In comparison with its counterpart from N. meningitides, all conserved motifs were found in the N-termini of E. coli CMP-NeuAc synthetase. E. coli CMP-NeuAc synthetase seems to have redundant C-termini with a less effect on its activity. To explain this speculation, a series of recombinant DNAs with deletion from 3'-end of CMP-NeuAc synthetase were produced by PCR, ligated into expression vector pET-15b and expressed in BL21(DE3)pLysS. After induction with IPTG, we found that the recombinant enzyme with deletion of 189 amino acids from C0termini retained its activity. This result demonstrates that the 229 amino acids of N-termini was the minimal functional domain of E. coli CMP-NeuAc synthetase. The deletions altered the optimum pH and thermostability of active truncated enzymes, indicating that the truncated C-terminal amino acids of E. coli CMP-NeuAc synthetase could affect the conformation of the enzymatic catalytic domain and therefore affect its catalytic activity and thermostability, although it is not involved in enzymatic activity directly.
Amino Acid Sequence ; Cytidine Monophosphate N-Acetylneuraminic Acid ; metabolism ; Enzyme Stability ; Escherichia coli ; enzymology ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Mutation ; N-Acylneuraminate Cytidylyltransferase ; chemistry ; physiology ; Structure-Activity Relationship

Aripiprazole is an atypical antipsychotic that acts as a partial agonist of dopamine type 2 receptors as well as 5-HT1A receptors. It is used in the treatment of schizophrenia and in type 1 bipolar disorder for mania. Because aripiprazole is well tolerated with few side effects it is used off-label in other psychotic disorders. The prevalence of abnormal liver function tests with antipsychotic use is 32%, with clinically significant effects in 4% of cases. No cases of aripiprazole-induced liver injury have been published. We report a 28-year-old female who presented with non-affective first-episode psychosis and who was treated with aripiprazole. Initially she was medicated with 10 mg per day, with an increase to 20 mg per day on the 12th day of hospitalization. Nine days after she became icteric, with nausea and had a vomiting episode. Laboratory analysis revealed a very high level of alanine aminotransferase, and minor to moderately high levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Aripiprazole was tapered and paliperidone was started with the improvement of clinical and laboratory findings.
Adult ; Alanine Transaminase ; Alkaline Phosphatase ; Aripiprazole ; Aspartate Aminotransferases ; Bilirubin ; Bipolar Disorder ; Dopamine ; Female ; Hepatitis ; Hospitalization ; Humans ; Liver ; Liver Function Tests ; Nausea ; Paliperidone Palmitate ; Prevalence ; Psychotic Disorders ; Receptor, Serotonin, 5-HT1A ; Schizophrenia ; Transaminases ; Transferases ; Vomiting

Extracellular ATP (exATP) has been known to be a critical ligand regulating skeletal muscle differentiation and contractibility. ExATP synthesis was greatly increased with the high level of adenylate kinase 1 (AK1) and ATP synthase beta during C2C12 myogenesis. The exATP synthesis was abolished by the knock-down of AK1 but not by that of ATP synthase beta in C2C12 myotubes, suggesting that AK1 is required for exATP synthesis in myotubes. However, membrane-bound AK1beta was not involved in exATP synthesis because its expression level was decreased during myogenesis in spite of its localization in the lipid rafts that contain various kinds of receptors and mediate cell signal transduction, cell migration, and differentiation. Interestingly, cytoplasmic AK1 was secreted from C2C12 myotubes but not from C2C12 myoblasts. Taken together all these data, we can conclude that AK1 secretion is required for the exATP generation in myotubes.
Adenosine Triphosphate/*biosynthesis ; Adenylate Kinase/*metabolism ; Animals ; Cell Line ; Extracellular Space/metabolism ; Isoenzymes/*metabolism ; Mice ; Muscles/cytology/*metabolism

