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Sample records for cyp450 enzyme induction

  1. [Interaction between CYP450 enzymes and metabolism of traditional Chinese medicine as well as enzyme activity assay].

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    Lu, Tu-lin; Su, Lian-lin; Ji, De; Gu, Wei; Mao, Chun-qin

    2015-09-01

    Drugs are exogenous compounds for human bodies, and will be metabolized by many enzymes after administration. CYP450 enzyme, as a major metabolic enzyme, is an important phase I drug metabolizing enzyme. In human bodies, about 75% of drug metabolism is conducted by CYP450 enzymes, and CYP450 enzymes is the key factor for drug interactions between traditional Chinese medicine( TCM) -TCM, TCM-medicine and other drug combination. In order to make clear the interaction between metabolic enzymes and TCM metabolism, we generally chose the enzymatic activity as an evaluation index. That is to say, the enhancement or reduction of CYP450 enzyme activity was used to infer the inducing or inhibitory effect of active ingredients and extracts of traditional Chinese medicine on enzymes. At present, the common method for measuring metabolic enzyme activity is Cocktail probe drugs, and it is the key to select the suitable probe substrates. This is of great significance for study drug's absorption, distribution, metabolism and excretion (ADME) process in organisms. The study focuses on the interaction between TCMs, active ingredients, herbal extracts, cocktail probe substrates as well as CYP450 enzymes, in order to guide future studies.

  2. [Progress on studies of impact on CYP450 enzymes activity of traditional Chinese medicine by Cocktail probe substrates approach].

    Science.gov (United States)

    Du, Xi; He, Xin; Huang, Yu-Hong; Li, Zi-Qiang

    2016-12-01

    Cocktail probe substrates approach is a fast, sensitive and high through put method to determine cytochrome P450 enzymes activity. It has been widely used to screen early drug development, analyze drug metabolism types and confirm the metabolism pathways, study drug-drug interactions, optimize clinical regimen, evaluate post marketing drugs and help liver/kidney pathological studies. This article reviewed characteristics of Cocktail probe substrates, focused on the application to traditional Chinese medicine to CYP450 system as follows: the metabolic pathway research of Chinese herb active ingredients; processing way and compatibility of medical herbs affect CYP450; find out the metabolic characteristic of Chinese patent medicine, study in pharmacy of national minority; do research in liver protective effect of traditional Chinese medicine and evaluate traditional Chinese medicine syndromes in animal models. This article make a summary of existing research results and also make a comparison of cocktail probe substrates approach application to western medicine and Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

  3. The coordinated role of CYP450 enzymes and P-gp in determining cancer resistance to chemotherapy.

    Science.gov (United States)

    Azzariti, Amalia; Porcelli, Letizia; Quatrale, Anna Elisa; Silvestris, Nicola; Paradiso, Angelo

    2011-10-01

    The relationship between CYP450 and P-gp occurs at different levels. It is known that certain substrates of P-gp undergo metabolic transformations by various CYP450 isoforms; in addition some of them demonstrated to be activators of both P-gp and CYP450. The majority of such compounds are well-known chemotherapeutics, therefore the purpose of this review is to clarify whether there is a relationship between the simultaneous modulation of CYP450 and P-gp and the onset of drug resistance in tumors treatment. Here, we discuss the biological aspects of the topic in relation to the various tissues distribution of CYP450 and P-gp, the recent findings regarding the ability of some chemotherapeutics in modulating both P-gp and CYP450, whether this modulation is ultimately responsible for the onset of drug resistance in cancer treatment and the promising role of gene polymorphisms in determining the interindividual variability in drug responses in clinical practice.

  4. [Effect of processed Polygonum multiflorum on mRNA expression level of five subtypes of CYP450 enzymes in rat liver].

    Science.gov (United States)

    Huang, Chun-Lian; Fan, Xue-Mei; Li, Qian; Wang, Yi-Ming; Wang, Shu-Mei; Gong, Meng-Juan; Luo, Guo-An

    2017-01-01

    To observe the effect of processed Polygonum multiflorum on mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. SD rats were randomly divided into the normal control group, processed P. multiflorum high dose and low dose groups (5.40 g•kg⁻¹ and 1.08 g•kg⁻¹). The rats in administration groups were continuously given with processed P. mutiflorum for 7 days by ig administration, and the rats in normal control group were given with the same volume of distilled water. After successive administration of 7 days, the serum biochemical indications were detected, and Real-time quantitative PCR technology was used to detect the mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. Experimental results showed that AST was decreased significantly in both low and high dose groups. ALT was significantly decreased in low dose group and significantly increased in high dose group. The mRNA expression levels of five subtypes of CYP450 enzymes in rat liver were decreased in high dose and low dose groups in a dose-dependent manner. Especially the high dose processed P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in rats. The study showed that high dose P. multiflorum water extract had hepatotoxicity, and the degree of liver damage was increased with the increase of dose. It shall be noted that 5.40 g•kg⁻¹ water extract of P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in the liver of rats. Copyright© by the Chinese Pharmaceutical Association.

