the second-round PCR were sequenced. Serum biochemical assay was performed and disclosed TTV in 31.48% (17/54) of patients in group A and 5.26% (3/57) in the control group B. TTV prevalence was significantly higher in patients with liver disease than in healthy donors. In group A, sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were analyzed in certain randomly selected patients and no significant difference in biochemical levels (p>0.05) was found when TTV infected and noninfected individuals were compared. Knowledge related to TTV has rapidly increased, but many fundamental aspects remain unclear. This led us to question the role of TTV and doubt remains as to whether or not it is just a commensal virus. Further studies are necessary to confirm and extend these findings.

  5. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection.

    Science.gov (United States)

    Mitchell, Mack C; Memisoglu, Asli; Silverman, Bernard L

    2012-11-01

    Naltrexone (Revia, Vivitrol) is recognized as having the potential for hepatotoxicity. We evaluated the safety of intramuscular extended-release naltrexone (XR-NTX) in a cohort of patients with a high prevalence of chronic hepatitis C virus (HC V) and HIV infection undergoing treatment for opioid dependence. A total of 250 (88% male) opioid-dependent patients were randomized to receive monthly injections of XR-NTX 380 mg or placebo. Of the 250 subjects, 222 (88.8%) had a history of HCV; 42% were positive for HIV. Liver chemistry tests for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl aminotransferase (GGT), alkaline phosphatase, serum albumin, and total protein were obtained at the screening visit, at baseline, and monthly for up to 6 months. In a longitudinal analysis, the frequency of elevations in AST, ALT, and GGT greater than three times the upper limit of normal (ULN) was not statistically different in patients treated with XR-NTX compared with placebo (p = .71). Most of the elevations greater than three times the ULN occurred in patients with chronic HCV infection. In patients who had a treatment-emergent elevation in AST or ALT greater than three times the ULN, the aminotransferases improved and returned toward baseline in those patients with available follow-up data. No specific symptoms were associated with any of the elevations in ALT, AST, or GGT. The frequency of elevations in AST and ALT during treatment in patients with HIV infection was not significantly different compared with that in patients without HIV infection. XR-NTX can be used safely in eligible patients with opioid dependence, including those with underlying mild to moderate chronic HCV and/or HIV infections.

  6. Efeito da inclusão de fontes lipídicas na dieta de cabras em lactação sobre os parâmetros sanguíneos Effect of fat source inclusion in the diet of lactating goats on blood parameters

    Directory of Open Access Journals (Sweden)

    Guilherme de Lira Sobral Silva

    2010-02-01

    seed.The experiment was developed in four experimental periods of 14 days, with 10 days of adaptation to diets and four days for samples collection. In the last day of each period were collected blood samples. The inclusion of oleaginous seed into the lactating goats' diet decreased the dry matter consumption for metabolic unit (CMU and consumption of crude protein for metabolic unit (CPMU. No significant differences in serum urea, creatinine, GGT (gamma glutamyltransferase, calcium, phosphorus, magnesium or glucose values were noticed in any of the four treatments. The serum levels of albumin in the animals that received TF were higher (P<0.05 than the animals of the control group. This work suggests that the oleaginous sources can be used as fat supplementation of lactating Saanen goats; however, animals fed the TF showed a healthier metabolic profile due to the fat supplement.

  7. Diagnóstico diferencial de colestase neonatal: parâmetros clínicos e laboratoriais Differential diagnosis of neonatal cholestasis: clinical and laboratory parameters

    Directory of Open Access Journals (Sweden)

    Maria Angela Bellomo-Brandao

    2010-02-01

    the covariance analysis (ANCOVA. The determination of accuracy of the clinical and laboratory variables for differentiation of the groups was made using the analysis of the ROC curve. RESULTS: One hundred and sixty-eight patients were evaluated (group I = 54.8% and group II = 45.2%. In the patients with less than 60 days of life there was predominance of intra-hepatic causes, whereas, in those older than 60 days, there was predominance of extra-hepatic etiology (p < 0.001. Median birth weight was lower in group I (p = 0.003, as well as length at birth (p = 0.007. Median values of direct bilirubin were higher in group II (p = 0.006. Values of gamma-glutamyltransferase (GGT (10 times higher than the limit of normality presented sensitivity of 56.3%, specificity of 91.5%, and accuracy of 75.7% for the diagnosis of extra-hepatic cholestasis. CONCLUSION: In the present study, extra-hepatic NC presented greater weight and length at birth, fecal hypocholia/acholia, choluria, hepatomegaly, increase in GGT (10.8 times higher than the limit of normality, and a delay for investigation in the tertiary center.

  8. Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial.

    Science.gov (United States)

    Ishibashi, Shun; Arai, Hidenori; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Yamashita, Shizuya

    To overcome the concerns associated with the use of fibrates, pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor modulator, was developed. In a previous phase 2 trial, we showed excellent efficacy and safety of pemafibrate in patients with dyslipidemia. The objective of the study was to evaluate the efficacy and safety of pemafibrate over 24 weeks in adults with dyslipidemia in comparison with fenofibrate. In this multicenter, 24-week, double-blind, clinical study, 225 patients with high triglyceride (TG; ≥150 mg/dL [1.7 mmol/L] and <500 mg/dL [5.7 mmol/L]) and relatively low high-density lipoprotein cholesterol (<50 mg/dL [1.3 mmol/L] in men or 55 mg/dL [1.4 mmol/L] in women) levels were randomized to receive either pemafibrate at 0.2 or 0.4 mg/d or fenofibrate 106.6 mg/d. Pemafibrate 0.2, 0.4 mg/d and fenofibrate significantly reduced TG levels from baseline by -46.2%, -45.9%, and -39.7%, respectively. As compared with fenofibrate, the least squares mean differences (95% confidence intervals) in TG were -6.5% (-12.0, -1.1) and -6.2% (-11.6, -0.8) in pemafibrate 0.2 and 0.4 mg/d respectively, which showed the superiority of these doses of pemafibrate to 106.6 mg/d of fenofibrate. The incidence rates of adverse drug reactions in pemafibrate groups (2.7% and 6.8%) were significantly lower than that in the fenofibrate group (23.7%). Pemafibrate significantly decreased alanine aminotransferase and gamma-glutamyltransferase levels, whereas fenofibrate increased both of them. The increments of serum creatinine and cystatin C were smaller in pemafibrate than those in fenofibrate. Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  9. Gastrointestinal symptoms in children with acute neuroinfections

    Directory of Open Access Journals (Sweden)

    A.I. Markov

    2018-02-01

    Full Text Available Background. In cases of severe forms of infectious di­seases, in addition to local inflammation, secondary lesions of the gastrointestinal organs may occur. We aimed to study the semiotics and epidemiology of gastrointestinal symptoms in children with acute neuroinfection. Materials and methods. This observational, retrospective, case-control study. We analyzed cases of in-patient treatment of children aged 1 month to 18 years with acute neuroinfections (meningitis, encephalitis and encephalomyelopolyneuropathy. Results. The study included 117 patients with acute central nervous system infections. Clinical symptoms of gastrointestinal infection were observed in 83 (70.9 % children. Among revealed symptoms, disorders of intestinal moti­lity, such as constipation and diarrhea, were prevalent. Manifestations of hepatobiliary system dysfunction included increased transaminase level (alanine aminotransferase (ALT, alkaline phosphatase, gamma-glutamyltransferase (GGTF and/or ultrasound changes (enlargement, diffuse structural changes and were observed in 39.1 % of patients. Among the laboratory parameters, elevated ALT level was observed in 8.3 % of patients, bilirubin was elevated in only one child, alkaline phosphatase was above the age norm in 11.8 %, an increased GGTF above the age norm was observed in 31.3 % of patients. The level of intestinal fatty acid binding protein (I-FABP was elevated in 86.4 %, and L-type fatty acid binding protein (L-FABP — in all (100 % children. Clinical manifestations of gastrointestinal dysfunction (the presence of at least one of the gastrointestinal symptoms had an inverse relationship with the child’s age (rpb = –0.19, p = 0.033, correlated with staying in intensive care unit (odds ratio (OR = +5.25; 95% confidence interval (CI 1.62–16.97, artificial ventilation (OR = +4.5; 95% CI 1.00–21.69 and level of I-FABP (rpb = 0.34, p = 0.019. Conclusions. Among gastrointestinal symptoms in children with

  10. The effects of moderate ethanol consumption on the liver of the monkey, Macaca fascicularis.

    Science.gov (United States)

    Ivester, Priscilla; Shively, Carol A; Register, Thomas C; Grant, Kathleen A; Reboussin, David M; Cunningham, Carol C

    2003-11-01

    Although evidence has accumulated for the cardioprotective effects of moderate ethanol consumption, little is known about the effects on the liver of consuming the equivalent of two drinks per day. The objective of this study was to determine the effects of moderate ethanol administration on the hepatic content of enzymes involved in ethanol oxidation, on hepatic lipid accumulation, and on serum markers of liver function/damage in the monkey, Macaca fascicularis. Ovariectomized, adult monkeys were maintained for 34 months on an atherogenic diet containing cholesterol 1.21 mg/kJ. They were trained to drink ethanol plus vehicle at a dose of 0.5 g/kg body weight, which was administered 5 days a week for 2 years. Blood was collected for ethanol concentrations (1 hr after ethanol administration) and was also assayed for gamma-glutamyltransferase, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. Liver obtained at necropsy was analyzed for triglyceride and cholesterol contents and for alcohol dehydrogenase, cytochrome P450 2E1, and cytochrome P450 3A4 by Western blots. The blood ethanol concentrations measured 1 hr after ethanol administration were relatively constant over the 2-year dosing period. Hepatic levels of alcohol dehydrogenase and the cytochrome P450s were not significantly different between ethanol-consuming animals and control animals. Ethanol-associated increases in liver triglyceride were not significant due to high variability in hepatic lipid content in both the controls and ethanol consumers. However, covariance analyses using pretreatment concentrations of plasma cholesterol and apolipoprotein A-I suggested that the ethanol-related increase in hepatic free cholesterol was significant. Relative to controls, alcohol consumers had higher levels of serum ALT and a transient increase in ALP at 5 months. The observations made in this study on primates administered an atherogenic diet suggest that moderate ethanol ingestion has modest

  11. Desempenho e características bioquímicas de leitões submetidos a dietas com aditivos probióticos, prebióticos, simbióticos e antibióticos Performance and biochemical parameters of piglets and the use of alternative additives as antibiotic replacement

    Directory of Open Access Journals (Sweden)

    M.L. Névoa

    2013-04-01

    experiment, fifty blood samples, ten samples of each treatment, were taken, and after separation of the clot, the serum was frozen at -20°C. Subsequently we analyzed the serum levels of total protein, albumin, globulin, albumin/globulin, ALP, creatinine, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, cholesterol, urea, calcium, phosphorus and calcium/phosphorus ratio. No significant differences in biochemical parameters or in the performance of piglets submitted to different diets were found.