BACKGROUND: The present study purposed to evaluate the clinical usefulness of biological indicators in identifying Korean female heavy drinkers. METHODS: Fifty five drinking women were selected among those who visited the Department of Family Medicine of Chungnam National University Hospital during the period from January to December 2006. We surveyed the alcohol intake during the recent one month. The correlation of alcohol intake with %CDT (carbohydrate- deficient transferrin), mean corpuscular volume (MCV), gamma glutamyl transferase (gammaGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was examined. The sensitivity, specificity, positive predictive value, negative predictive value and ROC (receiver operating characteristic) curve of the biomarkers for heavy drinking (more than 7 drinks per week, one drink= 14 g of alcohol) were also investigated. RESULTS: The mean weekly alcohol intake showed a significant positive correlation with %CDT (r=0.583, P< 0.01), MCV (r=0.290, P<0.05) and AST (r=0.423, P<0.01). The sensitivity of %CDT, MCV, gammaGT, AST and ALT to heavy drinking were 66.7%, 13.3%, 40.0%, 26.7% and 26.7%, respectively, and the specificity 80.0%, 97.4%, 71.1%, 90.0% and 85.0%, respectively, and positive predictive values 55.6%, 66.6%, 35.3%, 50.0% and 40.0%, respectively, and negative predictive values 86.5%, 74.5%, 75.0%, 76.6% and 75.6%, respectively. The areas under the ROC curve (95% confidence interval) of %CDT, MCV, gammaGT, AST and ALT were 0.873 (0.780~0.966), 0.806 (0.668~0.944), 0.549 (0.372~0.725), 0.519 (0.328~0.710) and 0.479 (0.293~0.666), respectively. CONCLUSION: %CDT is considered as the most useful marker for identifying Korean female heavy drinkers.
Alanine Transaminase ; Aspartate Aminotransferases ; Biomarkers ; Drinking ; Erythrocyte Indices ; Female ; Humans ; ROC Curve ; Sensitivity and Specificity ; Transferases

BACKGROUND: The evaluation of newly developed reagents for chemical analyzer is essential for an accurate testing of various samples. We evaluated the analytical performance of the DCS(TM) reagents (Cheongmeak, Korea). METHODS: Fifteen chemistry reagents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin, total protein, albumin, blood urea nitrogen (BUN), creatinine, glucose, calcium, inorganic phosphorus, total cholesterol, triglyceride and HDL-cholesterol were tested for precision, linearity and correlation according to CLSI guidelines in the Hitachi 7180 chemistry analyzer (Hitachi High-Technologies Co., Japan). RESULTS: The coefficients of variation (CV) of both within-run and total precision were below 3.98% for all analytes, which fully meets of CLIA 88 decision ranges. Good linearity was shown for all analytes in measurement ranges. Coefficients of correlation were also good for all analytes. CONCLUSIONS: DCS(TM) reagents showed good precision, linearity and correlation. Therefore, the DCS(TM) reagents could be acceptable for use in routine chemistry analyzers.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Blood Urea Nitrogen ; Calcium ; Cholesterol ; Creatinine ; Glucose ; Indicators and Reagents ; Phosphorus ; Transferases

PURPOSE: To estimate the roles of triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio and uric acid in predisposition for metabolic syndrome (MetS) and its components in healthy children. METHODS: Anthropometric and biochemical analyses were performed on 110 children, aged 5 to 12 years, from the Greek county of Laconia. The children were studied as a whole population and in separate groups according to age and predisposition to MetS after taking into consideration International Diabetes Federation criteria, body mass index, and lipid profile. RESULTS: Seventeen percent of children exhibited predisposition to MetS, while 39.1% had TG/HDL ratio >1, and 3.64% had high level of uric acid. According to a receiver operating characteristic curve analysis, the relative probability for MetS predisposition sextupled when TG/HDL ratio was ≥1 (odds ratio [OR], 5.986; 95% confidence interval [CI], 1.968–18.205). Children in the total population and those aged < 9 years had a greater probability for increased low-density lipoprotein (LDL) cholesterol (OR, 3.614; 95% CI, 1.561–8.365) when TG/HDL ratio was ≥ 1. The TG/HDL ratio was positively correlated with body mass index (BMI) (P=0.035) in children without MetS, cholesterol in the total population (P=0.06) and children ≥9 years old (P=0.026), and with LDL in the total population and both age groups (P=0.001). The TG/HDL ratio was also positively correlated with alanine aminotransferase in the total population (P=0.033) and gamma-glutamyl transferase in most studied groups (P<0.001). Uric acid was positively correlated with waist circumference in the total population (P=0.043) and in those without MetS (P=0.027). It was also positively correlated with BMI, TG, cholesterol, and TG/HDL ratio and negatively correlated with HDL in most studied groups (P<0.005). CONCLUSION: The studied parameters correlated with MetS components and could be characterized as effective indexes for childhood MetS, regardless of age and predisposition to MetS.
Alanine Transaminase ; Body Mass Index ; Causality ; Child ; Cholesterol ; Humans ; Lipoproteins ; ROC Curve ; Transferases ; Uric Acid ; Waist Circumference

