A pre-marketing ALT signal predicts post-marketing liver safety.

PubMed

Moylan, Cynthia A; Suzuki, Ayako; Papay, Julie I; Yuen, Nancy A; Ames, Michael; Hunt, Christine M

2012-08-01

Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety. Published by Elsevier Inc.

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

PubMed

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 < 0.001). Abdominal 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.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

PubMed Central

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure. PMID:25960751

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

PubMed

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Association of ALT and the metabolic syndrome among Mexican children.

PubMed

Elizondo-Montemayor, Leticia; Ugalde-Casas, Patricia A; Lam-Franco, Lorena; Bustamante-Careaga, Humberto; Serrano-González, Mónica; Gutiérrez, Norma G; Martínez, Ubaldo

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome (MetS); Hispanics being particularly predisposed. Alanine aminotransferase (ALT) is considered a marker of NAFLD. The aim of this study was to determine the prevalence and associations between ALT elevations and MetS in normal-weight, overweight and obese Mexican children and adolescents, since data in Mexico is scarce. Body mass index (BMI), waist circumference (WC), percentage body fat, blood pressure, glucose, lipid profiles, ALT and aspartate aminotransferase (AST) were measured in 236, 6-12yo normal-weight, overweight and obese Mexicans from eight public schools. The results showed that elevated ALT (>40 IU/L) was found in 17.7% of the obese and overweight population, with no gender difference. The prevalence of elevated ALT increased linearly across BMI categories (p = 0.001), from 0.0% for the normal-weight group (95%CI 0.0-€“8.0) to 22.4% for the obese one (95%CI 16.2-€“30.2). AST/ALT ratio <1 also increased linearly, as did the prevalence of MetS (p = 0.001), from 0.0% for the normal-weight group to 40.3% for the obese one. The prevalence of MetS was strongly associated with elevated ALT (p = 0.002), 50% in the elevated ALT group (95%CI 34.1-€“65.9) and 24.1% in the normal ALT one (95%CI 18.1-€“31.3). There was also a strong association between MetS and an AST/ALT ratio <1. WC was the best predictor of elevated ALT (AOR = 7.13). Pearson correlation showed that MetS components were significantly correlated with elevated ALT. Therefore elevated ALT levels were highly prevalent and strongly associated with MetS in Mexican children, it should be screened in overweight and obese children. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B.

PubMed

Wong, Grace Lai-Hung; Chan, Henry Lik-Yuen; Tse, Yee-Kit; Yip, Terry Cheuk-Fung; Lam, Kelvin Long-Yan; Lui, Grace Chung-Yan; Wong, Vincent Wai-Sun

2018-06-18

Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB). A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005-2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded. A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ± 1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49-0.77), 0.55 (0.45-0.67), 0.54 (0.44-0.65) and 0.51 (0.42-0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%-6.32%) in the no ALT-N group (p <0.001). Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients. We investigated 21,182 patients with chronic

Study on changes of clinical indicators and key proteins from fluoride exposure.

PubMed

He, Hong; Wang, Hongmei; Han, Mei; Jiao, Yuguo; Ma, Congli; Zhang, Han; Zhou, Zhou

2014-07-01

Few studies have evaluated the biomarker changes of fluoride exposure. In order to explore early and sensitive indicators, animal experiment was designed. Ninety-six healthy SD rats (48 males and 48 females) weighing approximately 60 g were randomly divided into six groups of 16 animals each by gender average. Control animals were supplied with distilled water only as group 1. Exposure groups' animals were treated with 2, 4, 8, 16, and 32 mg NaF/kg bw, respectively, as groups 2, 3, 4, 5, and 6. Our study found that contents of white blood cell (WBC), lymphocyte percentage (LYMPH%), lymphocyte (LYM), mean platelet volume (MPV), and platelet distribution width (PDW) increased significantly in high-fluoride-exposure groups (p < 0.05), which revealed that immune system may be interfered by high fluoride. Meanwhile, levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and ALT/AST in groups 5 and 6 decreased significantly compared to those in control group (p < 0.05), as well as the concentration of uric acid (UA) in groups 3, 4, 5, and 6 exhibited the same trends (p < 0.05). On the contrary, the level of blood B2 microglobulin (BB2MG) increased significantly (p < 0.05) in groups 4, 5, and 6. Changes of ALT, AST, UA, and BB2MG suggested the functions of the liver and kidney be altered by fluoride exposure. At the same time, the ATF4 content decreased gradually with the increase of fluoride concentration; furthermore, a highly significant (r = -0.586, p < 0.01) negative relationship between ATF4 content and fluoride exposure level was found. Results meant that clinical indicators cannot act as indicators of high fluoride exposure, and it also suggested that protein ATF4 might be the early and sensitive indicator in epidemiologic study of high fluoride exposure.

Molecular and phenotypic characterization of transgenic wheat and sorghum events expressing the barley alanine aminotransferase.

PubMed

Peña, Pamela A; Quach, Truyen; Sato, Shirley; Ge, Zhengxiang; Nersesian, Natalya; Dweikat, Ismail M; Soundararajan, Madhavan; Clemente, Tom

2017-12-01

The expression of a barley alanine aminotransferase gene impacts agronomic outcomes in a C3 crop, wheat. The use of nitrogen-based fertilizers has become one of the major agronomic inputs in crop production systems. Strategies to enhance nitrogen assimilation and flux in planta are being pursued through the introduction of novel genetic alleles. Here an Agrobacterium-mediated approach was employed to introduce the alanine aminotransferase from barley (Hordeum vulgare), HvAlaAT, into wheat (Triticum aestivum) and sorghum (Sorghum bicolor), regulated by either constitutive or root preferred promoter elements. Plants harboring the transgenic HvAlaAT alleles displayed increased alanine aminotransferase (alt) activity. The enhanced alt activity impacted height, tillering and significantly boosted vegetative biomass relative to controls in wheat evaluated under hydroponic conditions, where the phenotypic outcome across these parameters varied relative to time of year study was conducted. Constitutive expression of HvAlaAT translated to elevation in wheat grain yield under field conditions. In sorghum, expression of HvAlaAT enhanced enzymatic activity, but no changes in phenotypic outcomes were observed. Taken together these results suggest that positive agronomic outcomes can be achieved through enhanced alt activity in a C3 crop, wheat. However, the variability observed across experiments under greenhouse conditions implies the phenotypic outcomes imparted by the HvAlaAT allele in wheat may be impacted by environment.

Cardiorespiratory Fitness, Waist Circumference and Alanine Aminotransferase in Youth

PubMed Central

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

2012-01-01

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

Porcine alanine transaminase after liver allo-and xenotransplantation.

PubMed

Ekser, Burcin; Gridelli, Bruno; Cooper, David K C

2012-01-01

Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording. © 2012 John Wiley & Sons A/S.

Porcine alanine transaminase after liver allo-and xenotransplantation

PubMed Central

Ekser, Burcin; Gridelli, Bruno; Cooper, David K.C.

2013-01-01

Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3 Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3 Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording. PMID:22360753

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

PubMed

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.

An innovative alt-alt telescope for small observatories and amateur astronomers

NASA Astrophysics Data System (ADS)

Riva, M.; Basso, S.; Canestrari, R.; Conconi, P.; Fugazza, D.; Ghigo, M.; Landoni, M.; Pareschi, G.; Spanó, P.; Tomelleri, R.; Zerbi, F. M.

2012-09-01

This paper want to show an innovative amateur oriented telescope with an unconventional alt-alt conguration. The goal is to make a telescope with good optical quality reducing production costs by adopting a gimbal based mounting to develop an alt-alt conguration suitable for a telescope. Reduce costs while preserving the optical quality is a necessary condition to allow small groups of amateur astronomers, schools and cultural clubs, with reduced economic resources, to acquire an astronomical instrument that encourages learning and advancing astrophysical knowledge. This unconventional mechanism for the realization of a telescope alt-alt provides signicant advantages. The traditional rotary motors coupled with expensive precision bearings are replaced with two simple linear actuators coupled to a properly preloaded gimbal joint and the cell becomes the primary structure of the telescope. A second advantage would be secured by mechanical simplicity evident in the easy portability of the instrument. The frame alt-alt has some limitations on the horizon pointing but does not show the zenith blind spot of the alt-az mount. A dedicated alt-alt pointing and tracking model is under development to be compatible with commercial telescope softwares and with the proposed new mounting.

Alterations in carbohydrates and the protein metabolism of the harmful freshwater vector snail Lymnaea acuminata induced by the Euphorbia tirucalli latex extract.

PubMed

Tiwari, Sudhanshu; Singh, A

2005-11-01

To know the short- as well as long-term effect of aqueous latex extracts of Euphorbia tirucalli on carbohydrate and protein metabolism, the snail Lymnaea acuminata was exposed to sublethal doses of 0.37 and 0.55 mg/L for a 24-h and 0.20 and 0.31 mg/L for a 96-h exposure period. Significant (P<0.05) alterations in the glycogen, pyruvate, lactate, total protein, and free amino acid level, as well as in the activity of enzyme lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase, and alanine aminotransaminase were observed in the nervous, hepatopancreatic, and ovotestis tissues of the freshwater vector snail L. acuminata exposed to sublethal doses of E. tirucalli latex extract. The alterations in all biochemical parameters were significantly (P<0.05) time and dose dependent. After the 7th day of the withdrawal of treatment, there was significant (P<0.05) recovery in glycogen, pyruvate, lactate, total protein, and the free amino acid level and in the activity of the lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase and alanine aminotransaminase enzymes in all three of the studied tissues of the snail, which supports the view that the plant product is safe for use as a molluscicide for the control of harmful freshwater vector snails in the aquatic environment.

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

PubMed

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

2016-06-01

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

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

PubMed

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

2015-08-01

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

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

PubMed

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

2014-12-01

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

Effects of selenium-enriched Agaricus blazei Murill on liver metabolic dysfunction in mice, a comparison with selenium-deficient Agaricus blazei Murill and sodium selenite.

PubMed

Yu, Lei; Yang, Shaolong; Sun, Lei; Jiang, Yan-Fang; Zhu, Li-Ying

2014-07-01

In the present study, we investigated the effects of Se-enriched Agaricus blazei Murill (Se-AbM) on liver injury in mice induced by acute alcohol administration. Mice received ethanol (5 g/kg body weight (BW)) by gavage every 12 h for a total of 3 doses. Se-AbM was administrated before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), nuclear factor kappa B (NF-κB) level, polymorphonuclear cells (PMN) level, interleukin-1β (IL-1β) level, inducible nitric oxide synthase (iNOS) level, tumor necrosis factor-α (TNF-α) level, intercellular adhesion molecule 1 (ICAM-1), and cyclooxygenase-2 (COX-2) were determined by ELISA and immunohistochemistry, respectively. Se-AbM administration markedly (p < 005) decreased serum ALT, AST, and MDA levels, hepatic IL-1β and TNF-α levels, as well as PMN infiltration and the expression of ICAM-1, COX-2, iNOS, and NF-κB compared with alcohol administration. In conclusion, we observed that Se-AbM supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Differing clinical phenotype for higher alanine-aminotransferase (ALT) compared with high-risk NAFLD fibrosis score in type 2 diabetes mellitus.

PubMed

Williams, Kathryn H; Burns, Kharis; Twigg, Stephen M

2018-03-01

The impact of non-alcoholic fatty liver disease (NAFLD) presence and severity on the diabetes phenotype remains unclear. Our study aimed to explore and contrast the phenotypes associated with higher ALT and high-risk NAFLD fibrosis score (NFS) in type 2 diabetes. 324 patients with type 2 diabetes mellitus who were seen at a diabetes centre for a complications assessment with data for NFS were available for study. Data regarding co-morbidities and pathology were obtained at assessment and by file audit. Logistic regression was used to determine if there were significant relationships between pre-determined diabetes complications and co-morbidities and ALT or high-risk NFS (>0.675). Significant univariate associations with lower ALT included those of osteoporosis/osteopenia and inability to sense the monofilament. High-risk NFS was associated with arrhythmia, VPT ≥ 25 V and albuminuria. The associations of high-risk NFS with albuminuria and VPT ≥ 25 V remained after adjustment. In type 2 diabetes, the clinical phenotype of those with higher ALT is dissimilar, sometimes inverse, to those with high-risk NFS. More emphasis should be placed on liver fibrosis risk rather than on liver enzymes alone. Copyright © 2017. Published by Elsevier Inc.

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

PubMed

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

2015-09-01

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

Lack of clinical and histological progression of chronic hepatitis C in individuals with true persistently normal ALT: the result of a 17-year follow-up.

PubMed

Nunnari, G; Pinzone, M R; Cacopardo, B

2013-04-01

Thirty to 40% of patients with chronic hepatitis C have persistently normal alanine aminotransferase (PNALT). Even though traditionally considered as healthy people, most PNALT carriers actually have some degree of clinical progression and histological liver damage. We evaluated the clinical and histological outcome of a 17-year follow-up on a cohort of patients with chronic HCV infection and PNALT. Between 1994 and 2011, 70 PNALTs and 55 Hyper-alanine aminotransferase (ALT) subjects underwent a clinical, biochemical, virological and histological follow-up. At the end of the follow-up, all patients were alive. In the PNALT group, none of the patients developed hepatic decompensation, while 14.5% of Hyper-ALTs were diagnosed as affected by decompensated cirrhosis. No significant variation of the Metavir grading and staging scores was observed among PNALTs by comparing pre- and post-follow-up liver specimens. On the contrary, a significant increase in both Metavir grading and staging scores was noticed within the Hyper-ALT group. Finally, the analysis of IL28B single-nucleotide polymorphism rs12979860 revealed no difference between Hyper-ALTs and PNALTs in terms of frequency of C/C genotype. In conclusion, progression of chronic hepatitis C among PNALTs is slow or even absent, because at the end of the 17-year follow-up histological and clinical parameters had not worsened significantly. © 2012 Blackwell Publishing Ltd.

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

PubMed Central

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

2016-01-01

Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046–0.0143, P<0.001). Conclusions The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

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

PubMed

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

2013-09-01

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

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

PubMed

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

2010-10-01

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

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

PubMed

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

2017-07-14

Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD). Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT. Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

PubMed Central

Lv, Guo-Cai; Ma, Wen-Jiang; Ying, Lin-Jung; Jin, Xi; Zheng, Lin; Yang, Yi-Da

2010-01-01

AIM: To evaluate the efficacy and safety of telbivudine (LDT) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who have high baseline alanine aminotransferase (ALT) levels between 10 and 20 times the upper limit of normal. METHODS: Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk. Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls. We compared the virological, biochemical, serological and side effect profiles between the two groups at 52 wk. RESULTS: By week 52, the mean decrease in hepatitis B virus (HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group, respectively (P < 0.05). The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group, respectively (P < 0.05). In addition, 45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative, and 37.5% of those in the high baseline group and 22.5% of controls, respectively, had HBeAg seroconversion (P < 0.05) at week 52. Moreover, in the high baseline group, 4 out of 40 patients (10%) became hepatitis B surface antigen (HBsAg)-negative and 3 (7.5%) of them seroconverted (became HBsAg-positive). Only 1 patient in the control group became HBsAg-negative, but had no seroconversion. The ALT normalization rate, viral breakthrough, genotypic resistance to LDT, and elevations in creatine kinase levels were similar in the two groups over the 52 wk. CONCLUSION: High baseline ALT level is a strong predictor for optimal results during LDT treatment. PMID:20731026

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

PubMed

Grunenberg, R; Banik, N; Krüger, J

1995-06-01

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

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

PubMed

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

2011-10-01

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

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

PubMed

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

2011-08-01

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

Metabolic markers and ALT cutoff level for diagnosing nonalcoholic fatty liver disease: a community-based cross-sectional study.

PubMed

Miyake, Teruki; Kumagi, Teru; Hirooka, Masashi; Koizumi, Mitsuhito; Furukawa, Shinya; Ueda, Teruhisa; Tokumoto, Yoshio; Ikeda, Yoshio; Abe, Masanori; Kitai, Kohichiro; Hiasa, Yoichi; Matsuura, Bunzo; Onji, Morikazu

2012-06-01

Untreated nonalcoholic fatty liver disease (NAFLD) may progress to liver cirrhosis or failure and is associated with the development of hepatocellular carcinoma, diabetes, and cardiovascular disease. It is therefore essential to diagnose and treat NAFLD at an early stage. To assist in this effort, this retrospective study explored the risk factors for NAFLD, and derived new surrogates, a revised alanine aminotransferase (ALT) cutoff level and a novel NAFLD index, to identify previously undiagnosed cases of NAFLD. Using a community-based, cross-sectional design, the records of 6,370 Japanese subjects who had undergone at least 1 annual health check-up were reviewed for the identification of subjects meeting the diagnostic criteria for NAFLD and the variables associated with NAFLD for the estimation of ideal ALT cutoff levels. The results of multivariate analysis of the 1,346 subjects who met the diagnostic criteria for NAFLD confirmed that metabolic disease markers and a novel NAFLD index, using the variables derived from multivariate analysis, were also markers of NAFLD. The ALT cutoff levels for NAFLD diagnosis were estimated at 25 U/L for males and 17 U/L for females. ALT level and the novel NAFLD index were confirmed to be surrogate markers for NAFLD in addition to metabolic disease markers. The ALT cutoff level used in NAFLD diagnosis should be revised downward to identify subjects at risk of NAFLD to prevent NAFLD progression and the development of associated diseases.

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

PubMed Central

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

2005-01-01

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

ALT-114 and ALT-118 Alternative Approaches to NIST ...

EPA Pesticide Factsheets

In 2016, US EPA approved two separate alternatives (ALT 114 and ALT 118) for the preparation and certification of Hydrogen Chloride (HCl) and Mercury (Hg) cylinder reference gas standards that can serve as EPA Protocol gases where EPA Protocol are required, but unavailable. The alternatives were necessary due to the unavailability of NIST reference materials (SRM, NTRM, CRM or RGM) or VSL reference materials (VSL PRM or VSL CRM), reference materials identified in EPA’s Green Book as necessary to establish the traceability of EPA protocol gases. ALT 114 and ALT 118 provides a pathway for gas vendors to prepare and certify traceable gas cylinder standards for use in certifying Hg and HCl CEMS. In this presentation, EPA will describe the mechanics and requirements of the performance-based approach, provide an update on the availability of these gas standards and also discuss the potential for producing and certifying gas standards for other compounds using this approach. This presentation discusses the importance of NIST-traceable reference gases relative to regulatory source compliance emissions monitoring. Specifically this presentation discusses 2 new approaches for making necessary reference gases available in the absence of NIST reference materials. Moreover, these approaches provide an alternative approach to rapidly make available new reference gases for additional HAPS regulatory compliance emissions measurement and monitoring.

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

PubMed

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

2013-01-01

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

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

PubMed

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

2014-11-01

Current literature lacks data on markers of non-alcoholic fatty liver disease (NAFLD) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. We therefore, conducted a cross-sectional study to examine modifiable clinical and lifestyle factors associated with elevated alanine aminotransferase (ALT) levels as a marker of NAFLD in new T2DM patients. Alanine aminotransferase levels were measured in 1026 incident T2DM patients enrolled in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. We examined prevalence of elevated ALT (>38 IU/L for women and >50 IU/L for men) and calculated prevalence ratios associated with clinical and lifestyle factors using Poisson regression. We examined the association with other biomarkers by linear regression. The median value of ALT was 24 IU/L (interquartile range: 18-32 IU/L) in women and 30 IU/L (interquartile range: 22-41 IU/L) in men. Elevated ALT was found in 16% of incident T2DM patients. The risk of elevated ALT was increased in patients who were <40 years old at diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14/>21 drinks per week for women/men) (aPR: 1.60, 95% CI: 1.03-2.50), and in those with no regular physical activity (aPR: 1.42, 95% CI: 1.04-1.93). Obesity and metabolic syndrome per se showed no association with elevated ALT when adjusted for other markers, whereas we found positive associations of ALT with increased C-peptide (β = 0.14, 95% CI: 0.06-0.21) and fasting blood glucose (β = 0.07, 95% CI: 0.03-0.11). Among newly diagnosed T2DM patients, several modifiable clinical and lifestyle factors are independent markers of elevated ALT levels. Copyright © 2014 John Wiley & Sons, Ltd.

Gamma-glutamyltransferase, alanine transaminase and aspartate transaminase levels and the diagnosis of gestational diabetes mellitus.

PubMed

Tan, Peng Chiong; Aziz, Ainul Zahaniah; Ismail, Ikram Shah; Omar, Siti Zawiah

2012-10-01

To evaluate gamma-glutamyltransferase (GGT), alanine transaminases (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes mellitus (GDM). Random plasma glucose, GGT, ALT and AST and the 50-g glucose challenge test were done on antenatal women followed by diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was diagnosed by ADA (2011) criteria. The GDM rate was 12.2% (319/2610). Mean GGT level was higher in GDM women, 18 ± 12 vs. 16 ± 11 IU/L; P=0.03. The risk for GDM was higher for women in the highest GGT quartile band compared to the lowest: RR 1.35 95%CI 1.0-1.8; P=0.04. However, after adjustment for confounders, GGT was no longer associated with GDM. There was no correlation between ALT and AST levels and GDM. Liver transaminases do not predict GDM in contrast to type 2 diabetes. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

ALT-114 and ALT-118 Alternative Approaches to NIST-Traceable Reference Gases

EPA Science Inventory

In 2016, US EPA approved two separate alternatives (ALT 114 and ALT 118) for the preparation and certification of Hydrogen Chloride (HCl) and Mercury (Hg) cylinder reference gas standards that can serve as EPA Protocol gases where EPA Protocol are required, but unavailable. The a...

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

PubMed Central

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

1973-01-01

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

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

PubMed

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

2016-11-01

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

Juvenile Hormone Analogues, Methoprene and Fenoxycarb Dose-Dependently Enhance Certain Enzyme Activities in the Silkworm Bombyx Mori (L)

PubMed Central

Mamatha, Devi M.; Kanji, Vijaya K.; Cohly, Hari H.P.; Rao, M. Rajeswara

2008-01-01

Use of Juvenile Hormone Analogues (JHA) in sericulture practices has been shown to boost good cocoon yield; their effect has been determined to be dose-dependent. We studied the impact of low doses of JHA compounds such as methoprene and fenoxycarb on selected key enzymatic activities of the silkworm Bombyx mori. Methoprene and fenoxycarb at doses of 1.0 μg and 3.0fg/larvae/48 hours showed enhancement of the 5th instar B. mori larval muscle and silkgland protease, aspartate aminotransaminase (AAT) and alanine aminotransaminase (ALAT), adenosine triphosphate synthase (ATPase) and cytochrome-c-oxidase (CCO) activity levels, indicating an upsurge in the overall oxidative metabolism of the B.mori larval tissues. PMID:18678927

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

PubMed Central

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

2016-01-01

Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST) to alanine aminotransferase (ALT). However, the association of AST/ALT ratio with brain natriuretic peptide (BNP) levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL). There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile) was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality. PMID:27872510

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

PubMed

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.

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

PubMed Central

2011-01-01

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

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

PubMed

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

2011-08-17

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

Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet.

PubMed

Rivera, L R; Leung, C; Pustovit, R V; Hunne, B L; Andrikopoulos, S; Herath, C; Testro, A; Angus, P W; Furness, J B

2014-08-01

Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes. Mice were fed a high-fat, high-cholesterol diet (21% fat, 2% cholesterol) or normal chow for 33 weeks. Liver injury was assessed by hematoxylin and eosin, picrosirius red staining, and measurement of plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different types of enteric neurons. The mice developed steatosis, steatohepatitis, fibrosis, and a 10-fold increase in plasma ALT, indicative of liver disease. Oral glucose tolerance was unchanged. Loss and damage to enteric neurons occurred in the myenteric plexus of ileum, cecum, and colon. Total numbers of neurons were reduced by 15-30% and neurons expressing nitric oxide synthase were reduced by 20-40%. The RNA regulating protein, Hu, became more concentrated in the nuclei of enteric neurons after high-fat feeding, which is an indication of stress on the enteric nervous system. There was also disruption of the neuronal cytoskeletal protein, neurofilament medium. Enteric neuron loss and damage occurs in animals with fatty liver disease in the absence of glucose intolerance. The enteric neuron damage may contribute to the gastrointestinal complications of fatty liver disease. © 2014 John Wiley & Sons Ltd.

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

PubMed Central

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

2001-01-01

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

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

PubMed

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

2009-01-01

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

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

PubMed

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

2017-07-01

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

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

PubMed

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

2017-03-01

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

Distribution of the HLA class I allele in chronic hepatitis C and its association with serum ALT level in chronic hepatitis C.

PubMed

Kondo, Yasuteru; Kobayashi, Koju; Kobayashi, Tomoo; Shiina, Masaaki; Ueno, Yoshiyuki; Satoh, Takaomi; Shimosegawa, Tooru

2003-10-01

An essential process for resolution of viral infections is the efficient recognition and elimination of intracellular virus. Recognition of viral antigens in the form of short peptides associated with HLA class I molecule is a major task of CD8+ cytotoxic T lymphocytes. In this study, we have evaluated the frequency of the HLA class I alleles in patients with chronic hepatitis C. HLA-B51, -B52, -B55, -B56, -B61, B70, -Cw1, -Cw3, and -Cw4 are less frequent in patients with chronic hepatitis C than in Japanese individuals. The frequency of HLA-A2 is slightly lower in the patients but tends to be higher in patients with normal alanine aminotransferase (ALT) level than in those with elevated ALT level (p = 0.07). Other HLA alleles are not significantly different between two groups. Comparison of HLA homozygosity at HLA-A and -B or -C or at two or three loci did not show a significant association with levels of serum ALT or with the clinical outcome of interferon therapy in patients with hepatitis C. These results suggest a possibility that the alterations of host response, which depends on genetic background, influence disease activities of HCV infection.

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

PubMed Central

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

1970-01-01

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

Occult Hepatitis B Virus Among the Patients With Abnormal Alanine Transaminase

PubMed Central

Makvandi, Manoochehr; Neisi, Niloofar; Khalafkhany, Davod; Makvandi, Kamyar; Hajiani, Eskandar; Shayesteh, Ali Akbar; Masjedi Zadeh, Abdolrahim; Sina, Amir Hosein; Hamidifard, Mojtaba; Rasti, Mojtaba; Aryan, Ehsan; Ahmadi, Kambiz; Yad Yad, Mohammad Jafar

2014-01-01

Background: The occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the sera or in the liver biopsy and the absence of hepatitis B surface antigen (HBsAg) by serological test. Objectives: The current study aimed to evaluate the occult HBV infection by polymerase chain reaction (PCR) and determine HBV genotyping among the patients with abnormal alanine transaminase (ALT) in Ahvaz city, Iran. Patients and Methods: The sera of 120 patients, 54 (45%) females and 66 (55%) males, with abnormal ALT 40-152 IU were collected. All the patients were negative for HBsAg for more than one year. The patients` sera were tested by PCR using primers specified for the S region of HBV. Then the positive PCR products were sequenced to determine HBV genotyping and phylogenic tree. Results: Of these 120 subjects, 12 (10%) patients including 6 (5%) males and 6 (5%) females were found positive for HBV DNA by PCR, which indicated the presence of occult HBV infection among these patients. The sequencing results revealed that genotype D was predominant with sub-genotyping D1 among OBI patients. Conclusions: Occult hepatitis B infection is remarkably prevalent in Ahvaz, Iran, and should be considered as a potential risk factor for the transmission of Hepatitis B Virus throughout the community by the carriers. PMID:25485052

Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study.

PubMed

Viitasalo, A; Pihlajamaki, J; Lindi, V; Atalay, M; Kaminska, D; Joro, R; Lakka, T A

2015-04-01

PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase (ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after 2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up (P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. PNPLA3 148M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

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

PubMed

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

2010-12-16

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

Differences in levels of albumin, ALT, AST, γ-GT and creatinine in frail, moderately healthy and healthy elderly individuals.

PubMed

Edvardsson, Maria; Sund-Levander, Märtha; Milberg, Anna; Wressle, Ewa; Marcusson, Jan; Grodzinsky, Ewa

2018-02-23

Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and γ-glutamyl transferase (γ-GT) in frail, moderately healthy and healthy elderly indivuduals. Blood samples were collected from individuals >80 years old, nursing home residents, in the Elderly in Linköping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and γ-GT were analyzed using routine methods. Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of γ-GT variation. Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.

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

PubMed

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

2014-01-01

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

APPROACH & LANDING TEST (ALT) - SHUTTLE PATCH

NASA Image and Video Library

1976-11-01

S76-30340 (1976) --- This circular, red, white and blue emblem has been chosen as the official insignia for the Space Shuttle Approach and Landing Test (ALT) flights. A picture of the Orbiter 101 "Enterprise" is superimposed over a red triangle, which in turn is superimposed over a large inner circle of dark blue. The surnames of the members of the two ALT crews are in white in the field of blue. The four crew men are astronauts Fred W. Haise Jr., commander of the first crew; Joe H. Engle, commander of the second crew; and Richard H. Truly, pilot of the second crew. ALT is a series of flights with a modified Boeing 747 Shuttle Carrier Aircraft (SCA) as a ferry aircraft and airborne launch platform for the 67,300 kilogram (75-ton) "Enterprise". The Shuttle Orbiter atmospheric testing is in preparation for the first Earth-orbital flights scheduled in 1979.

Epigallocatechin-3-gallate (EGCG) attenuates concanavalin A-induced hepatic injury in mice.

PubMed

Liu, Dongmei; Zhang, Xiaoli; Jiang, Li; Guo, Yun; Zheng, Changqing

2014-05-01

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess anti-inflammatory and anti-oxidative properties. In this study, we investigated the protective effects of EGCG against concanavalin A (ConA)-induced liver injury and the underlying mechanisms. EGCG (5 mg/kg) was administered orally by gavage to mice twice daily for 10 days before an intravenous injection of ConA. We found that EGCG effectively rescued lethality, improved hepatic pathological damage, and decreased serum levels of alanine aminotransaminase (ALT) in ConA-challenged mice. Furthermore, EGCG also significantly prevented the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-6 in serum, reduced malondialdehyde (MDA) levels, and restored glutathione (GSH) content and superoxide dismutase (SOD) activity in liver tissues from ConA-challenged mice. Finally, nuclear factor (NF)-κB activation and expression levels of Toll-like receptor (TLR) 2, TLR4 and TLR9 protein in liver tissues were significantly inhibited by EGCG pretreatment. Taken together, our data suggest that EGCG possesses hepatoprotective properties against ConA-induced liver injury through its anti-inflammatory and anti-oxidant actions. Copyright © 2013 Elsevier GmbH. All rights reserved.

The ALTE mysteries: who's to blame?

PubMed

Wickham, Sara

2016-02-01

In this column, Sara Wickham takes a sideways look at issues relevant to midwives, students, women and families, inviting us to sit down with a cup of tea and ponder what we think we know. A recent paper on apparent life-threatening events (ALTEs) in newborn babies brought to mind an experience from practice, the cause of which remains a mystery. As many similar events are unexplained, is it acceptable that there is a tendency in the literature to claim that skin-to-skin contact and breastfeeding are risk factors for ALTEs?

Diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase.

PubMed

Tan, You-Wen; Zhou, Xing-Bei; Ye, Yun; He, Cong; Ge, Guo-Hong

2017-08-21

To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index (APRI), and liver stiffness measurement (LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase (PNALT). We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase (PIALT1) group [alanine transaminase (ALT) within 1-2 × upper limit of normal value (ULN)], and 64 in PIALT2 group (ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed. The pathological examination revealed moderate inflammatory necrosis ratios of 16.81% (16/95), 32.56% (28/86), and 45.31% (28/64), and moderate liver fibrosis of 24.2% (23/95), 33.72% (29/86), and 43.75% (28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group ( P < 0.05). No significant difference was found in the areas under the curve (AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group ( P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference ( P > 0.05) was found in AUCs for all comparisons ( P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI ( P < 0.05). APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

PubMed Central

Tan, You-Wen; Zhou, Xing-Bei; Ye, Yun; He, Cong; Ge, Guo-Hong

2017-01-01

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index (APRI), and liver stiffness measurement (LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase (PNALT). METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase (PIALT1) group [alanine transaminase (ALT) within 1-2 × upper limit of normal value (ULN)], and 64 in PIALT2 group (ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed. RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81% (16/95), 32.56% (28/86), and 45.31% (28/64), and moderate liver fibrosis of 24.2% (23/95), 33.72% (29/86), and 43.75% (28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group (P < 0.05). No significant difference was found in the areas under the curve (AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group (P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference (P > 0.05) was found in AUCs for all comparisons (P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI (P < 0.05). CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis. PMID:28883700

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

PubMed

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

2015-10-01

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

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

PubMed

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

2016-05-01

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

21 CFR 172.540 - DL-Alanine.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

PubMed

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

1991-05-01

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

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

PubMed

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

2016-04-01

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

Aerodynamic challenges of ALT

NASA Technical Reports Server (NTRS)

Hooks, I.; Homan, D.; Romere, P. O.

1985-01-01

The approach and landing test (ALT) of the Space Shuttle Orbiter presented a number of unique challenges in the area of aerodynamics. The purpose of the ALT program was both to confirm the use of the Boeing 747 as a transport vehicle for ferrying the Orbiter across the country and to demonstrate the flight characteristics of the Orbiter in its approach and landing phase. Concerns for structural fatigue and performance dictated a tailcone be attached to the Orbiter for ferry and for the initial landing tests. The Orbiter with a tailcone attached presented additional challenges to the normal aft sting concept of wind tunnel testing. The landing tests required that the Orbiter be separated from the 747 at approximately 20,000 feet using aerodynamic forces to fly the vehicles apart. The concept required a complex test program to determine the relative effects of the two vehicles on each other. Also of concern, and tested, was the vortex wake created by the 747 and the means for the Orbiter to avoid it following separation.

Characterisation of a flavonoid ligand of the fungal protein Alt a 1

PubMed Central

Garrido-Arandia, María; Silva-Navas, Javier; Ramírez-Castillejo, Carmen; Cubells-Baeza, Nuria; Gómez-Casado, Cristina; Barber, Domingo; Pozo, Juan C.; Melendi, Pablo G.; Pacios, Luis F.; Díaz-Perales, Araceli

2016-01-01

Spores of pathogenic fungi are virtually ubiquitous and cause human disease and severe losses in crops. The endophytic fungi Alternaria species produce host-selective phytotoxins. Alt a 1 is a strongly allergenic protein found in A. alternata that causes severe asthma. Despite the well-established pathogenicity of Alt a 1, the molecular mechanisms underlying its action and physiological function remain largely unknown. To gain insight into the role played by this protein in the pathogenicity of the fungus, we studied production of Alt a 1 and its activity in spores. We found that Alt a 1 accumulates inside spores and that its release with a ligand is pH-dependent, with optimum production in the 5.0–6.5 interval. The Alt a 1 ligand was identified as a methylated flavonoid that inhibits plant root growth and detoxifies reactive oxygen species. We also found that Alt a 1 changes its oligomerization state depending on the pH of the surrounding medium and that these changes facilitate the release of the ligand. Based on these results, we propose that release of Alt a 1 should be a pathogenic target in approaches used to block plant defenses and consequently to favor fungal entry into the plant. PMID:27633190

Characterisation of a flavonoid ligand of the fungal protein Alt a 1.

PubMed

Garrido-Arandia, María; Silva-Navas, Javier; Ramírez-Castillejo, Carmen; Cubells-Baeza, Nuria; Gómez-Casado, Cristina; Barber, Domingo; Pozo, Juan C; Melendi, Pablo G; Pacios, Luis F; Díaz-Perales, Araceli

2016-09-16

Spores of pathogenic fungi are virtually ubiquitous and cause human disease and severe losses in crops. The endophytic fungi Alternaria species produce host-selective phytotoxins. Alt a 1 is a strongly allergenic protein found in A. alternata that causes severe asthma. Despite the well-established pathogenicity of Alt a 1, the molecular mechanisms underlying its action and physiological function remain largely unknown. To gain insight into the role played by this protein in the pathogenicity of the fungus, we studied production of Alt a 1 and its activity in spores. We found that Alt a 1 accumulates inside spores and that its release with a ligand is pH-dependent, with optimum production in the 5.0-6.5 interval. The Alt a 1 ligand was identified as a methylated flavonoid that inhibits plant root growth and detoxifies reactive oxygen species. We also found that Alt a 1 changes its oligomerization state depending on the pH of the surrounding medium and that these changes facilitate the release of the ligand. Based on these results, we propose that release of Alt a 1 should be a pathogenic target in approaches used to block plant defenses and consequently to favor fungal entry into the plant.

β-Alanine supplementation and military performance.

PubMed

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

2015-12-01

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

Telomere sequence content can be used to determine ALT activity in tumours

PubMed Central

Lee, Michael; Teber, Erdahl T; Holmes, Oliver; Nones, Katia; Patch, Ann-Marie; Dagg, Rebecca A; Lau, Loretta M S; Lee, Joyce H; Napier, Christine E; Arthur, Jonathan W; Grimmond, Sean M; Hayward, Nicholas K; Johansson, Peter A; Mann, Graham J; Scolyer, Richard A; Wilmott, James S; Reddel, Roger R; Pearson, John V; Waddell, Nicola; Pickett, Hilda A

2018-01-01

Abstract The replicative immortality of human cancer cells is achieved by activation of a telomere maintenance mechanism (TMM). To achieve this, cancer cells utilise either the enzyme telomerase, or the Alternative Lengthening of Telomeres (ALT) pathway. These distinct molecular pathways are incompletely understood with respect to activation and propagation, as well as their associations with clinical outcomes. We have identified significant differences in the telomere repeat composition of tumours that use ALT compared to tumours that do not. We then employed a machine learning approach to stratify tumours according to telomere repeat content with an accuracy of 91.6%. Importantly, this classification approach is applicable across all tumour types. Analysis of pathway mutations that were under-represented in ALT tumours, across 1,075 tumour samples, revealed that the autophagy, cell cycle control of chromosomal replication, and transcriptional regulatory network in embryonic stem cells pathways are involved in the survival of ALT tumours. Overall, our approach demonstrates that telomere sequence content can be used to stratify ALT activity in cancers, and begin to define the molecular pathways involved in ALT activation. PMID:29718321

Maximization of orbiter altitude at ALT interface airspeed, mission planning, mission analysis and software

NASA Technical Reports Server (NTRS)

Glenn, G. M.

1976-01-01

The determination of the separation initial conditions (i.e. incidence angle) that maximize orbiter altitude at the ALT interface airspeed is considered. Optimum altitude airspeed profiles are generated for each orbiter incidence angle and tailcone configuration. Results show that the highest separation altitude does not result in the highest altitude at ALT interface airspeed. The altitude attainable at ALT interface airspeed should therefore be considered in the selection of the initial conditions (i.e. incidence angle). Without violating any known constraints, the incidence angles that maximize orbiter altitude at the ALT interface airspeeds are 7.0 deg for ALT free flight 1 and 5.5 deg for ALT free flight 6.