  12. Enzimas de função hepática na aflatoxicose aguda experimental em frangos de corte Hepatic enzimes function in experimental acute enzimes aflatoxicosis in broilers

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    Adriana Borsa

    1998-12-01

    Full Text Available Com o objetivo de avaliar a função hepática de aves experimentalmente intoxicadas por aflatoxina, com e sem uso de bentonita sódica, foram utilizados 40 (quarenta frangos de corte, machos, linhagem Ross, divididos em 4 (quatro grupos de 10 (dez. animais, sendo que cada grupo foi submetido a um tratamento: T1 - controle (ração sem aflatoxina ou bentonita, T2 - ração com 5ppm de aflatoxina, T3 - ração com 5ppm de aflatoxina e 0,5% de bentonita sódica e T4 - ração com 0,5% de bentonita sódica. Todos estes tratamentos foram aplicados do 1° ao 42 ° dia de vida das aves. Aos 21, 35 e 42 dias de idade, foram analisados os níveis séricos das enzimas aspartato aminotransferase (AST, alanina aminotransferase (ALT, lactato desidrogenase (LDH e gama glutamiltransferase (GGT, A análise da variância mostrou que houve interação entre os tratamentos e datas de colheita de material, para as seguintes variáveis: AST, LDH e GGT. Para estas, foi aplicado o teste de Tukey, comparando-se as médias de cada tratamento em cada data. Observou-se que as enzimas AST, ALT e GGT não apresentaram diferenças significativas entre tratamentos, porém, nos tratamentos l e 2, a AST apresentou um aumento linear (pThe aim ofthis study is to evaluate ïhe hepatic function of experimentally intoxicated broilers by aflatoxin with and without sodium bentonite. Forty Ross mole broilers, were used divided into 4 groups of 10 birds, and such groups have been submitted to the following treatments: T1- control (feed without aflatoxin or sodium bentonite, T2- feed containing 5ppm of aflatoxin, T3- feed containing 5ppm of aflatoxin and 0.5% of sodium bentonite and T4- feed containing 0.5% of sodium bentonite. Ali these treatments have been appiied from the l st to the 42nd day of lif e. On the days 21, 35 and 42, the serum leveis of the enzimes aspartate aminotransferase (AST, alanino aminotransferase (ALT, lactate dehydrogenase (LDH and gamma glutamiltransferase (GGT

  13. Keen are the eyes of the visitors, or are they? Glöggt er gests augað, eða hvað?

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    Þórhallur Guðlaugsson

    2011-06-01

    Full Text Available Image is a comprehensive concept and can have different meaning depending on circumstances. The first messages that a country transmits is often through the image it has as a tourist destination. That image can influence how outside parties see and evaluate the country in other areas and thereby affect the building of its image in general. The image of a destination also helps create desires and/or wants among tourists and can affect the destination´s attractiveness since tourists are more likely to choose destinations that are thought to have a more positive image. Image is a subjective concept and its measurement can therefore be difficult. At the same time a number of authors have been writing about the importance of measuring it. The main objective of this research is to study the image of Iceland in the eyes of foreign tourists and compare the findings to earlier research as well as the perception of Icelanders themselves. Questionnaires were used and the findings are presented with the aid of perceptual maps. The main findings are, that on the whole, the image of Iceland is thought to be strong and distinctive and in accordance with earlier research. Natural beauty and landscape are very strongly related to the image and in addition to being considered a safe and friendly place to visit it is thought possible to experience adventures. Both groups hold similar images of Iceland but there are some differences. In general the image is stronger among tourists than Icelanders themselves. In this respect it is necessary to realize that the sample among the Icelanders was a convenience sample since a large part of it was university students. It still is interesting how similar the findings are.Ímynd er yfirgripsmikið hugtak sem getur haft mismunandi merkingu eftir stað og stund. Fyrstu skilaboðin sem lönd senda frá sér eru oft í gegnum þá ímynd sem landið hefur sem ferðamannastaður. Sú ímynd getur haft áhrif á hvernig utanaðkomandi aðilar sjá og meta landið á öðrum sviðum og þannig haft áhrif á heildaruppbyggingu ímyndarinnar. Ímynd áfangastaða hjálpar einnig til við að skapa óskir og/eða langanir ferðamanna og getur haft áhrif á velgengi staðarins þar sem ferðamenn eru líklegri til þess að velja áfangastað sem talinn er hafa jákvæðari ímynd. Erfitt getur verið að mæla ímynd þar sem hún er huglæg en talsvert hefur þó verið skrifað um mikilvægi þess að hún sé mæld. Meginmarkmið þessarar rannsóknar er að rannsaka hver ímynd Íslands sé í augum erlendra ferðamanna og bera þá niðurstöðu saman við fyrri sambærilegar rannsóknir sem og skynjun Íslendinga sjálfra á henni. Lagðir voru fyrir spurningalistar og eru niðurstöðurnar settar fram með aðferðafræði vörukorta. Helstu niðurstöður eru þær að á heildina litið er ímynd Íslands talin vera sterk og skýr og í samræmi við þær rannsóknir sem borið er saman við. Náttúrufegurð og landslag eru mjög skýrt tengd við ímynd landsins og auk þess að vera talinn öruggur og vingjarnlegur staður eru þar taldir möguleikar á að lenda í ævintýrum. Ímyndin er á margan hátt svipuð hjá báðum hópum en í nokkrum atriðum er munur. Almennt er ímyndin sterkari meðal ferðamanna en Íslendinga sjálfra. Nauðsynlegt er þó að gera á þessu þann fyrirvara að úrtakið meðal Íslendinga er þægindaúrtak þar sem stór hluti svarenda eru háskólanemar. Það vekur eftir sem áður vissa athygli hve niðurstöður eru svipaðar.

  14. Prevention of Type 2 Diabetes by lifestyle intervention in an Australian primary health care setting: Greater Green Triangle (GGT Diabetes Prevention Project

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    Bunker Stephen

    2007-09-01

    Full Text Available Abstract Background Randomised controlled trials demonstrate a 60% reduction in type 2 diabetes incidence through lifestyle modification programmes. The aim of this study is to determine whether such programmes are feasible in primary health care. Methods An intervention study including 237 individuals 40–75 years of age with moderate or high risk of developing type 2 diabetes. A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006. Main outcome measures taken at baseline, three, and 12 months included weight, height, waist circumference, fasting plasma glucose and lipids, plasma glucose two hours after oral glucose challenge, blood pressure, measures of psychological distress and general health outcomes. To test differences between baseline and follow-up, paired t-tests and Wilcoxon rank sum tests were performed. Results At twelve months participants' mean weight reduced by 2.52 kg (95% confidence interval 1.85 to 3.19 and waist circumference by 4.17 cm (3.48 to 4.87. Mean fasting glucose reduced by 0.14 mmol/l (0.07 to 0.20, plasma glucose two hours after oral glucose challenge by 0.58 mmol/l (0.36 to 0.79, total cholesterol by 0.29 mmol/l (0.18 to 0.40, low density lipoprotein cholesterol by 0.25 mmol/l (0.16 to 0.34, triglycerides by 0.15 mmol/l (0.05 to 0.24 and diastolic blood pressure by 2.14 mmHg (0.94 to 3.33. Significant improvements were also found in most psychological measures. Conclusion This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care settings, with reductions in risk factors approaching those observed in clinical trials. Trial Number Current Controlled Trials ISRCTN38031372

  15. Liver enzyme and adipocytokine profiles are synergistically associated with insulin resistance: the J-SHIPP study.

    Science.gov (United States)

    Uetani, Eri; Tabara, Yasuharu; Igase, Michiya; Kido, Tomoko; Ochi, Namiko; Takita, Rie; Kohara, Katsuhiko; Miki, Tetsuro

    2012-01-01

    Alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) are associated with insulin resistance and arteriosclerotic disease. Since adiposity raises liver enzyme levels and causes insulin resistance, adipocytokines are thought to underlie the relationship between liver enzymes and insulin resistance. To clarify this hypothesis, we conducted a cross-sectional epidemiological study in a Japanese general population. The study subjects were 903 middle-aged to elderly persons. Plasma levels of adiponectin and leptin were measured, while other clinical parameters were obtained from personal health records of medical check-ups. Insulin resistance was assessed by a homeostasis model assessment index (HOMA-IR). Plasma levels of ALT (r=0.379, p<0.001), GGT (r=0.225, p<0.001), adiponectin (r= -0.346, p<0.001) and leptin (r=0.369, p<0.001) were significantly correlated with insulin resistance even on subgroup analysis by sex. Further, any combination of liver enzymes and adipocytokines was synergistically associated with insulin resistance (p<0.001) after adjustment for possible covariates (ALT*adiponectin: β=-0.098, p<0.001, ALT*leptin: β=0.129, p<0.001, GGT*adiponectin: β=-0.054, p=0.054, GGT*leptin: β=0.126, p<0.001); however, in simple obese subjects with normal adipocytokine levels, liver enzymes were not associated with insulin resistance (mean HOMA-IR: worsened adipocytokine +/visceral obesity +, 2.01±1.14; +/-, 1.39±0.84; -/+, 1.23± 0.55; -/-, 1.03±0.57; p<0.001). Plasma levels of ALT and GGT were independent determinants of insulin resistance only in subjects with a worsened adipocytokine profile. Use of liver enzyme levels as a marker of insulin resistance requires stratification by adipocytokine profile.