BACKGROUND: Currently, natural products have been shown to exhibit interesting biological and pharmacological activities and are used as chemotherapeutic agents. The purpose of this study, conducted on Wistar rats, was to evaluate the beneficial effects of Artemisia arborescens oil on oestroprogestative treatment induced damage on liver. MATERIALS/METHODS: A total of 36 Wistar rats were divided into 4 groups; a control group (n = 9), a group of rats who received oestroprogestative treatment by intraperitoneal injection (n = 9), a group pre-treated with Artemisia arborescens then injected with oestroprogestative treatment (n = 9), and a group pre-treated with Artemisia arborescens (n = 9). To minimize the handling stress, animals from each group were sacrificed rapidly by decapitation. Blood serum was obtained by centrifugation and the livers were removed, cleaned of fat, and stored at -80degrees C until use. RESULTS: In the current study, oestroprogestative poisoning resulted in oxidative stress, which was demonstrated by 1) a significant increase of lipid peroxidation level in hepatic tissue 2) increased levels of serum transaminases (aspartate amino transferase and serum alanine amino transferase), alkaline phosphatase, glycemia and triglycerides and a decrease in the level of cholesterol 3) alteration of hepatic architecture. Pre-administration of Artemisia arborescens oil was found to alleviate oestroprogestative treatment induced damage by lowering lipid peroxidation level and by increasing activity of catalase, superoxide-dismutase, and glutathione-peroxidase in liver and by reducing disruption of biochemical parameters. CONCLUSION: Therefore, the results obtained in this study confirmed that Artemisia essential oil protects against oestroprogestative administration induced hepatotoxicity by restoration of liver activities.
Alanine ; Alkaline Phosphatase ; Animals ; Artemisia* ; Biological Products ; Catalase ; Centrifugation ; Cholesterol ; Decapitation ; Injections, Intraperitoneal ; Lipid Peroxidation ; Liver ; Oxidative Stress ; Poisoning ; Rats ; Rats, Wistar ; Serum ; Transaminases ; Transferases ; Triglycerides

PURPOSE: There is concern about the potential adverse effects on hepatic function due to increased intraabdominal pressure during pneumoperitoneum. The changes in hepatic function following a laparoscopy assisted distal gastrectomy (LADG) and conventional open distal gastrectomy (ODG) for gastric cancer were compared. METHODS: Between July 2004 and May 2005, 60 patients diagnosed with early gastric cancer at Kangnam St' Mary's hospital; 30 each having undergone LADG and ODG were studied. The levels of alkaline phosphatase (ALP), total bilirubin (TB), aspartate transferase (AST) and alanine transferase (ALT) between the two groups were compared at 24 and 72 hours postoperatively. RESULTS: The age, sex, body mass index and preoperative hepatic function were not different between the two groups. The operative times were significantly longer in the LADG than the ODG group (298 vs. 184 minutes, P < 0.000). There was no postoperative hepatic failure or mortality in either group. The levels of ALP decreased, but those of total bilirubin remained unchanged from the preoperative baselines in both groups, with no significant difference between the two groups. After a LADG, the levels of AST and ALT increased 3.7 and 3.5 fold 24 hours after surgery, whereas after an ODG, the levels of AST and ALT increased 1.9 and 1.5 fold. In the LADG group, the levels of AST and ALT were significantly increased compared to the ODG group (P < 0.05), but returned close to the baseline levels within 72 hours. On the third postoperative day, there were no significant differences in the levels of AST and ALT between the two groups (P > 0.05). CONCLUSION: After a LADG, the levels of hepatic transaminases were immediately elevated, but returned to normal levels within 72 hours. A LADG with prolonged pneumoperitoneum is considered safe in patients with normal liver function prior to the operation. In addition, to evaluate the safety of a LADG in the patients with decreased hepatic function, a large scaled randomized prospective trial will be required.
Alanine ; Alkaline Phosphatase ; Aspartic Acid ; Bilirubin ; Body Mass Index ; Gastrectomy* ; Humans ; Laparoscopy ; Liver ; Liver Failure ; Mortality ; Operative Time ; Pneumoperitoneum ; Prospective Studies* ; Stomach Neoplasms ; Transaminases ; Transferases