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

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

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

2007-09-01

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

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

PubMed

Kim, Sang-Wook; Ha, Ki-Chan; Choi, Eun-Kyung; Jung, Su-Young; Kim, Min-Gul; Kwon, Dae-Young; Yang, Hye-Jung; Kim, Min-Jung; Kang, Hee-Joo; Back, Hyang-Im; Kim, Sun-Young; Park, Soo-Hyun; Baek, Hum-Young; Kim, Yong-Jae; Lee, Joon-Yeol; Chae, Soo-Wan

2013-03-08

Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the

Alanine increases blood pressure during hypotension

NASA Technical Reports Server (NTRS)

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

1990-01-01

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

Post-test navigation data analysis techniques for the shuttle ALT

NASA Technical Reports Server (NTRS)

1975-01-01

Postflight test analysis data processing techniques for shuttle approach and landing tests (ALT) navigation data are defined. Postfight test processor requirements are described along with operational and design requirements, data input requirements, and software test requirements. The postflight test data processing is described based on the natural test sequence: quick-look analysis, postflight navigation processing, and error isolation processing. Emphasis is placed on the tradeoffs that must remain open and subject to analysis until final definition is achieved in the shuttle data processing system and the overall ALT plan. A development plan for the implementation of the ALT postflight test navigation data processing system is presented. Conclusions are presented.

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

PubMed

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

1986-11-01

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

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

PubMed

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.

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

PubMed

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

2017-12-01

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

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

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

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

1988-05-03

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

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

PubMed

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

2005-07-01

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

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

PubMed Central

2013-01-01

Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels

Understanding and Targeting the ALT Pathway in Human Breast Cancer

DTIC Science & Technology

2013-09-01

in human cancers. The genetic basis for activation of ALT is not known, but recent data have identified mutations and loss of ATRX protein as being...hallmarks of ALT- immortalized cell lines and tumors. Our efforts to understand the mechanism by which loss of ATRX facilitates telomere recombination...nucleosomal organization as being relevant mechanisms contributing to this phenotype. I have also determined that ATRX does not function in the known

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

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

Huang, Chenhui; Jia, Pingping; Chastain, Megan

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

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

PubMed

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

2016-06-10

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

Some Features of "Alt" Texts Associated with Images in Web Pages

ERIC Educational Resources Information Center

Craven, Timothy C.

2006-01-01

Introduction: This paper extends a series on summaries of Web objects, in this case, the alt attribute of image files. Method: Data were logged from 1894 pages from Yahoo!'s random page service and 4703 pages from the Google directory; an img tag was extracted randomly from each where present; its alt attribute, if any, was recorded; and the…

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

PubMed

Bellinger, Phillip M; Minahan, Clare L

2016-01-01

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

EPR/alanine dosimetry for two therapeutic proton beams

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

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

PubMed

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

2017-01-01

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

Oligosaccharide nanomedicine of alginate sodium improves therapeutic results of posterior lumbar interbody fusion with cages for degenerative lumbar disease in osteoporosis patients by downregulating serum miR-155.

PubMed

Qu, Yang; Wang, Zhengming; Zhou, Haohan; Kang, Mingyang; Dong, Rongpeng; Zhao, Jianwu

2017-01-01

Degenerative lumbar disease (DLD) is a significant issue for public health. Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion rate and realignment on DLD. However, there are some complications following the surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory activities and may be suitable for infection therapy. MiR-155 is a biomarker associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of alginate sodium (ONAS) were prepared with ampicillin at size <200 nm. Ninety-six DLD osteoporosis patients received PLIFC and were evenly assigned into ONAS group (OG, oral administration of 100 mg ONAS daily) and control group (PG, 100 mg pluronic nanoparticles). Serum miR-155 level was measured by real-time quantitative PCR. The levels of superoxide dismutase (SOD), glutathione (GSH), aspartate aminotransaminase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1ra) were measured. Weighted mean difference (WMD), relative risk (RR), complications, surgery infection rate, fusion rate, and Japanese Orthopaedic Association (JOA) scores were used to evaluate therapeutic efficacy. After 1-month therapy, infection rates and side effects were lower in OG than those in PG (RR =0.64, 95% confidence interval [CI] [0.48, 0.84], P =0.001). The fusion rates were higher in OG than in PG (WMD =21.96, 95% CI [-0.24, 37.62], P =0.021). The JOA scores were higher in OG than in PG (RR =0.52, 95% CI [0.33, 0.84], P =0.007), and no significant difference was found for the visual analog scale and Oswestry Disability Index. Serum levels of miR-155, ALT, AST, and IL-1β were lower while SOD, GSH, and IL-1ra were higher in OG than in PG. MiR-155 mimic increased the levels of ALT, AST, and IL-1β and reduced the levels of SOD, GSH, and IL-1ra. In contrast, miR-155 inhibitor had reverse

Army AL&T, July-September 2008

DTIC Science & Technology

2008-09-01

Technology , and Logistics (AT&L) Workforce and will summarize best practices , specific initiatives, and relevant accomplishments of DOD and the...PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Army Acquisition, Logistics & Technology (AT&L...logistics, and technology (AL&T) community. We have a vast number of programs that range from developing transformational technologies for our

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

PubMed

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

2018-01-01

Coronary artery disease is the most common cause of death in the patients with nonalcoholic fatty liver disease (NAFLD). Studies have shown that there is a strong relation between the increase in the aminotransferase levels and fat accumulation in the liver with cardiovascular complications, independent of all aspects of the metabolic syndrome. This study aimed to examine the effect of virgin olive oil on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the severity of steatosis in the NAFLD patients undergoing a weight-loss diet. This clinical trial was carried out on 50 patients with nonalcoholic fatty liver (mean age of 45.91 ± 9.61 years, mean BMI of 29.7 ± 0.58 Kg/m 2 ) and the subjects were randomly assigned to the olive oil group (receiving the equivalent of 20% of their total daily energy requirement from olive oil) or the control group (with normal consumption of oil) for 12 weeks. All the patients received a hypocaloric diet during the study. At the beginning and the end of the study, the serum levels of ALT and AST and liver steatosis were measured. A significant decrease in the level of ALT enzymes was observed in the control group at the end of the study ( P = 0.004). In the olive oil group, both enzymes decreased compared to baseline measurements ( P < 0.01). There were significant differences in the ALT and AST levels between the two groups ( P < 0.02). The severity of liver steatosis did not change significantly during the study. The consumption of a low calorie diet enriched with olive oil, along with slight weight reduction, reinforces the desired effects of weight loss in improving the levels of the hepatic enzymes.

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

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

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

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

IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer

PubMed Central

Felices, M.; Chu, S.; Kodal, B.; Bendzick, L.; Ryan, C.; Lenvik, A.J.; Boylan, K.L.M.; Wong, H.C.; Skubitz, A.P.N.; Miller, J.S.; Geller, M.A.

2017-01-01

Objective Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. Methods NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays +/− ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. Results ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. Conclusions ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK-cell-based immunotherapeutic approaches for the treatment of ovarian cancer. PMID:28236454

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

PubMed

Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang

2017-06-15

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Dose response of alanine detectors irradiated with carbon ion beams

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

Herrmann, Rochus; Jaekel, Oliver; Palmans, Hugo

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

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

PubMed

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

2004-05-01

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

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

PubMed

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

2009-01-01

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

ImmunoPET imaging of tissue factor expression in pancreatic cancer with 89Zr-Df-ALT-836.

PubMed

Hernandez, Reinier; England, Christopher G; Yang, Yunan; Valdovinos, Hector F; Liu, Bai; Wong, Hing C; Barnhart, Todd E; Cai, Weibo

2017-10-28

Overexpression of tissue factor (TF) has been associated with increased tumor growth, tumor angiogenesis, and metastatic potential in many malignancies, including pancreatic cancer. Additionally, high TF expression was shown to strongly correlate with poor prognoses and decreased survival in pancreatic cancer patients. Herein, we exploited the potential targeting of TF for positron emission tomography (PET) imaging of pancreatic cancer. The TF-targeted tracer was developed through radiolabeling of the anti-human TF monoclonal antibody (ALT-836) with 89 Zr. The tracer was characterized by fluorescence microscopy and flow cytometry assays in BXPC-3 and PANC-1 cells, two pancreatic cancer cell lines with high and low TF expression levels, respectively. Non-invasive PET scans were acquired in tumor-bearing mice injected with 89 Zr-Df-ALT-836. Additionally, ex vivo biodistribution, blocking, and histological studies were performed to establish the affinity and specificity of 89 Zr-Df-ALT-836 for TF in vivo. 89 Zr-labeling of Df-ALT-836 was achieved in high yield and good specific activity. Flow cytometry and microscopy studies revealed no detectable difference in TF-binding affinity between ALT-836 and Df-ALT-836 in vitro. Longitudinal PET scans unveiled a lasting and prominent 89 Zr-Df-ALT-836 uptake in BXPC-3 tumors (peak at 31.5±6.0%ID/g at 48h post-injection; n=3), which was significantly abrogated (2.3±0.5%ID/g at 48h post-injection; n=3) when mice were pre-injected with a blocking dose (50mg/kg) of unlabeled ALT-836. Ex vivo biodistribution data confirmed the accuracy of the PET results, and histological analysis correlated high tumor uptake with in situ TF expression. Taken together, these results attest to the excellent affinity and TF-specificity of 89 Zr-Df-ALT-836. With elevated, persistent, and specific accumulation in TF-positive BXPC-3 tumors, PET imaging using 89 Zr-Df-ALT-836 promises to open new avenues for improving future diagnosis, stratification

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

PubMed

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

2008-06-01

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

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

PubMed

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

2010-06-01

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

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

NASA Technical Reports Server (NTRS)

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

1984-01-01

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

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

PubMed

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

2017-09-28

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

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

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

Code of Federal Regulations, 2010 CFR

2010-07-01

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

Atomic Layer Deposition of L-Alanine Polypeptide

DOE PAGES

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

2014-10-30

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

Army AL&T, April-June 2008

DTIC Science & Technology

2008-06-01

IR )/laser designator (LD)/laser range finder (LRF) sensor. The Class I UAS consists of a Class I UAV, a cen- tralized controller and a minimal set...utility of a backpackable, affordable, easy-to- operate and responsive reconnais- sance and surveillance system through experimentation. • Use EO/ IR ...ARMY AL&T 33APRIL - JUNE 2008 • “The IR sensor pinpointed the enemy even after the sun went down. We could have really used this in Iraq.” • “The UAV

A New Technique for Precision Photometry Using Alt/Az Telescopes

NASA Astrophysics Data System (ADS)

Kirkaptrick, Colin; Stacey, Piper; Swift, Jonathan

2018-06-01

We present and test a new method for flat field calibration of images obtained on telescopes with altitude-azimuth (Alt-Az) mounts. Telescopes using Alt-Az mounts typically employ a field “de-rotator” to account for changing parallactic angles of targets observed across the sky, or for long exposures of a single target. This “de-rotation” results in a changing orientation of the telescope optics with respect to the camera. This, in turn, can result in a flat field that is a function of camera orientation due to, for example, vignetting. In order to account for these changes we develop and test a new flat field technique using the observations of known transiting exoplanets.

Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease.

PubMed

Wong, D R; Coenen, M J H; Derijks, L J J; Vermeulen, S H; van Marrewijk, C J; Klungel, O H; Scheffer, H; Franke, B; Guchelaar, H-J; de Jong, D J; Engels, L G J B; Verbeek, A L M; Hooymans, P M

2017-02-01

Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment. The cohort study consisted of the first 270 IBD patients starting thiopurine treatment as part of the Dutch randomised-controlled trial evaluating pre-treatment thiopurine S-methyltransferase genotype testing (ClinicalTrials.gov NCT00521950). Blood samples for metabolite assessment were collected at T1. Hepatotoxicity was defined by alanine aminotransaminase elevations >2 times the upper normal limit or a ratio of alanine aminotransaminase/alkaline phosphatase ≥5. Forty-seven patients (17%) presented hepatotoxicity during the first 20 weeks of thiopurine treatment. A T1 6-MMPR threshold of 3615 pmol/8 × 10 8 erythrocytes was defined. Analysis of patients on stable thiopurine dose (n = 174) showed that those exceeding the 6-MMPR threshold were at increased risk of hepatotoxicity: OR = 3.8 (95% CI: 1.8-8.0). Age, male gender and BMI were significant determinants. A predictive algorithm was developed based on these determinants and the 6-MMPR threshold to assess hepatotoxicity risk [AUC = 0.83 (95% CI: 0.75-0.91)]. 6-MMPR concentrations above the threshold also correlated with gastrointestinal complaints: OR = 2.4 (95% CI: 1.4-4.3), and general malaise: OR = 2.0 (95% CI: 1.1-3.7). In more than 80% of patients, thiopurine-induced hepatotoxicity could be explained by elevated T1 6-MMPR concentrations and the independent risk factors age, gender and BMI, allowing personalised thiopurine treatment in IBD to prevent early failure. © 2016 John Wiley & Sons Ltd.

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

PubMed Central

la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

2013-01-01

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

The ASCUS/LSIL Triage Study for Cervical Cancer (ALTS) | Division of Cancer Prevention

Cancer.gov

ALTS was a clinical trial to find the best way to help women and their doctors decide what to do about the mildly abnormal and very common Pap test results known as ASCUS and LSIL. | ALTS was a clinical trial to find the best way to help women and their doctors decide what to do about the mildly abnormal and very common Pap test results known as ASCUS and LSIL.

Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function

PubMed Central

Gomez-Escobar, Natalia; Bennett, Clare; Prieto-Lafuente, Lidia; Aebischer, Toni; Blackburn, Clare C; Maizels, Rick M

2005-01-01

Background Parasites exploit sophisticated strategies to evade host immunity that require both adaptation of existing genes and evolution of new gene families. We have addressed this question by testing the immunological function of novel genes from helminth parasites, in which conventional transgenesis is not yet possible. We investigated two such novel genes from Brugia malayi termed abundant larval transcript (alt), expression of which reaches ~5% of total transcript at the time parasites enter the human host. Results To test the hypothesis that ALT proteins modulate host immunity, we adopted an alternative transfection strategy to express these products in the protozoan parasite Leishmania mexicana. We then followed the course of infection in vitro in macrophages and in vivo in mice. Expression of ALT proteins, but not a truncated mutant, conferred greater infectivity of macrophages in vitro, reaching 3-fold higher parasite densities. alt-transfected parasites also caused accelerated disease in vivo, and fewer mice were able to clear infection of organisms expressing ALT. alt-transfected parasites were more resistant to IFN-γ-induced killing by macrophages. Expression profiling of macrophages infected with transgenic L. mexicana revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, both associated with the Th2-type response observed in in vivo filarial infection. Conclusion Leishmania transfection is a tractable and informative approach to determining immunological functions of single genes from heterologous organisms. In the case of the filarial ALT proteins, our data suggest that they may participate in the Th2 bias observed in the response to parasite infection by modulating cytokine-induced signalling within immune system cells. PMID:15788098

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

NASA Astrophysics Data System (ADS)

Chatterjee, Subhojyoti; Ahmed, Marawan; Wang, Feng

2016-02-01

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

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

PubMed

Klatte, Stephanie; Wendisch, Volker F

2015-01-23

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

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

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

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

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

AltText: A Showcase of User Centred Design in the Netherlands

NASA Astrophysics Data System (ADS)

Asjes, Kathleen

In the information processing chain many documents are produced that are inaccessible to the reading impaired. The altText project aims to increase the accessibility of this content by: a) raising awareness among content providers about content adaption; b) allowing content providers to deliver content in a way that suits the needs of the information receiver; c) developing an online service that converts written text into several accessible formats (Braille, synthetic speech, large print or DaisyXML). The name of this service is the altText conversion portal. The paper argues that user centred innovation will be crucial to the success of this project.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-05-01

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

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

PubMed Central

Frizzell, Raymond A.; Schultz, Stanley G.

1970-01-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2016-10-01

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

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

PubMed

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

1994-08-01

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

Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes.

PubMed

Reddy, Sridhar M; Reddy, Pooja M; Amdare, Nitin; Khatri, Vishal; Tarnekar, Aaditya; Goswami, Kalyan; Reddy, Maryada Venkata Rami

2017-03-01

Type 1 diabetes (T1D) that accounts for about 5-10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasite Brugia malayi ( rBm ALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice. The diabetic mice on treatment with r Bm ALT-2 showed a significant ( p  < 0.0005) decrease in their fasting blood glucose levels. By the end of the second week after the initiation of treatment with the r Bm ALT-2, 28 % of the diabetic mice became normal and none of them were diabetic by the end of 5th week. The anti-diabetic effect of r Bm ALT-2 significantly correlated with the concomitant redressal of the pancreatic histopathological damage caused by STZ assault (rho = 0.87; p  < 0.0005). The sera of r Bm ALT-2 treated diabetic mice had increased levels of IgG1 antibodies associated with decreased IgG2a antibodies against the principal autoantigen insulin. The splenocyte proliferative response and the cytokine release in the treated mice showed marked bias against inflammation skewing the immune response to Th-2 type. From this study, it can be envisaged that that filarial proteins like r Bm ALT-2 with effective immunomodulatory activity and anti-diabetic effect are promising alternative therapeutic agents for T1D.

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

PubMed

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

2011-08-19

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

Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients.

PubMed

Tahara, Nobuhiro; Yamagishi, Sho-Ichi; Bekki, Munehisa; Kodama, Norihiro; Nakamura, Tomohisa; Sugiyama, Yoichi; Oshige, Tamami; Kumashiro, Yuki; Honda, Akihiro; Tahara, Atsuko; Igata, Sachiyo; Fukumoto, Yoshihiro

2016-01-01

Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a therapeutic target for type 2 diabetes (T2DM). Arterial stiffness, a predictor of future cardiovascular events and all-cause mortality, is augmented in these patients. However, effects of DPP-4 inhibitors on arterial stiffness remain unknown. In this study, we compared effects of anagliptin, an inhibitor of DPP-4 on arterial stiffness evaluated by cardio-ankle vascular index (CAVI) with those of an equipotent glucose-lowering agent, glimepiride in patients with T2DM. The study involved 50 consecutive outpatients (33 males and 17 females; mean age of 72.5±9.5 years) who visited our hospitals for a risk-screening test or treatment for T2DM. They underwent complete history and physical examination, and determination of blood chemistry and anthropometric variables, and then were randomized to receive either anagliptin (n=26) or glimepiride (n=24) for 6 months. After 6-months treatment, fasting plasma glucose and HbA1c values were comparably reduced in both groups. Anagliptin, but not glimepiride treatment significantly decreased low-density lipoprotein cholesterol, malondialdehyde-modified LDL, remnant-like particle (RLP) cholesterol, CAVI, alanine transaminase (ALT), γ-glutamyl transferase and visceral fat volume. In multiple regression analysis, absolute changes from baseline of RLP cholesterol and ALT after anagliptin treatment for 6 months (ΔRLP cholesterol and ΔALT) were independently correlated with ΔCAVI (R2=0.445). The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function.

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

PubMed

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

2016-07-31

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

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

PubMed

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

2014-10-06

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

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 582.5118 - Alanine.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

ALT1, a Snf2 Family Chromatin Remodeling ATPase, Negatively Regulates Alkaline Tolerance through Enhanced Defense against Oxidative Stress in Rice

PubMed Central

Guo, Mingxin; Wang, Ruci; Wang, Juan; Hua, Kai; Wang, Yueming; Liu, Xiaoqiang; Yao, Shanguo

2014-01-01

Alkaline salt stress adversely affects rice growth, productivity and grain quality. However, the mechanism underlying this process remains elusive. We characterized here an alkaline tolerant mutant, alt1 in rice. Map-based cloning revealed that alt1 harbors a mutation in a chromatin remodeling ATPase gene. ALT1-RNAi transgenic plants under different genetic background mimicked the alt1 phenotype, exhibiting tolerance to alkaline stress in a transcript dosage-dependent manner. The predicted ALT1 protein belonged to the Ris1 subgroup of the Snf2 family and was localized in the nucleus, and transcription of ALT1 was transiently suppressed after alkaline treatment. Although the absorption of several metal ions maintained well in the mutant under alkaline stress, expression level of the genes involved in metal ions homeostasis was not altered in the alt1 mutant. Classification of differentially expressed abiotic stress related genes, as revealed by microarray analysis, found that the majority (50/78) were involved in ROS production, ROS scavenging, and DNA repair. This finding was further confirmed by that alt1 exhibited lower levels of H2O2 under alkaline stress and tolerance to methyl viologen treatment. Taken together, these results suggest that ALT1 negatively functions in alkaline tolerance mainly through the defense against oxidative damage, and provide a potential two-step strategy for improving the tolerance of rice plants to alkaline stress. PMID:25473841

The Metabolic Effects of Consumption of Yellow Cassava (Manihot esculenta Crantz) on Some Biochemical Parameters in Experimental Rats.

PubMed

Udeme, Nelson; Okafor, Polycarp; Eleazu, Chinedum

2015-01-01

The metabolism of yellow cassava (variety TMS 01/1368) was investigated in male albino rats fed a diet containing yellow cassava for 7 to 28 days. There were significant increases (P < 0.05) in total and free cyanide and thiocyanate in the sera and urine samples of the experimental rats compared with the control, significant increases (P < 0.05) in serum glucose, alanine aminotransaminase, aspartate aminotransaminase, and alkaline phosphatase levels of the experimental rats compared with the control, significant decreases (P < 0.05) in serum albumin of the experimental rats compared with the control, but no significant differences (P > 0.05) in the serum total proteins of the experimental rats compared with the control. The experimental rats treated for 7, 14, 21, or 28 days exhibited body weight decreases of 5.11%, 11.10%, 19.16%, and 24.18%, respectively, whereas the control group showed 9.17% gain in body weight. Total and free cyanide concentrations were detected in the liver, kidney, and heart of most of the rats in both the experimental and control groups, except for free cyanide in the control group that was not detected. Metabolism of the yellow cassava variety in experimental rats was capable of exposing the animals to cyanide, underscoring the need for its proper processing before consumption by humans. © The Author(s) 2015.

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

PubMed

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

2004-01-01

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

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

PubMed

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

2005-02-01

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

Alanine transaminase level in a healthy population in Morocco.

PubMed

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

2012-03-01

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

Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane.

PubMed

Ma, Xiaoe; Zhou, Naizhen; Zhang, Tianzhu; Hu, Wanjun; Gu, Ning

2017-04-01

Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer β-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-β-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of β-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-09-01

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

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

PubMed

Fainstein, C; Winkler, E; Saravi, M

2000-05-01

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

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

PubMed Central

Qasem, Jamal R.

2012-01-01

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

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

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

Al-Karmi, Anan M.; Zraiqat, Fadi

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

Eating a healthy lunch improves serum alanine aminotransferase activity.

PubMed

Iwamoto, Masako; Yagi, Kaori; Yazumi, Kayoko; Komine, Airi; Shirouchi, Bungo; Sato, Masao

2013-09-14

Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the 'once-a-day' intervention of a healthy lunch on various metabolic parameters. For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. In summary, the 'once-a-day' intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition.

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

PubMed Central

Park, Joong-Won

2016-01-01

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

Crystal Structures of Aedes Aegypt Alanine Glyoxylate Aminotransferase

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

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

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 themore » 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.« less

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Telomere Length Maintenance in Cancer: At the Crossroad between Telomerase and Alternative Lengthening of Telomeres (ALT)

PubMed Central

De Vitis, Marco; Berardinelli, Francesco; Sgura, Antonella

2018-01-01

Eukaryotic cells undergo continuous telomere shortening as a consequence of multiple rounds of replications. During tumorigenesis, cells have to acquire telomere DNA maintenance mechanisms (TMMs) in order to counteract telomere shortening, to preserve telomeres from DNA damage repair systems and to avoid telomere-mediated senescence and/or apoptosis. For this reason, telomere maintenance is an essential step in cancer progression. Most human tumors maintain their telomeres expressing telomerase, whereas a lower but significant proportion activates the alternative lengthening of telomeres (ALT) pathway. However, evidence about the coexistence of ALT and telomerase has been found both in vivo in the same cancer populations and in vitro in engineered cellular models, making the distinction between telomerase- and ALT-positive tumors elusive. Indeed, after the development of drugs able to target telomerase, the capability for some cancer cells to escape death, switching from telomerase to ALT, was highlighted. Unfortunately, to date, the mechanism underlying the possible switching or the coexistence of telomerase and ALT within the same cell or populations is not completely understood and different factors could be involved. In recent years, different studies have tried to shed light on the complex regulation network that controls the transition between the two TMMs, suggesting a role for embryonic cancer origin, epigenetic modifications, and specific genes activation—both in vivo and in vitro. In this review, we examine recent findings about the cancer-associated differential activation of the two known TMMs and the possible factors implicated in this process. Furthermore, some studies on cancers are also described that did not display any TMM. PMID:29463031

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

PubMed Central

Gojković, Z; Sandrini, M P; Piskur, J

2001-01-01

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

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

PubMed Central

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

1996-01-01

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

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

PubMed

Anjos, Alessandra Marques dos; Nunes, Magda Lahorgue

2009-09-01

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

Prevalence of abnormal serum alanine aminotransferase levels in type 2 diabetic patients in Iran.

PubMed

Meybodi, M A; Afkhami-Ardekani, M; Rashidi, M

2008-09-15

This study was performed to estimate prevalence of transaminase levels in type 2 diabetic patients and identify contributing risk factors. In this cross-sectional study 348 patients with type 2 diabetes, who attended the diabetic clinic of Yazd Diabetes Research Center, were studied from October 2004 to December 2005. Patients with history of viral hepatitis, alcohol abuse and use of drug such as Amiodarone, Bleomycin, methotrexate, tamoxifen and sodium valporate was excluded. To examine the relationships between ALT, AST in individuals with type II diabetes and relation to various metabolic parameters like triglyceride, cholesterol, age, duration of diabetes, gender and BMI. Of 348 patients that entered the study, mean age was 58.8 +/- 11.5. Elevated ALT and AST were found in 10.4 and 3.3% of type 2 diabetic patients, respectively. Although the prevalence of elevated ALT increased with increasing age, FBS and triglyceride levels in subjects, but it was not statistically significant. There was a significant association between elevated ALT and gender as well as diabetes duration. The prevalence of elevated of ALT in type 2 diabetic patients is 1.6 times higher than general population in Iran unrelated to age, BMI, glycemic control, triglyceride levels. Identification risk factors and mechanisms of these elevations are very important and require further evaluation.

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

PubMed

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

2018-06-19

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

Approach & Landing Test (ALT) - Shuttle Free-Flight (FF)-2, News Release

NASA Image and Video Library

1977-09-13

S77-28138 (13 Sept 1977) --- The shuttle Orbiter 101 "Enterprise" makes a slight turn and bank maneuver during the second free flight of the Shuttle Approach and Landing Tests (ALT) conducted on September 13, 1977, at the Dryden Flight Research Center in Southern California. The "Enterprise" separated from the NASA 747 carrier aircraft and landed following a five-minute, 28-second unpowered flight. The Orbiter 101 crew was astronauts Joe H. Engle, commander, and Richard H. Truly, pilot. The ALT free flights are designed to verify orbiter subsonic airworthiness, integrated systems operations and pilot-guided approach and landing capability and satisfy prerequisites to automatic flight control and navigation mode. The orbiter soars above the dry California desert in this post-separation view. Astronaut C. Gordon Fullerton took this picture while riding in T-38 chase plane number one. He used a 35mm Nikon camera with a 50mm lens.

Baseline Serum Clinical Chemistry Values in African Green Monkeys Before and After Sulfur Mustard

DTIC Science & Technology

2007-05-01

aspartate transaminase (189 %), blood urea nitrogen (75 %), creatine kinase (721 %), and lactate dehydrogenase (114 %) one day after HD exposure...ALT, 93 %), aspartate transaminase (AST, 189 %), blood urea nitrogen (BUN, 75 %), creatine kinase (CK, 721 %), and lactate dehydrogenase (LDH, 114...alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), calcium (Ca2+), creatine kinase (CK

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

PubMed

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

2017-09-18

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

Discriminatory value of alanine aminotransferase for diabetes prediction: the Insulin Resistance Atherosclerosis Study.

PubMed

Lorenzo, C; Hanley, A J; Rewers, M J; Haffner, S M

2016-03-01

To examine the incremental usefulness of adding alanine aminotransferase to established risk factors for predicting future diabetes. The study population of the Insulin Resistance Atherosclerosis Study included 724 people aged 40-69 years. We excluded people who had excessive alcohol intake or were treated with lipid-lowering agents. Incident diabetes was assessed after a mean follow-up period of 5.2 years. Alanine aminotransferase had a non-linear relationship with incident diabetes (Wald chi-squared test, P < 0.001; P for linearity = 0.005) independent of demographic variables, family history of diabetes, BMI and fasting glucose; therefore, we used Youden's J statistic to dichotomize alanine aminotransferase [threshold ≥ 0.43 μkat/L ( ≥ 26 IU/l)]. Dichotomized alanine aminotransferase increased the area under the receiver-operating characteristic curve (0.805 vs. 0.823; P = 0.007) of a model that included demographic variables, family history of diabetes, BMI and fasting glucose as independent variables. The net reclassification improvement was 9.6% (95% CI 1.8-17.4; P = 0.016), and the integrated discrimination improvement was 0.031 (95% CI 0.011-0.050; P = 0.002). Dichotomized alanine aminotransferase reclassified a net of 9.6% of individuals more appropriately. Alanine aminotransferase may be useful for classifying individuals who are at risk of future diabetes after accounting for the effect of other risk factors, including family history, adiposity and plasma glucose. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Approach & Landing Test (ALT) - Shuttle Free-Flight (FF)-2 - New Release

NASA Image and Video Library

1977-09-13

S77-28141 (13 Sept 1977) --- The shuttle Orbiter 101 "Enterprise" makes a slight turn and bank maneuver during the second free flight of the Shuttle Approach and Landing Tests (ALT) conducted on September 13, 1977, at the Dryden Flight Research Center in Southern California. The "Enterprise" separated from the NASA 747 carrier aircraft and landed following a five-minute, 28-second unpowered flight. The Orbiter 101 crew was astronauts Joe H. Engle, commander, and Richard H. Truly, pilot. The ALT free flights are designed to verify orbiter subsonic airworthiness, integrated systems operations and pilot-guided approach and landing capability and satisfy prerequisites to automatic flight control and navigation mode. The orbiter soars above the dry California desert in this post-separation view. Photographer Bill Blunck of JSC's Photographic Technology Laboratory took this picture while riding in T-38 chase plane number two. He used a 70mm Hasselblad camera with an 80mm lens.

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

PubMed Central

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

2004-01-01

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

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

PubMed

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

2013-01-01

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

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

PubMed Central

2014-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2014-08-01

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

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

DTIC Science & Technology

2010-01-01

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

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

PubMed

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

2018-04-13

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

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

PubMed

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

2011-04-01

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

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

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

Liu, Ling; Xiong, Yi; Gao, Hongyun

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

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

PubMed

Wołoszyn, Łukasz; Ilczyszyn, Maria M

2018-03-15

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

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

DOE PAGES

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

2018-04-02

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

[Establishing biological reference intervals of alanine transaminase for clinical laboratory stored database].

PubMed

Guo, Wei; Song, Binbin; Shen, Junfei; Wu, Jiong; Zhang, Chunyan; Wang, Beili; Pan, Baishen

2015-08-25

To establish an indirect reference interval based on the test results of alanine aminotransferase stored in a laboratory information system. All alanine aminotransferase results were included for outpatients and physical examinations that were stored in the laboratory information system of Zhongshan Hospital during 2014. The original data were transformed using a Box-Cox transformation to obtain an approximate normal distribution. Outliers were identified and omitted using the Chauvenet and Tukey methods. The indirect reference intervals were obtained by simultaneously applying nonparametric and Hoffmann methods. The reference change value was selected to determine the statistical significance of the observed differences between the calculated and published reference intervals. The indirect reference intervals for alanine aminotransferase of all groups were 12 to 41 U/L (male, outpatient), 12 to 48 U/L (male, physical examination), 9 to 32 U/L (female, outpatient), and 8 to 35 U/L (female, physical examination), respectively. The absolute differences when compared with the direct results were all smaller than the reference change value of alanine aminotransferase. The Box-Cox transformation combined with the Hoffmann and Tukey methods is a simple and reliable technique that should be promoted and used by clinical laboratories.

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

PubMed

Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically

Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

PubMed

Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

2015-09-01

Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

DSLR Double Star Astrometry Using an Alt-Az Telescope

NASA Astrophysics Data System (ADS)

Frey, Thomas; Haworth, David

2014-07-01

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

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

PubMed

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

2014-03-01

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

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

PubMed

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

2015-02-03

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

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

PubMed Central

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

2000-01-01

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

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

PubMed

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

2017-07-04

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

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

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

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

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

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

DOE PAGES

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

2018-01-01

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

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

PubMed

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

2017-10-01

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

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

PubMed

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

2016-12-16

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

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

PubMed

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

2014-05-19

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

Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-(13)C]pyruvate.

PubMed

Josan, Sonal; Billingsley, Kelvin; Orduna, Juan; Park, Jae Mo; Luong, Richard; Yu, Liqing; Hurd, Ralph; Pfefferbaum, Adolf; Spielman, Daniel; Mayer, Dirk

2015-12-01

To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13)C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13)C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4-treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4-treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4-treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4-treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13)C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Role of insulin resistance and adipocytokines on serum alanine aminotransferase in obese patients with type 2 diabetes mellitus.

PubMed

de Luis, D A; Aller, R; Izaola, O; Gonzalez Sagrado, M; Conde, R; de la Fuente, B

2013-01-01

The aim of our study was to study the association of insulin resistance expressed by HOMA and adipokines in obese type 2 diabetic patients with or without hyper-transaminasemia. A population of 72 obese patients with type 2 diabetes mellitus was analyzed. HOMA-IR was calculated as indicator of insulin-resistance. Adipocytokines blood levels were measured. Patients were classified as group I (n=37) when serum ALT activity was normal or group II (NAFLD patients: n=35) when serum ALT activity was greater than the median value of the group (≥ 28 UI/L). In NAFLD group, BMI, weight, fat mass, waist to hip ratio, waist circumference, triglycerides, HOMA and insulin levels were higher than control group. In the logistic regression analysis with a dependent variable (ALT) and the statistical univariant variables as independent variables, the HOMA-IR remained in the model, with an Odd's ratio of 1.21 (CI:95%: 1.11-1.35) to have a high ALT level with each 1 unit of HOMA-IR adjusted by age, sex, weight, and dietary intake. Some metabolic parameters are associated with elevated ALT in female obese patients. However, adjusted by other variables, only insulin resistance remained associated.

Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold

NASA Astrophysics Data System (ADS)

Garrido-Arandia, María; Bretones, Jorge; Gómez-Casado, Cristina; Cubells, Nuria; Díaz-Perales, Araceli; Pacios, Luis F.

2016-05-01

Alt a 1 is a highly allergenic protein from Alternaria fungi responsible for several respiratory diseases. Its crystal structure revealed a unique β-barrel fold that defines a new family exclusive to fungi and forms a symmetrical dimer in a butterfly-like shape as well as tetramers. Its biological function is as yet unknown but its localization in cell wall of Alternaria spores and its interactions in the onset of allergy reactions point to a function to transport ligands. However, at odds with binding features in β-barrel proteins, monomeric Alt a 1 seems unable to harbor ligands because the barrel is too narrow. Tetrameric Alt a 1 is able to bind the flavonoid quercetin, yet the stability of the aggregate and the own ligand binding are pH-dependent. At pH 6.5, which Alt a 1 would meet when secreted by spores in bronchial epithelium, tetramer-quercetin complex is stable. At pH 5.5, which Alt a 1 would meet in apoplast when infecting plants, the complex breaks down. By means of a combined computational study that includes docking calculations, empirical p Ka estimates, Poisson-Boltzmann electrostatic potentials, and Molecular Dynamics simulations, we identified a putative binding site at the dimeric interface between subunits in tetramer. We propose an explanation on the pH-dependence of both oligomerization states and protein-ligand affinity of Alt a 1 in terms of electrostatic variations associated to distinct protonation states at different pHs. The uniqueness of this singular protein can thus be tracked in the combination of all these features.

Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold.

PubMed

Garrido-Arandia, María; Bretones, Jorge; Gómez-Casado, Cristina; Cubells, Nuria; Díaz-Perales, Araceli; Pacios, Luis F

2016-05-01

Alt a 1 is a highly allergenic protein from Alternaria fungi responsible for several respiratory diseases. Its crystal structure revealed a unique β-barrel fold that defines a new family exclusive to fungi and forms a symmetrical dimer in a butterfly-like shape as well as tetramers. Its biological function is as yet unknown but its localization in cell wall of Alternaria spores and its interactions in the onset of allergy reactions point to a function to transport ligands. However, at odds with binding features in β-barrel proteins, monomeric Alt a 1 seems unable to harbor ligands because the barrel is too narrow. Tetrameric Alt a 1 is able to bind the flavonoid quercetin, yet the stability of the aggregate and the own ligand binding are pH-dependent. At pH 6.5, which Alt a 1 would meet when secreted by spores in bronchial epithelium, tetramer-quercetin complex is stable. At pH 5.5, which Alt a 1 would meet in apoplast when infecting plants, the complex breaks down. By means of a combined computational study that includes docking calculations, empirical pKa estimates, Poisson-Boltzmann electrostatic potentials, and Molecular Dynamics simulations, we identified a putative binding site at the dimeric interface between subunits in tetramer. We propose an explanation on the pH-dependence of both oligomerization states and protein-ligand affinity of Alt a 1 in terms of electrostatic variations associated to distinct protonation states at different pHs. The uniqueness of this singular protein can thus be tracked in the combination of all these features.

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

USGS Publications Warehouse

Franson, J. Christian

1982-01-01

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

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

PubMed

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

2018-06-01

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

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

PubMed Central

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

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

PubMed

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

2014-11-01

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

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

PubMed

Ramadoss, Vijayaraj; Dehez, François; Chipot, Christophe

2016-06-27

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

Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.