  16. The relationship between normocytic, hypochromic anaemia and iron concentration together with hepatic enzyme activities in cattle infected with Fasciola hepatica.

    Science.gov (United States)

    Lotfollahzadeh, S; Mohri, M; Bahadori, Sh Ranjbar; Dezfouly, M R Mokhber; Tajik, P

    2008-03-01

    Erythrograms determined from whole blood analyses and serum analyses for aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) activities, and iron concentration, were used in infected and uninfected cattle to determine the type of anaemia and degree of hepatic damage caused by Fasciola hepatica. Blood samples from 86 infected and 30 uninfected cattle were taken at slaughter. Haematological analyses revealed decreased levels of packed cell volume (PCV), haemoglobin concentration, mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) in infected compared with uninfected cattle (P hepatic and bile duct injuries associated with chronic infection with F. hepatica.

  17. A Case of Meropenem Induced Cholestasis

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    Büşra Canbaz, Özgür Kara, Güneş Arık

    2016-12-01

    Full Text Available Meropenem is a broad-spectrum carbapenem antibiotic used for complicated hospital infections. Mild aminotransferase elevations have been reported in meropenem recipients, but cholestasis is rare. A 70 year old man was admitted for infected diabetic foot ulcer. ALP and GGT levels started increasing one week after the initiation of meropenem, with normal ALT, AST and bilirubin levels. Meropenem induced intrahepatic cholestasis was suspected and meropenem was discontinued, followed by normalization of liver enzymes. Drug induced liver injury should be suspected in patients with unexplained liver enzyme elevations. J Microbiol Infect Dis 2016;6(4: 190-191

  18. Valores bioquímicos séricos em potros da raça puro sangue inglês suplementados com diferentes tipos de gordura

    OpenAIRE

    Dittrich,Rosângela Locatelli; Dittrich,João Ricardo; Flenung,José Sidney; Pereira,Laertes; Harder,Simone; Saito,Mere Erika; Schmidt,Elizabeth Moreira dos Santos; Silva,Simone Ferreira Couto

    2000-01-01

    Determinaram-se as concentrações de glicose, ureia, GGT (gama glutamil transferase), CK (creatino quinase), AST (aspartato aminotransferase) e LDH (lactato desidrogenase) em equinos alimentados com dietas normal e suplementadas com gorduras. As amostras de sangue foram obtidas após os exercícios físicos. O delineamento experimental utilizado foi um ensaio rotativo em quadrado latino 4x4. Os quatro tratamentos foram: Tl - dieta normal; T2 - dieta normal, com 10% de óleo de milho (gordura insat...

  19. The ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT): the correlation of value with underlying severity of alcoholic liver disease.

    Science.gov (United States)

    Gurung, R B; Purbe, B; Gyawali, P; Risal, P

    2013-01-01

    Alcoholic liver disease is one of the most frequently diagnosed liver problems in the hospitalized patients in most tertiary care hospitals all over the world .The diagnosis of alcoholic liver disease is most of the time clinical. The AST/ALT ratio is a useful and reliable biochemical marker of liver injury due to alcohol. Whether the value of AST/ALT ratio correlates with clinical severity has not been studied. To study values of AST/ALT ratio in correlation with clinical severity of illness due to alcoholic liver disease using Child-Pugh's grading. This is a retrospective study. Inpatient records of all the patients admitted with diagnosis of alcoholic liver disease from July 2009 to 2011 June were analyzed. Data from 174 patients with the diagnosis of alcoholic liver disease-alcoholic hepatitis or alcoholic cirrhosis were retrieved; out of 174 patients, 138 were eligible for the study. The AST/ALT ratio and Child's grading of all the patients were calculated from the documented biochemical and clinical parameters on admission. Demographic profiles of all the patients were also recorded and analyzed. The data was analyzed using software SPPSS 16 version. A total of 138 patients diagnosed as alcoholic liver disease since July 2009 to June 2011 were analyzed. The male-female ratio was found to be 5.34: 1.The mean age of the patients at diagnosis was found to be 47.58 ± 12.83 years. Among 138 patients, Mongolians were found to have the highest prevalence of alcoholic liver disease (38.8%), followed by Newars ( 33.6%), Brahmin and Chhetri (19.1%) and Dalit (7.2%). With respect to AST/ALT ratio and Child's grading of ALD, the mean AST/ALT ratio was found to be 3.03 ± 2.24 in those patients who had Chlild's grade C; likewise the mean AST/ALT ratio was 2.28 ± 1.14, and 1.68 ± 0.83 in patients with Child B and Child A respectively. The higher value of AST/ALT ratio is indicative of more severe liver damage due to alcohol.

  20. Valor preditivo de marcadores séricos de fibrose hepática em pacientes portadores de hepatite crônica viral C Predictive value of serum markers of hepatic fibrosis in patients with chronic hepatitis C

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    Leila Maria Soares Tojal de Barros Lima

    2008-06-01

    Full Text Available INTRODUÇÃO: Os marcadores séricos têm sido empregados na avaliação da fibrose hepática em pacientes portadores de hepatite crônica C (HCC. OBJETIVOS: Avaliar a capacidade do índice aspartato aminotransferase (AST/alanina aminotransferase (ALT, dos níveis séricos de gama-glutamiltransferase (GGT, contagem de plaquetas, do índice AST/plaquetas (APRI e do ácido hialurônico (AH em predizer a intensidade da fibrose hepática na HCC e a variação desses marcadores após tratamento com interferon. PACIENTES E MÉTODOS: Em 72 pacientes portadores de hepatite C determinamos no soro o índice AST/ALT, GGT, plaquetas, índice APRI (obtido pelo quociente AST/plaquetas e o AH, que foram comparados ao estadiamento histológico, segundo os critérios de METAVIR. Receberam tratamento com interferon e ribavirina 65 pacientes. Os indivíduos que concluíram o tratamento (n = 33 realizaram nova dosagem dos marcadores séricos de fibrose para comparar com os níveis pré-tratamento. RESULTADOS: Observamos que a GGT, a contagem de plaquetas, o índice APRI e o AH se correlacionaram com estádio de doença hepática (p INTRODUCTION: Serum markers have been used in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC. AIMS: We evaluated the capacity of aspartate aminotransferase (AST/alanine aminotransferase (ALT ratio, gama-glutamyltransferase (GGT levels, platelet count, the AST to platelet ratio index (APRI and serum hyaluronic acid (HA to predict the intensity of hepatic fibrosis in patients with CHC and the variation of these markers after therapy with interferon. PATIENTS AND METHODS: In 72 patients with hepatitis C, AST/ALT ratio, GGT levels, platelet count, the APRI index (calculated as the ratio of AST to platelets and serum HA concentration were determined and compared to histological staging according to the scoring system of METAVIR. Sixty-five patients received interferon and ribavirin therapy. The individuals that

  1. Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line.

    Science.gov (United States)

    Honma, Kazue; Kamikubo, Michiko; Mochizuki, Kazuki; Goda, Toshinao

    2017-06-01

    Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Effects of structural injure in the bile bacterial contamination after balloon transduodenal sphincteroplasty (papillary dilation in dogs Efeitos da lesão estrutural na contaminação bacteriana biliar após a esfincteroplastia transduodenal (dilatação papilar em cães

    Directory of Open Access Journals (Sweden)

    Martin Zavadinack Netto

    2006-10-01

    Full Text Available PURPOSE: To evaluate, in dogs, the biliary sphincter subjected to dilation by hydrostatic balloon by the point of view of structural alterations of the papilla and the biochemestry and bacterial contamination of the bile. METHODS: Twenty dogs were submitted to laparotomy, duodenotomy, and enlargement of the major duodenal papilla- GA(n=10 - with balloon of 8mm inflated with pressure of 0,5atm, during 2 minutes or to the sham procedure - GB(n=10. Blood samples collected on times t(0day, t(7days and t(28days were subjected to dosages of alkaline phosphatase (ALP and gamma-glutamyltransferase (GGT for cholestasis evaluation. The collected material from the gall bladder at the same times were registered and numbered to be submitted to culture in BHI, blood agar (rich, non-selective element and Mac Conkey (selective element for Gram-negative bacillus. On the 28th day three fragments of the papilla were tranversally cut by the choledoc axis 3mm from the duodenal papilla and the cuts, stained with hematoxylin-eosin and Masson's tricome, were evaluated according to their inflammatory reaction. RESULTS: The GGT and ALP averages on the three periods in the groups A and B did not show significant differences, not being characterizes the cholestasis. The bacterian contamination was significantly higher in GA (2,19 than in GB (1,96; the contamination was lower in the initial time compared with 7 and 28 days (t0OBJETIVO: Avaliar, em cães, a papila duodenal maior submetida à dilatação por balão hidrostático sob o ponto de vista das alterações estruturais da papila e da bioquímica e contaminação bacteriana da bile. MÉTODOS: Vinte cães foram submetidos a laparotomia, duodenotomia, dilatação da papila maior GA (n=10 - com balão de 8mm insuflado com pressão de 0,5atm, durante 2 minutos ou ao procedimento simulado - GB(n=10. Amostras de sangue coletadas nos tempos t(0dia, t(7dias e t(28dias foram submetidas às dosagens da fosfatase alcalina (FA e

  3. Effects of endurance and endurance-strength exercise on biochemical parameters of liver function in women with abdominal obesity.