BACKGROUND: As many kinds of reagents for chemistry autoanalyzer have been developed, comprehensive evaluation of the reagents is needed for proper selection. We evaluated the analytical performances of the HiSense(TM) reagents (HBI Co., Ltd, An-yang, Korea). METHODS: Sixteen chemistry reagents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total protein, total bilirubin, albumin, glucose, blood urea nitrogen (BUN), creatinine, total calcium, phosphorus, lactate dehydrogenase (LDH), uric acid, total cholesterol, and triglyceride (TG) were evaluated for linearity, precision, interference, and correlation according to CLSI guidelines in the Toshiba ACCURATE chemistry autoanalyzer (Toshiba Medical Systems Co., Ltd., Tokyo, Japan). RESULTS: The coefficients of variation (CV) of both within-run and total precision were below 2.6% for all analytes. Good linearity was observed for all analytes in measurement ranges. Coefficients of correlation were also good for all analytes. There were clinically significant effects of interfering factors, hemoglobin and lipid, in LDH and total protein, respectively. CONCLUSIONS: HiSense reagents showed good precision, linearity, and correlation. We conclude that these reagents are appropriate for routine clinical use.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Blood Glucose ; Calcium ; Chemistry* ; Cholesterol ; Creatinine ; Indicators and Reagents* ; L-Lactate Dehydrogenase ; Nitrogen ; Phosphorus ; Transferases ; Triglycerides ; Urea ; Uric Acid

PURPOSE: This study is designed to ascertain the most effective quantity and injection route of hepatocytes in an acute liver failure model induced by massive liver resection in rats. METHODS: Rats weighing 450 to 650 gm underwent partial hepatectomy that was 80% of their liver weight, resulting in acute liver failure. Hepatocytes were obtained by perfusing collagenase (Wako, Japan) solution through portal vein into liver of the allogenic rat. These hepatocytes were injected into different places with different dosage. The experimental groups were divided into the Control group, Splenic group I (2x10(6) cells into splenic capsule), Splenic group II (2x10(7) cells into splenic capsule), Portal vein group (2x10(7) cells into portal vein), Subperitoneal group (2x10(7) cells into subperitoneum). The experimental animals were observed carefully for 5 days for assessment of survival and regeneration of liver. Liver function tests including serum alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (gamma-GTP) on postoperative 1, 2, 3, 5th days and histologic examinations of specimens obtained from each respective groups on postoperative 5th day were performed. RESULTS: Serum ALT level on postoperative day 1 peaked and then gradually normalized showing statistical significance (p=0.035). Study groups showing statistically significant difference under repeated anova analysis were between the Splenic group II and Control (p=0.035), and between the Splenic group II and Portal vein group (p=0.001) with respect to serum ALT levels. Also, progression of each study group showed statistical significance. (p=0.02). Serum total bilirubin and r-GTP did not show any significant difference. CONCLUSION: Hepatocyte transplantation of 2x10(7) cells into spleen showed the best results in the acute hepatic failure rat.
Alanine Transaminase ; Animals ; Bilirubin ; Cell Transplantation ; Collagenases ; Hepatectomy ; Hepatocytes ; Liver ; Liver Failure, Acute ; Liver Function Tests ; Portal Vein ; Rats ; Regeneration ; Spleen ; Transferases ; Transplants