PubMed

Miles, E D; McBride, B W; Jia, Y; Liao, S F; Boling, J A; Bridges, P J; Matthews, J C

2015-09-01

Aged beef cows (≥ 8 yr of age) produce calves with lower birth and weaning weights. In mammals, aging is associated with reduced hepatic expression of glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic Gln-Glu cycle function. To determine if the relative protein content of GS, ALT, aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs. young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and (b) aged mixed-breed cows with and without COMPUDOSE (17β-estradiol) ear implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young (3.62 ± 0.01 yr) and 13 aged (10.08 ± 0.42 yr) cows grazed the same mixed forage for 42 d (August-October). In Exp. 2, 12 young (3.36 ± 0.01 yr) and 12 aged (10.38 ± 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage-based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change ( ≥ 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1 and 2, respectively) was decreased ( ≤ 0.01), whereas GTRAP3-18 (an inhibitor of EAAC1 activity) increased ( ≤ 0.01; 170% and 136%) and AST, GLT-1, and EAAC1 contents did not differ ( ≥ 0.17) in aged vs. young cows. In Exp. 2, free concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged (> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of 17β-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant treatment. Treatment, time after implant (DAY), and TRT × DAY effects were assessed by ANOVA using

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

PubMed

Lawson, A

2010-01-01

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

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

PubMed

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

2003-01-01

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

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

PubMed

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

2015-11-01

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

On the Trajectories of the Predetermined ALT Model: What Are We Really Modeling?

ERIC Educational Resources Information Center

Jongerling, Joran; Hamaker, Ellen L.

2011-01-01

This article shows that the mean and covariance structure of the predetermined autoregressive latent trajectory (ALT) model are very flexible. As a result, the shape of the modeled growth curve can be quite different from what one might expect at first glance. This is illustrated with several numerical examples that show that, for example, a…

Preparation of a Sepia Melanin and Poly(ethylene-alt-maleic Anhydride) Hybrid Material as an Adsorbent for Water Purification.

PubMed

Panzarasa, Guido; Osypova, Alina; Consolati, Giovanni; Quasso, Fiorenza; Soliveri, Guido; Ribera, Javier; Schwarze, Francis W M R

2018-01-23

Meeting the increasing demand of clean water requires the development of novel efficient adsorbent materials for the removal of organic pollutants. In this context the use of natural, renewable sources is of special relevance and sepia melanin, thanks to its ability to bind a variety of organic and inorganic species, has already attracted interest for water purification. Here we describe the synthesis of a material obtained by the combination of sepia melanin and poly(ethylene- alt -maleic anhydride) (P(E- alt -MA)). Compared to sepia melanin, the resulting hybrid displays a high and fast adsorption efficiency towards methylene blue (a common industrial dye) for a wide pH range (from pH 2 to 12) and under high ionic strength conditions. It is easily recovered after use and can be reused up to three times. Given the wide availability of sepia melanin and P(E- alt -MA), the synthesis of our hybrid is simple and affordable, making it suitable for industrial water purification purposes.

Preparation of a Sepia Melanin and Poly(ethylene-alt-maleic Anhydride) Hybrid Material as an Adsorbent for Water Purification

PubMed Central

Osypova, Alina; Quasso, Fiorenza; Soliveri, Guido; Ribera, Javier; Schwarze, Francis W. M. R.

2018-01-01

Meeting the increasing demand of clean water requires the development of novel efficient adsorbent materials for the removal of organic pollutants. In this context the use of natural, renewable sources is of special relevance and sepia melanin, thanks to its ability to bind a variety of organic and inorganic species, has already attracted interest for water purification. Here we describe the synthesis of a material obtained by the combination of sepia melanin and poly(ethylene-alt-maleic anhydride) (P(E-alt-MA)). Compared to sepia melanin, the resulting hybrid displays a high and fast adsorption efficiency towards methylene blue (a common industrial dye) for a wide pH range (from pH 2 to 12) and under high ionic strength conditions. It is easily recovered after use and can be reused up to three times. Given the wide availability of sepia melanin and P(E-alt-MA), the synthesis of our hybrid is simple and affordable, making it suitable for industrial water purification purposes. PMID:29360734

Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis

PubMed Central

Valenti, Luca; Maggioni, Paolo; Piperno, Alberto; Rametta, Raffaela; Pelucchi, Sara; Mariani, Raffaella; Dongiovanni, Paola; Fracanzani, Anna Ludovica; Fargion, Silvia

2012-01-01

AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine aminotransaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin

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

PubMed

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

2010-04-01

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

Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem Bark Extract in Rats

PubMed Central

Okonkwo, T. J. N.; Okorie, O.; Okonta, J. M.; Okonkwo, C. J.

2010-01-01

The extracts of Anacardium occidentale have been used in the management of different cardiovascular disorders in Nigeria. These have necessitated the assessment of the toxicity of this plant extract in sub-chronic administration. The inner stem bark of Anacardium occidentale was extracted with 80 % methanol and quantitatively analysed for antinutrients and some heavy metals. The phytochemical compositions and acute toxicity of the extract were determined also. Toxicity profiles of the extract on some liver function parameters were evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87 g/kg. The phytochemical screening of extract revealed the presence of high amount of tannins, moderate saponins and trace of free reducing sugars. The antinutrient levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 % (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had LD50of 2.154g/kg p.o. in mice. Sub-chronic administration of the extract significantly increased the serum levels of alanine aminotransaminase and aspartate aminotransaminase, which are indicative of liver damage. The serum levels of alkaline phosphatase and total protein of the treated animals were not significantly increased. The effects of sub-chronically administered extract on hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and total protein levels in treated animals were not significant (p< 0.05). Thus, sub-chronic administrations of Anacardium occidentale inner stem bark extract did not significantly (p< 0.05) depress the function of hepatocytes in Wistar rats. PMID:21188045

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

PubMed

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

2017-05-01

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

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

PubMed

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

1996-01-01

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

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

EPA Science Inventory

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

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

PubMed

Brencher, Lisa; Verhaegh, Rabea; Kirsch, Michael

2017-05-01

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

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

PubMed Central

Dul, Michael J.; Young, Frank E.

1973-01-01

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

Diorganosilacetylene-alt-diorganosilvinylene polymers and a process of preparation

DOEpatents

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

1995-10-10

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

Diorganosilacetylene-alt-diorganosilvinylene polymers and a process of preparation

DOEpatents

Barton, T.J.; Ijadi-Maghsoodi, S.; Yi Pang.

1993-08-31

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

Diorganosilacetylene-alt-diorganosilvinylene polymers and a process of preparation

DOEpatents

Barton, T.J.; Ijadi-Maghsoodi, S.; Pang, Y.

1995-10-10

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

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

PubMed

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

2016-01-01

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

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

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

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

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

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

PubMed

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

2008-12-01

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

2008-03-01

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

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

PubMed Central

Cento, Valeria; Nguyen, Thi Huyen Tram; Di Carlo, Domenico; Biliotti, Elisa; Gianserra, Laura; Lenci, Ilaria; Di Paolo, Daniele; Calvaruso, Vincenza; Teti, Elisabetta; Cerrone, Maddalena; Romagnoli, Dante; Melis, Michela; Danieli, Elena; Menzaghi, Barbara; Polilli, Ennio; Siciliano, Massimo; Nicolini, Laura Ambra; Di Biagio, Antonio; Magni, Carlo Federico; Bolis, Matteo; Antonucci, Francesco Paolo; Di Maio, Velia Chiara; Alfieri, Roberta; Sarmati, Loredana; Casalino, Paolo; Bernardini, Sergio; Micheli, Valeria; Rizzardini, Giuliano; Parruti, Giustino; Quirino, Tiziana; Puoti, Massimo; Babudieri, Sergio; D’Arminio Monforte, Antonella; Andreoni, Massimo; Craxì, Antonio; Angelico, Mario; Pasquazzi, Caterina; Taliani, Gloria; Guedj, Jeremie; Ceccherini-Silberstein, Francesca

2017-01-01

Background Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted δ and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted λ, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of “cell-cure” by DAAs, leading to a fast improvement of liver homeostasis. PMID:28545127

Chemical characterisation and hepatoprotective potential of Cosmos sulphureus Cav. and Cosmos bipinnatus Cav.

PubMed

Saleem, Mohammad; Ali, Hafiz Akbar; Akhtar, Muhammad Furqan; Saleem, Uzma; Saleem, Ammara; Irshad, Iram

2017-12-11

This study was conducted to validate the hepatoprotective activity of Cosmos sulphureus and Cosmos bipinnatus. Aqua-methanolic extracts of both plants were evaluated for the presence of various phyto-constituents through HPLC. Different doses of both plant extracts were administered to rats for nine days. Standard control was silymarin 100 mg/kg. Paracetamol 1 gm/kg was administered 3 h post treatment on 9th day for induction of hepatotoxicity. Blood was collected for the evaluation of liver biochemical markers and livers were removed for histopathological evaluation 24 h post-paracetamol treatment. HPLC analysis revealed the presence of quercetin, gallic acid, caffeic acid and chlorogenic acid in both plant extracts. The extracts of both plants decreased the level of alanine aminotransaminase and total bilirubin significantly (p < 0.05), dose dependently and protected hepatocytes from paracetamol-induced hepatotoxicity. It can be concluded that both plants may possess hepatoprotective activity possibly due to the presence of quercetin and phenolic compounds.

Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC

PubMed Central

Basher, Fahmin; Jeng, Emily K.; Wong, Hing; Wu, Jennifer

2016-01-01

Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target. Whether targeting tumor-derived sMIC would enhance current active immunotherapy is not known. Here, we determined the in vivo therapeutic effect of an antibody co-targeting sMIC with the immunostimulatory IL-15 superagonist complex, ALT-803, using genetically engineered transplantable syngeneic sMIC+ tumor models. We demonstrate that combined therapy of a nonblocking antibody neutralizing sMIC and ALT-803 improved the survival of animals bearing sMIC+ tumors in comparison to monotherapy. We further demonstrate that the enhanced therapeutic effect with combined therapy is through concurrent augmentation of NK and CD8 T cell anti-tumor responses. In particular, expression of activation-induced surface molecules and increased functional potential by cytokine secretion are improved greatly by the administration of combined therapy. Depletion of NK cells abolished the cooperative therapeutic effect. Our findings suggest that administration of the sMIC-neutralizing antibody can enhance the anti-tumor effects of ALT-803. With ALT-803 currently in clinical trials to treat progressive solid tumors, the majority of which are sMIC+, our findings provide a rationale for co-targeting sMIC to enhance the therapeutic efficacy of ALT-803 or other IL-15 agonists. PMID:26625316

Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC.

PubMed

Basher, Fahmin; Jeng, Emily K; Wong, Hing; Wu, Jennifer

2016-01-05

Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target. Whether targeting tumor-derived sMIC would enhance current active immunotherapy is not known. Here, we determined the in vivo therapeutic effect of an antibody co-targeting sMIC with the immunostimulatory IL-15 superagonist complex, ALT-803, using genetically engineered transplantable syngeneic sMIC+ tumor models. We demonstrate that combined therapy of a nonblocking antibody neutralizing sMIC and ALT-803 improved the survival of animals bearing sMIC+ tumors in comparison to monotherapy. We further demonstrate that the enhanced therapeutic effect with combined therapy is through concurrent augmentation of NK and CD8 T cell anti-tumor responses. In particular, expression of activation-induced surface molecules and increased functional potential by cytokine secretion are improved greatly by the administration of combined therapy. Depletion of NK cells abolished the cooperative therapeutic effect. Our findings suggest that administration of the sMIC-neutralizing antibody can enhance the anti-tumor effects of ALT-803. With ALT-803 currently in clinical trials to treat progressive solid tumors, the majority of which are sMIC+, our findings provide a rationale for co-targeting sMIC to enhance the therapeutic efficacy of ALT-803 or other IL-15 agonists.

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

PubMed

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

2015-11-01

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

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

PubMed

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

2000-07-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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

PubMed

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

2017-03-27

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

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

ERIC Educational Resources Information Center

Waller, Francis J.; And Others

1977-01-01

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

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

PubMed Central

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

1982-01-01

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

[The effect of "living high and training low" on serum CK, LDH and ALT of rowing athletes].

PubMed

Liu, Jian-Hong; Zhou, Zhi-Hong; Ou, Ming-Hao; Xie, Min-Hao; Wang, Kui; Shi, Yu-Qi

2005-08-01

To investigate the influence of living high-training low for 4 weeks on serum CK, LDH and ALT of rowing athletes. 20 rowing athletes were divided into two groups: the one (ten subjects) spent 8-10 h per night in a tabernacle which was simulated altitude of 2 500 m in normobaric hypoxia (HiLo group), the another (ten subjects) slept at near sea level (control group). During the periods of test, all athletes were trained at the same relative or at the same intensity of work in normoxia state. The serum CK, LDH and ALT were measured at before, during 2 weeks, 4 weeks and 2 weeks after "living high and training low". Baseline serum values for CK, LDH and ALT were not different between two groups (P > 0.05). The levels of CK, LDH of HiLo group were significantly increased (P < 0.05) than those of control group at 3 rd week, however, it was contrary at 5th and 7th week. After exercise of 2 km and 5 km, the values of LDH and CK at a moment notice and 30min postexercise test in HiLo group were significant lower than those in control group. These results indicate that living high-training low may reduce the muscle damage associated with endurance exercise.

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

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

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

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

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

PubMed

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

2017-05-01

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

Persistent rotating shift work exposure is a tough second hit contributing to abnormal liver function among on-site workers having sonographic fatty liver.

PubMed

Lin, Yu-Cheng; Chen, Pau-Chung

2015-03-01

To investigate the relationship between elevated serum alanine-transaminase (e-ALT) and persistent rotating shift work (p-RSW) among employees with sonographic fatty liver (SFL), the authors performed a retrospective analysis on a cohort of electronics manufacturing workers. The records of 758 workers (507 men, 251 women) with initially normal ALT and a mean age of 32.9 years were analyzed. A total of 109 workers (14.4%) developed e-ALT after 5 years. Compared with those having neither initial SFL nor p-RSW exposure, multivariate analysis indicated that employees who had initial SFL but without p-RSW finally had a higher risk (odds ratio = 2.9; 95% confidence interval [CI] = 1.7-5.1) for developing e-ALT; workers with baseline SFL plus p-RSW had a 3.7-fold increased risk (95% CI = 1.8-7.5). SFL poses a conspicuous risk for the development of e-ALT, and persistent p-RSW exposure significantly aggravates the development of e-ALT among on-site workers with preexisting SFL. © 2012 APJPH.

β-alanine supplementation improves tactical performance but not cognitive function in combat soldiers

PubMed Central

2014-01-01

Background There are no known studies that have examined β-alanine supplementation in military personnel. Considering the physiological and potential neurological effects that have been reported during sustained military operations, it appears that β-alanine supplementation may have a potential benefit in maintaining physical and cognitive performance during high-intensity military activity under stressful conditions. The purpose of this study was to examine the effect of 28 days of β-alanine ingestion in military personnel while fatigued on physical and cognitive performance. Methods Twenty soldiers (20.1 ± 0.9 years) from an elite combat unit were randomly assigned to either a β-alanine (BA) or placebo (PL) group. Soldiers were involved in advanced military training, including combat skill development, navigational training, self-defense/hand-to-hand combat and conditioning. All participants performed a 4-km run, 5-countermovement jumps using a linear position transducer, 120-m sprint, a 10-shot shooting protocol with assault rifle, including overcoming a misfire, and a 2-min serial subtraction test to assess cognitive function before (Pre) and after (Post) 28 days of supplementation. Results The training routine resulted in significant increases in 4-km run time for both groups, but no between group differences were seen (p = 0.597). Peak jump power at Post was greater for BA than PL (p = 0.034), while mean jump power for BA at Post was 10.2% greater (p = 0.139) than PL. BA had a significantly greater (p = 0.012) number of shots on target at Post (8.2 ± 1.0) than PL (6.5 ± 2.1), and their target engagement speed at Post was also significantly faster (p = 0.039). No difference in serial subtraction performance was seen between the groups (p = 0.844). Conclusion Results of this study indicate that 4-weeks of β-alanine ingestion in young, healthy soldiers did not impact cognitive performance, but did enhance power

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

PubMed Central

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

2017-01-01

The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe2O4), cobalt ferrite (CoFe2O4), copper ferrite (CuFe2O4), zinc ferrite (ZnFe2O4), and manganese ferrite (MnFe2O4) nanoparticles surfaces, in the temperature range from 50–120 °C for 1–35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe2O4 produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe2O4 was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C. PMID:28346388

Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes

PubMed Central

Lee, Michael; Hills, Mark; Conomos, Dimitri; Stutz, Michael D.; Dagg, Rebecca A.; Lau, Loretta M.S.; Reddel, Roger R.; Pickett, Hilda A.

2014-01-01

Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during telomerase- and ALT-mediated telomere lengthening. Telomerase-mediated telomere extension resulted in biased repeat synthesis of variant repeats that differed from the canonical sequence at positions 1 and 3, but not at positions 2, 4, 5 or 6. This indicates that telomerase is most likely an error-prone reverse transcriptase that misincorporates nucleotides at specific positions on the telomerase RNA template. In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines. This is consistent with variant repeats spreading from proximal telomeric regions throughout telomeres in a stochastic manner by recombination-mediated templating of DNA synthesis. The presence of unexpectedly large numbers of variant repeats in cells utilizing either telomere maintenance mechanism suggests a conserved role for variant sequences at human telomeres. PMID:24225324

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

DOEpatents

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.

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

DOEpatents

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.

Understanding and Targeting the ALT Pathway in Human Breast Cancer

DTIC Science & Technology

2014-09-01

Figure 5 B Rif1 Actin He La 1. 3 WI 38 -VA 13 /2 RA T.1 D U2 OS BJ hT ER T S V4 0 a2 E6 E7 .c4 T.1 L T.1 M T.1 Q T.1 R T.1 J/5 H T.1 J/1 -3C RP E h TE...stability of replication forks, an increased sensitivity to replication inhibitors, as well as changes in gene transcription32, 33, 34, 31, 35, 36, 24...down to 46 genes of interest based on the presence of mutations in two distinct panels of ALT cell lines, thereby excluding likely SNPs

D-alanine carboxypeptidase activity of Micrococcus lysodeikticus released into the protoplasting medium.

PubMed

Linder, R; Salton, M R

1975-06-16

Conversion of whole cells of Micrococcus lysodeikticus to protoplasts allowed the release of a soluble form of a D-alanine carboxypeptidase into the protoplasting medium. The enzyme cleaves the terminal D-alanine from the radioactively labelled UDP-N-acetylmuramyl-pentapeptide containing L-lysine as the diamino acid. However, the enzyme is only minimally active in this fraction so that it had to be enriched and partially purified before its properties could be studied. Chromatography on carboxymethyl-Sephadex removed the lysozyme used in the protoplasting of the cells. The material which was unadsorbed to the column was applied to an affinity chromatography column of Ampicillin-Sepharose. Most of the contaminating protein was washed from the column while the D-alanine carboxypeptidase adhered to the resin and could be eluted with 0.5 M Tris-HCl buffer pH 8.6. Some of the properties of the enzymic activity were studied using this preparation. The enzyme was activated by Mg2+ ions with a broad optimum from 15--35 mM. It was maximally active when NaCl at a concentrations of 0.06--0.08 M was added to the assay, and the pH curve was biphasic with an alkaline optimum. The Km for substrate was found to be 0.118 mM. Enzymic activity was completely inhibited by low concentrations of Ampicillin and penicillin G.

Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

PubMed Central

Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S. Painelli, Vitor; Harris, Roger C.; Gualano, Bruno

2015-01-01

Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists. PMID:25875297

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

PubMed

Solis, Marina Yazigi; Cooper, Simon; Hobson, Ruth M; Artioli, Guilherme G; Otaduy, Maria C; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S Painelli, Vitor; Harris, Roger C; Gualano, Bruno; Sale, Craig

2015-01-01

Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

Synthesis and characterization of new nanocomposites films using alanine-Cu-functionalized graphene oxide as nanofiller and PVA as polymeric matrix for improving of their properties

NASA Astrophysics Data System (ADS)

Abdolmaleki, Amir; Mallakpour, Shadpour; Karshenas, Azam

2017-09-01

In the synthesis of polymer-graphene nanocomposites, for improving properties of nanocomposites, two factors dispersion and strong interfacial interactions between graphene and the polymer, are essential. In the present work, poly(vinyl alcohol) PVA/GO-Cu-alanine nanocomposite films were manufactured using concentrations 0, 1, 3 and 5 wt% of GO-Cu-alanine in water solution. For this purpose, L-alanine amino acid was located on the surface and edges of GO through copper(II) ion as a coordinating function. Then, flexible PVA/GO-Cu-alanine nanocomposite films were fabricated using GO-Cu-alanine as filler and PVA as matrix. Due to the existence of affective interaction between GO-Cu-alanine and PVA matrix, the acquired PVA/GO-Cu-alanine nanocomposites demonstrated great thermal and mechanical properties. Properties of manufactured materials were characterized by Fourier transform infrared, X-ray photoelectron spectroscopies (XPS), X-ray diffraction (XRD), Thermal gravimetric analysis, elemental analysis, field emission scanning electron microscopy, transmission electron microscopy and energy dispersive X-ray spectroscopy (EDX).

Prevalence of hepatitis A viral RNA and antibodies among Chinese blood donors.

PubMed

Sun, P; Su, N; Lin, F Z; Ma, L; Wang, H J; Rong, X; Dai, Y D; Li, J; Jian, Z W; Tang, L H; Xiao, W; Li, C Q

2015-12-09

Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.

Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide

PubMed Central

Johnston, Heather J.; Boys, Sarah K.; Makda, Ashraff; Carragher, Neil O.

2016-01-01

Abstract Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid‐phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose‐dependent response in IRS‐1 expression. Alanine scanning reveals a structural dependence to the cytotoxicity, actin targeting and pathway inhibition, and allows a new readily synthesised lead to be proposed. PMID:27304907

Antimicrobial susceptibility testing of a clinical isolate of vancomycin-dependent enterococcus using D-alanine-D-alanine as a growth supplement.

PubMed

Sng, L H; Cornish, N; Knapp, C C; Ludwig, M D; Hall, G S; Washington, J A

1998-04-01

Bacteremia due to a vancomycin-dependent enterococcus (VDE) occurred during long-term vancomycin therapy in a renal transplant recipient with underlying pancreatitis and a vancomycin-resistant enterococcal (VRE) wound infection and bacteremia. The VDE was isolated from blood during vancomycin therapy and grew only in the presence of vancomycin and D-alanine-D-alanine (DADA), a substance required for cell-wall synthesis. Colonies beyond the periphery of growth of the VDE around a vancomycin disk contained vancomycin-independent revertant mutants after 48 hours of incubation. Pulsed-field gel electrophoresis of the VDE, revertant mutant, the initial blood culture isolate of VRE, and an autopsy isolate showed that the four strains were identical. Antimicrobial susceptibility testing was performed using standard macrobroth and microbroth dilution methods. DADA was used as a growth supplement for macrobroth dilution susceptibility testing of the VDE isolate. Minimum inhibitory concentrations (MICs) were similar for the VRE isolate and the VDE revertant, which were both resistant to ampicillin, high-level gentamicin, ciprofloxacin, imipenem, vancomycin, and daptomycin, and were susceptible to fusidic acid, high-level streptomycin, rifampin, and a quinupristin-dalfopristin combination. The MICs of teicoplanin were 2 microg/mL or less and 16 microg/mL for the clinical VRE isolate and the VDE revertant, respectively. The autopsy isolate was resistant to all antimicrobials tested and showed a fourfold increase in MICs for quinupristin-dalfopristin compared with that of the original blood isolate. The VDE was susceptible to all drugs tested except vancomycin.

Orthologous Allergens and Diagnostic Utility of Major Allergen Alt a 1

PubMed Central

Moreno, Antonio; Alcover, Javier; Rodríguez, David; Palacios, Ricardo; Martínez-Naves, Eduardo

2016-01-01

Purpose Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi. The type of indoor fungi related to asthma/allergy varies according to geographic, climatic, and seasonal factors, making their study difficult. The aim of this study was to determine hypersensitivity to indoor fungi in a population from Cuenca, Spain. Methods Thirty-five patients with symptoms compatible with rhinitis or asthma who showed clear worsening of their symptoms in their homes or workplace were included. In vivo and in vitro tests were made with a battery of fungal allergens, including the species isolated in the home or workplace. Results Ulocladium botrytis (U. botrytis) and A. alternata were the most representative species as a source of home sensitization. These species showed very high concordance in skin tests, specific IgE, and histamine release. The allergen Alt a 1, which was recognized in all patients, was detected in A. alternata, U. botrytis, and Stemphylium botryosum (S. botryosum). Conclusions U. botrytis and A. alternata were the most representative species as a source of home sensitization. Alt a 1 was recognized in all patients and may be considered a non-species-specific allergen that could be used as a diagnostic source of sensitization to some species of the Pleosporaceae family. PMID:27334781

Effects of 4 Weeks of β-Alanine Supplementation on Swim-Performance Parameters in Water Polo Players.

PubMed

Brisola, Gabriel Motta Pinheiro; Milioni, Fabio; Papoti, Marcelo; Zagatto, Alessandro Moura

2017-08-01

In water polo, several high-intensity efforts are performed, leading to the fatigue process due to accumulation of hydrogen ions, and thus β-alanine supplementation could be an efficient strategy to increase the intramuscular acid buffer. Purpose To investigate whether 4 wk of β-alanine supplementation enhances parameters related to water polo performance. Methods Twenty-two highly trained male water polo players of national level were randomly assigned to receive 28 d of either β-alanine or a placebo (4.8 g/d of the supplement in the first 10 d and 6.4 g/d in the final 18 d). The participants performed 30-s maximal tethered swimming (30TS), 200-m swimming (P200m), and 30-s crossbar jumps (30CJ) before and after the supplementation period. Results The β-alanine group presented significant increases in 30TS for mean force (P = .04; Δ = 30.5% ± 40.4%) and integral of force (P = .05; Δ = 28.0% ± 38.0%), as well as P200m (P = .05; Δ = -2.2% ± 2.6%), while the placebo group did not significantly differ for mean force (P = .13; Δ = 24.1% ± 33.7%), integral of force (P = .12; Δ = 24.3% ± 35.1%), or P200m (P = .10; Δ = -1.6% ± 3.8%). However, there was no significant group effect for any variable, and the magnitude-based-inference analysis showed unclear outcomes between groups (Cohen d ± 95%CL mean force = 0.16 ± 0.83, integral of force = 0.12 ± 0.84, and P200m = 0.05 ± 0.30). For 30CJ the results were similar, with improvements in both groups (placebo, Δ = 14.9% ± 14.1%; β-alanine, Δ = 16.9% ± 18.5%) but with no significant interaction effect between groups and an unclear effect (0.14 ± 0.75). Conclusion Four weeks of β-alanine supplementation does not substantially improve performance of 30TS, P200m, or 30CJ in highly trained water polo athletes compared with a control group.

2017-04-28_W88 ALT 370 Program Overview(OUO).

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

Daniels, Vonceil

2017-04-01

All major program milestones have been met and the program is executing within budget. The ALT 370 program achieved Phase 6.4 authorization in February of this year. Five component Final Design Reviews (FDRs) have been completed, indicating progress in finalizing the design and development phase of the program. A series of ground-based qualification activities have demonstrated that designs are meeting functional requirements. The first fully functional flight test, FCET-53, demonstrated end-to-end performance in normal flight environments in February. Similarly, groundbased nuclear safety and hostile environments testing indicates that the design meets requirements in these stringent environments. The first in amore » series of hostile blast tests was successfully conducted in April.« less

Characterization of Lactobacillus salivarius alanine racemase: short-chain carboxylate-activation and the role of A131.

PubMed

Kobayashi, Jyumpei; Yukimoto, Jotaro; Shimizu, Yasuhiro; Ohmori, Taketo; Suzuki, Hirokazu; Doi, Katsumi; Ohshima, Toshihisa

2015-01-01

Many strains of lactic acid bacteria produce high concentrations of d-amino acids. Among them, Lactobacillus salivarius UCC 118 produces d-alanine at a relative concentration much greater than 50 % of the total d, l-alanine (100d/d, l-alanine). We characterized the L. salivarius alanine racemase (ALR) likely responsible for this d-alanine production and found that the enzyme was activated by carboxylates, which is an unique characteristic among ALRs. In addition, alignment of the amino acid sequences of several ALRs revealed that A131 of L. salivarius ALR is likely involved in the activation. To confirm that finding, an L. salivarius ALR variant with an A131K (ALR(A131K)) substitution was prepared, and its properties were compared with those of ALR. The activity of ALR(A131K) was about three times greater than that of ALR. In addition, whereas L. salivarius ALR was strongly activated by low concentrations (e.g., 1 mM) of short chain carboxylates, and was inhibited at higher concentrations (e.g., 10 mM), ALR(A131K) was clearly inhibited at all carboxylate concentrations tested (1-40 mM). Acetate also increased the stability of ALR such that maximum activity was observed at 35 °C and pH 8.0 without acetate, but at 50 °C in the presence of 1 mM acetate. On the other hand, maximum ALR(A131K) activity was observed at 45 °C and around pH 9.0 with or without acetate. It thus appears that A131 mediates the activation and stabilization of L. salivarius ALR by short chain carboxylates.

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

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

Space shuttle engineering and operations support. ALT separation reference trajectories for tailcone on orbiter forward and aft CG configurations. Mission planning, mission analysis and software formulation

NASA Technical Reports Server (NTRS)

Glenn, G. M.

1977-01-01

A preflight analysis of the ALT separation reference trajectories for the tailcone on, forward, and aft cg orbiter configurations is documented. The ALT separation reference trajectories encompass the time from physical separation of the orbiter from the carrier to orbiter attainment of the maximum ALT interface airspeed. The trajectories include post separation roll maneuvers by both vehicles and are generated using the final preflight data base. The trajectories so generated satisfy all known separation design criteria and violate no known constraints. The requirement for this analysis is given along with the specifications, assumptions, and analytical approach used to generate the separation trajectories. The results of the analytical approach are evaluated, and conclusions and recommendations are summarized.

Assessing microbial utilization of free versus sorbed Alanine by using position-specific 13C labeling and 13C-PLFA analysis

NASA Astrophysics Data System (ADS)

Herschbach, Jennifer; Apostel, Carolin; Spielvogel, Sandra; Kuzyakov, Yakov; Dippold, Michaela

2016-04-01

Microbial utilization is a key transformation process of soil organic matter (SOM). Sorption of low molecular weight organic substances (LMWOS) to soil mineral surfaces blocks or delays microbial uptake and therefore mineralization of LMWOS to CO2, as well as all other biochemical transformations. We used position-specific labeling, a tool of isotope applications novel to soil science, combined with 13C-phospholipid fatty acid (PLFA) analysis, to assess microbial utilization of sorbed and non-sorbed Alanine in soil. Alanine has various functional groups enabling different sorption mechanisms via its positive charge (e.g. to clay minerals by cation exchange), as well as via its negative charge (e.g. to iron oxides by ligand exchange). To assess changes in the transformation pathways caused by sorption, we added uniformly and position-specifically 13C and 14C labeled Alanine to the Ap of a loamy Luvisol in a short-term (10 days) incubation experiment. To allow for sorption of the tracer solution to an aliquot of this soil, microbial activity was minimized in this subsample by sterilizing the soil by γ-radiation. After shaking, the remaining solutions were filtered and the non-sorbed Alanine was removed with Millipore water and then added to non-sterilized soil. For the free Alanine treatment, solutions with Alanine of similar amount and isotopic composition were prepared, added to the soil and incubated as well. The respired CO2 was trapped in NaOH and its 14C-activity was determined at increasing times intervals. Microbial utilization of Alanine's individual C positions was evaluated in distinct microbial groups classified by 13C-PLFA analysis. Sorption to soil minerals delayed respiration to CO2 and reduced initial respiration rate by 80%. Irrespective of sorption, the highest amount was respired from the carboxylic position (C-1), whereas the amino-bound (C-2) and the methylic position (C-3) were preferentially incorporated into PLFA of microorganisms due to the

Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-aminoethylphosphonic acid (l-Ala-P)

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

Au, Kinfai; Ren, Jingshan; Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN

2008-05-01

Structures of BA0252, an alanine racemase from B. anthracis, in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) and determined by X-ray crystallography to resolutions of 2.1 and 1.47 Å, respectively, are described. Bacillus anthracis, the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high-throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) have determined by X-ray crystallo@@graphy to resolutions of 2.1 and 1.47 Å, respectively. Difficulties inmore » crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti-anthrax drugs: not only is d-alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis. These structures confirm the binding mode of l-Ala-P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti-anthrax therapies.« less

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

PubMed Central

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

2014-01-01

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

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

PubMed Central

Umpleby, A M; Trend, P S; Chubb, D; Conaglen, J V; Williams, C D; Hesp, R; Scobie, I N; Wiles, C M; Spencer, G; Sönksen, P H

1989-01-01

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect. PMID:2507747

Changes of ammonia, urea contents and transaminase activity in the body during aerial exposure and ammonia loading in Chinese loach Paramisgurnus dabryanus.

PubMed

Zhang, Yun-Long; Zhang, Hai-Long; Wang, Ling-Yu; Gu, Bei-Yi; Fan, Qi-Xue

2017-04-01

The Paramisgurnus dabryanus was exposed to 30 mmol L -1 NH 4 Cl solution and air to assessing the change of body ammonia and urea contents and the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST). After 48 h of ammonia exposure, ammonia concentration in the plasma, brain, liver and muscle were 3.3-fold, 5.6-fold, 3.5-fold and 4.2-fold, respectively, those of the control values. Plasma, brain, liver and muscle ammonia concentrations increased to 2.2-fold, 3.3-fold, 2.5-fold and 2.9-fold, respectively, those of control values in response to 48 h of aerial exposure. Within the given treatment (ammonia or aerial exposure), there was no change in plasma, brain and liver urea concentrations between exposure durations. The plasma ALT activity was significantly affected by exposure time during aerial exposure, while the liver ALT activity was not affected by ammonia or aerial exposure. Exposure to NH 4 Cl or air had no effect on either plasma or liver AST activity. Our results suggested that P. dabryanus could accumulate quite high level of internal ammonia because of the high ammonia tolerance in its cells and tissues, and NH 3 volatilization would be a possible ammonia detoxification strategy in P. dabryanus. Urea synthesis was not an effective mechanism to deal with environmental or internal ammonia problem. The significant increase of ALT activity in plasma during aerial exposure, indicating that alanine synthesis through certain amino acid catabolism may be subsistent in P. dabryanus.

VUV photodynamics and chiral asymmetry in the photoionization of gas phase alanine enantiomers.

PubMed

Tia, Maurice; Cunha de Miranda, Barbara; Daly, Steven; Gaie-Levrel, François; Garcia, Gustavo A; Nahon, Laurent; Powis, Ivan

2014-04-17

The valence shell photoionization of the simplest proteinaceous chiral amino acid, alanine, is investigated over the vacuum ultraviolet region from its ionization threshold up to 18 eV. Tunable and variable polarization synchrotron radiation was coupled to a double imaging photoelectron/photoion coincidence (i(2)PEPICO) spectrometer to produce mass-selected threshold photoelectron spectra and derive the state-selected fragmentation channels. The photoelectron circular dichroism (PECD), an orbital-sensitive, conformer-dependent chiroptical effect, was also recorded at various photon energies and compared to continuum multiple scattering calculations. Two complementary vaporization methods-aerosol thermodesorption and a resistively heated sample oven coupled to an adiabatic expansion-were applied to promote pure enantiomers of alanine into the gas phase, yielding neutral alanine with different internal energy distributions. A comparison of the photoelectron spectroscopy, fragmentation, and dichroism measured for each of the vaporization methods was rationalized in terms of internal energy and conformer populations and supported by theoretical calculations. The analytical potential of the so-called PECD-PICO detection technique-where the electron spectroscopy and circular dichroism can be obtained as a function of mass and ion translational energy-is underlined and applied to characterize the origin of the various species found in the experimental mass spectra. Finally, the PECD findings are discussed within an astrochemical context, and possible implications regarding the origin of biomolecular asymmetry are identified.

Thermodynamics of DL-alanine solvation in water-dimethylsulfoxide mixtures at 298.15 K

NASA Astrophysics Data System (ADS)

Roy, S.; Mahali, K.; Mondal, S.; Dolui, B. K.

2015-04-01

In this study we mainly discuss the transfer Gibbs free energy Δ G {/t 0}( i) and Δ S {/t 0}( i)entropy of DL-alanine at 298.15 K and consequently the involved chemical transfer free energy (Δ G {/t,ch 0}( i)) and entropy ( TΔ S {/t,ch 0}( i)) in aqueous mixtures of dimethylsulfoxide are discussed to clarify the solvation chemistry of DL-alanine. For the evaluation of these energy terms, solubility of this amino acid has been measured by formol titrimetry at five equidistant temperatures i.e., from 288.15 to 308.15 K in different composition of this mixed solvent system. The various solvent parameters as well as thermodynamic parameters like molar volume, density, dipole moment and solvent diameter of this solvent system have also been reported here. The chemical effects of the transfer Gibbs energies (Δ G {/t,ch 0}( i)) and entropies of transfer ( TΔ S {/t,ch 0}( i)) have been obtained after elimination of cavity effect and dipole-dipole interaction effects from the total transfer energies. Here the chemical contribution of transfer energetics of DL-alanine is mainly guided by the composite effects of increased dispersion interaction, basicity effect and decreased acidity, hydrogen bonding effects, hydrophilic hydration and hydrophobic hydration of aqueous DMSO mixtures as compared to that of reference solvent, water.

An aldonolactonase AltA from Penicillium oxalicum mitigates the inhibition of β-glucosidase during lignocellulose biodegradation.

PubMed

Peng, Shengjuan; Cao, Qing; Qin, Yuqi; Li, Xuezhi; Liu, Guodong; Qu, Yinbo

2017-05-01

Efficient deconstruction of lignocellulose is achieved by the synergistic action of various hydrolytic and oxidative enzymes. However, the aldonolactones generated by oxidative enzymes have inhibitory effects on some cellulolytic enzymes. In this work, D-glucono-1,5-lactone was shown to have a much stronger inhibitory effect than D-glucose and D-gluconate on β-glucosidase, a vital enzyme during cellulose degradation. AltA, a secreted enzyme from Penicillium oxalicum, was identified as an aldonolactonase which can catalyze the hydrolysis of D-glucono-1,5-lactone to D-gluconic acid. In the course of lignocellulose saccharification conducted by cellulases from P. oxalicum or Trichoderma reesei, supplementation of AltA was able to relieve the decrease of β-glucosidase activity obviously with a stimulation of glucose yield. This boosting effect disappeared when sodium azide and ethylenediaminetetraacetic acid (EDTA) were added to the saccharification system to inhibit the activities of oxidative enzymes. In summary, we describe the first heterologous expression of a fungal secreted aldonolactonase and its application as an efficient supplement of cellulolytic enzyme system for lignocellulose biodegradation.

Adsorption of alanine with heteroatom substituted fullerene for solar cell application: A DFT study.