  5. Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin

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    Chia-Hao Chen

    2012-01-01

    Full Text Available Red yeast rice (RYR can reduce cholesterol through its active component, lovastatin. This study was to investigate the pharmacokinetic properties of lovastatin in RYR products and potential RYR-drug interactions. Extracts of three registered RYR products (LipoCol Forte, Cholestin, and Xuezhikang were more effective than pure lovastatin in inhibiting the activities of cytochrome P450 enzymes and P-glycoprotein. Among CYP450 enzymes, RYR showed the highest inhibition on CYP1A2 and CYP2C19, with comparable inhibitory potencies to the corresponding typical inhibitors. In healthy volunteers taking the RYR product LipoCol Forte, the pharmacokinetic properties of lovastatin and lovastatin acid were linear in the dose range of 1 to 4 capsules taken as a single dose and no significant accumulation was observed after multiple dosing. Concomitant use of one LipoCol Forte capsule with nifedipine did not change the pharmacokinetics of nifedipine. Yet, concomitant use of gemfibrozil with LipoCol Forte resulted in a significant increase in the plasma concentration of lovastatin acid. These findings suggest that the use of RYR products may not have effects on the pharmacokinetics of concomitant comedications despite their effects to inhibit the activities of CYP450 enzymes and P-gp, whereas gemfibrozil affects the pharmacokinetics of lovastatin acid when used concomitantly with RYR products.

  6. Targeting CYP450 modulation to decrease the risk of induced cataract in the experimental model

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    Patel D

    2010-01-01

    Full Text Available Background: Diabetes is one of the major causes of cataract. Some drugs prescribed for the treatment of diabetes are the modulators of CYP450, which may alter the risk of cataract. Objective: To study the effect of CYP450 modulation in galactosemic cataract. Materials and Methods: Male Sprague-Dawley suckling rats were allotted to four groups (n = 6, as follows: Group 1: Normal control, Group 2: Galactose control, Group 3: CYP450 inhibitor pretreated and Group 4: CYP450 inducer pretreated. Cataract was induced in animals of all groups except group 1 by feeding them galactose (50%, 21 days after parturition. From the eighteenth day of life, CYP450 inhibitor (nifedipine; 8.1 mg/kg and CYP450 inducer (pioglitazone; 3.8 mg/kg were given orally to groups 3 and 4, respectively. The maturation pattern of the cataract was observed by an operating microscope, every third day. Biochemical changes in the lenses of all groups, for example, CYP450 activity expressed as ΅M NADPH oxidized / unit time, alterations in the levels of total proteins, soluble proteins, and reduced glutathione (GSH following the induction of cataract, were estimated. Results: The microscopic examination of the lenses indicated that CYP450 inhibitor pre-treatment delayed (fourteenth day the occurrence of cataract, while CYP450 inducer pretreatment demonstrated an early (ninth day cataract as compared to galactose control rats (twelfth day. A significant decrease and increase in CYP450 activity was observed with the CYP450 inhibitor and inducer pre-treatment, respectively. There was no alteration in the GSH level, but a significant increase in total and soluble protein was found in groups 3 and 4 as compared to group 2. Conclusion: CYP450 may have a role in the initiation of cataract without any effect on the maturation pattern, as revealed by the delayed occurrence of cataract with the CYP450 inhibitor and an early onset of cataract with the CYP450 inducer.

  7. Cytochrome P450 (CYP450) Tests

    Science.gov (United States)

    ... EGAPP/recommend/CYP450.htm. Accessed July 13, 2015. Genetic testing — General public: CYP450 genotyping and use of SSRI drugs for depression in adults. Centers for Disease Control and Prevention. ...

  8. Cytochrome P450 (CYP450) Tests

    Science.gov (United States)

    ... RH. Pharmacogenomic testing and personalized treatment of depression. Clinical Chemistry. 2014;60:53. AskMayoExpert. Antidepressant medications and pharmacogenomics. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2015. Samer CF, et al. Applications of CYP450 ...