    Science.gov (United States)

    Skrypnik, Damian; Ratajczak, Marzena; Karolkiewicz, Joanna; Mądry, Edyta; Pupek-Musialik, Danuta; Hansdorfer-Korzon, Rita; Walkowiak, Jarosław; Jakubowski, Hieronim; Bogdański, Paweł

    2016-05-01

    Obesity is a risk factor of nonalcoholic fatty liver disease. Although the standard therapy for obesity involves physical exercise, well-planned studies of the changes in liver function in response to different exercise intensities in obese subjects are scarce. The aim of the present study was to examine a question of how does exercise mode affect the liver function. 44 women with abdominal obesity were randomized into two exercise groups: endurance (group A) and endurance-strength (group B). Women in each group exercised for 60min 3 times/week for a 3-month period. Markers of liver function: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) activities, and bilirubin levels were quantified. We found significant differences in ALT (pexercise. Blood ALT and AST tended to decrease in group B, increase in group A. Significant reduction in serum GGT level after exercise in both groups was observed (pstrength exercise led to changes in serum ALP activity and total or direct bilirubin level. However, endurance-strength training resulted in significant decreases in serum indirect bilirubin (pstrength exercise (group B). The mode of exercise does matter: endurance-strength exercise led to a greater improvement, compared to endurance exercise, in the liver function in women with abdominal obesity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Changes in selected hematology and serum biochemistry in Turkish Angora cats (Felis catus during growth period

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    Ozkan Simsek

    2015-03-01

    Full Text Available The purpose of the present study was to determine the changes in selected hematology and serum biochemistry of Angora cats (Felis catus during growth period. A total of 32 Angora cats (16 adults and 16 kittens were used in this study. Blood samples were collected from the animals, and were analyzed for white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume (MCV, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, granulocytes, monocytes and lymphocytes numbers. In the serum, alanine aminotransferase, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma glutamyl transferase (GGT, lactate dehydrogenase (LDH, creatinine kinase (CK, total cholesterol, glucose, triglyceride, urea, creatinine, total protein, albumin, Ca, Mg, Pi levels were determined. Monocyte level was found higher, and ALP, LDH, CK activities and Pi levels were lower in adult cats as compared to the kittens. MCV was lower and GGT and AST activities, and glucose level were higher in kittens of 1.5-3 months old than in kittens of >3 months. Concentrations of total cholesterol and Mg were higher in kitten (1.5-3 months old than in adult cats. In conclusion, age related effects on hematological and biochemical blood parameters have been determined for the first time in Angora cats.

  5. A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.

    Science.gov (United States)

    Qin, Guangming; Lu, Lihong; Xiao, Yufei; Zhu, Yimiao; Pan, Wensheng; Xu, Xiang; Shen, Shengrong; Das, Undurti N

    2014-07-28

    The aim of this study was to investigate the possible correlation between levels of serum liver enzymes and impaired fasting glucose (IFG) in Chinese adults and to provide a new perspective for the prevention of pre-diabetes. Serum liver enzymes of the samples including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl transferase (GGT), as well as plasma glucose, blood lipids, and insulin, were measured. The cumulative incidences of IFG between different quartiles of liver enzymes were compared by the chi-square test. A logistic regression model (binary regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence interval (95% CI). The total incidence of IFG was 20.3% and the cumulative incidence of IFG was higher in men compared to women. In both sexes, IFG is more prevalent in higher quartiles of liver enzymes. After adjusting for age, BMI, blood pressure, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), the cumulative incidences of IFG were significantly higher in the highest quartiles of liver enzymes than in the lowest quartiles. A significantly higher cumulative incidence of IFG was found in the highest GGT quartile than in the lowest quartile for woman. The results of this study suggest that serum liver enzymes are related to the risk of IFG in Chinese adults. We infer that preserving the hepatic function may be an efficient way to prevent the development of IFG, especially in males.

  6. Routine testing of liver function before and after elective laparoscopic cholecystectomy: is it necessary?

    LENUS (Irish Health Repository)

    Ahmad, Nasir Zaheer

    2012-01-31

    BACKGROUND AND OBJECTIVES: Liver function tests (LFTs) include alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bilirubin. The role of routine testing before and after laparoscopic cholecystectomy was evaluated in this study. PATIENTS AND METHODS: A total of 355 patients were retrospectively analyzed by examining the LFTs the day before, the day after, and 3 weeks after the surgery. The Wilcoxon signed-rank test and Student t test were performed to determine statistical significance. RESULTS: Alterations in the serum AST, ALT, and GGT were seen on the first postoperative day. Minor changes were seen in bilirubin and ALP. An overall disturbance in the LFTs was seen in more than two-thirds of the cases. Repeat LFTs performed after 3 weeks on follow-up were found to be within normal limits. CONCLUSION: Mild-to-moderate elevation in preoperative LFTs may not be associated with any deleterious effect, and, in the absence of clinical indications, routine preoperative or postoperative liver function testing is unnecessary.

  7. L-lysine epsilon-aminotransferase involved in cephamycin C synthesis in Streptomyces lactamdurans.

    OpenAIRE

    Kern, B A; Hendlin, D; Inamine, E

    1980-01-01

    In Streptomyces lactamdurans, the precursor of the alpha-aminoadipoyl side-chain of cephamycin C is L-lysine. In this regard, streptomycetes differ strikingly from the fungi, which produce alpha-aminoadipic acid during the synthesis, rather than the breakdown, of L-lysine. Studies using a cell-free system showed that an aminoadipic acid. The product of this reaction was trapped and subsequently purified by ion-exchange chromatography. Thin-layer chromatography, spectrophotometry, and amino ac...

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

    Directory of Open Access Journals (Sweden)

    Solomon Chih-Cheng Chen

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    is associated with noncovalently bound pyridoxamine 5'-phosphate. NaBH4 reduction proved that the absorbance at 418 nm is from pyridoxal 5'-phosphate cofactor bound by a Schiff base to the protein. When the native, colorless, and yellow enzymes were subjected to electrospray ionization mass spectrometry, the B6...... of the protein are obtained by treatment with 4,5-dioxovalerate, 4,5-diaminovalerate, and acetylenic GABA, respectively. Compared to the native enzyme, the 418 nm absorption maximum in the yellow enzyme is enhanced and the 338 nm maximum reduced while the colorless enzyme has a heightened maximum at 338 nm...... cofactor dissociated from the protein and gave a molecular weight of 46,401-46,418. Acetylenic GABA and NaBH4 were used for protein modification, and they reacted with the native and yellow enzymes but had no effect on the colorless enzyme. Pyridoxal 5'-phosphate bound covalently to the protein after NaBH4...

  10. Relationship Between HCV RNA and Serum Alanine Aminotransferase and HCV Genotype Distribution

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    Dilara Yildirim

    2014-03-01

    Full Text Available Aim: Hepatitis C virus (HCV infections is an important health problem all over the world because of inveteracy ratio and causing hepatic failure, cirrhosis and hepatocellular carcinoma. Our aim in this study is to research HCV RNA in the patients detected anti-HCV positivity with enzyme immunoassay (ELISA and to analysis the association of HCV RNA in the serum of patients with alanine aminoransferase (ALT levels and HCV genotypes. Material and Method: In anti-HCV positive patients came from various departments to our laboratory HCV RNA level and genotyping were researched with quantitive real time polimerase chain reaction (PCR Montania 483 (Anatolia Geneworks HCV, Turkey and anti-HCV tests were studied with ELISA (Advia Centaur XP, Germany, ALT results were analysed retrospectively (Olympus AU2700. Results: In 123 of Anti HCV positive 338 serum (%37 were detected HCV RNA positivity. In the patients who have ALT level more than 40 (%77.6, HCV RNA is positive. Relationship between HCVRNA positive patients and the patients who have ALT level more than 40 is meaningful. (p

  11. Characterisation of Potential Antimicrobial Targets in Bacillus spp. I. Aminotransferases and Methionine Regeneration in Bacillus subtilis

    Science.gov (United States)

    2002-07-01

    m6thionine A partir de kdtomdthiobutyrate, en utilisant les aminoacides aromatiques et de chaine ramifi6e. Le produit g6nmtique ybgE 6tait le plus actif de...Ia ph6nylalanine et Ia tyrosine comme donneurs amines. Par consequent, deux transaminases aminoacides putatives de chaine ramifi~e ont 6t6 identifi...canaline against B. subtilis in nutrient broth is possibly due to antagonism by exogenous Met or binding of canaline to exogenous protein. Experiments are

  12. Isolation, characterization, and expression analyses of tryptophan aminotransferase genes in a maize dek18 mutant

    Science.gov (United States)

    The dek18 mutant of maize has decreased auxin content in kernels. Molecular and functional characterization of this mutant line offers the possibility to better understand auxin biology in maize seed development. Seeds of the dek18 mutants are smaller compared to wild type seeds and the vegetative d...

  13. Reference values for alanine and aspartate aminotransferase (ALT and AST) optimized by addition of pyridoxal phosphate.