PubMed

Dheivamalar, S; Sugi, L; Ravichandran, K; Sriram, S

2018-09-05

C 20 is the most important fullerene cage and alanine is the simplest representation of a backbone unit of the protein. The absorption feasibility of alanine molecule in the Si-doped C 20 and B-doped C 20 fullerenes has been studied based on calculated electronic properties of fullerenes using density functional theory (DFT). In this work, we explore the ability of Si-doped C 20 , B-doped C 20 fullerene to interact with alanine at the DFT-B3LYP/6-31G, RHF level of theory. We find that noticeable structural change takes place in C 20 when one of its carbon is substituted with Si or B. The molecular geometry, electronic properties and vibrational analysis have also been performed on the title compounds. The NMR study reveals the aromaticity of the pure and doped fullerene compounds. Stability of the doped fullerene - alanine compound arises from hyper conjugative interactions. It leads to one of the major property of bioactivity, charge transfer and delocalization of charge and this properties has been analyzed using Natural Bond Orbital (NBO) analysis. The energy gap of the doped fullerene reveals that there is a decrease in the size of energy gap significantly, making them more reactive as compared to C 20 fullerene. Theoretical studies of the electronic spectra by using time - dependent density functional theory (TD-DFT) method were helpful to interpret the observed electronic transition state. We aim to optimize the performance of the solar cells by altering the frontier orbital energy gaps. Considering all studied properties, it may be inferred that the applicability of C 20 fullerene as the non-linear optical (NLO) material and its NLO property would increase on doping fullerene with Si and B atom. Specifically C 19 Si would be better among them. Copyright © 2018. Published by Elsevier B.V.

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

PubMed

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

2010-10-01

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

Anaerobic Metabolism in the N-Limited Green Alga Selenastrum minutum: III. Alanine Is the Product of Anaerobic Ammonium Assimilation.

PubMed

Vanlerberghe, G C; Joy, K W; Turpin, D H

1991-02-01

We have determined the flow of (15)N into free amino acids of the N-limited green alga Selenastrum minutum (Naeg.) Collins after addition of (15)NH(4) (+) to aerobic or anaerobic cells. Under aerobic conditions, only a small proportion of the N assimilated was retained in the free amino acid pool. However, under anaerobic conditions almost all assimilated NH(4) (+) accumulates in alanine. This is a unique feature of anaerobic NH(4) (+) assimilation. The pathway of carbon flow to alanine results in the production of ATP and reductant which matches exactly the requirements of NH(4) (+) assimilation. Alanine synthesis is therefore an excellent strategy to maintain energy and redox balance during anaerobic NH(4) (+) assimilation.

Ultra-Rapid Crystallization of L-alanine Using Monomode Microwaves, Indium Tin Oxide and Metal-Assisted and Microwave-Accelerated Evaporative Crystallization.

PubMed

Lansiquot, Carisse; Boone-Kukoyi, Zainab; Shortt, Raquel; Thompson, Nishone; Ajifa, Hillary; Kioko, Bridgit; Constance, Edward Ned; Clement, Travis; Ozturk, Birol; Aslan, Kadir

2017-01-01

The use of indium tin oxide (ITO) and focused monomode microwave heating for the ultra-rapid crystallization of L-alanine (a model amino acid) is reported. Commercially available ITO dots (< 5 mm) attached to blank poly(methyl)methacrylate (PMMA, 5 cm in diameter with 21-well silicon isolators: referred to as the iCrystal plates) were found to withstand prolonged microwave heating during crystallization experiments. Crystallization of L-alanine was performed at room temperature (a control experiment), with the use of two microwave sources: a 2.45 GHz conventional microwave (900 W, power level 1, a control experiment) and 8 GHz (20 W) solid state, monomode microwave source with an applicator tip that focuses the microwave field to a 5-mm cavity. Initial appearance of L-alanine crystals and on iCrystal plates with ITO dots took 47 ± 2.9 min, 12 ± 7.6 min and 1.5 ± 0.5 min at room temperature, using a conventional microwave and focused monomode microwave heating, respectively. Complete evaporation of the solvent using the focused microwaves was achieved in 3.2 ± 0.5 min, which is ~52-fold and ~172-fold faster than that observed at room temperature and using conventional microwave heating, respectively. The size and number of L-alanine crystals was dependent on the type of the 21-well iCrystal plates and the microwave heating method: 33 crystals of 585 ± 137 μm in size at room temperature > 37 crystals of 542 ± 100 μm in size with conventional microwave heating > 331 crystals of 311 ± 190 μm in size with focused monomode microwave. FTIR, optical microscopy and powder X-ray diffraction analysis showed that the chemical composition and crystallinity of the L-alanine crystals did not change when exposed to microwave heating and ITO surfaces. In addition, theoretical simulations for the binding of L-alanine molecules to ITO and other metals showed the predicted nature of hydrogen bonds formed between L-alanine and these surfaces.

Ultra-Rapid Crystallization of L-alanine Using Monomode Microwaves, Indium Tin Oxide and Metal-Assisted and Microwave-Accelerated Evaporative Crystallization

PubMed Central

Lansiquot, Carisse; Boone-Kukoyi, Zainab; Shortt, Raquel; Thompson, Nishone; Ajifa, Hillary; Kioko, Bridgit; Constance, Edward Ned; Clement, Travis; Ozturk, Birol; Aslan, Kadir

2018-01-01

The use of indium tin oxide (ITO) and focused monomode microwave heating for the ultra-rapid crystallization of L-alanine (a model amino acid) is reported. Commercially available ITO dots (< 5 mm) attached to blank poly(methyl)methacrylate (PMMA, 5 cm in diameter with 21-well silicon isolators: referred to as the iCrystal plates) were found to withstand prolonged microwave heating during crystallization experiments. Crystallization of L-alanine was performed at room temperature (a control experiment), with the use of two microwave sources: a 2.45 GHz conventional microwave (900 W, power level 1, a control experiment) and 8 GHz (20 W) solid state, monomode microwave source with an applicator tip that focuses the microwave field to a 5-mm cavity. Initial appearance of L-alanine crystals and on iCrystal plates with ITO dots took 47 ± 2.9 min, 12 ± 7.6 min and 1.5 ± 0.5 min at room temperature, using a conventional microwave and focused monomode microwave heating, respectively. Complete evaporation of the solvent using the focused microwaves was achieved in 3.2 ± 0.5 min, which is ~52-fold and ~172-fold faster than that observed at room temperature and using conventional microwave heating, respectively. The size and number of L-alanine crystals was dependent on the type of the 21-well iCrystal plates and the microwave heating method: 33 crystals of 585 ± 137 μm in size at room temperature > 37 crystals of 542 ± 100 μm in size with conventional microwave heating > 331 crystals of 311 ± 190 μm in size with focused monomode microwave. FTIR, optical microscopy and powder X-ray diffraction analysis showed that the chemical composition and crystallinity of the L-alanine crystals did not change when exposed to microwave heating and ITO surfaces. In addition, theoretical simulations for the binding of L-alanine molecules to ITO and other metals showed the predicted nature of hydrogen bonds formed between L-alanine and these surfaces. PMID:29657884

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

PubMed

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

2004-11-01

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

The effect of taurine and β-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice.

PubMed

Horvath, Deanna M; Murphy, Robyn M; Mollica, Janelle P; Hayes, Alan; Goodman, Craig A

2016-11-01

This study investigated the effect of taurine and β-alanine supplementation on muscle function and muscle taurine transporter (TauT) protein expression in mdx mice. Wild-type (WT) and mdx mice (5 months) were supplemented with taurine or β-alanine for 4 weeks, after which in vitro contractile properties, fatigue resistance and force recovery, and the expression of the TauT protein and proteins involved in excitation-contraction (E-C) coupling were examined in fast-twitch muscle. There was no difference in basal TauT protein expression or basal taurine content between mdx than WT muscle. Supplementation with taurine and β-alanine increased and reduced taurine content, respectively, in muscle from WT and mdx mice but had no effect of TauT protein. Taurine supplementation reduced body and muscle mass, and enhanced fatigue resistance and force recovery in mdx muscle. β-Alanine supplementation enhanced fatigue resistance in WT and mdx muscle. There was no difference in the basal expression of key E-C coupling proteins [ryanodine receptor 1 (RyR1), dihydropyridine receptor (DHPR), sarco(endo)plasmic reticulum Ca 2+ -ATPase 1 (SERCA1) or calsequestrin 1 (CSQ1)] between WT and mdx mice, and the expression of these proteins was not altered by taurine or β-alanine supplementation. These findings suggest that TauT protein expression is relatively insensitive to changes in muscle taurine content in WT and mdx mice, and that taurine and β-alanine supplementation may be viable therapeutic strategies to improve fatigue resistance of dystrophic skeletal muscle.

Short-duration beta-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players.

PubMed

Hoffman, Jay R; Ratamess, Nicholas A; Faigenbaum, Avery D; Ross, Ryan; Kang, Jie; Stout, Jeffrey R; Wise, John A

2008-01-01

The purpose of this study was to examine the effect of 30 days of beta-alanine supplementation in collegiate football players on anaerobic performance measures. Subjects were randomly divided into a supplement (beta-alanine group [BA], 4.5 g x d(-1) of beta-alanine) or placebo (placebo group [P], 4.5 g x d(-1) of maltodextrin) group. Supplementation began 3 weeks before preseason football training camp and continued for an additional 9 days during camp. Performance measures included a 60-second Wingate anaerobic power test and 3 line drills (200-yd shuttle runs with a 2-minute rest between sprints) assessed on day 1 of training camp. Training logs recorded resistance training volumes, and subjects completed questionnaires on subjective feelings of soreness, fatigue, and practice intensity. No difference was seen in fatigue rate in the line drill, but a trend (P = .07) was observed for a lower fatigue rate for BA compared with P during the Wingate anaerobic power test. A significantly higher training volume was seen for BA in the bench press exercise, and a trend (P = .09) for a greater training volume was seen for all resistance exercise sessions. In addition, subjective feelings of fatigue were significantly lower for BA than P. In conclusion, despite a trend toward lower fatigue rates during 60 seconds of maximal exercise, 3 weeks of beta-alanine supplementation did not result in significant improvements in fatigue rates during high-intensity anaerobic exercise. However, higher training volumes and lower subjective feelings of fatigue in BA indicated that as duration of supplementation continued, the efficacy of beta-alanine supplementation in highly trained athletes became apparent.

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

PubMed

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

2015-01-01

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

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

PubMed

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

2010-02-01

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

Anaerobic metabolism in the N-limited green alga Selenastrum minutum. 3. Alanine is the product of anaerobic ammonium assimilation

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

Vanlerberghe, G.C.; Turpin, D.H.; Joy, K.W.

The authors have determined the flow of {sup 15}N into free amino acids of the N-limited green alga Selenastrum minutum (Naeg.) Collins after addition of {sup 15}NH{sub 4}{sup +} to aerobic or anaerobic cells. Under aerobic conditions, only a small proportion of the N assimilated was retained in the free amino acid pool. However, under anaerobic conditions almost all assimilated NH{sub 4}{sup +} accumulates in alanine. This is a unique feature of anaerobic NH{sub 4}{sup +} assimilation. The pathway of carbon flow to alanine results in the production of ATP and reductant which matches exactly the requirements of NH{sub 4}{supmore » +} assimilation. Alanine synthesis is therefore an excellent strategy to maintain energy and redox balance during anaerobic NH{sub 4}{sup +} assimilation.« less

Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

PubMed

Çakir, Evrim; Topaloğlu, Oya; Çolak Bozkurt, Nujen; Karbek Bayraktar, Başak; Güngüneş, Aşkın; Sayki Arslan, Müyesser; Öztürk Ünsal, İlknur; Tutal, Esra; Uçan, Bekir; Delıbaşi, Tuncay

2014-01-01

Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

Alanine and proline content modulate global sensitivity to discrete perturbations in disordered proteins

PubMed Central

Perez, Romel B.; Tischer, Alexander; Auton, Matthew; Whitten, Steven T.

2014-01-01

Molecular transduction of biological signals is understood primarily in terms of the cooperative structural transitions of protein macromolecules, providing a mechanism through which discrete local structure perturbations affect global macromolecular properties. The recognition that proteins lacking tertiary stability, commonly referred to as intrinsically disordered proteins, mediate key signaling pathways suggests that protein structures without cooperative intramolecular interactions may also have the ability to couple local and global structure changes. Presented here are results from experiments that measured and tested the ability of disordered proteins to couple local changes in structure to global changes in structure. Using the intrinsically disordered N-terminal region of the p53 protein as an experimental model, a set of proline and alanine to glycine substitution variants were designed to modulate backbone conformational propensities without introducing non-native intramolecular interactions. The hydrodynamic radius (Rh) was used to monitor changes in global structure. Circular dichroism spectroscopy showed that the glycine substitutions decreased polyproline II (PPII) propensities relative to the wild type, as expected, and fluorescence methods indicated that substitution-induced changes in Rh were not associated with folding. The experiments showed that changes in local PPII structure cause changes in Rh that are variable and that depend on the intrinsic chain propensities of proline and alanine residues, demonstrating a mechanism for coupling local and global structure changes. Molecular simulations that model our results were used to extend the analysis to other proteins and illustrate the generality of the observed proline and alanine effects on the structures of intrinsically disordered proteins. PMID:25244701

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

NASA Astrophysics Data System (ADS)

Younis, Elsayed M.

2015-05-01

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

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

DOEpatents

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

1994-05-17

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

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

DOEpatents

Barton, T.J.; Ijadi-Maghsoodi, S.; Pang, Y.

1994-05-17

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

Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

PubMed

Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

2017-04-01

The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2018-05-22

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

Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus

PubMed Central

Monteiro, Diana Amaral; Selistre-de-Araújo, Heloisa Sobreiro; Tavares, Driele; Kalinin, Ana Lúcia; Rantin, Francisco Tadeu

2017-01-01

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg−1, via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus, seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms. PMID:28956818

Survivability and reactivity of glycine and alanine in early oceans: effects of meteorite impacts.

PubMed

Umeda, Yuhei; Fukunaga, Nao; Sekine, Toshimori; Furukawa, Yoshihiro; Kakegawa, Takeshi; Kobayashi, Takamichi; Nakazawa, Hiromoto

2016-01-01

Prebiotic oceans might have contained abundant amino acids, and were subjected to meteorite impacts, especially during the late heavy bombardment. It is so far unknown how meteorite impacts affected amino acids in the early oceans. Impact experiments were performed under the conditions where glycine was synthesized from carbon, ammonia, and water, using aqueous solutions containing (13)C-labeled glycine and alanine. Selected amino acids and amines in samples were analyzed with liquid chromatography-mass spectrometry (LC/MS). In particular, the (13)C-labeled reaction products were analyzed to distinguish between run products and contaminants. The results revealed that both amino acids survived partially in the early ocean through meteorite impacts, that part of glycine changed into alanine, and that large amounts of methylamine and ethylamine were formed. Fast decarboxylation was confirmed to occur during such impact processes. Furthermore, the formation of n-butylamine, detected only in the samples recovered from the solutions with additional nitrogen and carbon sources of ammonia and benzene, suggests that chemical reactions to form new biomolecules can proceed through marine impacts. Methylamine and ethylamine from glycine and alanine increased considerably in the presence of hematite rather than olivine under similar impact conditions. These results also suggest that amino acids present in early oceans can contribute further to impact-induced reactions, implying that impact energy plays a potential role in the prebiotic formation of various biomolecules, although the reactions are complicated and depend upon the chemical environments as well.

Cellular and Physiological Effects of Dietary Supplementation with β-Hydroxy-β-Methylbutyrate (HMB) and β-Alanine in Late Middle-Aged Mice.

PubMed

Vallejo, Julian; Spence, Madoka; Cheng, An-Lin; Brotto, Leticia; Edens, Neile K; Garvey, Sean M; Brotto, Marco

2016-01-01

There is growing evidence that severe decline of skeletal muscle mass and function with age may be mitigated by exercise and dietary supplementation with protein and amino acid ingredient technologies. The purposes of this study were to examine the effects of the leucine catabolite, beta-hydroxy-beta-methylbutyrate (HMB), in C2C12 myoblasts and myotubes, and to investigate the effects of dietary supplementation with HMB, the amino acid β-alanine and the combination thereof, on muscle contractility in a preclinical model of pre-sarcopenia. In C2C12 myotubes, HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of all SR agonists tested (KCl, P<0.01; caffeine, P = 0.03; ionomycin, P = 0.03). HMB also improved C2C12 myoblast viability (25 μM HMB, P = 0.03) and increased proliferation (25 μM HMB, P = 0.04; 125 μM HMB, P<0.01). Furthermore, an ex vivo muscle contractility study was performed on EDL and soleus muscle from 19 month old, male C57BL/6nTac mice. For 8 weeks, mice were fed control AIN-93M diet, diet with HMB, diet with β-alanine, or diet with HMB and β-alanine. In β-alanine fed mice, EDL muscle showed a 7% increase in maximum absolute force compared to the control diet (202 ± 3vs. 188± 5 mN, P = 0.02). At submaximal frequency of stimulation (20 Hz), EDL from mice fed HMB plus β-alanine showed an 11% increase in absolute force (88.6 ± 2.2 vs. 79.8 ± 2.4 mN, P = 0.025) and a 13% increase in specific force (12.2 ± 0.4 vs. 10.8 ± 0.4 N/cm2, P = 0.021). Also in EDL muscle, β-alanine increased the rate of force development at all frequencies tested (P<0.025), while HMB reduced the time to reach peak contractile force (TTP), with a significant effect at 80 Hz (P = 0.0156). In soleus muscle, all experimental diets were associated with a decrease in TTP, compared to control diet. Our findings highlight beneficial effects of HMB and β-alanine supplementation on skeletal muscle function in aging mice.

Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials.

PubMed

Seko, Yuya; Sumida, Yoshio; Sasaki, Kazuyo; Itoh, Yoshito; Iijima, Hiroaki; Hashimoto, Toshio; Ishii, Shinichi; Inagaki, Nobuya

2018-01-01

We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT >30 U/L). This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12- and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT >30 or ≤30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated. The mean ALT change at 12 weeks was -10.3 ± 11.7 and -3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup (P = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P < 0.0001). The mean change in ALT at 52 weeks was -16.0 ± 18.8 U/L in the high ALT subgroup (P < 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2). In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated.

"Control-alt-delete": rebooting solutions for the E-waste problem.

PubMed

Li, Jinhui; Zeng, Xianlai; Chen, Mengjun; Ogunseitan, Oladele A; Stevels, Ab

2015-06-16

A number of efforts have been launched to solve the global electronic waste (e-waste) problem. The efficiency of e-waste recycling is subject to variable national legislation, technical capacity, consumer participation, and even detoxification. E-waste management activities result in procedural irregularities and risk disparities across national boundaries. We review these variables to reveal opportunities for research and policy to reduce the risks from accumulating e-waste and ineffective recycling. Full regulation and consumer participation should be controlled and reinforced to improve local e-waste system. Aiming at standardizing best practice, we alter and identify modular recycling process and infrastructure in eco-industrial parks that will be expectantly effective in countries and regions to handle the similar e-waste stream. Toxicity can be deleted through material substitution and detoxification during the life cycle of electronics. Based on the idea of "Control-Alt-Delete", four patterns of the way forward for global e-waste recycling are proposed to meet a variety of local situations.

Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players.

PubMed

Rosas, Fabián; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Caniuqueo, Alexis; Cañas-Jamet, Rodrigo; McCrudden, Emma; Meylan, Cesar; Moran, Jason; Nakamura, Fábio Y; Pereira, Lucas A; Loturco, Irineu; Diaz, Daniela; Izquierdo, Mikel

2017-09-01

Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability.

Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players

PubMed Central

Rosas, Fabián; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Cañas-Jamet, Rodrigo; McCrudden, Emma; Meylan, Cesar; Moran, Jason; Nakamura, Fábio Y.; Pereira, Lucas A.; Loturco, Irineu; Diaz, Daniela; Izquierdo, Mikel

2017-01-01

Abstract Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability. PMID:28828081

In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1-13 C]Alanine.

PubMed

Park, Jae Mo; Khemtong, Chalermchai; Liu, Shie-Chau; Hurd, Ralph E; Spielman, Daniel M

2017-05-01

The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD + ]. In this study, we assessed the use of hyperpolarized [1- 13 C]alanine and the subsequent detection of the intracellular products of [1- 13 C]pyruvate and [1- 13 C]lactate as a useful substrate for assessing redox levels in the liver in vivo. Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion. A solution of 80-mM hyperpolarized [1- 13 C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of 13 C MRS spectra. In vivo rat liver spectra showed peaks from [1- 13 C] alanine and the products of [1- 13 C]lactate, [1- 13 C]pyruvate, and 13 C-bicarbonate. A significantly increased 13 C-lactate/ 13 C-pyruvate ratio was observed after ethanol infusion (8.46 ± 0.58 at baseline versus 13.58 ± 0.69 after ethanol infusion; P < 0.001) consistent with the increased NADH produced by liver metabolism of ethanol to acetaldehyde and then acetate. A decrease in 13 C-bicarbonate production was also noted, potentially reflecting ethanol-induced mitochondrial redox changes. A method to measure in vivo tissue redox using hyperpolarized [1- 13 C]alanine is presented, with the validity of the proposed 13 C-pyruvate/ 13 C-lactate metric tested using an ethanol challenge to alter liver redox state. Magn Reson Med 77:1741-1748, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

β-Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro

PubMed Central

Mori, Masahiro; Gähwiler, Beat H; Gerber, Urs

2002-01-01

Electrophysiological and pharmacological properties of glycine receptors were characterized in hippocampal organotypic slice cultures. In the presence of ionotropic glutamate and GABAB receptor antagonists, pressure-application of glycine onto CA3 pyramidal cells induced a current associated with increased chloride conductance, which was inhibited by strychnine. Similar chloride currents could also be induced with β-alanine or taurine. Whole-cell glycine responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal cells and dentate granule cells, while responses to GABA were similar among these three cell types. Although these results demonstrate the presence of functional glycine receptors in the hippocampus, no evidence for their activation during synaptic stimulation was found. Gabazine, a selective GABAA receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor activation is not dependent on transporter-controlled levels of extracellular glycine, as no chloride current was observed in response to sarcosine, an inhibitor of glycine transporters. In contrast, application of guanidinoethanesulfonic acid, an uptake inhibitor of β-alanine and taurine, induced strychnine-sensitive chloride current in the presence of gabazine. These data indicate that modulation of transporters for the endogenous amino acids, β-alanine and taurine, can regulate tonic activation of glycine receptors, which may function in maintenance of inhibitory tone in the hippocampus. PMID:11850512

Effects of cafestol and kahweol from coffee grounds on serum lipids and serum liver enzymes in humans.

PubMed

Urgert, R; Schulz, A G; Katan, M B

1995-01-01

The diterpenes cafestol and kahweol are present in unfiltered coffee in oil droplets and floating fines. They elevate serum cholesterol and alanine aminotransferase (ALT). We measured fines in coffee brews, and examined diterpene availability from spent grounds in healthy volunteers. Turkish or Scandinavian boiled coffee contained 2-5 g fines/L and French press coffee contained 1.5 g fines/L. An intake of 8 g fine grounds/d for 3 wk increased cholesterol by 0.65 mmol/L (95% CI 0.41-0.89 mmol/L) and ALT by 18 U/L (95% CI 4-32 U/L) relative to control subjects (n = 7/group). In a crossover study (n = 15), mean serum cholesterol was 4.9 mmol/L after consumption of both fine and coarse grounds for 10 d (P = 0.43). Serum ALT activities were 29 U/L on fine and 21 U/L on coarse grounds (P = 0.02). Floating fines could contribute substantially to the hyperlipidemic and ALT-elevating effect of unfiltered coffee. Diterpene measurements in coffee brews should include the contribution of fines.

Role of aminotransferases in glutamate metabolism of human erythrocytes.

PubMed

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

2011-04-01

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

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

PubMed

Adeyemi, O S; Akanji, M A

2011-09-01

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

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

PubMed

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

2011-11-01

We compared clinical features and laboratory findings of 104 patients with hepatitis A and 197 patients with scrub typhus. Nausea, vomiting, abdominal pain, hepatomegaly, and jaundice were common in patient with hepatitis A, and fever and headache were significantly more common in patients with scrub typhus. At presentation, an alanine aminotransferase (ALT) level ≥ 500 U/L was observed in 1% of scrub typhus patients and in 87.5% of hepatitis A patients (P < 0.001). A bilirubin level ≥ 1.3 mg/dL was observed in 16.8% of scrub typhus patients and 90.4% of hepatitis A patients. The ALT:lactate dehydrogenase ratio was ≤ 5 in 97.4% of the patients with scrub typhus and > 5 in 95.2% of those with hepatitis A (P < 0.001). Fever, headache, rash, and eschar are findings that indicate scrub typhus. An ALT level ≥ 500 U/L (adjusted odds ratio = 0.011) a bilirubin level ≥ 1.3 (adjusted odds ratio = 0.024), an ALT:lactate dehydrogenase ratio > 5, and hepatomegaly are indications of viral hepatitis A.

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

PubMed Central

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

2011-01-01

We compared clinical features and laboratory findings of 104 patients with hepatitis A and 197 patients with scrub typhus. Nausea, vomiting, abdominal pain, hepatomegaly, and jaundice were common in patient with hepatitis A, and fever and headache were significantly more common in patients with scrub typhus. At presentation, an alanine aminotransferase (ALT) level ≥ 500 U/L was observed in 1% of scrub typhus patients and in 87.5% of hepatitis A patients (P < 0.001). A bilirubin level ≥ 1.3 mg/dL was observed in 16.8% of scrub typhus patients and 90.4% of hepatitis A patients. The ALT:lactate dehydrogenase ratio was ≤ 5 in 97.4% of the patients with scrub typhus and > 5 in 95.2% of those with hepatitis A (P < 0.001). Fever, headache, rash, and eschar are findings that indicate scrub typhus. An ALT level ≥ 500 U/L (adjusted odds ratio = 0.011) a bilirubin level ≥ 1.3 (adjusted odds ratio = 0.024), an ALT:lactate dehydrogenase ratio > 5, and hepatomegaly are indications of viral hepatitis A. PMID:22049041

Perspectives on English Education in the Japanese Public School System: The Views of Foreign Assistant Language Teachers (ALTs)

ERIC Educational Resources Information Center

Amaki, Yuki

2008-01-01

Public school students in Japan must take English as a required subject for three years in junior high school and for three more years in senior high school. In spite of the amount of classroom time invested, and in spite of the available learning support services, the foreign Assistant Language Teacher (ALT) system included, the English…

Ultraviolet radiation induces stress in etiolated Landoltia punctata, as evidenced by the presence of alanine, a universal stress signal: a ¹⁵N NMR study.

PubMed

Monselise, E B-I; Levkovitz, A; Kost, D

2015-01-01

Analysis with (15) N NMR revealed that alanine, a universal cellular stress signal, accumulates in etiolated duckweed plants exposed to 15-min pulsed UV light, but not in the absence of UV irradiation. The addition of 10 mm vitamin C, a radical scavenger, reduced alanine levels to zero, indicating the involvement of free radicals. Free D-alanine was detected in (15) N NMR analysis of the chiral amino acid content, using D-tartaric acid as solvent. The accumulation of D-alanine under stress conditions presents a new perspective on the biochemical processes taking place in prokaryote and eukaryote cells. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Tuning electronic transport via hepta-alanine peptides junction by tryptophan doping.

PubMed

Guo, Cunlan; Yu, Xi; Refaely-Abramson, Sivan; Sepunaru, Lior; Bendikov, Tatyana; Pecht, Israel; Kronik, Leeor; Vilan, Ayelet; Sheves, Mordechai; Cahen, David

2016-09-27

Charge migration for electron transfer via the polypeptide matrix of proteins is a key process in biological energy conversion and signaling systems. It is sensitive to the sequence of amino acids composing the protein and, therefore, offers a tool for chemical control of charge transport across biomaterial-based devices. We designed a series of linear oligoalanine peptides with a single tryptophan substitution that acts as a "dopant," introducing an energy level closer to the electrodes' Fermi level than that of the alanine homopeptide. We investigated the solid-state electron transport (ETp) across a self-assembled monolayer of these peptides between gold contacts. The single tryptophan "doping" markedly increased the conductance of the peptide chain, especially when its location in the sequence is close to the electrodes. Combining inelastic tunneling spectroscopy, UV photoelectron spectroscopy, electronic structure calculations by advanced density-functional theory, and dc current-voltage analysis, the role of tryptophan in ETp is rationalized by charge tunneling across a heterogeneous energy barrier, via electronic states of alanine and tryptophan, and by relatively efficient direct coupling of tryptophan to a Au electrode. These results reveal a controlled way of modulating the electrical properties of molecular junctions by tailor-made "building block" peptides.

Six weeks of β-alanine supplementation did not enhance repeated-sprint ability or technical performances in young elite basketball players.

PubMed

Milioni, Fabio; Redkva, Paulo E; Barbieri, Fabio A; Zagatto, Alessandro M

2017-06-01

Supplementation with β-alanine plays an important role as a precursor of carnosine, the most effective intramuscular buffer, and has been seen as a potential ergogenic aid, especially for high-intensity modalities such as basketball. Thus, the aim of the present study was to investigate the effects of 6 weeks of β-alanine supplementation on repeated sprint ability (RSA) and technical performances in young elite Brazilian basketball players. In total, 27 young basketball players (17±1 years) were randomized into a β-alanine group (Gβ - 6.4 g day -1 of β-alanine) and a placebo group (GP - 6.4 g day -1 of dextrose). Before and after the supplementation period the athletes performed a RSA test composed of ten 30 m sprints with two 180° changes of direction interspaced by 30 s of recovery. During the recovery period (i.e., after the sprints) the athletes performed a countermovement jump (CMJ) and a set of three free throws. After 48 h they performed a Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). Both groups increased the distance covered in the Yo-Yo IR1 after the supplementation period ( p = 0.001). On the other hand, both groups presented impairment in RSA time-performance (total time, best time, and mean time, p ≤ 0.04), while no significant changes were observed for technical task performances (i.e., CMJ and free throws) ( p ≥ 0.07). No between-group interactions were observed for any variable measured ( p ≥ 0.31). Thus, 6 weeks of β-alanine supplementation did not improve RSA or technical performances in young elite basketball players.

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

DTIC Science & Technology

1993-06-18

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

SU-E-T-799: Verification of a Simultaneous Treatment of Multiple Brain Metastases Using VMAT Technique by a Composite Alanine-Gel Dosimeter Phantom

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

Pavoni, J; Silveira, M; Filho, O Baffa

Purpose: This work presents an end-to-end test using a Gel-Alanine phantom to validate the three-dimensional (3D) dose distribution (DD) delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. Methods: Three cylindrical phantons containing MAGIC-f gel dosimeter were used to measure the 3D DD of a VMAT treatment, the first two were filled with the gel dosimeter (Gel 1 and 2) and the third one was filled with gel and 12 alanine dosimeters distributed along it (Gel 3). Gels 1 and 3 were irradiated and gel 2 was used to map the magnetic resonance imagemore » (MRI) scanner field inomogeneities. A CT scan of gel 3 was used for the VMAT treatment planning and 5 alanine pellets were chosen as lesions, around them a PTV was grown and different dose prescriptions were assigned for each one, varying from 5 to 9Gy. Before treatment, the plan was approved in a QA based on an ionization chamber absolute dose measurement, a radiochromic film planar dose measurement and a portal dosimetry per field verification; and also the phantons positioning were verified by ExacTrac 6D correction and OBI kV Cone Beam CT. The gels were irradiated, the MRIs were acquired 24 hours after irradiation and finally, the alanine dosimeters were analysed in a X-band Electron Spin Resonance spectrometer. Results: The association of the two detectors enabled the 3D dose evaluation by gel and punctually inside target volumes by alanine. In the gamma analyses (3%/3mm) comparing the 5 PTVs’ central images DD with TPS expected DD more than 95% of the points were approved. The alanine absolute dose measurements were in agreement with TPS by less than 5%. Conclusion: The gel-alanine phantom enabled the dosimetric validation of multiple brain metastases treatment using VMAT, being an almost ideal tool for this application. This work is partially supported by FAPESP.« less

Crystallization and preliminary X-ray data analysis of β-alanine synthase from Drosophila melanogaster

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

Lundgren, Stina; Andersen, Birgit; Piškur, Jure

2007-10-01

β-Alanine synthase catalyzes the last step in the reductive degradation pathway for uracil and thymine. Crystals of the recombinant enzyme from D. melanogaster belong to space group C2. Diffraction data to 3.3 Å resolution were collected and analyzed. β-Alanine synthase catalyzes the last step in the reductive degradation pathway for uracil and thymine, which represents the main clearance route for the widely used anticancer drug 5-fluorouracil. Crystals of the recombinant enzyme from Drosophila melanogaster, which is closely related to the human enzyme, were obtained by the hanging-drop vapour-diffusion method. They diffracted to 3.3 Å at a synchrotron-radiation source, belong tomore » space group C2 (unit-cell parameters a = 278.9, b = 95.0, c = 199.3 Å, β = 125.8°) and contain 8–10 molecules per asymmetric unit.« less

Effect of chronic hypo and hypervitaminosis C on the brush border enzymes and the intestinal uptake of glucose and alanine.

PubMed

Mahmood, A; Chauhan, V P; Lyall, V; Sarkar, A K

1979-08-15

Brush border sucrase and alkaline phosphatase activities are considerably enhanced in the intestine of ascorbic acid deficient guinea-pigs. Similar increase in the uptake of D-glucose and L-alanine also occurs in chronic vitamin C deficiency. However the permeability of D-glucose and L-alanine in the intestine of animals fed with large doses of vitamin C is severely depressed, with a reduction in the levels of sucrase and alkaline phosphatase activities.

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

PubMed

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

2015-01-01

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

Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function

PubMed Central

Lee, Shirley Y.; Pullen, Lester; Virgil, Daniel J.; Castañeda, Carlos A.; Abeykoon, Dulith; Bolon, Daniel N. A.; Fushman, David

2014-01-01

Mutations at solvent inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understood for most systems. Here, we determined the effects of alanine mutations at all 15 core positions in ubiquitin on function in yeast. The majority (13 of 15) of alanine substitutions supported yeast growth as the sole ubiquitin. The two null mutants (I30A and L43A) were both less stable to temperature-induced unfolding in vitro than wild-type, but were well folded at physiological temperatures. Heteronuclear NMR studies indicated that the L43A mutation reduces temperature stability while retaining a ground-state structure similar to wild-type. This structure enables L43A to bind to common ubiquitin receptors in vitro. Many of the core alanine ubiquitin mutants, including one of the null variants (I30A), exhibited an increased accumulation of high molecular weight species, suggesting that these mutants caused a defect in the processing of ubiquitin-substrate conjugates. In contrast, L43A exhibited a unique accumulation pattern with reduced levels of high molecular weight species and undetectable levels of free ubiquitin. When conjugation to other proteins was blocked, L43A ubiquitin accumulated as free ubiquitin in yeast. Based on these findings we speculate that ubiquitin's stability to unfolding may be required for efficient recycling during proteasome-mediated substrate degradation. PMID:24361330

Cellular and Physiological Effects of Dietary Supplementation with β-Hydroxy-β-Methylbutyrate (HMB) and β-Alanine in Late Middle-Aged Mice

PubMed Central

Vallejo, Julian; Spence, Madoka; Cheng, An-Lin; Brotto, Leticia; Edens, Neile K.; Garvey, Sean M.; Brotto, Marco

2016-01-01

There is growing evidence that severe decline of skeletal muscle mass and function with age may be mitigated by exercise and dietary supplementation with protein and amino acid ingredient technologies. The purposes of this study were to examine the effects of the leucine catabolite, beta-hydroxy-beta-methylbutyrate (HMB), in C2C12 myoblasts and myotubes, and to investigate the effects of dietary supplementation with HMB, the amino acid β-alanine and the combination thereof, on muscle contractility in a preclinical model of pre-sarcopenia. In C2C12 myotubes, HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of all SR agonists tested (KCl, P<0.01; caffeine, P = 0.03; ionomycin, P = 0.03). HMB also improved C2C12 myoblast viability (25 μM HMB, P = 0.03) and increased proliferation (25 μM HMB, P = 0.04; 125 μM HMB, P<0.01). Furthermore, an ex vivo muscle contractility study was performed on EDL and soleus muscle from 19 month old, male C57BL/6nTac mice. For 8 weeks, mice were fed control AIN-93M diet, diet with HMB, diet with β-alanine, or diet with HMB and β-alanine. In β-alanine fed mice, EDL muscle showed a 7% increase in maximum absolute force compared to the control diet (202 ± 3vs. 188± 5 mN, P = 0.02). At submaximal frequency of stimulation (20 Hz), EDL from mice fed HMB plus β-alanine showed an 11% increase in absolute force (88.6 ± 2.2 vs. 79.8 ± 2.4 mN, P = 0.025) and a 13% increase in specific force (12.2 ± 0.4 vs. 10.8 ± 0.4 N/cm2, P = 0.021). Also in EDL muscle, β-alanine increased the rate of force development at all frequencies tested (P<0.025), while HMB reduced the time to reach peak contractile force (TTP), with a significant effect at 80 Hz (P = 0.0156). In soleus muscle, all experimental diets were associated with a decrease in TTP, compared to control diet. Our findings highlight beneficial effects of HMB and β-alanine supplementation on skeletal muscle function in aging mice. PMID

Transferability of ASTM/NIST alanine-polyethylene recipe at ISS. American Society for Testing and Materials/National Institute for Standards and Technology. Istituto Superiore de Sanita

PubMed

De Angelis C; Fattibene; Onori; Petetti; Bartolotta; Sansone Santamaria A

2000-05-01

Alanine-polyethylene solid state dosimeters were prepared at Istituto Superiore di Sanita (ISS) following the recipe proposed by National Institute of Standards and Technology (NIST) with the goal of testing its transferability. Dosimeters were prepared using 95% alanine and 5% polyethylene, by weight. They are rugged and of increased sensitivity, repeatability and reproducibility as respect to the ISS alanine-paraffin pellets. Reproducibility of about 1% was obtained at 10 Gy and at 3 Gy if one single pellet or a stack of five dosimeters were used, respectively.

Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of D-alanine in their biological activity.