  9. Verapamil does not modify catalytic activity of CYP450 in rainbow trout after long-term exposure.

    Science.gov (United States)

    Burkina, V; Zamaratskaia, G; Randak, T; Li, Z H; Fedorova, G; Pickova, J; Zlabek, V

    2012-05-01

    Little is known about the effects of the cardiovascular drug verapamil (VRP) on metabolic processes in fish. Most calcium channel blockers including VRP are metabolized by cytochrome P450 (CYP450) enzymes. In this study we investigated the in vivo effect of VRP on some CYP450-mediated reactions in juvenile rainbow trout (Oncorhynchus mykiss). Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg l(-1)) for 0, 21, and 42 day. The following CYP450-mediated reactions were studied in hepatic microsomes: O-dealkylation of ethoxyresorufin, methoxyresorufin, and pentoxyresorufin, hydroxylation of coumarin, tolbutamide, and p-nitrophenol, and O-debenzylation of 7-benzyloxy-4-trifluoromethylcoumarin. The amounts of products of these reactions did not differ among fish exposed to different levels of VRP and control fish. This suggests that the levels of VPR used did not alter catalytic activity of the selected CYP450 enzymes. In conclusion, none of the investigated CYP450-mediated reactions has potential as a biomarker to monitor VRP contamination of the aquatic environment. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Docking studies of piperine - iron conjugate with human CYP450 3A4

    OpenAIRE

    Alugolu, Veerabrahmam; Rentala, Satyanarayana; Komarraju, Aruna Lakshmi; Parimi, Uma Devi

    2013-01-01

    Piperine, a major constituent of Piper nigrum (Black pepper), is one of the well known components in many Ayurvedic formulations. Piperine is most studied bioenhancer because it inhibits drug metabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates. However, there areno evidences on piperine-iron conjugate to inhibit human CYP450 3A4. We therefore investigated the influence of piperine-Fe conjugate to study the metabolism of iro...

  11. Intimal smooth muscle cells are a source but not a sensor of anti-inflammatory CYP450 derived oxylipins

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, Scott [Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU (United Kingdom); Edin, Matthew L.; Lih, Fred B. [Division of Intramural Research, NIEHS/NIH, Research Triangle Park, NC 27709 (United States); Davies, Michael [Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU (United Kingdom); Yaqoob, Muhammad M. [Barts and the London, Queen Mary University, Charterhouse Square, London EC1M 6BQ (United Kingdom); Hammock, Bruce D. [Department of Entomology and Comprehensive Cancer Center, University of California, Davies, CA 95616-8584 (United States); Gilroy, Derek [University College London, University Street, London (United Kingdom); Zeldin, Darryl C. [Division of Intramural Research, NIEHS/NIH, Research Triangle Park, NC 27709 (United States); Bishop-Bailey, David, E-mail: dbishopbailey@rvc.ac.uk [Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU (United Kingdom)

    2015-08-07

    Vascular pathologies are associated with changes in the presence and expression of morphologically distinct vascular smooth muscle cells. In particular, in complex human vascular lesions and models of disease in pigs and rodents, an intimal smooth muscle cell (iSMC) which exhibits a stable epithelioid or rhomboid phenotype in culture is often found to be present in high numbers, and may represent the reemergence of a distinct developmental vascular smooth muscle cell phenotype. The CYP450-oxylipin - soluble epoxide hydrolase (sEH) pathway is currently of great interest in targeting for cardiovascular disease. sEH inhibitors limit the development of hypertension, diabetes, atherosclerosis and aneurysm formation in animal models. We have investigated the expression of CYP450-oxylipin-sEH pathway enzymes and their metabolites in paired intimal (iSMC) and medial (mSMC) cells isolated from rat aorta. iSMC basally released significantly larger amounts of epoxy-oxylipin CYP450 products from eicosapentaenoic acid > docosahexaenoic acid > arachidonic acid > linoleic acid, and expressed higher levels of CYP2C12, CYP2B1, but not CYP2J mRNA compared to mSMC. When stimulated with the pro-inflammatory TLR4 ligand LPS, epoxy-oxylipin production did not change greatly in iSMC. In contrast, LPS induced epoxy-oxylipin products in mSMC and induced CYP2J4. iSMC and mSMC express sEH which metabolizes primary epoxy-oxylipins to their dihydroxy-counterparts. The sEH inhibitors TPPU or AUDA inhibited LPS-induced NFκB activation and iNOS induction in mSMC, but had no effect on NFκB nuclear localization or inducible nitric oxide synthase in iSMC; effects which were recapitulated in part by addition of authentic epoxy-oxylipins. iSMCs are a rich source but not a sensor of anti-inflammatory epoxy-oxylipins. Complex lesions that contain high levels of iSMCs may be more resistant to the protective effects of sEH inhibitors. - Highlights: • We examined oxylipin production in different