    Science.gov (United States)

    Plebani, M; Bonvicini, P; De Besi, T; Giordano, A; Pesarin, F; Ceriotti, G

    1980-01-01

    The increases of the activity of aspartate and alanine transaminases observed in sera of healthy male and female subjects by addition of pyridoxal phosphate have been determined. The reference values of the activated reactions, distinguished by sex and age classes, are presented.

  14. Identification of Bilophila wadsworthia by specific PCR which targets the taurine:pyruvate aminotransferase

    NARCIS (Netherlands)

    Laue, H.; Smits, T.H.M.; Schumacher, U.K.; Claros, M.C.; Hartemink, R.; Cook, A.M.

    2006-01-01

    The bile-resistant, strictly anaerobic bacterium Bilophila wadsworthia is found in human faecal flora, in human infections and in environmental samples. A specific PCR primer set for the gene encoding the first metabolic enzyme in the degradative pathway for taurine in B. wadsworthia,

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

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    Claudio Puoti

    2013-04-01

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

  16. Application of microfluidics for the development of intensified aminotransferase (ATA) processes

    DEFF Research Database (Denmark)

    Heintz, Søren

    to the separation steps will greatly influence the economic viability due to the constraints placed on the required process metrics. This thesis will therefore emphasise product recovery limitations and requirements in combination with the biocatalyst performance and limitations. Here the focus is mainly related......Development of biocatalytic processes is greatly dominated by well-established batch process based screening technologies, e.g. glass vials (mL) and microtiter plates (μL). However, there is still a need for improvement of currently available technologies and for new technologies enabling...... relatively easy screening and characterization of different process options. For example, small-scale microfluidic platforms enable testing of complex process options, by combining multiple process steps in a plug-and-play manner, that are difficult to assess with conventional methods. Early...

  17. Physical Activity Is Prospectively Associated With Adolescent Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Anderson, Emma L; Fraser, Abigail; Howe, Laura D; Callaway, Mark P; Sattar, Naveed; Day, Chris; Tilling, Kate; Lawlor, Debbie A

    2016-01-01

    The aim of the present study was to assess whether objectively measured physical activity at mean ages 12 and 14 years are prospectively associated with ultrasound scan liver fat and stiffness (alanine aminotransferase, aspartate aminotransferase [AST], and γ-glutamyl transferase [GGT]) assessed at mean age 17.8 years. Participants were from the Avon Longitudinal Study of Parents and Children. Total physical activity (counts per minute) and minutes of moderate to vigorous physical activity (MVPA) were measured using ActiGraph accelerometers at mean ages 12 and 14 years. Greater total physical activity and MVPA at ages 12 and 14 years were associated with lower odds of liver fat and lower GGT levels at mean age 17.8 years, such as per 15-minute increase in daily MVPA at age 12 years, the confounder adjusted odds ratio of liver fat was 0.47 (95% confidence interval [CI] 0.27-0.84). Associations attenuated after additional adjustment for fat mass as a potential confounder (eg, per 15-minute increase in daily MVPA at age 12 years, the odds ratio of liver fat attenuated to 0.65 [95% CI 0.35-1.21]) or a potential mediator (eg, per 15-minute increase in daily MVPA at age 12 years the odds ratio of liver fat attenuated to 0.59 [95% CI 0.32-1.09]). Results did not further attenuate after additional adjustment for insulin resistance. There was some evidence that greater total physical activity and MVPA at age 12 years were associated with the higher AST levels. Adolescents who were more active in childhood have lower odds of fatty liver and lower GGT levels. These findings are likely to be, at least in part, explained by adiposity.

  18. Activity of liver enzymes in multiple sclerosis patients with Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention.

    Science.gov (United States)

    Rezapour-Firouzi, Soheila; Arefhosseini, Seyed Rafie; Ebrahimi-Mamaghani, Mehrangiz; Baradaran, Behzad; Sadeghihokmabad, Elyar; Torbati, Mohammadali; Mostafaei, Somaiyeh; Chehreh, Mahtaj; Zamani, Fatemeh

    2014-12-01

    It is unknown whether diets with a high dietary total antioxidant capacity (TAC) can modify oxidative stress, low-grade inflammation, or liver dysfunction, all of which are risk factors for multiple sclerosis disease. This study assesses alanine amino-transferase (ALT), aspartate-aminotransferase (AST) and gamma-glutamyl transferase (GGT) activities in MS patients treated with co-supplemented hemp seed and evening primrose oils as well as Hot-nature diet and the therapeutic potential this intervention. In this double blind, randomized trial, 100 MS patients with EDSShemp seed and evening primrose oils with advised Hot-nature diet; "group B",who received olive oil; and "group C", who received the co-supplemented oils. Clinically, EDSS as well as serum level of liver enzymes (GGT, AST, and ALT) were assessed at baseline and after 6 months. Mean follow-up was 180±2.9 SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration of 6.80±4.33 years). There was no significant difference in the study parameters at baseline. Serum levels of liver enzymes (GGT, AST, and ALT) were serially monitored. Intervention was associated with liver function alteration in three groups. Significance decreased in EDSS score and the levels of liver enzymes were found in groups A and C, whereas elevated serum liver enzymes and EDSS score were observed in group B after the intervention. Selecting foods according to their Total antioxidant capacity such as co-supplemented hemp seed and evening primrose oils with Hot-nature diet affects antioxidant intake and can have beneficial effects on improving EDSS score and activity of liver enzymes in RRMS patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Haematinic deficiency and macrocytosis in middle-aged and older adults.

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    Therese McNamee

    Full Text Available OBJECTIVE: To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron and macrocytosis in blood from a national population-based study of middle-aged and older adults. METHODS: A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007. Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR, B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH, liver function, aminotransferase (AST and gamma-glutamyl transferase (GGT. RESULTS: The overall prevalence (95% C.I. of anaemia (Hb 21 nmol/ml only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (99fl was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF for macrocytosis associated with elevated GGT (25.0% and smoking (24.6% was higher than for excess alcohol intake (6.3%, folate deficiency (10.5% or vitamin B12 (3.4%. CONCLUSIONS: Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.

  20. Perfil bioquímico de algumas enzimas no plasma sangüíneo de potras da raça Brasileiro de Hipismo (BH criadas em Colina, Estado de São Paulo

    Directory of Open Access Journals (Sweden)

    Fernando José Benesi

    2009-08-01

    Full Text Available Com o propósito de avaliar o perfil bioquímico de algumas enzimas, em potras sadias da raça BH (Brasileiro de Hipismo, utilizaram-se 380 amostras de plasma sangüíneo colhidas de 19 animais desde o nascimento até 24 meses de vida. Na análise dos resultados evidenciou-se que os valores médios das enzimas FA (fosfatase alcalina e CK (creatina quinase foram máximos entre o nascimento e 24 horas de vida (FA-1995.50 UI/ ; CK-189.13UI/L, enquanto que para a LD (lactato desidrogenase e GGT (gama glutamiltransferase as maiores magnitudes ocorreram, respectivamente, entre 3 e 4 dias (LD-479.11UI/L e aos 10 dias de idade (GGT-18.70UI/L. As FA, CK, LD e GGT, mostraram diminuições dos valores médios, respectivamente, até 6 meses (FA-323.50UI/L, 20 dias (CK-51UI/ L, 19 meses (LD-214.00UI/L e 4 meses (GGT-11.40UI/L estabilizando-se a seguir, com pequenas variações. A atividade da AST (aspartato aminotransferase que foi mínima logo após o nascimento (AST- 43.38UI/L, aumentou até os sete dias de vida (AST-110.89UI/L, e a seguir diminuiu progressivamente, com pequenas oscilações, até o final do estudo. Todas as enzimas avaliadas sofreram variações influenciadas pelo fator etário, particularmente no período inicial de vida dos animais estudados.

  1. Liver steatosis (LS) evaluated through chemical-shift magnetic resonance imaging liver enzymes in morbid obesity; effect of weight loss obtained with intragastric balloon gastric banding.

    Science.gov (United States)

    Folini, Laura; Veronelli, Annamaria; Benetti, Alberto; Pozzato, Carlo; Cappelletti, Marco; Masci, Enzo; Micheletto, Giancarlo; Pontiroli, Antonio E

    2014-01-01

    The aim of this study was to evaluate in morbid obesity clinical and metabolic effects related to weight loss on liver steatosis (LS), measured through chemical-shift magnetic resonance imaging (MRI) and liver enzymes. Forty obese subjects (8 M/32 W; BMI 42.8 ± 7.12 kg/m(2), mean ± SD) were evaluated for LS through ultrasound (US-LS), chemical-shift MRI (MRI-LS), liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP)], anthropometric parameters [weight, BMI, waist circumference (WC)], lipids, insulin, insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), oral glucose tolerance test, and body composition [fat mass (FM) and fat-free mass (FFM) at bio-impedance analysis (BIA)]. Anthropometric measures, MRI-LS, BIA, and biochemical parameters were reevaluated 6 months later in 18 subjects undergoing restrictive bariatric approach, i.e., intragastric balloon (BIB, n = 13) or gastric banding (LAGB, n = 5), and in 13 subjects receiving hypocaloric diet. At baseline, US-LS correlates only with MRI-LS, and the latter correlates with ALT, AST, and GGT. After 6 months, subjects undergoing BIB or LAGB had significant changes of BMI, weight, WC, ALT, AST, GGT, ALP, HbA1c, insulin, HOMA-IR, FM, FFM, and MRI-LS. Diet-treated obese subjects had no significant change of any parameter under study; change of BMI, fat mass, and fat-free mass was significantly greater in LAGB/BIB subjects than in diet-treated subjects. Change of MRI-LS showed a significant correlation with changes in weight, BMI, WC, GGT, ALP, and basal MRI-LS. Significant weight loss after BIB or LAGB is associated with decrease in chemical-shift MRI-LS and with reduction in liver enzymes; chemical-shift MRI and liver enzymes allow monitoring of LS in follow-up studies.