PubMed

Villéger, Romain; Saad, Naima; Grenier, Karine; Falourd, Xavier; Foucat, Loïc; Urdaci, Maria C; Bressollier, Philippe; Ouk, Tan-Sothea

2014-10-01

Probiotics represent a potential strategy to influence the host's immune system thereby modulating immune response. Lipoteichoic Acid (LTA) is a major immune-stimulating component of Gram-positive cell envelopes. This amphiphilic polymer, anchored in the cytoplasmic membrane by means of its glycolipid component, typically consists of a poly (glycerol-phosphate) chain with D-alanine and/or glycosyl substitutions. LTA is known to stimulate macrophages in vitro, leading to secretion of inflammatory mediators such as Nitric Oxide (NO). This study investigates the structure-activity relationship of purified LTA from three probiotic Bacillus strains (Bacillus cereus CH, Bacillus subtilis CU1 and Bacillus clausii O/C). LTAs were extracted from bacterial cultures and purified. Chemical modification by means of hydrolysis at pH 8.5 was performed to remove D-alanine. The molecular structure of native and modified LTAs was determined by (1)H NMR and GC-MS, and their inflammatory potential investigated by measuring NO production by RAW 264.7 macrophages. Structural analysis revealed several differences between the newly characterized LTAs, mainly relating to their D-alanylation rates and poly (glycerol-phosphate) chain length. We observed induction of NO production by LTAs from B. subtilis and B. clausii, whereas weaker NO production was observed with B. cereus. LTA dealanylation abrogated NO production independently of the glycolipid component, suggesting that immunomodulatory potential depends on D-alanine substitutions. D-alanine may control the spatial configuration of LTAs and their recognition by cell receptors. Knowledge of molecular mechanisms behind the immunomodulatory abilities of probiotics is essential to optimize their use.

Relation between Liver Transaminases and Dyslipidaemia among 2-10 y.o. Northern Mexican Children.

PubMed

Bibiloni, Maria Del Mar; Salas, Rogelio; Nuñez, Georgina M; Villarreal, Jesús Z; Sureda, Antoni; Tur, Josep A

2016-01-01

The increase in overweight and obese children may be linked to increased rates of liver damage and dyslipidaemia. This study aimed to explore the associations of liver biomarkers with overweight/obesity and dyslipidaemia in Mexican children. The study was a population-based cross-sectional nutritional survey carried out in the State of Nuevo León, Mexico. The study included a 414 subjects aged between 2 and 10 years old (47.8% girls) who took part in the State Survey of Nutrition and Health-Nuevo León 2011/2012. Associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT/AST ratio, and major components of serum lipid profile were assessed. Children with high ALT (defined as ≥P75) showed higher prevalence of dyslipidaemia than their counterparts, with high prevalence of high TChol (P = 0.053), non-HDL-chol, TG, and low HDL-chol. Children with an AST/ALT ≥T3 ratio were 0.43-times (95% CI: 0.25-0.74) and 0.27-times (95% CI: 0.17-0.44) low likely to be overweight/obese and to have dyslipidaemia than those with an AST/ALT ALT ratio groups. Our results pose the need for further investigation on whether AST/ALT may be useful as screening test in the assessment of children with cardiometabolic risk.

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

PubMed

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.

Selection of tRNA(Asp) amber suppressor mutants having alanine, arginine, glutamine, and lysine identity.

PubMed Central

Martin, F; Reinbolt, J; Dirheimer, G; Gangloff, J; Eriani, G

1996-01-01

Elements that confer identity to a tRNA in the cellular environment, where all aminoacyl-tRNA synthetases are competing for substrates, may be delineated by in vivo experiments using suppressor tRNAs. Here we describe the selection of active Escherichia coli tRNAAsp amber mutants and analyze their identity. Starting from a library containing randomly mutated tRNA(CUA)Asp genes, we isolated four amber suppressors presenting either lysine, alanine, or glutamine activity. Two of them, presenting mainly alanine or lysine activity, were further submitted to a second round of mutagenesis selection in order to improve their efficiency of suppression. Eleven suppressors were isolated, each containing two or three mutations. Ten presented identities of the two parental mutants, whereas one had switched from lysine to arginine identity. Analysis of the different mutants revealed (or confirmed for some nucleotides) their role as positive and/or negative determinants in AlaRS, LysRS, and ArgRS recognition. More generally, it appears that tRNAAsp presents identity characteristics closely related to those of tRNALys, as well as a structural basis for acquiring alanine or arginine identity upon moderate mutational changes; these consist of addition or suppression of the corresponding positive or negative determinants, as well as tertiary interactions. Failure to isolate aspartic acid-inserting suppressors is probably due to elimination of the important G34 identity element and its replacement by an antideterminant when changing the anticodon of the tRNAAsp to the CUA triplet. PMID:8809018

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

PubMed

Scully, Peter; Zhao, Jie; Ba, Sujuan

2016-02-03

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

The role of metal ions in chemical evolution - Polymerization of alanine and glycine in a cation-exchanged clay environment

NASA Technical Reports Server (NTRS)

Lawless, J. G.; Levi, N.

1979-01-01

The effect of the exchangeable cation on the condensation of glycine and alanine was investigated using a series of homoionic bentonites. A cycling procedure of drying, warming and wetting was employed. Peptide bond formation was observed, and the effectiveness of metal ions to catalyze the condensation was Cu(2+) greater than Ni(2) approximately equals Zn(2+) greater than Na(+). Glycine showed 6% of the monomer incorporated into oligomers with the largest detected being the pentamer. Alanine showed less peptide bond formation (a maximum of 2%) and only the dimer was observed.

Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

PubMed

Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V

2016-04-01

Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed

Dennis, V W; Brazy, P C

1978-08-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport.

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed Central

Dennis, V W; Brazy, P C

1978-01-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport. PMID:670399

Effects of milk thistle seed against aflatoxin B1 in broiler model.

PubMed

Amiridumari, Halimeh; Sarir, Hadi; Afzali, Nazar; Fanimakki, Omid

2013-09-01

Consumption of aflatoxin B1 (AFB1) contaminated products can pose a risk of development of various diseases in human and animals due to radical production. The scope of this work is to evaluate the efficacy of milk thistle seed (MTS), as a radical scavenger, on serum biochemistry, lipid profile and liver enzymes against AFB1 in broiler chickens contaminated with AFB1. The effect of nine experimental treatments (3 × 3 factorial design) was assessed using 216 one-d-old Ross 308 male broiler chicks in a randomized complete design with four replicates of six birds for each dietary treatments: Control (T1), 250 ppb AFB1 (T2), 500 ppb AFB1 (T3), 0.5% MTS (T4), 0.5% MTS Plus 250 ppb AFB1 (T5), 0.5% MTS Plus 500 ppb AFB1 (T6), 1.0% MTS (T7), 1.0% MTS Plus 250 ppb AFB1 (T8), and 1.0% MTS Plus 500 ppb AFB1 (T9). The individual and combined effects of dietary AFB1 and MTS on serum biochemistry factors (Glucose, Calcium, Phosphorus, Iron, Creatinine, and Uric acid), lipid profile (Triglyceride, Cholesterol, Low density lipoprotein (LDL), and High density lipoprotein (HDL)) and liver enzymes aspartate amino-transferase and alanine amino-transaminase (ALT) in broilers were evaluated at 21 days of age. Also, statistical packages Macros-1.002 (2010) were used to perform the above analysis on computer. Consumption of 500 ppb AFB1 in to the diet significantly decreased HDL (58.13 ± 2.65), Calcium (7.11 ± 0.13), and Glucose (197.1 ± 7.42) compared to the control group (85.12 ± 1.95, 9.45 ± 0.17 and 223.1 ± 6.61, respectively), (P < 0.05). In contrast, it significantly increased creatinine (2.25 ± 0.011) and AST (244.51 ± 4.91). Using MTS together with AFB1 significantly reduced the effect of AFB1 on the above parameters. MTS can provide protection against the negative effects of AFB1 on broiler chicks.

Partial alanine scan of mast cell degranulating peptide (MCD): importance of the histidine- and arginine residues.

PubMed

Buku, Angeliki; Mendlowitz, Milton; Condie, Barry A; Price, Joseph A

2004-06-01

The influence of the two histidine and two arginine residues of mast cell degranulating peptide (MCD) in activity and binding was studied by replacing these amino acids in the MCD sequence with L-alanine. Their histamine releasing activity was determined on rat peritoneal mast cells. Their binding affinity to the FcepsilonRIalpha binding subunit of the human mast cell receptor protein, was carried out using fluorescence polarization. The histamine assay showed that replacement of His13 by Ala o ccurred without loss of activity compared with the activity of MCD. Alanine substitutions for Arg7 and His8 resulted in an approximately 40 fold increase, and for Arg16 in a 14-fold increase in histamine-releasing activity of MCD. The binding affinities of the analogs were tested by competitive displacement of bound fluorescent MCD peptide from the FcepsilonRIalpha binding protein of the mast cell receptor by the Ala analogs using fluorescence polarization. The analogs Ala8 (for His) and Ala16 (for Arg) showed the same binding affinities as MCD, whereas analog Ala7 (for Arg) and analog Ala13 (for His) showed slightly better binding affinity than the parent compound. This study showed that the introduction of alanine residues in these positions resulted in MCD agonists of diverse potency. These findings will be useful in further MCD structure-activity studies.

Comparison Study II: Double Star Measurements Made Using an Equatorial Mounted Refractor and an Alt-Az Mounted Reflector

NASA Astrophysics Data System (ADS)

Frey, Thomas G.; Coombs, Lee C.

2012-07-01

Eight double stars with separations between 13 and 48 arc seconds were studied. Their separations and position angles were measured using an equatorial mounted refractor and and alt-az mounted reflector. A 2x Barlow lens was used along with a Celestron Micro Guide eyepiece to magnify the separation. Comparison of the possible effect of magnitude difference on the separation and position angle measurements was investigated.

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

NASA Astrophysics Data System (ADS)

McEwen, Malcolm; Sharpe, Peter; Vörös, Sándor

2015-04-01

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

Intrachain versus interchain electron transport in poly(fluorene-alt-benzothiadiazole): a quantum-chemical insight.

PubMed

Van Vooren, Antoine; Kim, Ji-Seon; Cornil, Jérôme

2008-05-16

Poly(9,9-di-n-octylfluorene-alt-benzothiadiazole) [F8BT], displays very different charge-transport properties for holes versus electrons when comparing annealed and pristine thin films and transport parallel (intrachain) and perpendicular (interchain) to the polymer axes. The present theoretical contribution focuses on the electron-transport properties of F8BT chains and compares the efficiency of intrachain versus interchain transport in the hopping regime. The theoretical results rationalize significantly lowered electron mobility in annealed F8BT thin films and the smaller mobility anisotropy (mu( parallel)/mu( perpendicular)) measured for electrons in aligned films (i.e. 5-7 compared to 10-15 for holes).

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

DTIC Science & Technology

1993-07-09

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

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2011-05-01

in urine output and decreased urine osmolality as compared to dextrose-infused and no infusion controls; however, at the completion of the infusion...levels of alanine amino transferase (ALT) and blood urea nitrogen (BUN), markers of hepatic and renal damage and dysfunction respectively. To examine...hepatic injury and dysfunction, as well as blood urea nitrogen (BUN) and creatinine, makers of renal dysfunction, were elevated following delayed

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

NASA Astrophysics Data System (ADS)

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

2015-01-01

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

Kinetic enantioselectivity of a protonated bis(diamido)-bridged basket resorcin[4]arene towards alanine peptides.

PubMed

Fraschetti, C; Montagna, M; Crestoni, M E; Calcaterra, A; Aiello, F; Santi, L; Filippi, A

2017-02-01

Efficient enantiodiscrimination of some alanine-containing di- and tri-peptides by using chiral protonated bis(diamido)-bridged basket resorcin[4]arenes depends on several factors, including the basicity of the amino acid residues at the C- and N-termini of the peptide.

Frequency and Prognostic Significance of Abnormal Liver Function Tests in Patients With Cardiogenic Shock.

PubMed

Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Parissis, John; Pulkki, Kari; Sionis, Alessandro; Silva-Cardoso, Jose; Køber, Lars; Banaszewski, Marek; Spinar, Jindrich; Fuhrmann, Valentin; Tolonen, Jukka; Carubelli, Valentina; diSomma, Salvatore; Mebazaa, Alexandre; Lassus, Johan

2017-10-01

Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS. We measured LFTs in 178 patients in CS from serial blood samples taken at 0 hours, 12 hours, and 24 hours. The associations of LFT abnormalities and their early changes with all-cause 90-day mortality were estimated using Fisher's exact test and Cox proportional hazards regression analysis. Baseline alanine aminotransferase (ALT) was abnormal in 58% of the patients, more frequently in nonsurvivors. Abnormalities in other LFTs analyzed (alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin) were not associated with short-term mortality. An increase in ALT of >20% within 24 hours (ΔALT>+20%) was observed in 24% of patients. ΔALT>+20% was associated with a more than 2-fold increase in mortality compared with those with stable or decreasing ALT (70% and 28%, p <0.001). Multivariable regression analysis showed that ΔALT>+20% was associated with increased 90-day mortality independent of other known risk factors. In conclusion, an increase in ALT in the initial phase was seen in 1/4 of patients in CS and was independently associated with 90-day mortality. This finding suggests that serial ALT measurements should be incorporated in the clinical assessment of patients in CS. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

2018-04-01

Introduction To determine the factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methodology All patients aged >18 years and having a fatty liver on abdominal ultrasound (US), presenting from January 2011 to January 2017, were included. A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. Liver biopsy showed non-alcoholic steatohepatitis (NASH) in 78 (81.3%) patients. Factors associated with NASH were male gender, body mass index (BMI) > 27 kg/m 2 , DFL and raised alanine aminotransferase (ALT). A GULAB score (based on gender, US liver findings, lipid (fasting) levels, ALT level and BMI) of ≥5 predicted NASH with 82.05% sensitivity. Factors associated with advanced fibrosis in NAFLD were age >40 years, diabetes mellitus, AST/ALT ratio > 1 and raised GGT. Conclusion NASH is common in patients with male gender, high BMI, DFL on liver US, raised ALT and GULAB score ≥5.

Oxygenated N-Acyl Alanine Methyl Esters (NAMEs) from the Marine Bacterium Roseovarius tolerans EL-164.

PubMed

Bruns, Hilke; Herrmann, Jennifer; Müller, Rolf; Wang, Hui; Wagner Döbler, Irene; Schulz, Stefan

2018-01-26

The marine bacterium Roseovarius tolerans EL-164 (Rhodobacteraceae) can produce unique N-acylalanine methyl esters (NAMEs) besides strucutrally related N-acylhomoserine lactones (AHLs), bacterial signaling compounds widespread in the Rhodobacteraceae. The structures of two unprecedented NAMEs carrying a rare terminally oxidized acyl chain are reported here. The compounds (Z)-N-16-hydroxyhexadec-9-enoyl-l-alanine methyl ester (Z9-16-OH-C16:1-NAME, 3) and (Z)-N-15-carboxypentadec-9-enoyl-l-alanine methyl ester (16COOH-C16:1-NAME, 4) were isolated, and the structures were determined by NMR and MS experiments. Both compounds were synthesized to prove assignments and to test their biological activity. Finally, non-natural, structurally related Z9-3-OH-C16:1-NAME (18) was synthesized to investigate the mass spectroscopy of structurally related NAMEs. Compound 3 showed moderate antibacterial activity against microorganisms such as Bacillus, Streptococcus, Micrococcus, or Mucor strains. In contrast to AHLs, quorum-sensing or quorum-quenching activity was not observed.

Relation between Liver Transaminases and Dyslipidaemia among 2-10 y.o. Northern Mexican Children

PubMed Central

Bibiloni, Maria del Mar; Salas, Rogelio; Nuñez, Georgina M.; Villarreal, Jesús Z.; Sureda, Antoni

2016-01-01

Background and Aims The increase in overweight and obese children may be linked to increased rates of liver damage and dyslipidaemia. This study aimed to explore the associations of liver biomarkers with overweight/obesity and dyslipidaemia in Mexican children. Methods The study was a population-based cross-sectional nutritional survey carried out in the State of Nuevo León, Mexico. The study included a 414 subjects aged between 2 and 10 years old (47.8% girls) who took part in the State Survey of Nutrition and Health–Nuevo León 2011/2012. Associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT/AST ratio, and major components of serum lipid profile were assessed. Results Children with high ALT (defined as ≥P75) showed higher prevalence of dyslipidaemia than their counterparts, with high prevalence of high TChol (P = 0.053), non-HDL-chol, TG, and low HDL-chol. Children with an AST/ALT ≥T3 ratio were 0.43-times (95% CI: 0.25–0.74) and 0.27-times (95% CI: 0.17–0.44) low likely to be overweight/obese and to have dyslipidaemia than those with an AST/ALT ALT ratio groups. Conclusions Our results pose the need for further investigation on whether AST/ALT may be useful as screening test in the assessment of children with cardiometabolic risk. PMID:27203747

R76 in transmembrane domain 3 of the aspartate:alanine transporter AspT is involved in substrate transport.

PubMed

Suzuki, Satomi; Nanatani, Kei; Abe, Keietsu

2016-01-01

The L-aspartate:L-alanine antiporter of Tetragenococcus halophilus (AspT) possesses an arginine residue (R76) within the GxxxG motif in the central part of transmembrane domain 3 (TM3)-a residue that has been estimated to transport function. In this study, we carried out amino acid substitutions of R76 and used proteoliposome reconstitution for analyzing the transport function of each substitution. Both l-aspartate and l-alanine transport assays showed that R76K has higher activity than the AspT-WT (R76), whereas R76D and R76E have lower activity than the AspT-WT. These results suggest that R76 is involved in AspT substrate transport.

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

PubMed

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

1995-05-15

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

Effect of Segregation of Secondary Phase Particles and "S" Line on Tensile Fracture Behavior of Friction Stir-Welded 2024Al-T351 Joints

NASA Astrophysics Data System (ADS)

Zhang, Z.; Xiao, B. L.; Ma, Z. Y.

2013-09-01

A 5-mm-thick 2024Al-T351 plate was friction stir welded (FSWed) at welding speeds of 100, 200, and 400 mm min-1 with a constant rotation rate of 800 rpm, and the microstructure and tensile fracture behavior of the joints were investigated in detail. FSW resulted in the redistribution of secondary phase particles along the recrystallized grain boundaries at the nugget zone (NZ), forming linear segregation bands consisting of secondary phase particles. The segregation bands, mainly present in the shoulder-driven zone, were believed to result from periodic material flow, with the average band spacing on the longitudinal and horizontal cross sections equal to the tool advancement per revolution. At a low welding speed of 100 mm min-1, in spite of the highest density of segregation bands, the FSWed 2024Al-T351 joint fractured along the low hardness zone (LHZ) of the heat-affected zone because of large hardness gap between NZ and LHZ. Increasing the welding speed to 200 and 400 mm min-1 reduced both the hardness gap between NZ and LHZ and the density of segregation bands. In this case, the segregation bands played a role, resulting in unusual fracture of the joints along the segregation bands. The "S" line originated from the oxide film on the initial butting surfaces and did not affect the fracture behavior of the FSWed 2024Al-T351 joints.

Mechanical stability analysis of the protein L immunoglobulin-binding domain by full alanine screening using molecular dynamics simulations.

PubMed

Glyakina, Anna V; Likhachev, Ilya V; Balabaev, Nikolay K; Galzitskaya, Oxana V

2015-03-01

This article is the first to study the mechanical properties of the immunoglobulin-binding domain of protein L (referred to as protein L) and its mutants at the atomic level. In the structure of protein L, each amino acid residue (except for alanines and glycines) was replaced sequentially by alanine. Thus, 49 mutants of protein L were obtained. The proteins were stretched at their termini at constant velocity using molecular dynamics simulations in water, i.e. by forced unfolding. 19 out of 49 mutations resulted in a large decrease of mechanical protein stability. These amino acids were affecting either the secondary structure (11 mutations) or loop structures (8 mutations) of protein L. Analysis of mechanical unfolding of the generated protein that has the same topology as protein L but consists of only alanines and glycines allows us to suggest that the mechanical stability of proteins, and specifically protein L, is determined by interactions between certain amino acid residues, although the unfolding pathway depends on the protein topology. This insight can now be used to modulate the mechanical properties of proteins and their unfolding pathways in the desired direction for using them in various biochips, biosensors and biomaterials for medicine, industry, and household purposes. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inelastic neutron scattering, Raman, vibrational analysis with anharmonic corrections, and scaled quantum mechanical force field for polycrystalline L-alanine

NASA Astrophysics Data System (ADS)

Williams, Robert W.; Schlücker, Sebastian; Hudson, Bruce S.

2008-01-01

A scaled quantum mechanical harmonic force field (SQMFF) corrected for anharmonicity is obtained for the 23 K L-alanine crystal structure using van der Waals corrected periodic boundary condition density functional theory (DFT) calculations with the PBE functional. Scale factors are obtained with comparisons to inelastic neutron scattering (INS), Raman, and FT-IR spectra of polycrystalline L-alanine at 15-23 K. Calculated frequencies for all 153 normal modes differ from observed frequencies with a standard deviation of 6 wavenumbers. Non-bonded external k = 0 lattice modes are included, but assignments to these modes are presently ambiguous. The extension of SQMFF methodology to lattice modes is new, as are the procedures used here for providing corrections for anharmonicity and van der Waals interactions in DFT calculations on crystals. First principles Born-Oppenheimer molecular dynamics (BOMD) calculations are performed on the L-alanine crystal structure at a series of classical temperatures ranging from 23 K to 600 K. Corrections for zero-point energy (ZPE) are estimated by finding the classical temperature that reproduces the mean square displacements (MSDs) measured from the diffraction data at 23 K. External k = 0 lattice motions are weakly coupled to bonded internal modes.

Annealing improves tribological property of poly(octadecene- alt -maleic anhydride) self-assembled film

NASA Astrophysics Data System (ADS)

Song, Shiyong; Liu, Lei; Zhang, Junyan

2011-09-01

A poly(octadecene-alt-maleic anhydride) (POMA) film was covalently immobilized on N-[3-(trimethoxylsilyl)propyl]ethylenediamine self-assembled monolayer modified silicon surface. Attenuated total reflectance Fourier transform infrared spectra were used to confirm the chemical bonding. Water contact angles and ellipsometric thicknesses were measured before and after annealing treatment. Atomic force microscopy was applied for top morphology, surface adhesion force and friction force. Anti-wear properties of the films were also evaluated on a ball-on-plate tribometer. It was found that annealing treatment which would evoke a conformation transform thermodynamically, was a critical step in the preparation of anti-wear films, especially for polymer ones. The correlation between structure and tribological property was revealed, which has profound meaning in designing excellent anti-wear nano-coatings used in microelectronic mechanical systems (MEMS).

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

USGS Publications Warehouse

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

2001-01-01

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

Folding and Function of a T4 Lysozyme Containing 10 Consecutive Alanines Illustrate the Redundancy of Information in an Amino Acid Sequence

NASA Astrophysics Data System (ADS)

Heinz, Dirk W.; Baase, Walt A.; Matthews, Brian W.

1992-05-01

Single and multiple Xaa -> Ala substitutions were constructed in the α-helix comprising residues 39-50 in bacteriophage T4 lysozyme. The variant with alanines at 10 consecutive positions (A40-49) folds normally and has activity essentially the same as wild type, although it is less stable. The crystal structure of this polyalanine mutant displays no significant change in the main-chain atoms of the helix when compared with the wild-type structure. The individual substitutions of the solvent-exposed residues Asn-40, Ser-44, and Glu-45 with alanine tend to increase the thermostability of the protein, whereas replacements of the buried or partially buried residues Lys-43 and Leu-46 are destabilizing. The melting temperature of the lysozyme in which Lys-43 and Leu-46 are retained and positions 40, 44, 45, 47, and 48 are substituted with alanine (i.e., A40-42/44-45/47-49) is increased by 3.1^circC relative to wild type at pH 3.0, but reduced by 1.6^circC at pH 6.7. In the case of the charged amino acids Glu-45 and Lys-48, the changes in melting temperature indicate that the putative salt bridge between these two residues contributes essentially nothing to the stability of the protein. The results clearly demonstrate that there is considerable redundancy in the sequence information in the polypeptide chain; not every amino acid is essential for folding. Also, further evidence is provided that the replacement of fully solvent-exposed residues within α-helices with alanines may be a general way to increase protein stability. The general approach may permit a simplification of the protein folding problem by retaining only amino acids proven to be essential for folding and replacing the remainder with alanine.

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

PubMed

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

2016-06-01

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

Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

PubMed

Williams, K H; Sullivan, D R; Veillard, A S; O'Brien, R; George, J; Jenkins, A J; Young, S; Ehnholm, C; Duffield, A; Twigg, S M; Keech, A C

2016-03-01

To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively (P = 0.001). No relationship was found for gamma-glutamyltransferase. The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) from Haemophilus influenzae.

PubMed

Mol, Clifford D; Brooun, Alexei; Dougan, Douglas R; Hilgers, Mark T; Tari, Leslie W; Wijnands, Robert A; Knuth, Mark W; McRee, Duncan E; Swanson, Ronald V

2003-07-01

UDP-N-acetylmuramic acid:L-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan. The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg(2+) and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-L-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn(2+) have been determined to 1.85- and 1.7-A resolution, respectively. These structures reveal a conserved, three-domain architecture with the binding sites for UNAM and ATP formed at the domain interfaces: the N-terminal domain binds the UDP portion of UNAM, and the central and C-terminal domains form the ATP-binding site, while the C-terminal domain also positions the alanine. An active enzyme structure is thus assembled at the common domain interfaces when all three substrates are bound. The MurC active site clearly shows that the gamma-phosphate of AMPPNP is positioned between two bound metal ions, one of which also binds the reactive UNAM carboxylate, and that the alanine is oriented by interactions with the positively charged side chains of two MurC arginine residues and the negatively charged alanine carboxyl group. These results indicate that significant diversity exists in binding of the UDP moiety of the substrate by MurC and the subsequent ligases in the bacterial cell wall biosynthesis pathway and that alterations in the domain packing and tertiary structure allow the Mur ligases to bind sequentially larger UNAM peptide substrates.

Radiolysis of alanine adsorbed in a clay mineral

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

Aguilar-Ovando, Ellen Y.; Negron-Mendoza, Alicia

2013-07-03

Optical activity in molecules is a chemical characteristic of living beings. In this work, we examine the hypothesis of the influence of different mineral surfaces on the development of a specific chirality in organic molecules when subjected to conditions simulating the primitive Earth during the period of chemical evolution. By using X-ray diffraction techniques and HPLC/ELSD to analyze aqueous suspensions of amino acids adsorbed on minerals irradiated in different doses with a cobalt-60 gamma source, the experiments attempt to prove the hypothesis that some solid surfaces (like clays and meteorite rocks) may have a concentration capacity and protective role againstmore » external sources of ionizing radiation (specifically {gamma}-ray) for some organic compounds (like some amino acids) adsorbed on them. Preliminary results show a slight difference in the adsorption and radiolysis of the D-and L-alanine.« less

Structures and ice-binding faces of the alanine-rich type I antifreeze proteins.

PubMed

Patel, Shruti N; Graether, Steffen P

2010-04-01

Antifreeze proteins (AFPs) protect cold-blooded organisms from the damage caused by freezing through their ability to inhibit ice growth. The type I AFP family, found in several fish species, contains proteins that have a high alanine content (>60% of the sequence) and structures that are almost all alpha-helical. We examine the structure of the type I AFP isoforms HPLC6 from winter flounder, shorthorn sculpin 3, and the winter flounder hyperactive type I AFP. The HPLC6 isoform structure consists of a single alpha-helix that is 37 residues long, whereas the shorthorn sculpin 3 isoform consists of two helical regions separated by a kink. The high-resolution structure of the hyperactive type I AFP has yet to be determined, but circular dichroism data and analytical ultracentrifugation suggest that the 195 residue protein is a side-by-side dimer of two alpha-helices. The alanine-rich ice-binding faces of HPLC6 and hyperactive type I AFP are discussed, and we propose that the ice-binding face of the shorthorn sculpin 3 AFP contains Ala14, Ala19, and Ala25. We also propose that the denaturation of hyperactive type I AFP at room temperature is explained by the stabilization of the dimerization interface through hydrogen bonds.

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

PubMed Central

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

2015-01-01

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

Crystal structure and confirmation of the alanine:glyoxylate aminotransferase activity of the YFL030w yeast protein.

PubMed

Meyer, Philippe; Liger, Dominique; Leulliot, Nicolas; Quevillon-Cheruel, Sophie; Zhou, Cong-Zhao; Borel, Franck; Ferrer, Jean-Luc; Poupon, Anne; Janin, Joël; van Tilbeurgh, Herman

2005-12-01

We have determined the three-dimensional crystal structure of the protein encoded by the open reading frame YFL030w from Saccharomyces cerevisiae to a resolution of 2.6 A using single wavelength anomalous diffraction. YFL030w is a 385 amino-acid protein with sequence similarity to the aminotransferase family. The structure of the protein reveals a homodimer adopting the fold-type I of pyridoxal 5'-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure. The protein shows close structural resemblance with the human alanine:glyoxylate aminotransferase (EC 2.6.1.44), an enzyme involved in the hereditary kidney stone disease primary hyperoxaluria type 1. In this paper we show that YFL030w codes for an alanine:glyoxylate aminotransferase, highly specific for its amino donor and acceptor substrates.

Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men.

PubMed

Bassinello, Diogo; de Salles Painelli, Vitor; Dolan, Eimear; Lixandrão, Manoel; Cajueiro, Monique; de Capitani, Mariana; Saunders, Bryan; Sale, Craig; Artioli, Guilherme G; Gualano, Bruno; Roschel, Hamilton

2018-06-15

β-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day -1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day -1 ) improved isometric, but not isokinetic or isotonic endurance performance.

In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci.

PubMed

Lee, Ji-Young; Ko, Kwan Soo; Peck, Kyong Ran; Oh, Won Sup; Song, Jae-Hoon

2006-06-01

To investigate appropriate antimicrobial agents, the optimal concentration and treatment duration for the antibiotic lock technique (ALT) to treat catheter-related infections caused by Staphylococcus epidermidis and Staphylococcus aureus. We evaluated the bacterial killing activity of vancomycin, teicoplanin, ciprofloxacin, rifampicin, cefazolin, gentamicin, nafcillin and erythromycin against biofilms formed by two strains of S. aureus and two strains of S. epidermidis. The effectiveness of the antibiotic lock was assayed after exposure to antibiotics (1, 5 and 10 mg/mL) for 1, 3, 5, 7, 10 or 14 days using an in vitro model of biofilms on polyurethane film. The biofilms were completely sterile after exposure to vancomycin (5 mg/mL) for 5 days and teicoplanin (5 and 10 mg/mL) for 7 days. Ciprofloxacin and rifampicin (both 5 mg/mL) achieved eradication of the biofilms of both staphylococcal species more rapidly than vancomycin or teicoplanin. Significant biofilm eradication was not achieved with cefazolin, nafcillin, gentamicin and erythromycin at any of the time exposures examined. The data suggest that 5 mg/mL vancomycin, ciprofloxacin or rifampicin can eradicate S. epidermidis and S. aureus biofilms within 5 days. These findings warrant prospective clinical trials for the evaluation of the clinical efficacy of ALT for less than 10 days.

l-glutamine and l-alanine supplementation increase glutamine-glutathione axis and muscle HSP-27 in rats trained using a progressive high-intensity resistance exercise.

PubMed

Leite, Jaqueline Santos Moreira; Raizel, Raquel; Hypólito, Thaís Menezes; Rosa, Thiago Dos Santos; Cruzat, Vinicius Fernandes; Tirapegui, Julio

2016-08-01

In this study we investigated the chronic effects of oral l-glutamine and l-alanine supplementation, either in their free or dipeptide form, on glutamine-glutathione (GLN-GSH) axis and cytoprotection mediated by HSP-27 in rats submitted to resistance exercise (RE). Forty Wistar rats were distributed into 5 groups: sedentary; trained (CTRL); and trained supplemented with l-alanyl-l-glutamine, l-glutamine and l-alanine in their free form (GLN+ALA), or free l-alanine (ALA). All trained animals were submitted to a 6-week ladder-climbing protocol. Supplementations were offered in a 4% drinking water solution for 21 days prior to euthanasia. Plasma glutamine, creatine kinase (CK), myoglobin (MYO), and erythrocyte concentration of reduced GSH and glutathione disulfide (GSSG) were measured. In tibialis anterior skeletal muscle, GLN-GSH axis, thiobarbituric acid reactive substances (TBARS), and the expression of heat shock factor 1 (HSF-1), 27-kDa heat shock protein (HSP-27), and glutamine synthetase were determined. In CRTL animals, high-intensity RE reduced muscle glutamine levels and increased GSSG/GSH rate and TBARS, as well as augmented plasma CK and MYO levels. Conversely, l-glutamine-supplemented animals showed an increase in plasma and muscle levels of glutamine, with a reduction in GSSG/GSH rate, TBARS, and CK. Free l-alanine administration increased plasma glutamine concentration and lowered muscle TBARS. HSF-1 and HSP-27 were high in all supplemented groups when compared with CTRL (p < 0.05). The results presented herein demonstrate that l-glutamine supplemented with l-alanine, in both a free or dipeptide form, improve the GLN-GSH axis and promote cytoprotective effects in rats submitted to high-intensity RE training.

Crystal Structures of Active Fully Assembled Substrate- and Product-Bound Complexes of UDP-N-Acetylmuramic Acid:l-Alanine Ligase (MurC) from Haemophilus influenzae

PubMed Central

Mol, Clifford D.; Brooun, Alexei; Dougan, Douglas R.; Hilgers, Mark T.; Tari, Leslie W.; Wijnands, Robert A.; Knuth, Mark W.; McRee, Duncan E.; Swanson, Ronald V.

2003-01-01

UDP-N-acetylmuramic acid:l-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan. The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg2+ and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-l-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn2+ have been determined to 1.85- and 1.7-Å resolution, respectively. These structures reveal a conserved, three-domain architecture with the binding sites for UNAM and ATP formed at the domain interfaces: the N-terminal domain binds the UDP portion of UNAM, and the central and C-terminal domains form the ATP-binding site, while the C-terminal domain also positions the alanine. An active enzyme structure is thus assembled at the common domain interfaces when all three substrates are bound. The MurC active site clearly shows that the γ-phosphate of AMPPNP is positioned between two bound metal ions, one of which also binds the reactive UNAM carboxylate, and that the alanine is oriented by interactions with the positively charged side chains of two MurC arginine residues and the negatively charged alanine carboxyl group. These results indicate that significant diversity exists in binding of the UDP moiety of the substrate by MurC and the subsequent ligases in the bacterial cell wall biosynthesis pathway and that alterations in the domain packing and tertiary structure allow the Mur ligases to bind sequentially larger UNAM peptide substrates. PMID:12837790

Effect of taurine on the concentrations of glutamate, GABA, glutamine and alanine in the rat striatum and hippocampus.

PubMed

Molchanova, Svetlana M; Oja, Simos S; Saransaari, Pirjo

2007-01-01

Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.25, 0.5 and 1 g/kg taurine led to a gradual increase in taurine tissue concentrations in both hippocampus and striatum. Glutamate and GABA also increased in the hippocampus, but not in the striatum. Glutamine increased and alanine decreased markedly in both brain structures. The results corroborate the neuromodulatory role of taurine in the brain. Taurine administration results in an imbalance in inhibitory and excitatory neurotransmission in the glutamatergic (hippocampus) and GABAergic (striatum) brain structures, affecting more markedly the neurotransmitter precursors.

New Poly(amide-imide)/Nanocomposites Reinforced Silicate Nanoparticles Based on N-pyromellitimido-L-phenyl Alanine Containing Ether Moieties

NASA Astrophysics Data System (ADS)

Faghihi, Khalil; Shabanian, Meisam; Dadfar, Ehsan

2012-02-01

A series of Poly(amide-imide)/montmorillonite nanocomposites containing N-pyromellitimido-L-phenyl alanine moiety in the main chain were synthesized by a convenient solution intercalation technique. Poly(amide-imide) (PAI) 5 as a source of polymer matrix was synthesized by the direct polycondensation reaction of N-pyromellitimido-L-phenyl alanine 3 with 4,4'-diamino diphenyl ether 4 in the presence of triphenyl phosphite (TPP), CaCl2, pyridine and N-methyl-2-pyrrolidone (NMP). The resulting nanocomposite films were characterized by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that organo-modified clay was dispersed homogeneously in PAI matrix. TGA indicated an enhancement of thermal stability of new nanocomposites compared with the pure polymer.

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

PubMed

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

2016-12-01

The favourable effects of coffee on liver enzymes have been reported worldwide. This study investigated the association between coffee consumption and serum aminotransferase concentration in Korean adults. Data were obtained from the fourth and fifth Korea National Health and Nutrition Examination Surveys. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentration were defined as >30 IU/L for men and >19 IU/L for women. The risk of elevated ALT and AST according to general characteristics and frequency of coffee consumption were tested by chi-square tests and multiple logistic regression analyses. The prevalence of elevated ALT was 27.4%, 27.8%, and 26.9% in subjects who drank <1, 1, and >=2 times/day, respectively. The proportions of individuals with elevated AST were 32.5%, 33.1%, and 26.7% in subjects who drank <1, 1, and >=2 times/day, respectively. The aORs for elevated ALT and AST were significantly lower in subjects who drank >=2 times of coffee/day than in those who drank <1 time/day (ALT: aOR=0.86, 95% CI=0.79-0.94; AST: aOR=0.83, 95% CI=0.76-0.91). In subgroup analysis, consumption of >=2 times/day was associated with lower ORs for elevated ALT in the high-risk group overall and in the viral hepatitis and obesity subgroups, respectively. In sensitivity analysis, reduced frequency of coffee consumption was associated with an increased risk for elevated liver enzymes, although an association between coffee consumption and elevated ALT was not observed in women or current smokers. Higher coffee consumption was associated with lower risk of elevated aminotransferase concentration in Korean adults.

Understanding the antimicrobial properties/activity of an 11-residue Lys homopeptide by alanine and proline scan.

PubMed

Carvajal-Rondanelli, P; Aróstica, M; Álvarez, C A; Ojeda, C; Albericio, F; Aguilar, L F; Marshall, S H; Guzmán, F

2018-05-01

Previous work demonstrated that lysine homopeptides adopt a polyproline II (PPII) structure. Lysine homopeptides with odd number of residues, especially with 11 residues (K11), were capable of inhibiting the growth of a broader spectrum of bacteria than those with an even number. Confocal studies also determined that K11 was able to localize exclusively in the bacterial membrane, leading to cell death. In this work, the mechanism of action of this peptide was further analyzed focused on examining the structural changes in bacterial membrane induced by K11, and in K11 itself when interacting with bacterial membrane lipids. Moreover, alanine and proline scans were performed for K11 to identify relevant positions in structure conformation and antibacterial activity. To do so, circular dichroism spectroscopy (CD) was conducted in saline phosphate buffer (PBS) and in lipidic vesicles, using large unilamellar vesicles (LUV), composed of 2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) or bacterial membrane lipid. Antimicrobial activity of K11 and their analogs was evaluated in Gram-positive and Gram-negative bacterial strains. The scanning electron microscopy (SEM) micrographs of Staphylococcus aureus ATCC 25923 exposed to the Lys homopeptide at MIC concentration showed blisters and bubbles formed on the bacterial surface, suggesting that K11 exerts its action by destabilizing the bacterial membrane. CD analysis revealed a remarkably enhanced PPII structure of K11 when replacing some of its central residues by proline in PBS. However, when such peptide analogs were confronted with either DMPG-LUV or membrane lipid extract-LUV, the tendency to form PPII structure was severely weakened. On the contrary, K11 peptide showed a remarkably enhanced PPII structure in the presence of DMPG-LUV. Antibacterial tests revealed that K11 was able to inhibit all tested bacteria with an MIC value of 5 µM, while proline and alanine analogs have a reduced activity on Listeria

Effects of beta-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial.