  12. NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic β-cells.

    Science.gov (United States)

    Gray, Joshua P; Karandrea, Shpetim; Burgos, Delaine Zayasbazan; Jaiswal, Anil A; Heart, Emma A

    2016-11-16

    NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic β-cell metabolism under basal conditions and oxidant challenge have not been characterized. Using NQO1 inhibition, over-expression and knock out, we have demonstrated that, in addition to protection of β-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides, suggesting other role(s) beside that of an antioxidant enzyme. In contrast, over-expression of NADPH cytochrome P450 oxidoreductase (CYP450OR) resulted in enhanced redox cycling activity and decreased cellular viability, consistent with the enhanced generation of superoxide and H2O2. Basal expression of NQO1 and CYP450OR was comparable in isolated islets and liver. However, NQO1, but not CYP450OR, was strongly induced in β-cells exposed to menadione. NQO1 and CYP450OR exhibited a reciprocal preference for reducing equivalents in β-cells: while CYP450OR preferentially utilized NADPH, NQO1 primarily utilized NADH. Together, these results demonstrate that NQO1 and CYP450OR reciprocally regulate oxidant metabolism in pancreatic β-cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC# 101).

    Science.gov (United States)

    McGraw, Joseph E; Waller, Donald P

    2006-05-26

    Polychlorinated biphenyl IUPAC# 101-PCB 101 (chlorination pattern-2,2',4',5,5') is a common, persistent non-coplanar PCB congener found in the ambient environment but information related to its metabolism in humans is lacking. Previous studies indicate PCB 101 is rapidly metabolized in mammals through CYP 2B and 3A family enzymes. Recently, PCB metabolism through a 2A family isoform in hamsters was also reported. To specifically identify the human CYP 450 isoforms responsible for PCB 101 metabolism, we compared human microsome metabolism to metabolism using several specific recombinant human CYP isoforms. These data characterized selective and extensive metabolism by human CYP 2A6. The product formed was the 4-hydroxy-PCB 101 metabolite (4-hydroxy-2,2',4',5,5') and was the only major metabolite observed in the recombinant and human microsome investigation. This is important information for predicting human specific toxicokinetics of PCBs.

  14. Cloning and expression of SgCYP450-4 from Siraitia grosvenorii

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    Dongping Tu

    2016-10-01

    Full Text Available CYP450 plays an essential role in the development and growth of the fruits of Siraitia grosvenorii. However, little is known about the SgCYP450-4 gene in S. grosvenorii. Here, based on transcriptome data, a full-length cDNA sequence of SgCYP450-4 was cloned by reverse transcriptase-polymerase chain reaction (RT-PCR and rapid-amplification of cDNA ends (RACE strategies. SgCYP450-4 is 1677 bp in length (GenBank accession No. AEM42985.1 and contains a complete open reading frame (ORF of 1422 bp. The deduced protein was composed of 473 amino acids, the molecular weight is 54.01 kDa, the theoretical isoelectric point (PI is 8.8, and the protein was predicted to possess cytochrome P450 domains. SgCYP450-4 gene was highly expressed in root, diploid fruit and fruit treated with hormone and pollination. At 10 days after treatment with pollination and hormones, the expression of SgCYP450-4 had the highest level and then decreased over time, which was consistent with the development of fruits of S. Grosvenorii. Hormonal treatment could significantly induce the expression of SgCYP450-4. These results provide a reference for regulation of fruit development and the use of parthenocarpy to generate seedless fruit, and provide a scientific basis for the production of growth regulator application agents.

  15. Exposure to potential CYP450 pharmacokinetic drug-drug interactions among osteoarthritis patients: incremental risk of multiple prescriptions.

    Science.gov (United States)

    Pergolizzi, Joseph V; Labhsetwar, Sumedha A; Puenpatom, R Amy; Joo, Seongjung; Ben-Joseph, Rami; Summers, Kent H