  2. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests

    Energy Technology Data Exchange (ETDEWEB)

    Kukuk, Guido M.; Schaefer, Stephanie G.; Hadizadeh, Dariusch R.; Schild, Hans H.; Willinek, Winfried A. [University of Bonn, Department of Radiology, Bonn (Germany); Fimmers, Rolf [University of Bonn, Department of Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Ezziddin, Samer [Department of Nuclear Medicine, Bonn (Germany); Spengler, Ulrich [Department of Internal Medicine I, Bonn (Germany)

    2014-10-15

    To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. (orig.)

  3. Valores bioquímicos séricos em potros da raça puro sangue inglês suplementados com diferentes tipos de gordura Serum biochemical in thoroughbred horses supplemented with fat

    Directory of Open Access Journals (Sweden)

    Rosângela Locatelli Dittrich

    2000-08-01

    Full Text Available Determinaram-se as concentrações de glicose, ureia, GGT (gama glutamil transferase, CK (creatino quinase, AST (aspartato aminotransferase e LDH (lactato desidrogenase em equinos alimentados com dietas normal e suplementadas com gorduras. As amostras de sangue foram obtidas após os exercícios físicos. O delineamento experimental utilizado foi um ensaio rotativo em quadrado latino 4x4. Os quatro tratamentos foram: Tl - dieta normal; T2 - dieta normal, com 10% de óleo de milho (gordura insaturada; T3 - dieta normal, com 10% de gordura de coco (gordura saturada; T4 - dieta normal, com 5% de óleo de milho e 5% de gordura de coco. Os resultados encontrados para glicose, ureia e GGT não apresentaram diferenças significativas entre as dietas. Os resultados para a AST e LDH foram maiores nos equinos alimentados com dietas sem gordura, e os valores da CK, em UI/L. foram de 118,01 (Tl; 84,24 (T2; 60,37 (T3 e 76,28 (T4, sendo significativamente menores (PThis experiment determined lhe concentrations of blood glucose, urea, GGT (gama glutamyltransferase, creatine kinase (CK, aspartate aminotransferase (AST and lactate dehydrogenase (LDH in horses after the exercises, with normal diet and additional dietary fat. It was used the 4x4 Latin square design. The four diets were Tl-normal diet; T2-normal diet with 10% com oil; T3-nonnal diet with 10% coconut oil; T4-nonnal diet with 5% com oil and 5% coconut oil. There were no signifi cam changes in glucose, urea and GGT leveis due to diet. The serum concentrations of AST and LDH were higher in horses fed a diet withoutfat, and the resultsfound to CK (Ul/L were 118.01 (Tl; 84.24 (T2; 60.37 (T3 and 76.28 (T4. Serum leveis ofCK were significantiy smaller (P<0.05 in horses suppiemented with saturated fat, suggesting a smaller damage to the muscle fibers after the exercises.

  4. Hemograma, proteinograma, ionograma e dosagens bioquímicas e enzimáticas de ovinos acometidos por conidiobolomicose no nordeste do Brasil Hematology and blood biochemistry in sheep with conidiobolomycosis in northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Maria do Carmo de S. Batista

    2009-01-01

    Full Text Available Foram realizados eritrogramas, leucogramas, dosagens séricas de proteínas totais, albumina, globulinas, cálcio, fósforo, magnésio, cloretos, uréia, creatinina, bilirrubina total, direta e indireta e atividade sérica de aspartato aminotransferase (AST, fosfatase alcalina (FA e gama-glutamiltransferase (GGT de 56 ovinos afetados por conidiobolomicose e de 371 ovinos sadios provenientes dos mesmos rebanhos dos casos da doença. Os resultados revelaram que os ovinos com conidiobolomicose apresentam anemia arregenerativa normocítica normocrômica, leucocitose com neutrofilia e discreto desvio à esquerda regenerativo, com elevação da relação neutrófilo:linfócito, monocitose moderada, trombocitose, hipoproteinemia (hipoglobulinemia, hipomagnesemia, hipocalcemia e elevação dos teores de fósforo. As atividades séricas de AST e GGT estavam aumentadas e as de FA diminuídas. Não houve alteração nos níveis de uréia e creatinina, mas ocorreu hipoglicemia e hiperbilirrubinemia. Estes resultados podem ser utilizados para estudos experimentais da doença, em ensaios com tratamentos e para identificar casos precoces da enfermidade que não apresentem sinais clínicos. Além disso, os valores encontrados em 371 ovinos deslanados hígidos podem ser utilizados como valores referenciais para este tipo de ovinos na região semi-árida do Brasil.Hematologic values, serum levels of albumin, globulins, total proteins, calcium, phosphorus, magnesium, chloride, urea nitrogen, creatinine, total, direct and indirect bilirrubin, and serum activities of aspartate aminotransferase (AST, alkalin phosphatase (AF and gama-glutamyltransferase (GGT were determined in 56 hair sheep with conidiobolomycosis and 371 healthy hair sheep from the same flocks. Sheep with conidiobolomycosis had nonregenerative, normocytic and normochromic anemia, leucocytosis with neutrophilia and increased nutrophil:lymphocyte rate, moderate monocytosis, moderate thrombocytosis

  5. Systematic review and meta-analysis: bezafibrate in patients with primary biliary cirrhosis

    Directory of Open Access Journals (Sweden)

    Yin Q

    2015-09-01

    Full Text Available Qin Yin,1,2,* Jingjing Li,3,* Yujing Xia,3 Rong Zhang,3,4 Jianrong Wang,3,4 Wenxia Lu,3,4 Yuqing Zhou,1,2 Yuanyuan Zheng,3 Huerxidan Abudumijiti,3 Rongxia Chen,3 Kan Chen,3 Sainan Li,3 Tong Liu,3 Fan Wang,3 Jie Lu,3 Yingqun Zhou,3 Chuanyong Guo3 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 2The First Affiliated Hospital of Soochow University, Suzhou, 3Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 4The First Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work and should be considered co-first authors Background and aim: Ursodeoxycholic acid (UDCA is the standard treatment for primary biliary cirrhosis (PBC, but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC.Results: Nine trials, with a total of 269 patients, were included in the analysis. The bias risk of these trials was high. Compared with UDCA alone, the combination with bezafibrate improved the Mayo risk score (mean difference [MD], 0.60; 95% confidence interval [CI], 0.25–0.95; P=0.0008 and liver biochemistry: alkaline phosphatase (MD, -238.21 IU/L; 95% CI, -280.83 to -195.60; P<0.00001; gamma-glutamyltransferase (MD, -38.23 IU/L; 95% CI, -50.16 to -25.85; P<0.00001; immunoglobulin M (MD, -128.63 IU/L; 95% CI, -151.55 to -105.71; P<0.00001; bilirubin (MD, -0.20 mg/dL; 95% CI, -0.33 to -0.07; P=0.002; triglycerides (MD, -26.84 mg/dL; 95% CI, -36.51 to -17.17; P<0.0001; total cholesterol (MD, -21.58 mg/dL; 95% CI, -30.81 to -12.34; P<0.0001, and serum alanine aminotransferase (MD, -10.24 IU/L; 95% CI, -12.65 to -78.5; P<0.00001. However

  6. The Impact of 10 weeks of Aerobic Exercise and Supplementation of Green Tea on Lipid Profile, Insulin Resistance and Liver Enzymes (GGT, ALT, AST in Obese Diabetic Women (type 2

    Directory of Open Access Journals (Sweden)

    M Izadi Ghahfarokhi

    2015-05-01

    Conclusions: Green tea supplements with aerobic training were effective in controlling obesity and type 2 diabetes. By increasing the duration of the exercise and supplementation, it may find desirable results on serum cholesterol and triglycerides.

  7. Serum calcium levels are associated with novel cardiometabolic risk factors in the population-based CoLaus study.

    Directory of Open Access Journals (Sweden)

    Idris Guessous

    Full Text Available BACKGROUND: Associations of serum calcium levels with the metabolic syndrome and other novel cardio-metabolic risk factors not classically included in the metabolic syndrome, such as those involved in oxidative stress, are largely unexplored. We analyzed the association of albumin-corrected serum calcium levels with conventional and non-conventional cardio-metabolic risk factors in a general adult population. METHODOLOGY/PRINCIPAL FINDINGS: The CoLaus study is a population-based study including Caucasians from Lausanne, Switzerland. The metabolic syndrome was defined using the Adult Treatment Panel III criteria. Non-conventional cardio-metabolic risk factors considered included: fat mass, leptin, LDL particle size, apolipoprotein B, fasting insulin, adiponectin, ultrasensitive CRP, serum uric acid, homocysteine, and gamma-glutamyltransferase. We used adjusted standardized multivariable regression to compare the association of each cardio-metabolic risk factor with albumin-corrected serum calcium. We assessed associations of albumin-corrected serum calcium with the cumulative number of non-conventional cardio-metabolic risk factors. We analyzed 4,231 subjects aged 35 to 75 years. Corrected serum calcium increased with both the number of the metabolic syndrome components and the number of non-conventional cardio-metabolic risk factors, independently of the metabolic syndrome and BMI. Among conventional and non-conventional cardio-metabolic risk factors, the strongest positive associations were found for factors related to oxidative stress (uric acid, homocysteine and gamma-glutamyltransferase. Adiponectin had the strongest negative association with corrected serum calcium. CONCLUSIONS/SIGNIFICANCE: Serum calcium was associated with the metabolic syndrome and with non-conventional cardio-metabolic risk factors independently of the metabolic syndrome. Associations with uric acid, homocysteine and gamma-glutamyltransferase were the strongest. These

  8. Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk-driving among previously convicted drunk-driving offenders: results from the recidivism of alcohol-impaired driving (ROAD) study.