PubMed

Smith, Abbie E; Walter, Ashley A; Graef, Jennifer L; Kendall, Kristina L; Moon, Jordan R; Lockwood, Christopher M; Fukuda, David H; Beck, Travis W; Cramer, Joel T; Stout, Jeffrey R

2009-02-11

Intermittent bouts of high-intensity exercise result in diminished stores of energy substrates, followed by an accumulation of metabolites, promoting chronic physiological adaptations. In addition, beta-alanine has been accepted has an effective physiological hydrogen ion (H+) buffer. Concurrent high-intensity interval training (HIIT) and beta-alanine supplementation may result in greater adaptations than HIIT alone. The purpose of the current study was to evaluate the effects of combining beta-alanine supplementation with high-intensity interval training (HIIT) on endurance performance and aerobic metabolism in recreationally active college-aged men. Forty-six men (Age: 22.2 +/- 2.7 yrs; Ht: 178.1 +/- 7.4 cm; Wt: 78.7 +/- 11.9; VO2peak: 3.3 +/- 0.59 l.min-1) were assessed for peak O2 utilization (VO2peak), time to fatigue (VO2TTE), ventilatory threshold (VT), and total work done at 110% of pre-training VO2peak (TWD). In a double-blind fashion, all subjects were randomly assigned into one either a placebo (PL - 16.5 g dextrose powder per packet; n = 18) or beta-alanine (BA - 1.5 g beta-alanine plus 15 g dextrose powder per packet; n = 18) group. All subjects supplemented four times per day (total of 6 g/day) for the first 21-days, followed by two times per day (3 g/day) for the subsequent 21 days, and engaged in a total of six weeks of HIIT training consisting of 5-6 bouts of a 2:1 minute cycling work to rest ratio. Significant improvements in VO2peak, VO2TTE, and TWD after three weeks of training were displayed (p < 0.05). Increases in VO2peak, VO2TTE, TWD and lean body mass were only significant for the BA group after the second three weeks of training. The use of HIIT to induce significant aerobic improvements is effective and efficient. Chronic BA supplementation may further enhance HIIT, improving endurance performance and lean body mass.

Precision and sensitivity of the measurement of 15N enrichment in D-alanine from bacterial cell walls using positive/negative ion mass spectrometry

NASA Technical Reports Server (NTRS)

Tunlid, A.; Odham, G.; Findlay, R. H.; White, D. C.

1985-01-01

Sensitive detection of cellular components from specific groups of microbes can be utilized as 'signatures' in the examination of microbial consortia from soils, sediments or biofilms. Utilizing capillary gas chromatography/mass spectrometry and stereospecific derivatizing agents, D-alanine, a component localized in the prokaryotic (bacterial) cell wall, can be detected reproducibly. Enrichments of D-[15N]alanine determined in E. coli grown with [15N]ammonia can be determined with precision at 1.0 atom%. Chemical ionization with methane gas and the detection of negative ions (M - HF)- and (M - F or M + H - HF)- formed from the heptafluorobutyryl D-2 butanol ester of D-alanine allowed as little as 8 pg (90 fmol) to be detected reproducibly. This method can be utilized to define the metabolic activity in terms of 15N incorporation at the level of 10(3)-10(4) cells, as a function of the 15N-14N ratio.

Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis.

PubMed

Ward, Jeanine; Kanchagar, Chitra; Veksler-Lublinsky, Isana; Lee, Rosalind C; McGill, Mitchell R; Jaeschke, Hartmut; Curry, Steven C; Ambros, Victor R

2014-08-19

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

Relationship between analytic values and canine obesity.

PubMed

Peña, C; Suárez, L; Bautista, I; Montoya, J A; Juste, M C

2008-06-01

The objective of this study was to assess the relationship between canine body condition and metabolic parameters like serum lipids, blood glucose and alanine aminotransferase (ALT) concentrations. We selected 127 dogs (42 males and 85 females) that were taken to our veterinary medicine service during routine visits. The mean age was 6.67 +/- 5.24 years. Body condition (BC) was measured by Laflamme scale and dogs were considered as obese when BC score was over 6. The following variables were collected: total cholesterol, high-density lipoprotein cholesterol, triglycerides, basal glucose and ALT. 66.1% of the dog cohort were obese. Total cholesterol and triglycerides were found to be higher (p < 0.05) in obese dogs with respect to normal weight dogs. In conclusion, obesity in dogs is associated with higher serum lipid levels.

Clearance of hepatitis C viral RNA in cirrhotic patients with antiviral therapy.

PubMed

Ono, S K; da Silva, L C; Carrilho, F J; da Fonseca, L E; Mendes, L C; Madruga, C L; Farias, A de Q; Laudanna, A A

1996-01-01

Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has been reported as a bad response factor to the therapy. Fifteen cirrhotic patients with HCV, undergoing treatment with recombinant interferon-alpha, ribavirin and/or ursodeoxycholic acid were studied. They were followed-up and evaluated with dosages of alanine aminotransferase and HCV RNA investigation by PCR technique. Of the 15 cirrhotic patients, seven were negative for HCV RNA after antiviral treatment, however ALT was normal in only three of them. Of the eight patients who were not negative, two had normal ALT. Biochemical-virological discrepancy in the follow-up of the patients after antiviral treatment observed in this study has also been reported by other authors. These reports show that the criteria for response to the treatment is to be established.

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

PubMed

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

2016-05-01

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

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

PubMed

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

2008-06-01

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

Enhanced poly(3-hydroxypropionate) production via β-alanine pathway in recombinant Escherichia coli

PubMed Central

Lacmata, Stephen Tamekou; Kuiate, Jules-Roger; Ding, Yamei; Xian, Mo; Liu, Huizhou; Boudjeko, Thaddée; Feng, Xinjun; Zhao, Guang

2017-01-01

Poly(3-hydroxypropionate) (P3HP) is a thermoplastic with great compostability and biocompatibility, and can be produced through several biosynthetic pathways, in which the glycerol pathway achieved the highest P3HP production. However, exogenous supply of vitamin B12 was required to maintain the activity of glycerol dehydratase, resulting in high production cost. To avoid the addition of VB12, we have previously constructed a P3HP biosynthetic route with β-alanine as intermediate, and the present study aimed to improve the P3HP production of this pathway. L-aspartate decarboxylase PanD was found to be the rate-limiting enzyme in the β-alanine pathway firstly. To improve the pathway efficiency, PanD was screened from four different sources (Escherichia coli, Bacillus subtilis, Pseudomonas fluorescens, and Corynebacterium glutamicum). And PanD from C. glutamicum was found to have the highest activity, the P3HP production was improved in flask cultivation with this enzyme. To further improve the production, the host strain was screened and the culture condition was optimized. Under optimal conditions, production and content of P3HP reached to 10.2 g/L and 39.1% (wt/wt [cell dry weight]) in an aerobic fed-batch fermentation. To date, this is the highest P3HP production without VB12. PMID:28253372

Biochemical profile of Biomphalaria glabrata (Mollusca: Gastropoda) after infection by Echinostoma paraensei (Trematoda: Echinostomatidae).

PubMed

Tunholi, Victor M; Lustrino, Danilo; Tunholi-Alves, Vinícius M; Mello-Silva, Clélia C C; Maldonado, Arnaldo; Pinheiro, Jairo; Rodrigues, Maria de Lurdes de A

2011-09-01

The effect of infection by Echinostoma paraensei on the activity of the enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the concentration of total proteins, uric acid and urea in the hemolymph of Biomphalaria glabrata were investigated after exposure to five or 50 miracidia. The biochemical concentrations were measured weekly until the end of the fourth week after exposure. There was a significant decrease in the concentrations of total proteins in the snails exposed both to five and 50 miracidia, as well as an increase in the nitrogenous products of excretion, ALT and AST activities. The higher ALT activity in the hemolymph of the snails after infection with 50 miracidia suggests highest energetic requirement in these snails in relation to snails exposed to five miracidia. The results also suggest an increase in the use of total proteins, since there was increased formation of nitrogenous catabolites, in conformity with an increase in the aminotransferase activities, frequently associated with tissue damages. This can be explained by damage due to penetration by the miracidia and subsequent development of intramolluscan sporocysts and rediae.

Analysis of Consequences of Birth Asphyxia in Infants: A Regional Study in Southern Punjab, Pakistan.

PubMed

Samad, Noreen; Farooq, Samia; Hafeez, Kinza; Maryam, Mukharma; Rafi, Muhammad Aftab

2016-12-01

To evaluate the biochemical consequences and platelet counts of birth asphyxia in neonates. Cohort study. Department of Child Health, Nishter Medical College and Hospital, Multan, from September to November 2015. The data of 50 (50%) asphyxiated neonates and 50 (50%) non-asphyxiated neonates, with age range less than 1 month, was collected from Children Ward of Nishtar Hospital, Multan, Pakistan. Data on platelet count in blood, kidney function tests (creatinine, urea), liver function tests (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and cardiac enzyme test (lactate dehydrogenase (LDH)) were analysed by paired sample t-test by SPSS software. Sociodemographic data of those neonate's mothers was also collected. In asphyxiated neonates LDH, ALT, AST, creatinine, bilirubin, urea levels were higher than healthy infants, while the platelet count was smaller in asphyxiated neonates than healthy infants. There was a higher rate of alteration in platelet count, levels of LDH, AST, ALT, urea creatinine and bilirubin in asphyxiated infants. These alterations may be correlated with damage of vital organ of asphyxiated neonates.

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

PubMed

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

2008-12-01

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

Prevalence and Predictors of Abnormal Liver Enzymes in Young Women with Anorexia Nervosa

PubMed Central

Fong, Hiu-fai; DiVasta, Amy D.; DiFabio, Diane; Ringelheim, Julie; Jonas, Maureen M.; Gordon, Catherine M.

2008-01-01

Objective To determine the prevalence and predictors of abnormal liver enzyme levels in ambulatory young women with anorexia nervosa (AN). Study design In this cross-sectional study of 53 females with AN, serum concentrations of liver enzymes and hormones were measured. Anthropometric, dietary, and body composition information was collected. Correlational analyses were performed between liver enzyme concentrations and these variables. Results Elevated alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels were found in 14 subjects (26%) and 5 subjects (9%), respectively. ALT and GGT were inversely correlated with body mass index (r = −0.27 to −0.30, p ≤ 0.049) and percentage body fat (r = −0.36 to −0.47, p ≤ 0.007), but showed no relationship with lean body mass. Subjects with percentage body fat < 18% had higher ALT levels than those above this threshold (median 26.5 vs. 18.0 U/L, p = 0.01). Liver enzyme concentrations did not correlate with dietary variables, except for GGT and percentage of calories from protein (r = 0.28, p = 0.04). Conclusions Serum ALT and GGT concentrations are inversely related to adiposity in young women with AN. Future studies are needed to determine if these liver enzyme elevation signify unrecognized, clinically relevant liver disease. PMID:18534220

Association between liver function and metabolic syndrome in Chinese men and women

PubMed Central

Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

2017-01-01

Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS. PMID:28317840

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

NASA Astrophysics Data System (ADS)

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

2007-10-01

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

Autoantibodies in infectious mononucleosis have specificity for the glycine-alanine repeating region of the Epstein-Barr virus nuclear antigen

PubMed Central

1987-01-01

Viruses have been postulated to be involved in the induction of autoantibodies by: autoimmunization with tissue proteins released by virally induced tissue damage; immunization with virally encoded antigens bearing molecular similarities to normal tissue proteins; or nonspecific (polyclonal) B cell stimulation by the infection. Infectious mononucleosis (IM) is an experiment of nature that provides the opportunity for examining these possibilities. We show here that IgM antibodies produced in this disease react with at least nine normal tissue proteins, in addition to the virally encoded Epstein-Barr nuclear antigen (EBNA-1). The antibodies are generated to configurations in the glycine-alanine repeat region of EBNA-1 and are crossreactive with the normal tissue proteins through similar configurations, as demonstrated by the effectiveness of a synthetic glycine-alanine peptide in inhibiting the reactions. The antibodies are absent in preillness sera and gradually disappear over a period of months after illness, being replaced by IgG anti-EBNA-1 antibodies that do not crossreact with the normal tissue proteins but that are still inhibited by the glycine-alanine peptide. These findings are most easily explained by either a molecular mimicry model of IgM autoantibody production or by the polyclonal activation of a germline gene for a crossreactive antibody. It also indicates a selection of highly specific, non-crossreactive anti-EBNA-1 antibodies during IgM to IgG isotype switching. PMID:2435830

Brain oxygen utilization is unchanged by hypoglycemia in normal humans: lactate, alanine, and leucine uptake are not sufficient to offset energy deficit.

PubMed

Lubow, Jeffrey M; Piñón, Ivan G; Avogaro, Angelo; Cobelli, Claudio; Treeson, David M; Mandeville, Katherine A; Toffolo, Gianna; Boyle, Patrick J

2006-01-01

During hypoglycemia, substrates other than glucose have been suggested to serve as alternate neural fuels. We evaluated brain uptake of endogenously produced lactate, alanine, and leucine at euglycemia and during insulin-induced hypoglycemia in 17 normal subjects. Cross-brain arteriovenous differences for plasma glucose, lactate, alanine, leucine, and oxygen content were quantitated. Cerebral blood flow (CBF) was measured by Fick methodology using N(2)O as the dilution indicator gas. Substrate uptake was measured as the product of CBF and the arteriovenous concentration difference. As arterial glucose concentration fell, cerebral oxygen utilization and CBF remained unchanged. Brain glucose uptake (BGU) decreased from 36.3+/-2.6 to 26.6+/-2.1 micromol.100 g of brain(-1).min(-1) (P<0.001), equivalent to a drop in ATP of 291 micromol.100 g(-1).min(-1). Arterial lactate rose (P<0.001), whereas arterial alanine and leucine fell (P<0.009 and P<0.001, respectively). Brain lactate uptake (BLU) increased from a net release of -1.8+/- 0.6 to a net uptake of 2.5+/-1.2 micromol.100 g(-1).min(-1) (P<0.001), equivalent to an increase in ATP of 74 micromol.100 g(-1).min(-1). Brain leucine uptake decreased from 7.1+/-1.2 to 2.5 +/- 0.5 micromol.100 g(-1).min(-1) (P<0.001), and brain alanine uptake trended downward (P<0.08). We conclude that the ATP generated from the physiological increase in BLU during hypoglycemia accounts for no more than 25% of the brain glucose energy deficit.

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.

PubMed

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 < 0.001), ln(γGT) (P < 0.01) and ln(ALT) (P < 0.05) were the best biochemical predictors of recidivism of 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 < 25%; second tertile; P < 0.001) and a low recidivism risk (ROAD index < 16%; first tertile; P < 0.05). Of all routinely used indirect alcohol markers, percentage of carbohydrate-deficient transferrin is the major predictor of recidivism of 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

Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae

PubMed Central

De Benedetti, Stefania; Bühl, Henrike; Gaballah, Ahmed; Klöckner, Anna; Otten, Christian; Schneider, Tanja; Sahl, Hans-Georg; Henrichfreise, Beate

2014-01-01

For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly. D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L-alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin. PMID:24616885

Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae.

PubMed

De Benedetti, Stefania; Bühl, Henrike; Gaballah, Ahmed; Klöckner, Anna; Otten, Christian; Schneider, Tanja; Sahl, Hans-Georg; Henrichfreise, Beate

2014-01-01

For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly. D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L-alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin.

Difference in the structures of alanine tri- and tetra-peptides with antiparallel β-sheet assessed by X-ray diffraction, solid-state NMR and chemical shift calculations by GIPAW.

PubMed

Asakura, Tetsuo; Yazawa, Koji; Horiguchi, Kumiko; Suzuki, Furitsu; Nishiyama, Yusuke; Nishimura, Katsuyuki; Kaji, Hironori

2014-01-01

Alanine oligomers provide a key structure for silk fibers from spider and wild silkworms.We report on structural analysis of L-alanyl-L-alanyl-L-alanyl-L-alanine (Ala)4 with anti-parallel (AP) β-structures using X-ray and solid-state NMR. All of the Ala residues in the (Ala)4 are in equivalent positions, whereas for alanine trimer (Ala)3 there are two alternative locations in a unit cell as reported previously (Fawcett and Camerman, Acta Cryst., 1975, 31, 658-665). (Ala)4 with AP β-structure is more stable than AP-(Ala)3 due to formation of the stronger hydrogen bonds. The intermolecular structure of (Ala)4 is also different from polyalanine fiber structure, indicating that the interchain arrangement of AP β-structure changes with increasing alanine sequencelength. Furthermore the precise (1)H positions, which are usually inaccesible by X-ray diffraction method, are determined by high resolution (1)H solid state NMR combined with the chemical shift calculations by the gauge-including projector augmented wave method. Copyright © 2013 Wiley Periodicals, Inc.

Risk of Liver Toxicity with Nivolumab Immunotherapy in Cancer Patients.

PubMed

Zarrabi, Kevin; Wu, Shenhong

2018-01-01

Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random- or fixed-effects models with 95% confidence intervals (CIs). The incidences of all-grade and high-grade elevations in AST were 5.4% (95% CI 3.2-9.1) and 1.6% (95% CI 0.9-3.0), respectively. The incidences of all-grade and high-grade elevations in ALT were 4.9% (95% CI 2.9-8.2) and 1.7% (95% CI 0.9-3.1), respectively. Elevations of both laboratory markers were significantly increased when compared to control (p < 0.001). Nivolumab significantly increased the RR of AST/ALT elevations; RRs were 1.58 (95% CI 1.1-2.2) for all-grade AST elevation, and 1.62 (95% CI 1.2-2.3) for all-grade ALT elevation. Subgroup analysis of all-grade AST or ALT elevation revealed a signi-ficant variation among tumor types (p < 0.001) and with combination with ipilimumab (p < 0.001). Nivolumab is associated with significantly increased risk of liver toxicity. © 2018 S. Karger AG, Basel.

Conformational Changes of the Alanine Dipeptide in Water-Ethanol Binary Mixtures.

PubMed

Almeida, Glauco G; Cordeiro, João M M; Martín, M Elena; Aguilar, Manuel A

2016-04-12

Experimental work developed in the last years has evidenced the capacity of alcohols and polyalcohols to modify the energy landscape of peptides and proteins. However, the mechanism underlying this effect is not clear. Taking as a model system the alanine dipeptide (AD) we perform a QM/MM study in water, ethanol, and a 40-60% in volume water-ethanol mixture. The AD molecule was described at the MP2/aug-cc-pVDZ level. In polar solution, only αR and PPII conformers contribute in an appreciable way to the conformational equilibrium. The final in solution αR-PPII free energy difference is determined from the interplay between the internal energy of the dipeptide and the solute-solvent interaction free energy. Internal energy favors the formation of PPII, whereas, on the contrary, solute-solvent interaction is favorable to αR, so any factor that decreases the solute-solvent interaction free energy will increase the PPII population. The addition of ethanol increases the stability of the PPII conformer. Our results point to the presence of preferential solvation in this system, the composition of the first solvation shell in the binary mixture being dominated by water molecules. Remarkably, this fact does not affect the differential conformational stability that is controlled by long-range interactions. From the analysis of solvent density maps it is concluded that, in the water-ethanol mixture, ethanol molecules are more likely found around the alanine side chain and the carbonyl group, but while in PPII ethanol molecules interact mainly with the carbonyl group of the N-terminal end, in C5 the interaction is with the carbonyl group of the C-terminal end. In αR, ethanol interacts with both carbonyl groups.

Synthesis, characterization and biological evaluation of poly [LA-co-(Glc-alt-Lys)] for nerve regeneration scaffold

NASA Astrophysics Data System (ADS)

Yin, Yi-Xia; Yi, Ji-Ling; Xie, Li-Juan; Yan, Qiong-Jiao; Dai, Hong-Lian; Li, Shi-Pu

2014-03-01

A novel nerve repairing material poly [LA-co-(Glc-alt-Lys)] (PLGL) was synthesized. The viability and growth of Schwann cells (SCs) co-cultured with poly (D, Llactic acid) (PDLLA) films (control group) and PLGL films were evaluated by MTTassay and SEM observation. Then, contact angle measurement, histological assessment and enzyme-linked immunosorbent assay (ELISA) testing on inflammatory-related cytokines such as IL-10 and TGF-β1 were performed. The results showed that, compared with PDLLA, PLGL films possesses better hydrophilicity, biocompatibility, degradation property and less inflammatory reaction. The present study indicated that PLGL scaffolds would meet the requirements of artificial nerve scaffold and have a potential application in the fields of nerve regeneration.

Hepatoprotective Effects and Mechanisms of Action of Triterpenoids from Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) on α-Amanitin-Induced Liver Injury in Mice.

PubMed

Wu, Huihui; Tang, Shanshan; Huang, Zhaoqin; Zhou, Qian; Zhang, Ping; Chen, Zuohong

2016-01-01

Most fatal mushroom poisonings are caused by species of the genus Amanita; the amatoxins are responsible for acute liver failure and death in humans. Ganoderma lucidum is a well-known traditional medicinal mushroom that has been shown to have obvious hepatoprotective effects. This study evaluated the hepatoprotective effects of triterpenoids from G. lucidum on liver injury induced by a-amanitin (α-AMA) in mice and the mechanisms of action of these triterpenoids, including radical scavenging and antiapoptosis activities. Mice were treated with α-AMA, followed by G. lucidum total triterpenoids or individual triterpenoids, and their hepatoprotective effects were compared with those of the reference drug silibinin (SIL). Treatment with SIL, G. lucidum total triterpenoids, and each of the 5 individual triterpenoids significantly reduced serum alanine aminotransaminase and aspartate ami- notransaminase concentrations and reduced mortality rates 20-40%. Moreover, triterpenoids and SIL significantly enhanced superoxide dismutase and catalase activity and reduced malondialdehyde content in livers. Treatment with ganoderic acid C2 significantly inhibited DNA fragmentation and decreased caspase-3, -8, and -9 activities. The results demonstrated that triterpenoids have hepatoprotective effects on α-AMA-induced liver injury and that their hepatoprotective mechanisms may be the result of their antioxidative and radical scavenging activities and their inhibition of apoptosis.

A large‐scale, multicentre, double‐blind trial of ursodeoxycholic acid in patients with chronic hepatitis C

PubMed Central

Omata, Masao; Yoshida, Haruhiko; Toyota, Joji; Tomita, Eiichi; Nishiguchi, Shuhei; Hayashi, Norio; Iino, Shiro; Makino, Isao; Okita, Kiwamu; Toda, Gotaro; Tanikawa, Kyuichi; Kumada, Hiromitsu

2007-01-01

Background Combined pegylated interferon and ribavirin has improved chronic hepatitis C (CH‐C) therapy; however, sustained virological response is achieved in only about half of the patients with a 1b genotype infection. We assessed oral ursodeoxycholic acid (UDCA) on serum biomarkers as a possible treatment for interferon non‐responders. Methods CH‐C patients with elevated alanine aminotransferase (ALT) were assigned randomly to 150 (n = 199), 600 (n = 200) or 900 mg/day (n = 197) UDCA intake for 24 weeks. Changes in ALT, aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) were assessed. This study is registered at ClinicalTrial.gov, identifier NCT00200343. Results ALT, AST and GGT decreased at week 4 and then remained constant during drug administration. The median changes (150, 600 and 900 mg/day, respectively) were: ALT, −15.3, −29.2 and −36.2%; AST, −13.6, −25.0 and −29.8%; GGT, −22.4, −41.0 and −50.0%. These biomarkers decreased significantly less in the 150 mg/day than in the other two groups. Although changes in ALT and AST did not differ between the 600 and 900 mg/day groups, GGT was significantly lower in the 900 mg/day group. In subgroup analysis, ALT decreased significantly in the 900 mg/day group when the baseline GGT exceeded 80 IU/l. Serum HCV‐RNA did not change in any group. Adverse effects were reported by 19.1% of the patients, with no differences between groups. Conclusions A 600 mg/day UDCA dose was optimal to decrease ALT and AST levels in CH‐C patients. The 900 mg/day dose decreased GGT levels further, and may be preferable in patients with prevailing biliary injuries. PMID:17573387

A Single Glycine-Alanine Exchange Directs Ligand Specificity of the Elephant Progestin Receptor

PubMed Central

Wierer, Michael; Schrey, Anna K.; Kühne, Ronald; Ulbrich, Susanne E.

2012-01-01

The primary gestagen of elephants is 5α-dihydroprogesterone (DHP), which is unlike all other mammals studied until now. The level of DHP in elephants equals that of progesterone in other mammals, and elephants are able to bind DHP with similar affinity to progesterone indicating a unique ligand-binding specificity of the elephant progestin receptor (PR). Using site-directed mutagenesis in combination with in vitro binding studies we here report that this change in specificity is due to a single glycine to alanine exchange at position 722 (G722A) of PR, which specifically increases DHP affinity while not affecting binding of progesterone. By conducting molecular dynamics simulations comparing human and elephant PR ligand-binding domains (LBD), we observed that the alanine methyl group at position 722 is able to push the DHP A-ring into a position similar to progesterone. In the human PR, the DHP A-ring position is twisted towards helix 3 of PR thereby disturbing the hydrogen bond pattern around the C3-keto group, resulting in a lower binding affinity. Furthermore, we observed that the elephant PR ligand-binding pocket is more rigid than the human analogue, which probably explains the higher affinity towards both progesterone and DHP. Interestingly, the G722A substitution is not elephant-specific, rather it is also present in five independent lineages of mammalian evolution, suggesting a special role of the substitution for the development of distinct mammalian gestagen systems. PMID:23209719

Influence of the composition of aqueous dimethylsulfoxide solvent on thermodynamics of complexing between 18-crown-6-ether and D,L-alanine

NASA Astrophysics Data System (ADS)

Usacheva, T. R.; Kuzmina, I. A.; Sharnin, V. A.; Chernov, I. V.; Matteoli, E.

2012-07-01

Standard thermodynamic parameters (log K o, Δr H o, TΔr S o) of complexing 18-crown-6 ether (18C6) with D,L-alanine (Ala) in mixed water-dimethysulfoxide (H2O-DMSO) solvents are calculated on the basis of calorimetric titration results. A rise in the DMSO concentration in mixed solvent is found to increase stability and increase the exothermicity of the formation of [Ala-18C6] molecular complex. Changes in the reaction energetic are shown to be determined by changes in the solvation state of 18C6 that is the characteristic of the reactions of molecular complex formation between 18C6 and D,L-alanine or glycine in water-organic solvents.

The GABA uptake inhibitor beta-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis.

PubMed

Ishiwari, Keita; Mingote, Susana; Correa, Merce; Trevitt, Jennifer T; Carlson, Brian B; Salamone, John D

2004-12-30

Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker beta-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of beta-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. beta-Alanine (250-500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of beta-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.

Atherosclerosis and Liver Function Tests in Coronary Angiography Patients.

PubMed

Doganer, Y C; Rohrer, J E; Aydogan, U; Agerter, D C; Cayci, T; Barcin, C

2015-09-01

Elevated aminotransferase levels indicating liver function, even in the normal range, have attracted great concern as potential novel markers of cardiovascular risk assessment. We hypothesized the possibility that liver function test variations in the normal range might be meaningfully associated to coronary artery disease (CAD). Eighty-eight patients were randomly selected from those who underwent coronary angiography from June 2010 to June 2011 after applying to the outpatient cardiology clinic in Gulhane Military Medical Academy. According to the results of angiographies, patients were classified into three groups as normal, non-critical (< 50% involvement in coronaries), and critical (≥ 50% involvement in coronaries). In addition to angiographic intervention, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, albumin and the other serum parameters were performed in all patients. The patient groups of CAD were balanced (28 critical cases, 30 non-critical cases and 30 normal cases). Mean age was 51.93 ± 9.3 (range 32-65) years and 19.3 per cent (n = 17) were females. Multiple linear regression analysis of all three liver function tests explained a significant portion of the variance, but adjusted r-squares were small (AST = 0.174, ALT = 0.242, albumin = 0.124). Albumin was significantly higher for patients with critical CAD than for patients with no CAD (beta = 3.205, p = 0.002). Non-critical CAD was not significantly different from no CAD for any of the dependent variables. Mean AST was significantly higher for patients taking aspirin (beta = 0.218, p = 0.049), as was mean ALT (beta = 0.264, p = 0.015). Alanine aminotransferase and AST may not be associated with angiographically determined coronary atherosclerosis. Albumin may be more sensitive to demonstrate the burden of atherosclerosis. These results indicate that the association between the liver function tests and coronary atherosclerosis may be more

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

PubMed

Uchida, Nancy Sayuri; Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Silva-Comar, Francielli Maria de Souza; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

2017-01-01

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

The effects of vitamin D supplementation on hepatic dysfunction, vitamin D status, and glycemic control in children and adolescents with vitamin D deficiency and either type 1 or type 2 diabetes mellitus.

PubMed

Nwosu, Benjamin Udoka; Maranda, Louise

2014-01-01

The effects of vitamin D supplementation on mild hepatic dysfunction and glycemic control are unclear in children and adolescents with either type 1 (T1D) or type 2 diabetes (T2D). Vitamin D supplementation will improve hepatic dysfunction and glycemic control. To determine the effect of vitamin D supplementation on alanine transaminase (ALT), hemoglobin A1c (HbA1c), and serum 25-hydroxyvitamin D [25(OH)D] concentration. A retrospective study of 131 subjects with either T1D (n = 88 ∶ 46 females, 42 males), or T2D (n = 43 ∶ 26 females, 17 males) of ages 3-18 years between 2007-2013. All subjects had (1) a diagnosis of diabetes for > 12 mo, (2) received vitamin D supplementation for the management of vitamin D deficiency (3) had baseline and subsequent simultaneous measurements of HbA1c, ALT, and 25(OH)D. Vitamin D deficiency was defined as 25(OH)D concentration of < 50 nmol/L (20 ng/mL). At baseline, vitamin D deficiency occurred in 72.1% of patients with T2D and in 37.5% of T1D patients (p < 0.001). Patients with T2D had significantly higher values for BMI SDS (p < 0.001), alanine transaminase (ALT) (p = 0.001), but lower 25(OH)D p < 0.001), and no difference in HbA1c (p = 0.94), and total daily dose (TDD) of insulin per kg body weight (p = 0.48) as compared to T1D patients. After 3 months of vitamin D supplementation, there was a significant increase in 25(OH)D in both T2D (p = 0.015), and T1D patients (p < 0.001); significant reduction in BMI SDS (p = 0.015) and ALT (p = 0.012) in T2D, but not in T1D. There was a clinically-significant decrease in HbA1c in T2D from 8.5 ± 2.9% at baseline to 7.7 ± 2.5 at 3 mo, but not in T1D, 8.5 ± 1.2 to 8.53 ± 1.1%. Vitamin D supplementation in subjects with T2D was associated with statistically significant decreases in BMI SDS, ALT, and a clinically-significant decrease in HbA1c.

NAD(+)-aminoaldehyde dehydrogenase candidates for 4-aminobutyrate (GABA) and β-alanine production during terminal oxidation of polyamines in apple fruit.

PubMed

Zarei, Adel; Trobacher, Christopher P; Shelp, Barry J

2015-09-14

The last step of polyamine catabolism involves the oxidation of 3-aminopropanal or 4-aminobutanal via aminoaldehyde dehydrogenase. In this study, two apple (Malus x domestica) AMADH genes were selected (MdAMADH1 and MdAMADH2) as candidates for encoding 4-aminobutanal dehydrogenase activity. Maximal activity and catalytic efficiency were obtained with NAD(+) and 3-aminopropanal, followed by 4-aminobutanal, at pH 9.8. NAD(+) reduction was accompanied by the production of GABA and β-alanine, respectively, when 4-aminobutanal and 3-aminopropanal were utilized as substrates. MdAMADH2 was peroxisomal and MdAMADH1 cytosolic. These findings shed light on the potential role of apple AMADHs in 4-aminobutyrate and β-alanine production. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Topology of AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, determined by site-directed fluorescence labeling.

PubMed

Nanatani, Kei; Fujiki, Takashi; Kanou, Kazuhiko; Takeda-Shitaka, Mayuko; Umeyama, Hideaki; Ye, Liwen; Wang, Xicheng; Nakajima, Tasuku; Uchida, Takafumi; Maloney, Peter C; Abe, Keietsu

2007-10-01

The gram-positive lactic acid bacterium Tetragenococcus halophilus catalyzes the decarboxylation of L-aspartate (Asp) with release of L-alanine (Ala) and CO(2). The decarboxylation reaction consists of two steps: electrogenic exchange of Asp for Ala catalyzed by an aspartate:alanine antiporter (AspT) and intracellular decarboxylation of the transported Asp catalyzed by an L-aspartate-beta-decarboxylase (AspD). AspT belongs to the newly classified aspartate:alanine exchanger family (transporter classification no. 2.A.81) of transporters. In this study, we were interested in the relationship between the structure and function of AspT and thus analyzed the topology by means of the substituted-cysteine accessibility method using the impermeant, fluorescent, thiol-specific probe Oregon Green 488 maleimide (OGM) and the impermeant, nonfluorescent, thiol-specific probe [2-(trimethylammonium)ethyl]methanethiosulfonate bromide. We generated 23 single-cysteine variants from a six-histidine-tagged cysteineless AspT template. A cysteine position was assigned an external location if the corresponding single-cysteine variant reacted with OGM added to intact cells, and a position was assigned an internal location if OGM labeling required cell lysis. The topology analyses revealed that AspT has a unique topology; the protein has 10 transmembrane helices (TMs), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3. Moreover, the three-dimensional structure constructed by means of the full automatic modeling system indicates that the large hydrophilic cytoplasmic loop of AspT possesses a TrkA_C domain and a TrkA_C-like domain and that the three-dimensional structures of these domains are similar to each other even though their amino acid sequences show low similarity.

Piezoelectric and pyroelectric properties of DL-alanine and L-lysine amino-acid polymer nanofibres

NASA Astrophysics Data System (ADS)

de Matos Gomes, Etelvina; Viseu, Teresa; Belsley, Michael; Almeida, Bernardo; Costa, Maria Margarida R.; Rodrigues, Vitor H.; Isakov, Dmitry

2018-04-01

The piezoelectric and pyroelectric properties of electrospun polyethylene oxide nanofibres embedded with polar amino acids DL-alanine and L-lysine hemihydrate are reported. A high pyroelectric coefficient of 150 μC m‑2 K‑1 was measured for L-lysine hemihydrate and piezoelectric current densities up to 7 μA m‑2 were obtained for the nanofibres. The study reveals a potential for polymer amino-acid nanofibres to be used as biocompatible energy harvesters for autonomous circuit applications like in implantable electronics.

The Effect of gadolinium on the ESR response of alanine and ammonium tartrate exposed to thermal neutrons.

PubMed

Marrale, Maurizio; Brai, Maria; Gennaro, Gaetano; Bartolotta, Antonio; D'Oca, Maria Cristina

2008-02-01

Many efforts have been made to develop neutron capture therapy (NCT) for cancer treatment. Among the challenges in using NCT is the characterization of the features of the mixed radiation field and of its components. In this study, we examined the enhancement of the ESR response of pellets of alanine and ammonium tartrate with gadolinium oxide exposed to a thermal neutron beam. In particular, the ESR response of these dosimeters as a function of the gadolinium content inside the dosimeter was analyzed. We found that the addition of gadolinium improves the sensitivity of both alanine and ammonium tartrate. However, the use of gadolinium reduces or abolishes tissue equivalence because of its high atomic number (Z(Gd) = 64). Therefore, it is necessary to find the optimum compromise between the sensitivity to thermal neutrons and the reduction of tissue equivalence. Our analysis showed that a low concentration of gadolinium oxide (of the order of 5% of the total mass of the dosimeter) can enhance the thermal neutron sensitivity more than 13 times with an insignificant reduction of tissue equivalence.

Interaction of L-alanyl-L-valine and L-valyl-L-alanine with organic vapors: thermal stability of clathrates, sorption capacity and the change in the morphology of dipeptide films.

PubMed

Ziganshin, Marat A; Gubina, Nadezhda S; Gerasimov, Alexander V; Gorbatchuk, Valery V; Ziganshina, Sufia A; Chuklanov, Anton P; Bukharaev, Anastas A

2015-08-21

The strong effect of the amino acid sequence in L-alanyl-L-valine and L-valyl-L-alanine on their sorption properties toward organic compounds and water, and the thermal stability of the inclusion compounds of these dipeptides have been found. Generally, L-valyl-L-alanine has a greater sorption capacity for the studied compounds, but the thermal stability of the L-alanyl-L-valine clathrates is higher. Unusual selectivity of L-valyl-L-alanine for vapors of few chloroalkanes was observed. The correlation between the change in the surface morphology of thin film of dipeptides and stoichiometry of their clathrates with organic compounds was found. This discovery may be used to predict the influence of vapors on the morphology of films of short-chain oligopeptides.

Rapid development of new protein biosensors utilizing peptides obtained via phage display.

PubMed

Wu, Jun; Park, Jong Pil; Dooley, Kevin; Cropek, Donald M; West, Alan C; Banta, Scott

2011-01-01

There is a consistent demand for new biosensors for the detection of protein targets, and a systematic method for the rapid development of new sensors is needed. Here we present a platform where short unstructured peptides that bind to a desired target are selected using M13 phage display. The selected peptides are then chemically synthesized and immobilized on gold, allowing for detection of the target using electrochemical techniques such as electrochemical impedance spectroscopy (EIS). A quartz crystal microbalance (QCM) is also used as a diagnostic tool during biosensor development. We demonstrate the utility of this approach by creating a novel peptide-based electrochemical biosensor for the enzyme alanine aminotransferase (ALT), a well-known biomarker of hepatotoxicity. Biopanning of the M13 phage display library over immobilized ALT, led to the rapid identification of a new peptide (ALT5-8) with an amino acid sequence of WHWRNPDFWYLK. Phage particles expressing this peptide exhibited nanomolar affinity for immobilized ALT (K(d,app) = 85±20 nM). The newly identified ALT5-8 peptide was then chemically synthesized with a C-terminal cysteine for gold immobilization. The performance of the gold-immobilized peptides was studied with cyclic voltammetry (CV), QCM, and EIS. Using QCM, the sensitivity for ALT detection was 8.9±0.9 Hz/(µg/mL) and the limit of detection (LOD) was 60 ng/mL. Using EIS measurements, the sensitivity was 142±12 impedance percentage change %/(µg/mL) and the LOD was 92 ng/mL. In both cases, the LOD was below the typical concentration of ALT in human blood. Although both QCM and EIS produced similar LODs, EIS is preferable due to a larger linear dynamic range. Using QCM, the immobilized peptide exhibited a nanomolar dissociation constant for ALT (K(d) = 20.1±0.6 nM). These results demonstrate a simple and rapid platform for developing and assessing the performance of sensitive, peptide-based biosensors for new protein targets.