    2011-01-01

    Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system experience a drug-drug exposure (DDE), which puts them at risk for a potential pharmacokinetic drug-drug interaction (DDI), defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Any patient subjected to a DDE is at risk for a potentially serious DDI, the epidemiology of which has not been thoroughly studied. Many drugs are metabolized primarily via the CYP450 enzyme system, including certain opioids used to manage moderate to severe chronic pain. We conducted a retrospective analysis of a large commercial claims database and a Medicare database to assess the prevalence of DDEs among patients with osteoarthritis taking CYP450-metabolized opioids. The overall prevalence of DDEs in this population was 26%, with females more likely to experience DDEs than males (28.4% vs. 21.0%, respectively). The number of unique concurrent prescriptions at baseline, gender, age, and Charlson Comorbidity Index were statistically significant predictors of DDEs (P risk of DDE. However, the number of prescriptions the patient received in the 90-day window prior to the index date was a risk factor. For patients taking at least two medications in the 90-day period prior to the index date, every additional prescription taken increased their risk for a DDE during the observation period by 138% (on average). The risk of DDE during the study period was threefold greater for patients with one medication in the 90-day period before index date compared with similar patients with no prescriptions in that same period before the index date. DDEs are more common than may be generally believed in patients with osteoarthritis, regardless of age, and can occur even in patients taking few medications. When selecting an opioid analgesic to treat osteoarthritis, physicians should consider the potential for exposure of these patients to

  16. [Effect of clinical doses of Realgar-Indigo Naturalis formula and large-dose of realgar on CYP450s of rat liver].

    Science.gov (United States)

    Xu, Huan-Hua; Wang, Mei-Xi; Tan, Hong-Ling; Wang, Yu-Guang; Tang, Xiang-Lin; Xiao, Cheng-Rong; Li, Hua; Gao, Yue; Ma, Zeng-Chun

    2017-02-01

    To investigate the effect of clinical dose of Realgar-Indigo Naturais formula (RIF) and large-dose of Realgar on main drug-metabolizing enzymes CYP450s of rat liver, as well as its regulatory effect on mRNA expression. Wistar rats were administrated orally with tested drugs for 14 days. A Cocktail method combined with HPLC-MS/MS was used in the determination of 4 cytochrome P450 isozymes (CYP1A2, CYP2B, CYP3A and CYP2C) in liver of the rats, and the mRNA expression levels of the above subtypes were detected by real-time fluorescent quantitative PCR. The results showed that RIF can significantly induce CYP1A2 and CYP2B enzyme activity, and inhibit CYP3A enzyme activity. This result was consistent with the mRNA expression. However, its single compound showed weaker or even contrary phenomenon. Different doses of Realgar also showed significant inconsistencies on CYP450 enzymes activity and mRNA expression. These phenomena may be relevant with RIF compatibility synergies or toxicity reduction. The results can also prompt drug interactions when RIF is combined with other medicines in application. Copyright© by the Chinese Pharmaceutical Association.

  17. Effect of codeine on CYP450 isoform activity of rats.

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    Wang, Shuanghu; Dong, Yanwen; Su, Ke; Zhang, Jing; Wang, Linyi; Han, Anyue; Wen, Congcong; Wang, Xianqin; He, Yan

    2017-12-01

    Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. Sprague-Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC(0-t), Cmax increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.

  18. [Transfection of eucaryotic cells using cytochrome CYP450 2B6 gene: sensitivity to cyclophosphamide].

    Science.gov (United States)

    Kolomeĭchuk, S N; Abakumova, O Iu; Maslov, M A; Kalashnikova, E A; Morozova, N G; Serebrennikova, G A; Shvets, V I; Sokolov, N N

    2002-01-01

    Sensitivity of 293 human epithelial kidney cells transfected by human cytochrome CYP450 gene to cyclophosphamide was investigated. Transfection was carried out by plasmid DNA containing CYP2B6 gene complexed with cationic liposomes. Liposomes were prepared from mixture of cationic lipids and cholesterol at different molar ratios. Experimental protocol included the following steps: transfection of epithelial kidney cells by complexes of plasmid DNA-cationic liposomes, clone selection in the medium with antibiotic Geneticin G418, selected clone harvesting and their treatment by cyclophosphamide as following cytotoxicity evaluation. It was shown that addition of 0.25 mM of cyclophosphamide resulted in death of 40-45% transfected cell population.

  19. The influence of combination use of CYP450 inducers on the pharmacokinetics of voriconazole: a systematic review.

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    Li, T-Y; Liu, W; Chen, K; Liang, S-Y; Liu, F