    Science.gov (United States)

    Maenhout, Thomas M; Poll, Anneleen; Vermassen, Tijl; De Buyzere, Marc L; Delanghe, Joris R

    2014-01-01

    In several European countries, drivers under the influence (DUI), suspected of chronic alcohol abuse are referred for medical and psychological examination. This study (the ROAD study, or Recidivism Of Alcohol-impaired Driving) investigated the usefulness of indirect alcohol biomarkers for predicting drunk-driving recidivism in previously convicted drunk-driving offenders. The ROAD study is a prospective study (2009-13) that was performed on 517 randomly selected drivers in Belgium. They were convicted for drunk-driving for which their licence was confiscated. The initial post-arrest blood samples were collected and analysed for percentage carbohydrate-deficient transferrin (%CDT), transaminsase activities [alanine amino transferase (ALT), aspartate amino transferase (AST)], gamma-glutamyltransferase (γGT) and red cell mean corpuscular volume (MCV). The observation time for each driver was 3 years and dynamic. A logistic regression analysis revealed that ln(%CDT) (P drunk-driving. The ROAD index (which includes ln(%CDT), ln(γGT), -ln(ALT) and the sex of the driver) was calculated and had a significantly higher area under the receiver operator characteristic curve (0.71) than the individual biomarkers for drunk-driving recidivism. Drivers with a high risk of recidivating (ROAD index ≥ 25%; third tertile) could be distinguished from drivers with an intermediate risk (16% ≤ ROAD index drunk-driving. The association with gamma-glutamyltransferase, alanine amino transferase and the sex of the driver could have additional value for identifying drunk-drivers at intermediate risk of recidivism. Non-specific indirect alcohol markers, such as alanine amino transferase, gamma-glutamyltransferase, aspartate amino transferase and red cell mean corpuscular volume have minimal added value to % carbohydrate-deficient transferrin for distinguishing drunk drivers with a low or high risk of recidivism. © 2013 Society for the Study of Addiction.

  9. Serum albumin level is a notable profiling factor for non-B, non-C hepatitis virus-related hepatocellular carcinoma: A data-mining analysis.

    Science.gov (United States)

    Yamada, Shingo; Kawaguchi, Atsushi; Kawaguchi, Takumi; Fukushima, Nobuyoshi; Kuromatsu, Ryoko; Sumie, Shuji; Takata, Akio; Nakano, Masahito; Satani, Manabu; Tonan, Tatsuyuki; Fujimoto, Kiminori; Shima, Hiroji; Kakuma, Tatsuyuki; Torimura, Takuji; Charlton, Michael R; Sata, Michio

    2014-08-01

    Various factors are underlying for the onset of non-B, non-C hepatitis virus-related hepatocellular carcinoma (NBNC-HCC). We aimed to investigate the independent risk factors and profiles associated with NBNC-HCC using a data-mining technique. We conducted a case-control study and enrolled 223 NBNC-HCC patients and 669 controls from a health checkup database (n = 176 886). Multivariate analysis, random forest analysis and a decision-tree algorithm were employed to examine the independent risk factors, factors distinguishing between the case and control groups, and to identify profiles for the incidence of NBNC-HCC, respectively. In multivariate analysis, besides γ-glutamyltransferase (GGT) levels and the Brinkman index, albumin level was an independent negative risk factor for the incidence of NBNC-HCC (odds ratio = 0.67; 95% confidence interval = 0.60-0.70; P decision-tree algorithm was created for albumin and GGT levels, the aspartate aminotransferase-to-platelet ratio index (APRI) and the Brinkman index. The serum albumin level was selected as the initial split variable, and 82.5% of the subjects with albumin levels of less than 4.01 g/dL were found to have NBNC-HCC. Data-mining analysis revealed that serum albumin level is an independent risk factor and the most distinguishable factor associated with the incidence of NBNC-HCC. Furthermore, we created an NBNC-HCC profile consisting of albumin and GGT levels, the APRI and the Brinkman index. This profile could be used in the screening strategy for NBNC-HCC. © 2013 The Japan Society of Hepatology.

  10. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study.

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    Jang, Eun Sun; Jeong, Sook-Hyang; Hwang, Sung Ho; Kim, Hyun Young; Ahn, So Yeon; Lee, Jaebong; Lee, Sang Hyub; Park, Young Soo; Hwang, Jin Hyeok; Kim, Jin-Wook; Kim, Nayoung; Lee, Dong Ho

    2012-10-18

    Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

  11. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study

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    Jang Eun

    2012-10-01

    Full Text Available Abstract Background Liver function tests (LFTs can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. Methods We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Results Coffee consumption was closely related to male gender, high body mass index (BMI, alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST. On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Conclusions Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

  12. DINÂMICA PRÉ E PÓS-COLOSTRAL DE PARÂMETROS BIOQUÍMICOS EM CORDEIROS

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    Damaris Ferreira de Souza

    2014-09-01

    Full Text Available This study aimed to verify the influence of colostrum in serum biochemical parameters in newborn lambs. Blood samples were taken of 28 lambs, determining the protein, energy and kidney function indicators, bilirrubins and the enzymes aspartate aminotransferase (AST, gammaglutamyl transferase (GGT and creatine kinase (CK, in pre and post-colostrum moments. The data were analyzed comparing the variability of the parameters between the two moments. There was an elevation (P<0.001 in total protein concentrations, in response to substantial increase (P<0.01 in total globulin levels, and a slight decrease (P<0.05 in albumin concentration, after colostral intake. We also observed higher values of total and conjugated bilirubins (P<0.001, and variation of kidney metabolites, with an elevation of urea levels (P<0.01 concomitant to decrease of creatinine values (P<0.001 in the postcolostrum moment. There was an increase (P<0.001 in glycemia, total cholesterol and triglycerides, as well as of the enzymatic activities (P<0.001 of AST and GGT, between the moments evaluated. In conclusion, the dynamics of biochemical profile in newborn lambs suffers the effect of colostrum intake and of adaptations of physiological functions to extrauterine life. The parameters values vary markedly in the postnatal period, being recommended to use proper reference values for this phase.

  13. INCREASE OF GLYCOSAMINOGLYCANS AND METALLOPROTEINASES 2 AND 9 IN LIVER EXTRACELLULAR MATRIX ON EARLY STAGES OF EXTRAHEPATIC CHOLESTASIS

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    Pedro Luiz Rodrigues GUEDES

    2014-12-01

    Full Text Available Context Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Objective Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs activities. Methods Animals (6-8 weeks; n = 40 were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT, alkaline phosphatase (Alk-P, alanine and aspartate aminotransferases (ALT and AST, tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Results Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7 (P = 0.0064 and 14 (P = 0.0002 groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667, MMP-2 (P = 0.0003 and MMP-9 (P<0.0001 activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. Conclusions Cholestasis led to many changes on rats’ liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content.

  14. Evaluation of biochemical alterations produced by combined exposure of fenvalerate and nitrate in Bubalus bubalis

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    Kamalpreet Kaur Gill

    2014-03-01

    Full Text Available Aim: Evaluation of combined effect of fenvalerate and nitrate on biochemical parameters in buffalo calves. Materials and Methods: Sixteen male buffalo calves were divided into four groups of four calves each. Group I receiving no treatment served as the control. Group II and III animals were orally administered with fenvalerate (1.0 mg/kg/day and sodium nitrate (20 mg/kg/day, respectively, for 21 consecutive days and were kept as positive control. Group IV animals were co-administered with fenvalerate and sodium nitrate at the above dose rates for 21 consecutive days. Biochemical parameters including Aspartate aminotransferase (AST, Alkaline phosphatase (ALP, Gamma-glutamyl transpeptidase (GGT, Lactate dehydrogenase (LDH, Glucose, Total protein, Albumin, Cholesterol, Blood urea nitrogen (BUN and Creatinine were determined on 0, 3, 7, 10, 14, 17 and 21 day of treatment. Estimation of these parameters was also done on 7th day of post-treatment period. Results: Co-administration of fenvalerate and sodium nitrate produced significant increase in the plasma levels of AST, ALP, GGT, LDH, glucose, BUN, cholesterol and creatinine while significant decrease in the plasma levels of total proteins was observed. No significant alteration was observed in albumin levels. Extent of organ damage as evidenced by biochemical alterations was more pronounced in calves exposed to combination of fenvalerate and sodium nitrate as compared to their individual exposures. Conclusion: Fenvalerate and sodium nitrate co-administration potentiates the toxicological injury produced, in comparison to their individual exposure.