Calibration of helical tomotherapy machine using EPR/alanine dosimetry.

PubMed

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

2011-03-01

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

Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis.

PubMed

Sookoian, Silvia; Pirola, Carlos J

2013-11-01

Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis. Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD. From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation. Routine assessment of liver enzymes and liver damage should be implemented in OSA patients because they have an increase of 13.3% of ALT and 4.4% of AST levels, and a 2.6-fold higher risk of liver fibrosis when they have NAFLD, which is 2.6 times more frequent in OSA patients.

Hepatitis C prevalence and the significance of liver enzyme elevations in the insurance population.

PubMed

Stout, R L

1997-01-01

Liver enzyme elevation(s) are a common finding in the insurance applicant population. Hepatitis C infection results in histological and functional changes in the liver with both short and long term changes in serum liver enzyme levels. The prevalence of antibodies to HCV in the general population is estimated to be 4%. This paper reports on the prevalence of antibodies to HCV in the insurance applicant population and their relationship to the liver enzyme(s). Antibodies to HCV are present in 1.8% of a random sampling of insurance applicants. Alanine aminotransferase (ALT) elevations occur in 95.4% of all samples positive for antibodies to HCV. More than half of positive samples (56.7%) have ALT elevations of less than two time the upper range of normal. Antibody prevalence is lowest in samples with single enzyme elevation, 4.2%. In comparison, the prevalence is 16.4% in samples with all three enzymes, ALT, AST, and GGT, elevated. For maximal specificity two immunoassays, configured with different HCV antigens, should be performed sequentially on all positive applicant samples. HCV is the most prevalent, chronic viral infection in the insurance population. HCV prevalence is 40 times HIV prevalence. In an evaluation of enzyme reflex markers ALT was positive for antibodies to HCV 8.6% of the time while identifying 95.4% of HCV antibody positive applicants.

Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

PubMed

Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

2016-02-01

Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. Copyright © 2015 Elsevier B.V. All rights reserved.

Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats.

PubMed

Kober, Helena; Tatsch, Etiane; Torbitz, Vanessa Dorneles; Cargnin, Lara Peruzzolo; Sangoi, Manuela Borges; Bochi, Guilherme Vargas; da Silva, Andreia Regina Haas; Barbisan, Fernanda; Ribeiro, Euler Esteves; da Cruz, Ivana Beatrice Mânica; Moresco, Rafael Noal

2016-01-01

Several biological effects of Paullinia cupana (guarana) have been demonstrated, but little information is available on its effects on the liver. The current study was designed to evaluate the hepatoprotective and genoprotective effects of powder seeds from guarana on CCl4-induced liver injury in rats. Male Wistar rats were pretreated with guarana powder (100, 300 and 600 mg/kg) or silymarin 100 mg/kg daily for 14 days before treatment with a single dose of CCl4 (50% CCl4, 1 mL/kg, intraperitoneally). The treatment with CCl4 significantly increased the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, CCl4 increased the DNA damage index in hepatocytes. Guarana in all concentrations was effective in decreasing the ALT and AST activities when compared with the CCl4-treated group. The treatment with guarana decreased DNA damage index when compared with the CCl4-treated group. In addition, the DNA damage index showed a significant positive correlation with AST and ALT. These results indicate that the guarana has hepatoprotective activity and prevents the DNA strand breakage in the CCl4-induced liver damage in rats.

Simulation and experimental research on micro-channel for detecting cell status in bio-artificial liver.

PubMed

Wu, Changzhe; Cao, Yue; Huo, Xiaolin; Li, Ming

2015-01-01

Bioartificial liver support system (BALSS) based on culturing hepatocytes is an important research field for the treatment of acute liver failure. It is necessary to monitor the state of liver cell functions during the treatment of BALSS in order to guide clinical treatment. To design a micro-channel chip to achieve flash mixing for timely detection of liver cell status in bioreactors and improving liver cells growth environment to ensure the efficacy of the bio-artificial liver support system. Alanine aminotransferase (ALT) and Urea are chosen as detection indicators to reflect the degree of liver cell injury and the detoxification function. A diamond tandem structure micro-channel is designed and optimized to achieve the efficient mixing of serum and ALT or Urea reagent. The simulation and experimental results show that the diamond tandem structure micro-channel can significantly improve the mixing efficiency and meet the online detecting requirements. The easily controllable diamond tandem structure micro-channel combines the advantages of active and passive mixer and can effectively mix the serum and ALT or Urea reagent. It lays the foundation for online monitoring of liver cells and will help to improve the viability of liver cell in the bioreactor.

Selection and Evaluation of Indexes Commonly Used to Determine Contamination with T-2 Toxin in Pacific White Shrimp Litopenaeus vannamei by the Grey Relational Method.

PubMed

Lu, Pengli; Wang, Yaling; Dai, Zhe; Sun, Lijun; Xu, Defeng; Liu, Ying; Ye, Riying; Gooneratne, Ravi; Bi, Siyuan

2017-09-01

The objectives of the present study were to evaluate the effects of different concentrations of the mycotoxin T-2 toxin in feed on muscle performance in the Pacific white shrimp Litopenaeus vannamei, evaluate indexes of physiological variables that indicate T-2 toxin contamination in the shrimp using the grey relational method, and determine the dose-response relationships between T-2 toxin and the indexes. Of the 6 physical, 7 biochemical, and 17 nutritional indexes examined, the values of the grey relational coefficients were highest for the hepatopancreas: body weight ratio (HBR), alanine aminotransferase (ALT) activity, and serine (SER) content (0.83, 0.68, and 0.82, respectively). Therefore, the HBR, ALT activity, and SER content were selected as appropriate indexes for contamination of Pacific white shrimp muscle with T-2 toxin. Based on their dose-response relationship curves, mean effective doses of 1.45, 1.69, and 1.33 mg of T-2 toxin/kg of feed were obtained for the HBR, ALT activity, and SER content, respectively. These results offer technical reference points for the evaluation and control of T-2 toxin in shrimp feed. Received April 28, 2016; accepted April 9, 2017.

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo.

PubMed

Chuang, Cheng-Hung; Tsai, Cheng-Chih; Lin, En-Shyh; Huang, Chin-Shiu; Lin, Yun-Yu; Lan, Chuan-Ching; Huang, Chun-Chih

2016-10-31

The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study

PubMed Central

Melchart, Dieter; Hager, Stefan; Albrecht, Sabine; Dai, Jingzhang; Weidenhammer, Wolfgang; Teschke, Rolf

2017-01-01

AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine (TCM) in order to evaluate the frequency of newly detected liver injury. METHODS Patients with normal values of alanine aminotransferase (ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method (RUCAM) was used. RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and large-scale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal (ULN) in 844 patients (3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients (0.12%) experienced higher ALT values of ≥ 5 × ULN (300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26 (0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality. PMID:29085558

Effect of increasing maximal aerobic exercise on serum muscles enzymes in professional field hockey players.

PubMed

Hazar, Muhsin; Otag, Aynur; Otag, Ilhan; Sezen, Mehmet; Sever, Ozan

2014-11-04

Exercise results in oxidative enzyme increase and micro-injuries in skeletal muscles. The aim of this study was to investigate the effect of maximal aerobic exercise on serum muscle enzymes in professional field hockey players. This study aims to determine the effect of increasing maximal aerobic exercise on creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. 31 young professional field hockey players (13 female and 18 male players) volunteered for this study. All participants underwent the shuttle run test. Blood samples were taken from each participant before the shuttle run test. Post test blood samples were taken immediately after exercise and one hour after respectively. Pre and post test CK, CK-MB, AST and ALT values were measured by means of auto analyzer using original kits. The acute post test measure of the CK level increased in male (p=0.002) and female (p=0.00) sportsmen. CK-MB values obtained one hour after the exercise was lower than those before the exercise in males (p=0.02). In females (p=0.017) and males (p=0.05) AST activity significantly increased immediately after exercise and decreased to resting activity 1 h recovery. ALT significantly increased immediately after exercise in female (p=0.03) and male (p=0.00) athletes and after 1 h recovery ALT activities decreased below resting values. The timing and severity of exercise used in our study increased CK values, decreased CK-MB values and AST, ALT values increased in female and male field hockey players.

Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients

PubMed Central

Losekann, Alexandre; Weston, Antonio C.; de Mattos, Angelo A.; Tovo, Cristiane V.; de Carli, Luis A.; Espindola, Marilia B.; Pioner, Sergio R.; Coral, Gabriela P.

2015-01-01

The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease. PMID:26512661

Efficacy and safety of Chlorella supplementation in adults with chronic hepatitis C virus infection

PubMed Central

Azocar, Jose; Diaz, Arley

2013-01-01

AIM: To evaluate the safety and efficacy of Chlorella in 18 patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: Eighteen adults with chronic infection by HCV genotype 1 received daily oral supplementation of Chlorella for 12 wk. Changes in the RNA levels of HCV, as well as those of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated following this treatment period. Paired t tests were conducted to compare the means of the different variables at the beginning and end of the study. Side effects and quality of life aspects were also compared between weeks 0 and 12 of the study period. RESULTS: A majority 84.61% of the patients had a significant decrease in their ALT levels from week 0 to week 12. Evaluation of side effects showed that Chlorella was well tolerated. Quality of life assessment showed that 76.9 of the participants reported an improvement in their energy levels and 46.1% reported an improvement in their perception of general health. Although 69.23% also showed a decrease in their AST levels, this was not statistically significant. Most patients that exhibited an improvement in their ALT and AST levels also showed a tendency toward a decreased HCV viral load. The HCV RNA levels showed a decrease in 69.23% of the patients, which along with changes in AST/ALT ratios from week 0 to week 12, these results were not statistically significant. CONCLUSION: Chlorella supplementation was well tolerated in patients with chronic HCV and associated with a significant decrease in ALT liver enzyme levels. PMID:23467073

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

PubMed

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

2018-03-15

Poly-l-alanine (PLA) sequences are a key element in the structure of the crystalline domains of spider dragline silks, wild silkworm silks, antifreeze proteins, and amyloids. To date, no atomic-level structures of antiparallel (AP)-PLA longer than Ala 4 have been reported using the single-crystal X-ray diffraction analysis. In this work, dipolar-assisted rotational resonance solid-state NMR spectra were observed to determine the effective internuclear distances of 13 C uniformly labeled alanine tetramer with antiparallel (AP) β-sheet structure whose atomic coordinates are determined from the X-ray crystallographic analysis. Initial build-up rates, R j, k , were obtained from the build-up curves of the cross peaks by considering the internuclear distances arising in the master equation. Subsequently, experimentally obtained effective internuclear distances, r eff j, k (obs), were compared with the calculated r eff j, k (calc) values obtained from the X-ray crystallographic data. Fairly good correlation between r eff j, k (obs) and r eff j, k (calc) was obtained in the range of 1.0-6.0 Å, with the standard deviation of 0.244 Å, without considering the zero-quantum line-shape functions. It was further noted that the internuclear distances of intermolecular contributions provide details relating to the molecular packing in solid-state samples. Thus, the present data agree well with AP-β-sheet packing but do not agree with P-β-sheet packing.

Integrating diffusion maps with umbrella sampling: Application to alanine dipeptide

NASA Astrophysics Data System (ADS)

Ferguson, Andrew L.; Panagiotopoulos, Athanassios Z.; Debenedetti, Pablo G.; Kevrekidis, Ioannis G.

2011-04-01

Nonlinear dimensionality reduction techniques can be applied to molecular simulation trajectories to systematically extract a small number of variables with which to parametrize the important dynamical motions of the system. For molecular systems exhibiting free energy barriers exceeding a few kBT, inadequate sampling of the barrier regions between stable or metastable basins can lead to a poor global characterization of the free energy landscape. We present an adaptation of a nonlinear dimensionality reduction technique known as the diffusion map that extends its applicability to biased umbrella sampling simulation trajectories in which restraining potentials are employed to drive the system into high free energy regions and improve sampling of phase space. We then propose a bootstrapped approach to iteratively discover good low-dimensional parametrizations by interleaving successive rounds of umbrella sampling and diffusion mapping, and we illustrate the technique through a study of alanine dipeptide in explicit solvent.

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

NASA Astrophysics Data System (ADS)

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

1994-07-01

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

Topology of AspT, the Aspartate:Alanine Antiporter of Tetragenococcus halophilus, Determined by Site-Directed Fluorescence Labeling▿ †

PubMed Central

Nanatani, Kei; Fujiki, Takashi; Kanou, Kazuhiko; Takeda-Shitaka, Mayuko; Umeyama, Hideaki; Ye, Liwen; Wang, Xicheng; Nakajima, Tasuku; Uchida, Takafumi; Maloney, Peter C.; Abe, Keietsu

2007-01-01

The gram-positive lactic acid bacterium Tetragenococcus halophilus catalyzes the decarboxylation of l-aspartate (Asp) with release of l-alanine (Ala) and CO2. The decarboxylation reaction consists of two steps: electrogenic exchange of Asp for Ala catalyzed by an aspartate:alanine antiporter (AspT) and intracellular decarboxylation of the transported Asp catalyzed by an l-aspartate-β-decarboxylase (AspD). AspT belongs to the newly classified aspartate:alanine exchanger family (transporter classification no. 2.A.81) of transporters. In this study, we were interested in the relationship between the structure and function of AspT and thus analyzed the topology by means of the substituted-cysteine accessibility method using the impermeant, fluorescent, thiol-specific probe Oregon Green 488 maleimide (OGM) and the impermeant, nonfluorescent, thiol-specific probe [2-(trimethylammonium)ethyl]methanethiosulfonate bromide. We generated 23 single-cysteine variants from a six-histidine-tagged cysteineless AspT template. A cysteine position was assigned an external location if the corresponding single-cysteine variant reacted with OGM added to intact cells, and a position was assigned an internal location if OGM labeling required cell lysis. The topology analyses revealed that AspT has a unique topology; the protein has 10 transmembrane helices (TMs), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3. Moreover, the three-dimensional structure constructed by means of the full automatic modeling system indicates that the large hydrophilic cytoplasmic loop of AspT possesses a TrkA_C domain and a TrkA_C-like domain and that the three-dimensional structures of these domains are similar to each other even though their amino acid sequences show low similarity. PMID:17660287

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

PubMed

Sivaramakrishna, D; Swamy, Musti J

2015-09-08

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

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

PubMed

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

2017-08-01

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

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

PubMed Central

Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Bersani-Amado, Ciomar Aparecida

2017-01-01

High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP. PMID:28717379

Cardioprotective and hepatoprotective effects of Citrus hystrix peels extract on rats model

PubMed Central

Putri, Herwandhani; Nagadi, Standie; Larasati, Yonika Arum; Wulandari, Nindi; Hermawan, Adam

2013-01-01

Objective To observe the combination effect of doxorubicin and Citrus hystrix (kaffir lime's) peel ethanolic extract (ChEE) on blood serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity and cardio-hepato-histopathology of female Sprague Dawley rats. Methods Doxorubicin and ChEE (5 rats per group) were administered in five groups of 3 rats each for 11 d. Group I: doxorubicin (dox) 4.67 mg/kg body weight; Group II: dox+ChEE 500 mg/kg body weight; Group III: dox+ChEE 1 000 mg/kg body weight; Group IV: ChEE 1 000 mg/kg body weight; Group V: untreated (control). Results ChEE repaired cardiohistopathology profile of doxorubicin induced cardiotoxicity and hepatotoxicity rats, but did not repair neither hepatohistopathology profile nor reduce serum activity of ALT and AST. Conclusion ChEE has potency to be developed as cardioprotector agent in chemotherapy. PMID:23646300

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

NASA Astrophysics Data System (ADS)

Kakey, Musher Ismail Salih; Abdoulrahman, Kamaran Kaiani

2017-09-01

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

Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis.

PubMed

Iacobellis, Angelo; Marcellini, Matilde; Andriulli, Angelo; Perri, Francesco; Leandro, Gioacchino; Devito, Rita; Nobili, Valerio

2006-12-28

To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). BMI helps identify children with NASH who might have fibrotic deposition in the liver.

Liver injury following small intestinal ischemia reperfusion in rats is attenuated by Pistacia lentiscus oil: antioxidant and anti-inflammatory effects.

PubMed

Saidi, Saber Abdelkader; Ncir, Marwa; Chaaben, Rim; Jamoussi, Kamel; van Pelt, Jos; Elfeki, Abdelfattah

2017-10-01

Intestinal ischemia-reperfusion (IIR) not only leads to severe intestine damage but also induced subsequent destruction of remote organs. We investigated the protective effect of Pistascia lentiscus L. (Anacardiaceae) oil on IIR. Wistar rats were divided into three groups: sham, intestinal IR and P. lentiscus pretreatment (n = 18 each). In the pretreatment group, oil was administered 1 h before induction of warm ischemia. IIR led to severe liver damage manifested as a significant (p < .05) increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Pistacia lentiscus oil decreased the visible intestinal damage, as well as a significant decrease in serum AST and ALT levels. In addition, Pistacia lentiscus reduce liver injury, as evidenced by the decrease in liver tissue myeloperoxidase activity and lipoperoxidation (MDA) level. Pistascia lentiscus attenuates liver injury induced by IIR, attributable to the antioxidant and anti-inflammatory effect.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: comparison between theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2008-01-01

The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid-base properties in alanine-based peptides. Hence, the acid-base properties of three alanine-based peptides: Ac-KK-(A)(7)-KK-NH(2) (KAK), Ac-OO-(A)(7)-DD-NH(2) (OAD), Ac-KK-(A)(7)-EE-NH(2) (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH-metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson-Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, pK(a1) and pK(a2) correspond to the acidic side chains. For all three compounds in both solvents, the pK(a1) value is remarkably lower than the pK(a) of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method.

Alanine and proline content modulate global sensitivity to discrete perturbations in disordered proteins.

PubMed

Perez, Romel B; Tischer, Alexander; Auton, Matthew; Whitten, Steven T

2014-12-01

Molecular transduction of biological signals is understood primarily in terms of the cooperative structural transitions of protein macromolecules, providing a mechanism through which discrete local structure perturbations affect global macromolecular properties. The recognition that proteins lacking tertiary stability, commonly referred to as intrinsically disordered proteins (IDPs), mediate key signaling pathways suggests that protein structures without cooperative intramolecular interactions may also have the ability to couple local and global structure changes. Presented here are results from experiments that measured and tested the ability of disordered proteins to couple local changes in structure to global changes in structure. Using the intrinsically disordered N-terminal region of the p53 protein as an experimental model, a set of proline (PRO) and alanine (ALA) to glycine (GLY) substitution variants were designed to modulate backbone conformational propensities without introducing non-native intramolecular interactions. The hydrodynamic radius (R(h)) was used to monitor changes in global structure. Circular dichroism spectroscopy showed that the GLY substitutions decreased polyproline II (PP(II)) propensities relative to the wild type, as expected, and fluorescence methods indicated that substitution-induced changes in R(h) were not associated with folding. The experiments showed that changes in local PP(II) structure cause changes in R(h) that are variable and that depend on the intrinsic chain propensities of PRO and ALA residues, demonstrating a mechanism for coupling local and global structure changes. Molecular simulations that model our results were used to extend the analysis to other proteins and illustrate the generality of the observed PRO and alanine effects on the structures of IDPs. © 2014 Wiley Periodicals, Inc.

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

PubMed

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

2015-01-01

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

Low accuracy of the national reporting system of acute hepatitis C infection in Taiwan, 1995-2004.

PubMed

Kee, Kwong-Ming; Hung, Chi-Ming; Wang, Jing-Houng; Hung, Chao-Hung; Chen, Pao-Fei; Lin, Kuo-Sin; Lu, Sheng-Nan

2010-07-01

This study attempted to clarify accuracy of acute hepatitis C (AHC) and its clinical characteristics. We reviewed 632 reported cases from national surveillance data of the Taiwan Center for Disease Control between 1995 and 2004, and reclassified diagnoses. A definite case was defined as alanine aminotransferase (ALT) > 10 x the upper limit of normal (ULN) with seroconversion of anti-hepatitis C virus antibody (anti-HCV). A probable case was defined as (i) seroconversion of anti-HCV and/or elevated ALT levels; or (ii) anti-HCV(+) but titers increased (from < 40 S/CO to >or= 40 S/CO) and ALT > 10 x the ULN. A suspected case was defined as initial anti-HCV(+) and ALT level > 10 x the ULN and/or jaundice. Excluded cases were defined as ALT levels less than 10 x ULN with initial positive anti-HCV Ab. A total of 310 (49%) cases were confirmed as AHC; these included 95 (15%) definite and 215 (34%) probable cases. Higher incidence rates and accuracy of AHC were demonstrated in the southern area significantly if compared with northern, eastern and central areas, respectively (all P < 0.05). On comparison between blood centers and hospitals, more AHC cases were found in Southern Taiwan than in other areas (157/73 vs 24/40, P < 0.001), younger mean age (33.3 +/- 11.1 vs 49.3 +/- 16.4, P < 0.001), lower ALT levels (263.1 +/- 200.9 vs 1264.2 +/- 706.8, P < 0.001) and male predominance (191/39 vs 46/18, P = 0.046). This study showed our reporting system over-estimated the AHC diagnosis, which is also a common issue worldwide. Greater efforts are needed to establish appropriate reporting systems, as well as more supplemental methods to distinguish between prevalent and incident cases.

Salivary lactate dehydrogenase and aminotransferases in diabetic patients

PubMed Central

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

2016-01-01

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

Salivary lactate dehydrogenase and aminotransferases in diabetic patients.

PubMed

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

2016-11-01

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

Promoter scanning of the Human COX-2 gene with 8-ring polyamides: unexpected weakening of polyamide-DNA binding and selectivity by replacing an internal N-Me-pyrrole with β-alanine

PubMed Central

Aston, Karl; Ramos, Joseph P.; Koeller, Kevin J.; Nanjunda, Rupesh; He, Gaofei

2012-01-01

Rules for polyamide DNA recognition have proved invaluable for the design of sequence-selective DNA-binding agents in cell-free systems. However, these rules are not fully transferrable to predicting activity in cells, tissues or animals, and additional refinements to our understanding of DNA recognition would help biomedical studies. Similar complexities are encountered when using internal β-alanines as polyamide building blocks in place of N-methyl pyrrole; β-alanines were introduced in polyamide designs to maintain good hydrogen bonding registry with the target DNA, especially for long polyamides or those with several GC bp (P.B. Dervan, A.R. Urbach, Essays Contemp. Chem. (2001) 327–339). Thus, to clarify important subtleties of molecular recognition, we studied the effects of replacing a single pyrrole with β-alanine in 8-ring polyamides designed against the Ets-1 transcription factor. Replacement of a single internal N-methylpyrrole with β-alanine to generate a β/Im pairing in two 8-ring polyamides causes a decrease in DNA binding affinity by two orders of magnitude and decreases DNA binding selectivity, contrary to expectations based on the literature. Measurements were made by fluorescence spectroscopy, quantitative DNA footprinting and surface plasmon resonance, with these vastly different techniques showing excellent agreement. Furthermore, results were validated for a range of DNA substrates from small hairpins to long dsDNA sequences. Docking studies helped show that β-alanine does not make efficient hydrophobic contacts with the rest of the polyamide or nearby DNA, in contrast to pyrrole. These results help refine design principles and expectations for polyamide-DNA recognition. PMID:23023196

[Alanine dehydrogenase of the cyanobacterium Plectonema boryanum in the early period of cyanophage LPP-3 development].

PubMed

Perepelitsa, S I; Koltukova, N V; Mendzhul, M I

1995-01-01

It has been studied how reproduction of LPP-3 in Plectonema boryanum cells influences the alanine dehydrogenase activity. It has been found that immediately after the virus adsorption the enzyme activity falls by 50% and the anabolic reaction is blocked. Physicochemical properties of the enzyme vary as well. An infected cell has one isoenzyme-octamer with pl 9.1-9.2, pH-optimum by action 9-10, molecular weight about 27 kDa.

Determination of ammonium ion using a reagentless amperometric biosensor based on immobilized alanine dehydrogenase.

PubMed

Tan, Ling Ling; Musa, Ahmad; Lee, Yook Heng

2011-01-01

The use of the enzyme alanine dehydrogenase (AlaDH) for the determination of ammonium ion (NH(4)(+)) usually requires the addition of pyruvate substrate and reduced nicotinamide adenine dinucleotide (NADH) simultaneously to effect the reaction. This addition of reagents is inconvenient when an enzyme biosensor based on AlaDH is used. To resolve the problem, a novel reagentless amperometric biosensor using a stacked methacrylic membrane system coated onto a screen-printed carbon paste electrode (SPE) for NH(4)(+) ion determination is described. A mixture of pyruvate and NADH was immobilized in low molecular weight poly(2-hydroxyethyl methacrylate) (pHEMA) membrane, which was then deposited over a photocured pHEMA membrane (photoHEMA) containing alanine dehydrogenase (AlaDH) enzyme. Due to the enzymatic reaction of AlaDH and the pyruvate substrate, NH(4)(+) was consumed in the process and thus the signal from the electrocatalytic oxidation of NADH at an applied potential of +0.55 V was proportional to the NH(4)(+) ion concentration under optimal conditions. The stacked methacrylate membranes responded rapidly and linearly to changes in NH(4)(+) ion concentrations between 10-100 mM, with a detection limit of 0.18 mM NH(4)(+) ion. The reproducibility of the amperometrical NH(4)(+) biosensor yielded low relative standard deviations between 1.4-4.9%. The stacked membrane biosensor has been successfully applied to the determination of NH(4)(+) ion in spiked river water samples without pretreatment. A good correlation was found between the analytical results for NH(4)(+) obtained from the biosensor and the Nessler spectrophotometric method.

Loss of Mitochondrial Pyruvate Carrier 2 in the Liver Leads to Defects in Gluconeogenesis and Compensation via Pyruvate-Alanine Cycling.

PubMed

McCommis, Kyle S; Chen, Zhouji; Fu, Xiaorong; McDonald, William G; Colca, Jerry R; Kletzien, Rolf F; Burgess, Shawn C; Finck, Brian N

2015-10-06

Pyruvate transport across the inner mitochondrial membrane is believed to be a prerequisite for gluconeogenesis in hepatocytes, which is important for the maintenance of normoglycemia during prolonged food deprivation but also contributes to hyperglycemia in diabetes. To determine the requirement for mitochondrial pyruvate import in gluconeogenesis, mice with liver-specific deletion of mitochondrial pyruvate carrier 2 (LS-Mpc2(-/-)) were generated. Loss of MPC2 impaired, but did not completely abolish, hepatocyte conversion of labeled pyruvate to TCA cycle intermediates and glucose. Unbiased metabolomic analyses of livers from fasted LS-Mpc2(-/-) mice suggested that alterations in amino acid metabolism, including pyruvate-alanine cycling, might compensate for the loss of MPC2. Indeed, inhibition of pyruvate-alanine transamination further reduced mitochondrial pyruvate metabolism and glucose production by LS-Mpc2(-/-) hepatocytes. These data demonstrate an important role for MPC2 in controlling hepatic gluconeogenesis and illuminate a compensatory mechanism for circumventing a block in mitochondrial pyruvate import. Copyright © 2015 Elsevier Inc. All rights reserved.

Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine, a neurotoxic amino acid.

PubMed

Cox, Paul Alan; Banack, Sandra Anne; Murch, Susan J; Rasmussen, Ulla; Tien, Georgia; Bidigare, Robert Richard; Metcalf, James S; Morrison, Louise F; Codd, Geoffrey A; Bergman, Birgitta

2005-04-05

Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, beta-N-methylamino-L-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.

Diverse taxa of cyanobacteria produce β-N-methylamino-l-alanine, a neurotoxic amino acid

PubMed Central

Cox, Paul Alan; Banack, Sandra Anne; Murch, Susan J.; Rasmussen, Ulla; Tien, Georgia; Bidigare, Robert Richard; Metcalf, James S.; Morrison, Louise F.; Codd, Geoffrey A.; Bergman, Birgitta

2005-01-01

Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, β-N-methylamino-l-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure. PMID:15809446

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

PubMed Central

Kozhushkov, Sergei I; Yufit, Dmitrii S; Grosse, Christian; Kaiser, Marcel

2014-01-01

Summary Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a–c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity. PMID:25550751

AMELIORATIVE ROLE OF Vernonia cinerea IN CARBON TETRACHLORIDE INDUCED HEPATIC DYSFUNCTION IN RATS

PubMed Central

Gokilaveni, C.; Nishadh, A.; Selvi, V.

2006-01-01

The ameliorative activity of herbal powder prepared from Veronia cinerea leaves on CCl4 (0.2ml/kg body wt. intraperitoneally (ip) and liquid paraffin (0.2 ml / kg body wt:ip) induced hepatotoxicity was studied in rats. The liver marker enzymes namely alanine transmainase (ALT), aspartate transaminase (AST), acid phosphatase and alkaline phosphatase (ALP) activities were decreased in 10% w/v liver homogenates of hepatotoxicity induced rats. The results of both post treated and pre treated groups suggest the hepatoprotective activity of Veronia cinerea in CCl4 induced rats. PMID:22557198

AMELIORATIVE ROLE OF Vernonia cinerea IN CARBON TETRACHLORIDE INDUCED HEPATIC DYSFUNCTION IN RATS.

PubMed

Gokilaveni, C; Nishadh, A; Selvi, V

2006-01-01

The ameliorative activity of herbal powder prepared from Veronia cinerea leaves on CCl(4) (0.2ml/kg body wt. intraperitoneally (ip) and liquid paraffin (0.2 ml / kg body wt:ip) induced hepatotoxicity was studied in rats. The liver marker enzymes namely alanine transmainase (ALT), aspartate transaminase (AST), acid phosphatase and alkaline phosphatase (ALP) activities were decreased in 10% w/v liver homogenates of hepatotoxicity induced rats. The results of both post treated and pre treated groups suggest the hepatoprotective activity of Veronia cinerea in CCl(4) induced rats.

Loss of Mitochondrial Pyruvate Carrier 2 in Liver Leads to Defects in Gluconeogenesis and Compensation via Pyruvate-Alanine Cycling

PubMed Central

McCommis, Kyle S.; Chen, Zhouji; Fu, Xiaorong; McDonald, William G.; Colca, Jerry R.; Kletzien, Rolf F.; Burgess, Shawn C.; Finck, Brian N.

2015-01-01

SUMMARY Pyruvate transport across the inner mitochondrial membrane is believed to be a prerequisite step for gluconeogenesis in hepatocytes, which is important for maintenance of normoglycemia during prolonged food deprivation, but also contributes to hyperglycemia in diabetes. To determine the requirement for mitochondrial pyruvate import in gluconeogenesis, mice with liver-specific deletion of mitochondrial pyruvate carrier 2 (LS-Mpc2−/−) were generated. Loss of MPC2 impaired, but did not completely abolish, hepatocyte pyruvate metabolism, labelled pyruvate conversion to TCA cycle intermediates and glucose, and glucose production from pyruvate. Unbiased metabolomic analyses of livers from fasted LS-Mpc2−/− mice suggested that alterations in amino acid metabolism, including pyruvate-alanine cycling, might compensate for loss of MPC2. Indeed, inhibition of pyruvate-alanine transamination further reduced mitochondrial pyruvate metabolism and glucose production by LS-Mpc2−/− hepatocytes. These data demonstrate an important role for MPC2 in controlling hepatic gluconeogenesis and illuminate a compensatory mechanism for circumventing a block in mitochondrial pyruvate import. PMID:26344101

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

PubMed

Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

2015-09-01

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

Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis.

PubMed

Jin, Shanshan; Jiang, Suwen; Hu, Airong

2018-01-15

The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) has been an issue of great concern. The primary purpose of this study was to determine the influence of OSA on the levels of liver enzymes including alanine transaminase (ALT) and aspartate transaminase (AST). The secondary purpose was to estimate the effect of OSA on the histological lesions of NAFLD, such as steatosis, lobular inflammation, ballooning degeneration, fibrosis, as well as NAFLD activity score (NAS). A systematic literature review using PubMed, Cochrane Library, Embase, and Ovid technologies from January 2007 to April 2017 was performed, and 9 studies (2272 participants) that met the selection criteria were evaluated. The present study demonstrated that OSA was related to ALT levels, but no significant correlation was found with AST levels. The subgroup analysis showed that the severity of OSA was associated with ALT levels, not with AST levels. The meta-regression analysis showed that age, sex, homeostasis model assessment, diabetes mellitus, body mass index, and waist circumference did not have a significant effect on the levels of ALT and AST. OSA was also found to be significantly correlated with steatosis, lobular inflammation, ballooning degeneration, and fibrosis, but was not correlated with NAS. OSA was independently related to the development and progression of NAFLD in terms of liver enzyme level and histological alterations. Future studies should investigate the possible relevant mechanisms, thereby guiding the exploration of potential therapeutic implications to prevent the progression of disease.

Rifampicin treatment of canine pyoderma due to multidrug-resistant meticillin-resistant staphylococci: a retrospective study of 32 cases.

PubMed

De Lucia, Michela; Bardagi, Mar; Fabbri, Elisabetta; Ferreira, Diana; Ferrer, Lluis; Scarampella, Fabia; Zanna, Giordana; Fondati, Alessandra

2017-04-01

Rifampicin has received increased interest in veterinary dermatology because of its activity against multidrug-resistant meticillin-resistant staphylococci (MRS). There is limited knowledge about the efficacy and safety of rifampicin in dogs. To provide information on response to treatment and adverse effects in dogs treated with rifampicin for multidrug-resistant MRS pyoderma. Thirty two dogs treated with rifampicin for rifampicin-susceptible multidrug-resistant MRS pyoderma. Retrospective review of medical records, including alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum activity levels and total bilirubin concentrations, obtained before and throughout the treatment, was performed. Oral rifampicin as sole systemic antimicrobial therapy (median dose 5 mg/kg twice daily) was effective in 71.88% of cases. Topical antimicrobials were used in most cases. Median duration of rifampicin treatment was five weeks for superficial pyoderma and four weeks for deep pyoderma. Gastrointestinal signs were reported in 15% of treated dogs. Statistically significant increases of ALT (P = 0.045) and ALP (P = 0.0002) values after 3-4 weeks of treatment was observed. The median increase was equal to 0.3 and ×1.5 the upper limit of the reference ranges for ALT and ALP, respectively. Oral rifampicin combined with topical antimicrobials can be considered an effective therapeutic option for canine superficial and deep pyoderma caused by rifampicin-susceptible multidrug-resistant MRS. Liver enzyme induction might be the most important cause of ALT and ALP increase associated with rifampicin therapy in dogs. © 2016 ESVD and ACVD.

Autoimmune hepatitis triggered by acute hepatitis A.

PubMed

Tanaka, Hiroto; Tujioka, Hiroto; Ueda, Hiroki; Hamagami, Hiroko; Kida, Youhei; Ichinose, Masakazu

2005-10-14

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (X320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

DPP-4 inhibitors improve liver dysfunction in type 2 diabetes mellitus.

PubMed

Kanazawa, Ippei; Tanaka, Ken-ichiro; Sugimoto, Toshitsugu

2014-09-17

Dipeptidyl peptidase-4 (DPP-4) inhibitors might have pleiotropic effects because receptors for incretin exist in various tissues, including liver. We examined whether DPP-4 inhibitors affect liver function in patients with type 2 diabetes. A retrospective review of 459 patients with type 2 diabetes who were prescribed DPP-4 inhibitors was performed. After exclusion of patients with hepatitis B or C, steroid use, and other diseases that might affect liver function and diabetes status, 224 patients were included in the analysis. Forty-four patients (19.6%) with liver injury defined by aspartate transaminase (AST) or alanine transaminase (ALT) over the normal level of 40 U/L. In the patients with liver injury, AST and ALT were significantly decreased after 6 months from the first date of DPP-4 prescription, with mean changes of -6.2 U/L [95% confidence interval (CI) -10.9 to -1.4, p=0.012] and of -11.9 U/L (95%CI -19.5 to -4.2, p=0.003), respectively. Percent changes in AST were significantly and negatively correlated with baseline AST and ALT (r=-0.27, p<0.001 and r=-0.23, p=0.002, respectively), and percent changes in ALT were also negatively correlated with them (r=-0.23, p=0.001 and r=-0.27, p<0.001, respectively). DPP-4 inhibitors improved liver dysfunction in patients with type 2 diabetes.

Idiopathic liver function test abnormality in pregnancy is associated with assisted reproduction techniques.

PubMed

Kopylov, Uri; Avidan, Benjamin; Papageorgiou, Neofytos P; Katz, Lior H; Sivan, Eyal; Zimlichman, Eyal; Hussein, Haya; Maor, Yaakov

2013-02-01

To examine the prevalence, etiology, risk factors, and outcomes of liver abnormality in pregnancy, in a tertiary medical center, and to study the potential impact of artificial reproduction techniques (ART) on the incidence and the outcome of pregnancy-related liver abnormality. A retrospective case-control study using an electronic database and patients' files. Tertiary referral center. Women in the third trimester of pregnancy who were hospitalized for delivery. None. Development of significant elevation of alanine aminotransferase (ALT ≥ 100 IU/L). Secondary outcomes included development of maternal and fetal complications. The upper limit of normal of ALT was ≥ 1.5 times and it occurred in 440 (1.6%) pregnancies; of those, 228 (0.8%) had ALT ≥ 100 IU/L. The etiology of significant liver test abnormality was idiopathic in 47% of patients. Compared with spontaneous pregnancies (295/23,793), ART was significantly associated with liver test abnormality (145/4, 520). The presence of ALT ≥ 100 IU/L in the third trimester was associated with higher rates of cesarean sections, prematurity, low birthweight, and fetal complications. A definite etiology was not determined in about half of pregnancy-associated liver test abnormality. The ART was significantly associated with liver test elevation. Significant liver test abnormality in the third trimester may have an impact on maternal and fetal/neonatal outcomes. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Longitudinal monitoring of liver stiffness by acoustic radiation force impulse imaging in patients with chronic hepatitis B receiving entecavir.