    2017-04-01

    Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when co-administered with a known CYP450 inducer, which may lead to treatment failure. The influence of some CYP450 inducers on the pharmacokinetics of voriconazole has been described in previous studies, but a systematic review was lacking. In this study, we carried out a systematic review to assess the influence of CYP450 inducers on the pharmacokinetic (PK) parameters of voriconazole. Pubmed, Embase, Cochrane Library, Clinicaltrials.gov and three Chinese databases (CNKI, CBM and WanFang) were searched through January 2016. Interventional and observational studies comparing the PK parameters of voriconazole used alone or with CYP450 inducers in healthy volunteers and patients were included. The outcomes included were the area under the plasma concentration-time curve (AUC), peak plasma concentrations (C max ) and trough plasma concentrations (C min ). The quality of the included studies was assessed using Cochrane's risk of bias tool, Newcastle-Ottawa Scale (NOS) and a modified risk of bias tool for pharmacokinetic before-and-after studies. Sixteen studies were included in this review: three randomized controlled trials (RCTs), five single-arm before-after studies (SBAs), six cohort studies and two case reports. All studies except case reports had moderate to high quality. Of the 11 inducers reviewed, efavirenz, ritonavir (chronic use), phenytoin, rifampin and rifabutin significantly decreased mean AUC and C max of voriconazole; St John's wort significantly decreased only mean AUC; rifampin, rifabutin, phenobarbital and carbamazepine significantly decreased mean C min . Etravirine and Ginkgo biloba did not reveal any such influence. The influence of glucocorticoids may depend on its type and dose. To conclude, the combination use of high-dose efavirenz, high-dose ritonavir, St John's wort, rifampin, phenobarbital

  20. Comparison of cytochrome P450 inhibition assays for drug discovery using human liver microsomes with LC-MS, rhCYP450 isozymes with fluorescence, and double cocktail with LC-MS.

    Science.gov (United States)

    Di, Li; Kerns, Edward H; Li, Susan Q; Carter, Guy T

    2007-04-20

    The disparity of IC(50)s from CYP450 inhibition assays used to assess drug-drug interaction potential was investigated, in order to have evidence for selecting a reliable in vitro CYP450 inhibition assay to support drug discovery. Three assays were studied: individual rhCYP isozymes and corresponding coumarin derivative-probe substrates with fluorescent detection, human liver microsomes (HLM) and cocktail drug-probe substrates with LC-MS detection, and double cocktail rhCYP isozymes mix and drug-probe mix with LC-MS detection. Data comparisons showed that the rhCYP-fluorescent assay and the cocktail assay with HLM-LC-MS had weak correlation. Detection method and probe substrates were shown to not be the major cause of the disparity in IC(50)s. However, the enzyme source and composition (HLM versus, rhCYP) caused disparity in IC(50)s. Specifically, the high concentrations of CYP isozymes often used with HLM-based assays produced high probe substrate conversion and test compound metabolism, which should both contribute to artificially higher IC(50)s. Non-specific binding of substrate to higher concentration proteins and lipids in the HLM-based assays should also contribute to higher IC(50)s. The modified double cocktail assay was found to overcome limitations of the other two assays. It uses an rhCYP isozymes mix, drug-probe substrate mix, low protein concentration, and LC-MS detection. The double cocktail assay is sensitive, selective, and high throughout for use in drug discovery to provide an early alert to potential toxicity with regard to drug-drug interaction, prioritize chemical series, and guide structural modification to circumvent CYP450 inhibition.

  1. Highly sensitive LC-MS/MS methods for the determination of seven human CYP450 activities using small oral doses of probe-drugs in human.

    Science.gov (United States)

    Grangeon, Alexia; Gravel, Sophie; Gaudette, Fleur; Turgeon, Jacques; Michaud, Veronique

    2017-01-01

    Cocktails composed of several Cytochrome P450 (CYP450)-selective probe drugs have been shown of value to characterize in vivo drug-metabolism activities. Our objective was to develop and validate highly sensitive and selective LC-MS/MS assays allowing the determination of seven major human CYP450 isoenzyme activities following administration of low oral doses of a modified CYP450 probe-drug cocktail in patients. The seven-drug cocktail was composed of caffeine, bupropion, tolbutamide, omeprazole, dextromethorphan, midazolam (all administered concomitantly) and chlorzoxazone (administered separately) to phenotype for CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5 and 2E1, respectively. Serial plasma and urine samples were collected over an 8h period. The probe-drugs and their respective metabolites were measured in both human plasma and urine, except for omeprazole (plasma only) and chlorzoxazone (urine only). Samples were analyzed by high performance liquid chromatography with heated electrospray ionization tandem mass spectrometry (HPLC-HESI-MS/MS) using a Phenomenex Luna PFP (2) analytical column (3μm PFP(2) 150×3mm) for chromatographic separation. Optimal detection was achieved based on 3 different analytical methods; (1) isocratic elution with a mobile phase consisting of acetonitrile and water both fortified with 0.01% formic acid for the analysis of bupropion, tolbutamide, chlorzoxazone and their respective metabolites; (2) isocratic elution with a mobile phase composed of acetonitrile and ammonium formate (pH 3; 10mM) for omeprazole, dextromethorphan, midazolam and their metabolites; (3) for caffeine and paraxanthine, gradient elution using acetonitrile and 0.01% formic acid in water was used. All calibration functions were linear for all probe drugs and metabolites in both matrices over wide analytical ranges. The main advantages of our methods are the use of specific probe drugs available in most countries, the administration of small doses of probe drugs, small

  2. Early bichemical markers of effects: Enzyme induction, oncogene activation and markers of oxidative damage

    DEFF Research Database (Denmark)

    Poulsen, Henrik E.; Loft, Steffen

    1995-01-01

    Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein......Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein...