  15. Liver function tests in Nigerian women with severe preeclampsia

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    Ifeoma C Udenze

    2014-01-01

    Full Text Available Background: Preeclampsia is a common complication of pregnancy with high maternal and perinatal morbidity and mortality. The new American College of Obstetricians and Gynecologists (ACOG guideline now includes elevation of liver enzymes as a criterion for the diagnosis of preeclampsia. Objectives: The objectives of this study is to compare liver function tests in preeclampsia and normotensive pregnancy and determine their relationship with systolic and diastolic blood pressure, plasma creatinine, and uric acid levels in Nigerian women with severe preeclampsia. Materials and Methods: This was a case-control study of 46 women with severe preeclampsia and 21 pregnant women as controls. These women attended the Antenatal Clinic at the Lagos University Teaching Hospital, Lagos where women were consecutively recruited. Results: There was a statistically significant difference in the systolic blood pressure (P = 0.002, diastolic blood pressure (P = 0.004, plasma creatinine (P = 0.007, uric acid (P = 0.0001, plasma albumin (P = 0.029, alkaline phosphatase (ALP (P = 0.0001, aspartate aminotransferase (AST (P = 0.0001, γ-glutamyl transferase (GGT (P = 0.035, and unconjugated bilirubin (P = 0.023 between the group with severe preeclampsia and the normotensive pregnancy control group. Alanine aminotransferase (ALT was however not significantly elevated. AST elevation was the most common anomaly in severe preeclampsia occurring in 54.3% of cases. There was no association between systolic and diastolic blood pressure, plasma creatinine, and uric acid in severe preeclampsia with and without abnormal liver function tests. Conclusion: Elevation of AST, ALP, GGT, and unconjugated bilirubin are common in Nigerian women with severe preeclampsia but may not all be of liver origin. These parameters were also not associated with indices of disease severity. The use of liver enzyme concentrations as adjuncts in preeclampsia diagnosis should be applied with caution in

  16. Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome

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    Udenze Ifeoma Christiana

    2015-01-01

    Full Text Available Aims and objectives: The aim of this study is to determine the plasma levels of the liver enzymes alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT, and lactate dehydrogenase (LDH in people with metabolic syndrome and to determine the association between the liver enzymes and obesity, insulin resistance, interleukin 6 (IL-6, and C-reactive protein (CRP in adult Nigerians with metabolic syndrome. Materials and Methods: This was a case control study of 50 adult men and women with metabolic syndrome, and 50 age- and sex-matched males and females without metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Program (NCEP-Adult Treatment Panel III (ATPIII criteria. Written informed consent was obtained from the participants. Sociodemographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an overnight fast. The ethics committee of the Lagos University Teaching Hospital in Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the student′s t-test. Regression and correlation analysis were used to determine the associations between variables. Statistical significance was set at P < 0.05. Results: There was a statistically significant increase in the liver enzymes ALP (P = 0.031, ALT (P = 0.019, and GGT (P = 0.037, as well as in the inflammatory markers CRP (P = 0.019 and the cytokine IL-6 (P = 0.040 between the two study groups. ALP and ALT showed significant correlation with waist circumference, BMI, fasting insulin, and waist/hip ratio (P < 0.05. Multivariate regression also identified ALT, AST, and ALP to be associated with IL-6 and CRP (P < 0.05. Conclusion: Liver enzyme levels were increased in metabolic syndrome and associated with obesity, fasting insulin, and CRP. Elevated liver enzymes may indicate dysmetabolism and increased

  17. Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

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    Elias Adikwu

    2018-03-01

    Full Text Available Objective: Hepatotoxicity is a clinical challenge associated with the use of efavirenz (EFV. This study investigated the effects of n-acetylcysteine (NAC, vitamins C and E on EFV-induced hepatotoxicity in albino rats. Methods: Rats were divided into groups and administered with NAC (20mg/kg, Vit C (50mg/kg, Vit  E (50mg/kg, Vit C+ E and 60mg/kg of EFV respectively. Rats were also divided into groups and pretreated with NAC, Vit C, E, and combined doses of Vit C+E prior to treatment with EFV for 15 days respectively. After drug administration rats were sacrificed and serum was collected and evaluated for liver function parameters. Rats were dissected, liver was collected weighed and evaluated for alkaline phosphatase (ALP, alanine aminotransferase (AST, aspartate aminotransferase (ALT, gamma glutamyl transferase (GGT, lactate dehydrogenase (LDH, malondialdehyde (MDA, super oxide dismutase (SOD, catalase (CAT, glutathione (GSH, gluthatione peroxidase (GPX levels and pathological damage. Results: Effects were not significant (p>0.05 on body and liver weights, however, the levels of AST, ALT, AST, GGT, LDH, CB, TB and MDA were increased significantly (p<0.05 whereas SOD, CAT, SOD, GSH and GPX were decreased significantly (p<0.05 in EFV-treated rats in comparison to control. The liver of EFV-treated rats showed necrosis of hepatocytes. Nevertheless, EFV-induced alterations in the above parameters were significantly (p<0.05 ameliorated in antioxidants pretreated rats.  The combined doses of Vit C and E produced the best and significant (p<0.05 ameliorative effects in comparison to their individual doses. Conclusion: This study shows the prospects of antioxidants as candidates for the treatments of efavirenz-induced hepatotoxicity.

  18. A Cross-Sectional Investigation of Chronic Exposure to Microcystin in Relationship to Childhood Liver Damage in the Three Gorges Reservoir Region, China

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    Li, Yan; Chen, Ji-an; Zhao, Qing; Pu, Chaowen; Qiu, Zhiqun; Zhang, Renping

    2011-01-01

    Background: Microcystin-producing Microcystis bloom is a severe water problem in the world. Some reports indicate that chronic exposure to microcystin may result in liver damage in adults, but information on effects in children is limited. Objective: We investigated the relationship between microcystin exposure and liver damage in children. Methods: We measured microcystin concentrations in drinking water and aquatic food (carp and duck) from two lakes and four wells. Participants were 1,322 children 7–15 years of age who obtained drinking water from one of the tested sources, completed questionnaires, and provided blood samples for serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT)] and serum microcystin analysis. Multivariable logistic regression was used to identify risk factors associated with liver damage (two or more abnormal serum enzyme levels in ALT, AST, ALP, or GGT). Results: Microcystin was detected in most samples of water and aquatic food from two lakes. Children who drank water from the lake with the highest microcystin concentrations had a total estimated daily microcystin intake of 2.03 μg, a value much higher than the tolerable daily intake (0.40 μg) proposed by the World Health Organization for children. Hepatitis B virus (HBV) infection, use of hepatotoxic medicines, and microcystin exposure were associated with liver damage. AST and ALP levels were significantly higher in high-microcystin-exposed children than in low-exposed children and unexposed children when participants who were HBV-positive or hepatotoxic medicine users were excluded from the analysis. Conclusion: These results suggest that chronic exposure to microcystin may be associated with liver damage in children in the Three Gorges Reservoir Region. PMID:21561830

  19. Recommendation to Exclude Bile-Duct-Cannulated Rats with Hyperbilirubinemia for Proper Conduct of Biliary Drug Excretion Studies.

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    Kato, Koji; Hasegawa, Yoshitaka; Iwata, Katsuya; Ichikawa, Takuya; Yahara, Tohru; Tsuji, Satoshi; Sugiura, Masayuki; Yamaguchi, Jun-Ichi

    2016-08-01

    Hyperbilirubinemia (HB) is sometimes encountered following bile-duct cannulation in rats. It possibly originates from the reduced functioning of multidrug resistance-associated protein 2 (Mrp2) and subsequent adaptive alterations in the expression of Mrp3 and the organic anion transporting polypeptides (Oatps). Our aim was to clarify the importance of excluding bile-duct-cannulated (BDC) rats with HB for proper conduct of drug excretion studies. We detected HB [serum total bilirubin concentration (TBIL) ≥0.20 mg/dl] in 16% of all BDC rats prepared. The serum activities of aspartate aminotransferase, alanine aminotransferase, leucine aminopeptidase, and alkaline phosphatase were within the respective normal ranges in the BDC rats with mild HB (TBIL, 0.20-0.79 mg/dl), indicating the absence of hepatic failure. In the pharmacokinetics of pravastatin, an Oatps/Mrp2 probe drug in the BDC rats, the apparent volume of distribution and the clearance were smaller in the mild HB group as compared with the normal group, suggesting the reduction of apparent hepatic uptake and hepatobiliary elimination. The biliary excretion (percentage of dose) was significantly reduced by 54%, suggesting that the biliary efflux activity via Mrp2 was reduced to a greater extent relative to metabolic activity in hepatocytes. The serum γ-glutamyltransferase (GGT) activity correlated with TBIL and inversely correlated with biliary excretion of pravastatin, a finding which could serve as a clue to uncover the regulatory system involving cooperation between GGT and Mrp2. In conclusion, BDC rats with HB, however mild, should be excluded from drug excretion studies to avoid the risk of underestimation of the biliary excretion of drugs. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Enteral nutrition is superior to total parenteral nutrition for pancreatic cancer patients who underwent pancreaticoduodenectomy.

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    Liu, Changli; Du, Zhi; Lou, Cheng; Wu, Chenxuan; Yuan, Qiang; Wang, Jun; Shu, Guiming; Wang, Yijun

    2011-01-01

    To determine the effects of total parenteral nutrition (TPN) and enteral nutrition (EN) on biochemical and clinical outcomes in pancreatic cancer patients who underwent pancreaticoduodenectomy. From the year 2006 to 2008, 60 patients who underwent pancreaticoduodenectomy in Tianjin Third Central Hospital were enrolled in this study. They were randomly divided into the EN group and the TPN group. The biochemical and clinical parameters were recorded and analyzed between the two groups. There was no significant difference in the nutritional status, liver and kidney function, and blood glucose levels between the TPN and EN groups on the preoperative day, the 1st and 3 rd postoperative days. However, on the 7th postoperative day, there was significant difference between the two groups in 24 h urinary nitrogen, serum levels of, total protein (TP), transferrin (TF), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptadase (GGT), blood urea nitrogen (BUN) and creatinine (Cr). On the 14th postoperative day, there was a significant difference between the two groups in terms of urinary levels of 24 h nitrogen, TP, TF, retinol binding protein, ALT, AST, ALP, GGT, total bilirubin, direct bilirubin, BUN, Cr, and glucose. The incidence of delayed gastric emptying in the EN and TPN groups was 0% and 20%, respectively. Moreover, the incidence of pancreatic fistulas and hemorrhages in the EN group were 3.6% and 3.6%, versus 26.7% and 30% in the TPN group, respectively. EN is better than TPN for pancreatic cancer patients who received pancreaticoduodenectomy.