PubMed

Wu, Sheng-Di; Ding, Hong; Liu, Li-Li; Zhuang, Yuan; Liu, Yun; Cheng, Li-Sha; Wang, Si-Qi; Tseng, Yu-Jen; Wang, Ji-Yao; Jiang, Wei

2018-06-01

Acoustic radiation force impulse (ARFI) imaging measures liver stiffness (LS), which significantly correlates with the stage of liver fibrosis in treatment-naive patients with chronic hepatitis B (CHB). We aimed to prospectively assess the clinical usefulness of ARFI during long-term antiviral therapy in CHB. Seventy-one CHB patients were consecutively recruited and paired liver biopsies were performed in 27 patients. LS was assessed by ARFI semiannually during entecavir therapy. LS gradually decreased with treatment and continued to decrease after normalization of alanine aminotransaminase. Overall, 97.2% patients achieved improvement of LS, whereas 19.7% patients had more than 30% reduction in LS values between baseline and week 104. Multivariate linear regression analysis showed that the degree of LS reduction significantly correlated with the baseline levels of LS value, platelet and cholinesterase. In the 27 patients who underwent paired liver biopsies, LS significantly correlated with stage of fibrosis and inflammatory grade at baseline. LS values decreased more significantly in patients with fibrosis regression than those with static histological fibrosis. In CHB patients, LS assessed by ARFI was gradually reduced during antiviral therapy. Longitudinal monitoring of LS may be a promising noninvasive assessment of fibrosis regression during long-term antiviral therapy in CHB. Further large sample studies are needed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of sub-acute methanol extract treatment of Calliandra portoricensis root bark on antioxidant defence capacity in an experimental rat model.

PubMed

Siemuri, Ese O; Akintunde, Jacob K; Salemcity, Anuoluwapo J

2015-07-01

The attendant side effects associated with some synthetic drugs used in the management of diseases have led to the search for safer alternative therapies that are relatively cheaper with minimal side effects. The methanol extract of Calliandra portoricensis root bark (CPRB) was orally administered at the doses of 5, 10, 20, and 25 mg/kg body weight for 14 consecutive days of 5 rats in each group. The control rats were given distilled water. The 95% methanol extract of CPRB significantly (p<0.05) scavenged NO• and OH• radicals compared to vitamin C. The level of lipid peroxidative products (malondialdehyde, MDA) was significantly (p<0.05) attenuated in a dose-dependent manner. Antioxidant enzymes including superoxide dismutase and catalase were significantly (p<0.05) exercabated in both liver and kidney in a dose-dependent manner. Furthermore, serum AST, alanine aminotransaminase and γ-glutamyltransferase (GGT) activity depicted non-significant (p>0.05) increase in the treated animals. The histological examination showed mild vacuolar, portal congestion and cell infiltration by mononuclear of the hepatic tissues. The study then concluded that a therapeutic dose of the methanol extract of CPRB triggered the antioxidant defence systems in male rats. It is, therefore, recommended that the doses should be carefully and clinically chosen because higher doses may cause some health risks.

96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B.

PubMed

Hui, Chee-Kin; Zhang, Hai-Ying; Bowden, Scott; Locarnini, Stephen; Luk, John M; Leung, Kar-Wai; Yueng, Yui-Hung; Wong, April; Rousseau, Frank; Yuen, Kwok-Yung; Naoumov, Nikolai N; Lau, George K K

2008-05-01

In order to prevent the occurrence of drug-resistant mutants associated with treatment for chronic hepatitis B virus (HBV) infection, combination therapy is being developed. To determine the efficacy of adefovir dipivoxil (ADV) plus emtricitabine (FTC) combination therapy in chronic HBV infection. Thirty treatment-nai ve, HBeAg-positive patients were randomized to combination ADV plus FTC (n=14) or ADV plus placebo monotherapy (n=16) for 96 weeks. HBV DNA was measured by polymerase chain reaction. Treatment was stopped in those with HBeAg seroconversion. The median decrease in HBV DNA at week 96 was higher in the combination group (-5.30 vs. -3.98 log(10)copies/ml, p=0.05). More patients in the combination group had normalization of alanine aminotransaminase and HBV DNA<300 copies/ml at week 96 when compared with the monotherapy group [11 of the 14 patients (78.6%) vs. 6 of the 16 patients (37.5%), p=0.03]. However, HBeAg seroconversion at week 96 was similar in the 2 groups [2/14 (14.3%) vs. 4/16 (25.0%), p=NS]. No ADV or FTC resistance was detected at week 96. In those with HBeAg seroconversion, 50.0% had post-treatment relapse. Combination ADV plus FTC resulted in more potent suppression of HBV DNA over 96 weeks of therapy.

Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand.

PubMed

Lucas, Gregory M; Young, Alicia; Donnell, Deborah; Richardson, Paul; Aramrattana, Apinun; Shao, Yiming; Ruan, Yuhua; Liu, Wei; Fu, Liping; Ma, Jun; Celentano, David D; Metzger, David; Jackson, J Brooks; Burns, David

2014-09-01

Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX. We compared rates of alanine aminotransferase (ALT) elevation≥grade 3 (ALT≥5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants. Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation≥grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations≥grade 2 occurred in 2% of subjects, with no significant difference between arms. Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2014-01-01

Metabolic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in Indian teleostean fishes, namely, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch), for an exposure to 30 days of Excel Mera 71 (17.2 mg/L), a glyphosate formulation, and subsequent depuration under Liv.52, a plant extract at a dose of 187.5 mg/d/250 L for the same period in the same tissues under laboratory condition. ALT activity was significantly increased (P<0.05) in all the tissues and raised up to 229.19% in liver of A. testudineus (229.19%) and 128.61% in liver of H. fossilis. AST also increased significantly (P<0.05) and was maximum in liver of H. fossilis (526.19%) and minimum in gill of A. testudineus (124.38%). ALP activity was also raised highly in intestine of H. fossilis (490.61%) but was less in kidney of H. fossilis (149.48%). The results indicated that Excel Mera 71 caused alterations in the metabolic enzymatic activities in fish tissues and AST showed the highest alteration in both the fishes, while lowest in ALP and ALT in A. testudineus and H. fossilis, respectively. During depuration under Liv.52, all the enzyme activities came down towards the control condition which indicated the compensatory response by the fish against this herbicidal stress and it was in the following order: AST>ALT>ALP, in A. testudineus, while H. fossilis showed the following trend: ALT>AST>ALP. Therefore, these parameters could be used as indicators of herbicidal pollution in aquatic organisms and were recommended for environmental monitoring for investigating the mechanism involved in the recovery pattern.

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. The Consensus Interferon Study Group.

PubMed

Heathcote, E J; James, S; Mullen, K D; Hauser, S C; Rosenblate, H; Albert, D G

1999-08-01

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a "breakthrough" while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-alpha2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =.102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P =.014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

Excess of L-Alanine in Amino Acids Synthesized in a Plasma Torch Generated by a Hypervelocity Meteorite Impact Reproduced in the Laboratory

NASA Technical Reports Server (NTRS)

Managadze, George G.; Engle, Michael H.; Getty, Stephanie A.; Wurz, Peter; Brinckerhoff, William B.; Shokolov, Anatoly; Sholin, Gennady; Terent'ev, Sergey A.; Chumikov, Alexander E.; Skalkin, Alexander S

2016-01-01

We present a laboratory reproduction of hypervelocity impacts of a carbon containing meteorite on a mineral substance representative of planetary surfaces. The physical conditions of the resulting impact plasma torch provide favorable conditions for abiogenic synthesis of protein amino acids: We identified glycine and alanine, and in smaller quantities serine, in the produced material. Moreover, we observe breaking of alanine mirror symmetry with L excess, which coincides with the bioorganic world. Therefore the selection of L-amino acids for the formation of proteins for living matter could have been the result from plasma processes occurring during the impact meteorites on the surface. This indicates that the plasma torch from meteorite impacts could play an important role in the formation of biomolecular homochirality. Thus, meteorite impacts possibly were the initial stage of this process and promoted conditions for the emergence of a living matter.

The snakehead Channa asiatica accumulates alanine during aerial exposure, but is incapable of sustaining locomotory activities on land through partial amino acid catabolism.

PubMed

Chew, Shit F; Wong, Mei Y; Tam, Wai L; Ip, Yuen K

2003-02-01

The freshwater snakehead Channa asiatica is an obligatory air-breather that resides in slow-flowing streams and in crevices near riverbanks in Southern China. In its natural habitat, it may encounter bouts of aerial exposure during the dry seasons. In the laboratory, the ammonia excretion rate of C. asiatica exposed to terrestrial conditions in a 12 h:12 h dark:light regime was one quarter that of the submerged control. Consequently, the ammonia contents in the muscle, liver and plasma increased significantly, and C. asiatica was able to tolerate quite high levels of ammonia in its tissues. Urea was not the major product of ammonia detoxification in C. asiatica, which apparently did not possess a functioning ornithine urea cycle. Rather, alanine increased fourfold to 12.6 micromol g(-1) in the muscle after 48 h of aerial exposure. This is the highest level known in adult teleosts exposed to air or an ammonia-loading situation. The accumulated alanine could account for 70% of the deficit in ammonia excretion during this period, indicating that partial amino acid catabolism had occurred. This would allow the utilization of certain amino acids as energy sources and, at the same time, maintain the new steady state levels of ammonia in various tissues, preventing them from rising further. There was a reduction in the aminating activity of glutamate dehydrogenase from the muscle and liver of specimens exposed to terrestrial conditions. Such a phenomenon has not been reported before and could, presumably, facilitate the entry of alpha-ketoglutarate into the Krebs cycle instead of its amination to glutamate, as has been suggested elsewhere. However, in contrast to mudskippers, C. asiatica was apparently unable to reduce the rates of proteolysis and amino acid catabolism, because the reduction in nitrogenous excretion during 48 h of aerial exposure was completely balanced by nitrogenous accumulation in the body. Alanine accumulation also occurred in specimens exposed to

[Effect of Low-Intensity 900 MHz Frequency Electromagnetic Radiation on Rat Brain Enzyme Activities Linked to Energy Metabolism].

PubMed

Petrosyan, M S; Nersesova, L S; Gazaryants, M G; Meliksetyan, G O; Malakyan, M G; Bajinyan, S A; Akopian, J I

2015-01-01

The research deals with the effect of low-intensity 900 MHz frequency electromagnetic radiation (EMR), power density 25 μW/cm2, on the following rat brain and blood serum enzyme activities: creatine kinase (CK), playing a central role in the process of storing and distributing the cell energy, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) that play a key role in providing the conjunction of carbohydrate and amino acid metabolism. The comparative analysis of the changes in the enzyme activity studied at different times following the two-hour single, as well as fractional, radiation equivalent of the total time showed that the most radiosensitive enzyme is the brain creatine kinase, which may then be recommended as a marker of the radio frequency radiation impact. According to the analysis of the changing dynamics of the CK, ALT and AST activity level, with time these changes acquire the adaptive character and are directed to compensate the damaged cell energy metabolism.

Oxidative stress and antioxidant biomarker responses after a moderate-intensity soccer training session.

PubMed

Mello, Rodrigo; Mello, Ricardo; Gomes, Diego; Paz, Gabriel Andrade; Nasser, Igor; Miranda, Humberto; Salerno, Verônica P

2017-01-01

The present study investigated the effects of a moderate-intensity soccer training session on the production of reactive oxygen species (ROS) and the antioxidant capacity in athletes along with the biomarkers creatine kinase and transaminases for lesions in muscle and liver cells. Twenty-two male soccer players participated in this study. Blood samples were collected 5 min before and after a moderate-intensity game simulation. The results showed a decrease in the concentration of reduced glutathione (GSH) from an elevation in the production of ROS that maintained the redox homeostasis. Although the session promoted an elevated energy demand, observed by an increase in lactate and glucose levels, damage to muscle and/or liver cells was only suggested by a significant elevation in the levels of alanine transaminase (ALT). Of the two biomarkers analysed, the results suggest that measurements of the ALT levels could be adopted as a method to monitor recovery in athletes.

Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis

PubMed Central

Iacobellis, Angelo; Marcellini, Matilde; Andriulli, Angelo; Perri, Francesco; Leandro, Gioacchino; Devito, Rita; Nobili, Valerio

2006-01-01

AIM: To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). METHODS: All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). RESULTS: At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). CONCLUSION: BMI helps identify children with NASH who might have fibrotic deposition in the liver. PMID:17203527

Fibrosis Progression in Paired Liver Biopsies from HIV/HCV-Coinfected Patients without Prior Treatment of Hepatitis C.

PubMed

Leite, Andréa G B; Duarte, Maria Irma S; Mendes-Correa, Maria Cássia

2015-01-01

Several studies have demonstrated that HIV/hepatitis C virus (HCV)-coinfected patients experience more rapid fibrosis progression. In this study, to estimate the annual rate of direct liver fibrosis progression, we used analyses of paired biopsy samples from HIV/HCV-coinfected patients without prior treatment of hepatitis and assessed the possible association of fibrosis progression with certain clinical variables. We evaluated 30 HIV/HCV-coinfected patients, with no history of prior treatment of hepatitis C, who underwent paired liver biopsies. All patients were under antiretroviral therapy at first and second biopsies. The average annual progression rate was 0.13 fibrosis unit/year, with 36.7% of patients defined as progressors. Liver fibrosis progression was associated with alanine aminotransferase (ALT; P < .001) and aspartate aminotransferase (AST; P < .0340) levels over 3 times the upper limit of normal present at first biopsy. Elevated ALT and AST levels appear to be associated with more accelerated liver fibrosis progression among HIV/HCV-coinfected patients. © The Author(s) 2015.

Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice.

PubMed

Tsai, Chia-Fang; Hsu, Yu-Wen; Chen, Wen-Kang; Chang, Wen-Huei; Yen, Cheng-Chieh; Ho, Yung-Chyuan; Lu, Fung-Jou

2009-08-01

The study investigated the protective effect of electrolyzed reduced water (ERW) against carbon tetrachloride (CCl(4))-induced liver damage. Male ICR mice were randomly divided into control, CCl(4), CCl(4)+silymarin, and CCl(4)+ERW groups. CCl(4)-induced liver lesions include leukocytes infiltration, hepatocyte necrosis, ballooning degeneration, mitosis, calcification, fibrosis and an increase of serum alanine aminotransferase (ALT), and aminotransferase (AST) activity. In addition, CCl(4) also significantly decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). By contrast, ERW or silymarin supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of hepatic enzyme markers (ALT and AST) and increased the activities of SOD, catalase, and GSH-Px in liver. Therefore, the results of this study show that ERW can be proposed to protect the liver against CCl(4)-induced oxidative damage in mice, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenging effect.

Effects of nonlethal sea lamprey attack on the blood chemistry of lake trout

USGS Publications Warehouse

Edsall, Carol Cotant; Swink, William D.

2001-01-01

A laboratory study examined changes in the blood chemistry of field-caught and hatchery-reared lake trout Salvelinus namaycush subjected to a nonlethal attack by sea lampreys Petromyzon marinus. We measured glucose, total protein, amylase, alkaline phosphatase (ALKP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase, calcium, magnesium, triglycerides, sodium, and potassium with a Kodak Ektachem DT60 Analyzer, Ektachem DTSC Module, and the DTE Module. Mean levels of total protein, AST, ALKP, hematocrit, calcium, magnesium, and sodium decreased significantly (Pa?? 0.05), and mean levels of ALT and potassium increased significantly (Pa?? 0.05) after sea lamprey feeding. Lake trout condition (K) and hematocrit levels also decreased significantly (Pa?? 0.05) after the sea lamprey attack. Frequency distributions of eight lake trout blood chemistry variables and the hematocrit were significantly different before and after a sea lamprey attack. A second study that used hatchery lake trout broodstock measured changes in hematocrit before and after a sea lamprey attack.

Synthesis and characterization of new polyamides derived from alanine and valine derivatives

PubMed Central

2012-01-01

Background Many efforts have been recently devoted to design, investigate and synthesize biocompatible, biodegradable polymers for applications in medicine for either the fabrication of biodegradable devices or as drug delivery systems. Many of them consist of condensation of polymers having incorporated peptide linkages susceptible to enzymatic cleavage. Polyamides (PAs) containing α-amino acid residues such as L-leucine, L-alanine and L-phenylalanine have been reported as biodegradable materials. Furthermore, polyamides (PAs) derived from C10 and C14 dicarboxylic acids and amide-diamines derived from 1,6-hexanediamine or 1,12-dodecanediamine and L-phenylalanine, L-valyl-L-phenylalanine or L-phenylalanyl-L-valine residues have been reported as biocompatible polymers. We have previously described the synthesis and thermal properties of a new type of polyamides-containing amino acids based on eight new symmetric meta-oriented protected diamines derived from coupling of amino acids namely; Fomc-glycine, Fmoc-alanine, Fomc-valine and Fomc-leucine with m-phenylene diamine or 2,6-diaminopyridine. Results revealed that incorporation of pyridine onto the polymeric backbone of all series decreases the thermal stability. Here we describe another family of polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and α-amino acid linked to benzidine and 4,4′-oxydianiline to study the effect of the dicarboxylic acid as well as the amino acids on the nature and thermal stability of the polymers. Results We report here the preparation of a new type of polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and α-amino acid linked to benzidine and 4,4′-oxydianiline to study the effect of the dicarboxylic acid as well as the amino acids on the nature and thermal stability of polymers. The thermal properties of the polymers were evaluated by different techniques. Results revealed that structure-thermal property correlation based on

A Critical Review of the Postulated Role of the Cyanobacterial Metabolite, Beta-N-Methylamino-L-Alanine (BMAA) in Neurodegenerative Disease in Humans

EPA Science Inventory

The compound BMAA (β-N-methylamino-L-alanine) has been hypothesized to play a significant role in four serious neurological diseases in humans: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, parkinsonism, and dementia that occur...

Enzymatic biosensor based on entrapment of d-amino acid oxidase on gold nanofilm/MWCNTs nanocomposite modified glassy carbon electrode by sol-gel network: Analytical applications for d-alanine in human serum.

PubMed

Shoja, Yalda; Rafati, Amir Abbas; Ghodsi, Javad

2017-05-01

Sensing and determination of d-alanine is studied by using an enzymatic biosensor which was constructed on the basis of d-amino acid oxidase (DAAO) immobilization by sol-gel film onto glassy carbon electrode surface modified with nanocomposite of gold nanofilm (Au-NF) and multiwalled carbon nanotubes (MWCNTs). The Au-NF/MWCNT nanocomposite was prepared by applying the potentiostatic technique for electrodeposition of Au-NF on the MWCNT immobilized on glassy carbon electrode surface. The modified electrode is investigated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), linear sweep voltammetry (LSV) and cyclic voltammetry(CV) techniques. The linear sweep voltammetry was used for determination of d-alanine and the results showed an excellent linear relationship between biosensor response and d-alanine concentration ranging from 0.25μM to 4.5μM with correction coefficient of 0.999 (n=20). Detection limit for the fabricated sensor was calculated about 20nM (for S/N=3) and sensitivity was about 56.1μAμM -1 cm -2 . The developed biosensor exhibited rapid and accurate response to d-alanine, a good stability (4 weeks) and an average recovery of 98.9% in human serum samples. Copyright © 2017 Elsevier Inc. All rights reserved.

The differing influence of several factors on the development of fatty liver with elevation of liver enzymes between genders with metabolic syndrome: A cross-sectional study.

PubMed

Sogabe, Masahiro; Okahisa, Toshiya; Nakasono, Masahiko; Fukuno, Hiroshi; Miyamoto, Yoshihiko; Okada, Yasuyuki; Okazaki, Jun; Miyoshi, Jinsei; Tomonari, Tetsu; Taniguchi, Tatsuya; Goji, Takahiro; Kitamura, Shinji; Miyamoto, Hiroshi; Muguruma, Naoki; Takayama, Tetsuji

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is known to be strongly associated with obesity, visceral fat, metabolic syndrome (MS), lifestyle, and lifestyle-related diseases in both males and females. However, the prevalence of NAFLD, MS, and clinical backgrounds is different between males and females. We conducted a cross-sectional study to examine the differing influence of lifestyle-related factors and visceral fat on fatty liver (FL) with elevation of liver enzymes between males and females with MS. We enrolled 42,134 persons who underwent a regular health check-up, and after excluding subjects who fulfilled excluding criteria, the remaining subjects were 2,110 persons with MS. We examined the differing influence of lifestyle-related factors and visceral fat on FL with elevation of alanine aminotransferase (ALT) (ALT elevation was defined as ALT level of ≥31 IU/l in the present study). The odds rations for FL with ALT elevation were as follows: WC, 1.83 (95% confidence interval (CI) 1.36-2.46); dyslipidemia, 1.89 (95% CI 1.34-2.68); hemoglobin A1c, 1.36 (95% CI 1.00-1.85); visceral fat type MS (V-type MS), 5.78 (95% CI 4.29-7.80); and light drinker, 0.56 (95% CI 0.41-0.78) in males with MS and BMI, 2.18 (95% CI 1.43-3.33); WC, 1.85 (95% CI 1.27-2.70); diastolic blood pressure, 1.69 (95% CI 1.16-2.45); triglyceride, 2.22 (95% CI 1.56-3.17); impaired glucose tolerance, 1.66 (95% CI 1.11-2.47); and V-type MS, 3.83 (95% CI 2.57-5.70) in females with MS. The prevalence of FL with ALT elevation and ALT was significantly higher in V-type MS than in the subcutaneous fat type MS in both males and females with MS (P < 0.001). Although V-type MS and WC is a common significant predictor of an increased prevalence of FL with ALT elevation in both males and females with MS, gender, lifestyle-related factors, and MS type in individuals with MS should be considered for the development of FL with ALT elevation.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B

PubMed Central

Nam, Soon Woo; Bae, Si Hyun; Lee, Seung Woo; Kim, Yeon Soo; Kang, Sang Bum; Choi, Jong Young; Cho, Se Hyun; Yoon, Seung Kew; Han, Joon-Yeol; Yang, Jin Mo; Lee, Young Suk

2008-01-01

AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naïve chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by ≥ 2 log10 copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy. PMID:18350610

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats.

PubMed

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use.

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats

PubMed Central

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

Effect of chlorpyrifos and enrofloxacin on selected enzymes in rats.

PubMed

Barski, D; Spodniewska, A

2018-03-01

This study examined the effect of chlorpyrifos and/or enrofloxacin on the activity of acetylcholinesterase (AChE) in the blood and brain, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. The experiment was conducted on Wistar strain rats. Chlorpyrifos was administered with a stomach tube at a dose of 0.04 LD50 for 28 days and enrofloxacin at a dose of 5 mg/kg bw for 5 consecutive days. The experiment found that enrofloxacin changed the activity of the enzymes under study only to a small extent. At the dose applied in the experiment, chlorpyrifos decreased the activity of AChE significantly, both in blood and in the brain, and increased the activity of ALT and AST in rat serum. The administration of chlorpyrifos in combination with enrofloxacin changed the activity of the enzymes under study only slightly. A weaker, but longer, inhibition of AChE activity in both blood and the brain was observed in this group compared to the animals exposed only to chlorpyrifos. However, although enrofloxacin, like chlorpyrifos, increases the activity of ALT and AST in serum, their combined administration did not increase the hepatotoxic effect. Copyright© by the Polish Academy of Sciences.

Alanine/EPR dosimetry applied to the verification of a total body irradiation protocol and treatment planning dose calculation using a humanoid phantom

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

Schaeken, B.; Lelie, S.; Meijnders, P.

2010-12-15

Purpose: To avoid complications in total body irradiation (TBI), it is important to achieve a homogeneous dose distribution throughout the body and to deliver a correct dose to the lung which is an organ at risk. The purpose of this work was to validate the TBI dose protocol and to check the accuracy of the 3D dose calculations of the treatment planning system. Methods: Dosimetry based on alanine/electron paramagnetic resonance (EPR) was used to measure dose at numerous locations within an anthropomorphic phantom (Alderson) that was irradiated in a clinical TBI beam setup. The alanine EPR dosimetry system was calibratedmore » against water calorimetry in a Co-60 beam and the absorbed dose was determined by the use of ''dose-normalized amplitudes'' A{sub D}. The dose rate of the TBI beam was checked against a Farmer ionization chamber. The phantom measurements were compared to 3D dose calculations from a treatment planning system (Pinnacle) modeled for standard dose calculations. Results: Alanine dosimetry allowed accurate measurements which were in accordance with ionization chamber measurements. The combined relative standard measurement uncertainty in the Alderson phantom was U{sub r}(A{sub D})=0.6%. The humanoid phantom was irradiated to a reference dose of 10 Gy, limiting the lung dose to 7.5 Gy. The ratio of the average measured dose midplane in the craniocaudal direction to the reference dose was 1.001 with a spread of {+-}4.7% (1 sd). Dose to the lung was measured in 26 locations and found, in average, 1.8% lower than expected. Lung dose was homogeneous in the ventral-dorsal direction but a dose gradient of 0.10 Gy cm{sup -1} was observed in the craniocaudal direction midline within the lung lobe. 3D dose calculations (Pinnacle) were found, in average, 2% lower compared to dose measurements on the body axis and 3% lower for the lungs. Conclusions: The alanine/EPR dosimetry system allowed accurate dose measurements which enabled the authors to validate

Alanine synthesis from glyceraldehyde and ammonium ion in aqueous solution

NASA Technical Reports Server (NTRS)

Weber, A. L.

1985-01-01

The formation of alanine (ala) form C(14)-glyceraldehyde and ammonium phosphate in the presence or absence of a thiol is reported. At ambient temperature, ala synthesis was six times more rapid in the presence of 3-mercaptopropionic acid than in its absence (0.6 and 0.1 percent, respectively, after 60 days). Similarly, the presence of another thiol, N-acetylcysteinate, increased the production of ala, as well as of lactate. The reaction pathway of thiol-catalyzed synthesis of ala, with the lactic acid formed in a bypath, is suggested. In this, dehydration of glyceraldehyde is followed by the formation of hemithioacetal. In the presence of ammonia, an imine is formed, which eventually yields ala. This pathway is consistent with the observation that the rate ratio of ala/lactate remains constant throughout the process. The fact that the reaction takes place under anaerobic conditions in the presence of H2O and with the low concentrations of simple substrates and catalysts makes it an attractive model prebiotic reaction in the process of molecular evolution.

Air motions inside dome room of Big Telescope Alt-azimuth at Special Astrophysical Observatory RAS. Numerical solutions of Navier-Stokes equations

NASA Astrophysics Data System (ADS)

Nosov, V. V.; Lukin, V. P.; Nosov, E. V.; Torgaev, A. V.

2017-11-01

The structure of air turbulent motion inside the closed dome room of Big Telescope Alt-azimuth at Special Astrophysical Observatory of the Russian Academy of Sciences (RAS) has been experimentally and theoretically studied. Theoretical results have been reached by numerical solving of boundary value problem for Navier-Stokes equations. Solitary large vortices (coherent structures, topological solitons) are observed indoors. Coherent breakdown of these vortices leads to the coherent turbulence. In the case of identical boundary conditions the pattern of air motions as a result of the simulation and the pattern, registered experimentally using the compact portable ultrasonic weather station, are practically the same.

Identification of myristoylated alanine-rich C kinase substrate (MARCKS) in astrocytes.

PubMed

Vitkovic, Ljubisa; Aloyo, Vincent J; Maeda, Shigeru; Benzil, Deborha L; Bressler, Joseph P; Hilt, Dana C

2005-01-01

We have characterized membrane-associated substrates of Ca2+-dependent kinases in primary rat astrocytes by in vitro phosphorylation, 2-dimensional gel electrophoresis and autoradiography. The most prominent among these were three acidic, protein kinase C (PKC) substrates. These are important because they likely transduce cytokine and other neuro-immune modulatory signals mediated by PKC. We now show that one of these phosphoproteins is myristoylated alanine-rich PKC kinase substrate (MARCKS) or phosphomyristin C. The identity was corroborated by one- and 2- dimensional immunoblotting with an MARCKS-specific polyclonal antibody. Exposing primary astrocytes to phorbol 12-myristate 13-acetate stimulated phosphorylation of this protein. The level of MARCKS appeared inversely proportional to the proliferative potential of astrocytes because it was lower in spontaneously transformed as compared to passaged or confluent cells. These data are consistent with previous reports and indicate that one of three major acidic membrane-associated PKC substrates in astrocytes is MARCKS. Thus, MARCKS is likely near-proximal transducer of PKC-mediated signals in astrocytes.

Energy Level Tuning of Poly(phenylene-alt-dithienobenzothiadiazole)s for Low Photon Energy Loss Solar Cells.

PubMed

Heuvel, Ruurd; van Franeker, Jacobus J; Janssen, René A J

2017-03-01

Six poly(phenylene- alt -dithienobenzothiadiazole)-based polymers have been synthesized for application in polymer-fullerene solar cells. Hydrogen, fluorine, or nitrile substitution on benzo-thiadiazole and alkoxy or ester substitution on the phenylene moiety are investigated to reduce the energy loss per converted photon. Power conversion efficiencies (PCEs) up to 6.6% have been obtained. The best performance is found for the polymer-fullerene combination with distinct phase separation and crystalline domains. This improves the maximum external quantum efficiency for charge formation and collection to 66%. The resulting higher photocurrent compensates for the relatively large energy loss per photon ( E loss = 0.97 eV) in achieving a high PCE. By contrast, the poly-mer that provides a reduced energy loss ( E loss = 0.49 eV) gives a lower photocurrent and a reduced PCE of 1.8% because the external quantum efficiency of 17% is limited by a suboptimal morphology and a reduced driving force for charge transfer.

Enzymatic properties of the glycine D-alanine [corrected] aminopeptidase of Aspergillus oryzae and its activity profiles in liquid-cultured mycelia and solid-state rice culture (rice koji).

PubMed

Marui, Junichiro; Matsushita-Morita, Mayumi; Tada, Sawaki; Hattori, Ryota; Suzuki, Satoshi; Amano, Hitoshi; Ishida, Hiroki; Yamagata, Youhei; Takeuchi, Michio; Kusumoto, Ken-Ichi

2012-01-01

The gdaA gene encoding S12 family glycine-D-alanine aminopeptidase (GdaA) was found in the industrial fungus Aspergillus oryzae. GdaA shares 43% amino acid sequence identity with the D-aminopeptidase of the Gram-negative bacterium Ochrobactrum anthropi. GdaA purified from an A. oryzae gdaA-overexpressing strain exhibited high D-stereospecificity and efficiently released N-terminal glycine and D-alanine of substrates in a highly specific manner. The optimum pH and temperature were 8 to 9 and 40°C, respectively. This enzyme was stable under alkaline conditions at pH 8 to 11 and relatively resistant to acidic conditions until pH 5.0. The chelating reagent EDTA, serine protease inhibitors such as AEBSF, benzamidine, TPCK, and TLCK, and the thiol enzyme inhibitor PCMB inhibited the enzyme. The aminopeptidase inhibitor bestatin did not affect the activity. GdaA was largely responsible for intracellular glycine and D-alanine aminopeptidase activities in A. oryzae during stationary-phase growth in liquid media. In addition, the activity increased in response to the depletion of nitrogen or carbon sources in the growth media, although the GdaA-independent glycine aminopeptidase activity highly increased simultaneously. Aminopeptidases of A. oryzae attract attention because the enzymatic release of a variety of amino acids and peptides is important for the enhancement of the palatability of fermented foods. GdaA activity was found in extracts of a solid-state rice culture of A. oryzae (rice koji), which is widely used as a starter culture for Japanese traditional fermented foods, and was largely responsible for the glycine and D-alanine aminopeptidase activity detected at a pH range of 6 to 9.

Feasibility study of entrance and exit dose measurements at the contra lateral breast with alanine/electron spin resonance dosimetry in volumetric modulated radiotherapy of breast cancer

NASA Astrophysics Data System (ADS)

Wagner, Daniela M.; Hüttenrauch, Petra; Anton, Mathias; von Voigts-Rhetz, Philip; Zink, Klemens; Wolff, Hendrik A.

2017-07-01

The Physikalisch-Technische Bundesanstalt has established a secondary standard measurement system for the dose to water, D W, based on alanine/ESR (Anton et al 2013 Phys. Med. Biol. 58 3259-82). The aim of this study was to test the established measurement system for the out-of-field measurements of inpatients with breast cancer. A set of five alanine pellets were affixed to the skin of each patient at the contra lateral breast beginning at the sternum and extending over the mammilla to the distal surface. During 28 fractions with 2.2 Gy per fraction, the accumulated dose was measured in four patients. A cone beam computer tomography (CBCT) scan was generated for setup purposes before every treatment. The reference CT dataset was registered rigidly and deformably to the CBCT dataset for 28 fractions. To take the actual alanine pellet position into account, the dose distribution was calculated for every fraction using the Acuros XB algorithm. The results of the ESR measurements were compared to the calculated doses. The maximum dose measured at the sternum was 19.9 Gy  ±  0.4 Gy, decreasing to 6.8 Gy  ±  0.2 Gy at the mammilla and 4.5 Gy  ±  0.1 Gy at the distal surface of the contra lateral breast. The absolute differences between the calculated and measured doses ranged from  -1.9 Gy to 0.9 Gy. No systematic error could be seen. It was possible to achieve a combined standard uncertainty of 1.63% for D W  =  5 Gy for the measured dose. The alanine/ESR method is feasible for in vivo measurements.

Solvent effect on post-irradiation grafting of styrene onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) films

NASA Astrophysics Data System (ADS)

Napoleão Geraldes, Adriana; Augusto Zen, Heloísa; Ribeiro, Geise; Fernandes Parra, Duclerc; Benévolo Lugão, Ademar

2013-03-01

Radiation-induced grafting of styrene onto ETFE films in different solvent was investigated after simultaneous irradiation (in post-irradiation condition) using a 60Co source. Grafting of styrene followed by sulfonation onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) are currently studied for synthesis of ion exchange membranes. The ETFE films were immersed in styrene/toluene, styrene/methanol and styrene/isopropyl alcohol and irradiated at 20 and 100 kGy doses at room temperature. The post-irradiation time was established at 14 day and the grafting degree was evaluated. The grafted films were sulfonated using chlorosulfonic acid and 1,2-dichloroethane 20:80 (v/v) at room temperature for 5 h. The degree of grafting (DOG) was determined gravimetrically and physical or chemical changes were evaluated by differential scanning calorimeter analysis (DSC), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The ion exchange capacity (IEC) values showed the best performance of sulfonation for ETFE membranes grafted in toluene solvent. Surface images of the grafted films by SEM technique have presented a strong effect of the solvents on the films morphology.

Alanine scanning of the rabies virus glycoprotein antigenic site III using recombinant rabies virus: implication for post-exposure treatment.

PubMed

Papaneri, Amy B; Wirblich, Christoph; Marissen, Wilfred E; Schnell, Matthias J

2013-12-02

The safety and availability of the human polyclonal sera that is currently utilized for post-exposure treatment (PET) of rabies virus (RABV) infection remain a concern. Recombinant monoclonal antibodies have been postulated as suitable alternatives by WHO. To this extent, CL184, the RABV human antibody combination comprising monoclonal antibodies (mAbs) CR57 and CR4098, has been developed and has delivered promising clinical data to support its use for RABV PET. For this fully human IgG1 cocktail, mAbs CR57 and CR4098 are produced in the PER.C6 human cell line and combined in equal amounts in the final product. During preclinical evaluation, CR57 was shown to bind to antigenic site I whereas CR4098 neutralization was influenced by a mutation of position 336 (N336) located within antigenic site III. Here, alanine scanning was used to analyze the influence of mutations within the potential binding site for CR4098, antigenic site III, in order to evaluate the possibility of mutated rabies viruses escaping neutralization. For this approach, twenty flanking amino acids (10 upstream and 10 downstream) of the RABV glycoprotein (G) asparagine (N336) were exchanged to alanine (or serine, if already alanine) by site-directed mutagenesis. Analysis of G expression revealed four of the twenty mutant Gs to be non-functional, as shown by their lack of cell surface expression, which is a requirement for the production of infectious RABV. Therefore, these mutants were excluded from further study. The remaining sixteen mutants were introduced in an infectious clone of RABV, and recombinant RABVs (rRABVs) were recovered and utilized for in vitro neutralization assays. All of the viruses were effectively neutralized by CR4098 as well as by CR57, indicating that single amino acid exchanges in this region does not affect the broad neutralizing capability of the CL184 mAb combination. Copyright © 2013 Elsevier Ltd. All rights reserved.

EPR parameters of L-α-alanine radicals in aqueous solution: a first-principles study

NASA Astrophysics Data System (ADS)

Janbazi, Mehdi; T. Azar, Yavar; Ziaie, Farhood

2018-07-01

EPR (electron paramagnetic resonance) response for a wide range of possible alanine radicals has been analysed employing quantum chemical methods. The strong correlation between geometry and EPR parameter structure of these radicals has been shown in this research work. Significant solvent effect on EPR parameters has been shown employing both explicit and implicit solvent models. In a relatively good agreement with the experiment, stable conformation of these radicals in acidic and basic conditions was determined, and a new conformation was suggested based on possible proton transfer in the intermediate pH range. The employed methodology along with experimental results may be used for the characterisation of different radiation-induced amino acid radicals.

Glycine and alanine synthesis from formaldehyde and hydroxylamine in the field of ultrasound waves.

PubMed

Sokolskaya, A

1976-08-01

High intensity ultrasound waves coupled with other form of energy obviously were initiators of pre-biochemical reactions; these reactions occurred in the water masses of the primordial Earth. Essential biological substances like formaldehyde, ammonia, hydrocyanic acid, and amino acids compounds similar to carbohydrates by their properties were synthesized in the field of ultrasound waves in model experiments. The main partners of these reactions are water and gases of reductional atomosphere: hydrogen, carbon monoxide, methane, nitrogen and argon. Formation of amino acids takes place in aqueous solutions of formaldehyde and hydroxylamine. The sonication yielded alanine and glycine, 2.0 X 10(-7) and 1.8 X 10(-7) molecules per 100 eV respectively.

Synthesis of Cis, syndiotactic A -alt-B Copolymers from Two Enantiomerically Pure Trans -2,3-Disubstituted-5,6-Norbornenes

DOE PAGES

Jang, Eun Sil; John, Jeremy M.; Schrock, Richard R.

2016-09-06

Cis,syndiotactic A-alt-B copolymers, where A and B are two enantiomerically pure trans-2,3-disubstituted-5,6-norbornenes with “opposite” chiralities, can be prepared with stereogenic-at-metal initiators of the type M(NR)(CHR')(OR”)(pyrrolide). Formation of a high percentage of alternating AB copolymer linkages relies on an inversion of chirality at the metal with each propagating step and a relatively fast formation of an AB sequence as a consequence of a preferred diastereomeric relationship between the chirality at the metal and the chirality of the monomer. Finally, this approach to formation of an alternating AB copolymer contrasts dramatically with the principle of forming AB copolymers from achiral monomers andmore » catalysts.« less