  3. The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method.

    Science.gov (United States)

    Cai, Jinzhang; Zhang, Qingwei; Lin, Kezhi; Hu, Lufeng; Zheng, Yuancai

    2015-01-01

    MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi), has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In order to investigate the effects of MGCD0103 on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of human CYP2B1, CYP1A2, CYP2C11, CYP2D6, CYP3A4, and CYP2C9. The rats were randomly divided into MGCD0103 group (Low, Medium, and High) and control group. The MGCD0103 group rats were given 20, 40, and 80 mg/kg (Low, Medium, and High) MGCD0103 by continuous intragastric administration for 7 days. Six probe drugs, bupropion, phenacetin, tolbutamide, metoprolol, testosterone, and omeprazole, were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for tolbutamide in rats were observed by comparing MGCD0103 group with control group. Continuous 7-day intragastric administration of MGCD0103 slightly induces the activities of CYP2C11 of rats.

  4. The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method

    Directory of Open Access Journals (Sweden)

    Jinzhang Cai

    2015-01-01

    Full Text Available MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi, has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In order to investigate the effects of MGCD0103 on the metabolic capacity of cytochrome P450 (CYP enzymes, a cocktail method was employed to evaluate the activities of human CYP2B1, CYP1A2, CYP2C11, CYP2D6, CYP3A4, and CYP2C9. The rats were randomly divided into MGCD0103 group (Low, Medium, and High and control group. The MGCD0103 group rats were given 20, 40, and 80 mg/kg (Low, Medium, and High MGCD0103 by continuous intragastric administration for 7 days. Six probe drugs, bupropion, phenacetin, tolbutamide, metoprolol, testosterone, and omeprazole, were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for tolbutamide in rats were observed by comparing MGCD0103 group with control group. Continuous 7-day intragastric administration of MGCD0103 slightly induces the activities of CYP2C11 of rats.

  5. Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone.

    Science.gov (United States)

    Prill, Sebastian; Bavli, Danny; Levy, Gahl; Ezra, Elishai; Schmälzlin, Elmar; Jaeger, Magnus S; Schwarz, Michael; Duschl, Claus; Cohen, Merav; Nahmias, Yaakov

    2016-05-01

    Prediction of drug-induced toxicity is complicated by the failure of animal models to extrapolate human response, especially during assessment of repeated dose toxicity for cosmetic or chronic drug treatments. In this work, we present a 3D microreactor capable of maintaining metabolically active HepG2/C3A spheroids for over 28 days in vitro under stable oxygen gradients mimicking the in vivo microenvironment. Mitochondrial respiration was monitored using two-frequency phase modulation of phosphorescent microprobes embedded in the tissue. Phase modulation is focus independent and unaffected by cell death or migration. This sensitive measurement of oxygen dynamics revealed important information on the drug mechanism of action and transient subthreshold effects. Specifically, exposure to antiarrhythmic agent, amiodarone, showed that both respiration and the time to onset of mitochondrial damage were dose dependent showing a TC50 of 425 μm. Analysis showed significant induction of both phospholipidosis and microvesicular steatosis during long-term exposure. Importantly, exposure to widely used analgesic, acetaminophen, caused an immediate, reversible, dose-dependent loss of oxygen uptake followed by a slow, irreversible, dose-independent death, with a TC50 of 12.3 mM. Transient loss of mitochondrial respiration was also detected below the threshold of acetaminophen toxicity. The phenomenon was repeated in HeLa cells that lack CYP2E1 and 3A4, and was blocked by preincubation with ascorbate and TMPD. These results mark the importance of tracing toxicity effects over time, suggesting a NAPQI-independent targeting of mitochondrial complex III might be responsible for acetaminophen toxicity in extrahepatic tissues.

  6. Interaction of IBA and NAA with enzymes in root induction of Crocus ...

    African Journals Online (AJOL)

    Effect of auxin type on some antioxidative enzymes during in vitro root induction of saffron (Crocus sativus L.) was investigated to reveal the variation of activities and isoenzyme banding patterns during root induction of saffron (C. sativus L.). Indole-3- butyric acid (IBA) and naphtalene acetic acid (NAA) at different ...

  7. Nuclear receptor-mediated induction of drug metabolizing enzymes and transporters by anticancer drugs

    NARCIS (Netherlands)

    Harmsen, S.

    2009-01-01

    Role of nuclear receptors in adverse anticancer drug reactions? Unwanted drug-drug interactions and the development of multidrug resistance are ongoing concerns in the treatment of cancer patients. A common factor that is shared by both phenomena is enzyme induction. Especially, the induction of

  8. Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo

    DEFF Research Database (Denmark)

    Ngo, Thuc Anh; Riemann, Mads; von Holstein-Rathlou, Niels-Henrik

    2013-01-01

    ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mec......ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance...

  9. Induction of defensive enzymes (isozymes) during defense against ...

    African Journals Online (AJOL)

    ... related to mitigating pathogen-induced oxidative damage which result in the decrease of calli decay, and this implies that antioxidant defense response may be involved in the mechanisms of plant against fungal pathogen. Keywords: Pear callus, fungi infection, defense enzyme, isozyme, biochemical defense mechanism ...

  10. Temporal changes of sleep disturbances and their associations with CYP450 2B6 polymorphism and plasma drug level in HIV patients on efavirenz

    Directory of Open Access Journals (Sweden)

    K To

    2012-11-01

    Full Text Available Neurological and sleep disturbances were commonly reported among HIV patients on efavirenz (EFV, the pharmacokinetic pattern varies with different CYP450 2B6 G516T genotypes. This prospective study aims to detect temporal changes and differences in the profile of these adverse reactions and their relation to plasma EFV level and host genotypes. HIV patients of Chinese ethnicity on an EFV-containing HAART regimen were recruited from a specialist clinic. Blood for CYP2B6 G516T genotypes was taken. A questionnaire assessing adverse neurological problems and sleep disturbance was administered, alongside testing for plasma EFV levels at baseline, 4 weeks, 8 months and 1 year intervals after treatment. Analysis was performed using χ2 and t-test. A total of 64 patients (31 GG, 27 GT, 6 TT genotypes, 59 male, and 5 female, mean age of 41±9.9 were recruited. At 4 weeks after EFV, 49 (76% gave a history of any one of the neurological side effects: dizziness, headache and drunk feeling. Sleep disturbances were common: bizarre dream (45%, nightmares (35%, waking at night (73%, poor sleep quality (31%, nocturia (84% and difficulty in falling asleep (67%. The mean plasma EFV level of GG genotype was 2.8 µg/ml and 3 µg/ml, GT genotype was 3.8 µg/ml and 3.9 µg/ml, at 4 weeks and 1 year respectively. The mean plasma EFV level of TT genotype was 11.9 µg/ml and 9.7 µg/ml at 4 weeks and 1 year respectively. There was no significant variation of drug level within each genotype over time (p>0.08, while EFV level of TT was significantly higher at all time points (p<0.01. Overall, nightmares and difficulty to fall asleep were significantly related to the plasma EFV level (p=0.021 and 0.017 respectively. However, the sleep quality, nocturnal awakening, nocturia or requirement of sleeping pills was not significantly associated with EFV level (p=0.28, 0.06, 0.1 and 0.5 respectively. When the side effects were separately evaluated according to time points, they all

  11. In vitro oxidative metabolism of cajaninstilbene Acid by human liver microsomes and hepatocytes: involvement of cytochrome p450 reaction phenotyping, inhibition, and induction studies.

    Science.gov (United States)

    Hua, Xin; Peng, Xiao; Tan, Shengnan; Li, Chunying; Wang, Wei; Luo, Meng; Fu, Yujie; Zu, Yuangang; Smyth, Hugh

    2014-10-29

    Cajaninstilbene acid (CSA, 3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid), an active constituent of pigeonpea leaves, an important tropical crop, is known for its clinical effects in the treatment of diabetes, hepatitis, and measles and its potential antitumor effect. In this study, the effect of the cytochrome P450 isozymes on the activity of CSA was investigated. Two hydroxylation metabolites were identified in the study. The reaction phenotype study showed that CYP3A4, CYP2C9, and CYP1A2 were the major cytochrome P450 isozymes in the metabolism of CSA. The metabolic food-drug interaction potential was also evaluated in vitro. The effect of CSA inhibition/induction of enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro was estimated by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques. CSA showed different inhibitory effects on different isozymes. CSA reversibly inhibited CYP3A4 and CYP2C9 activities in human liver microsomes with IC50 values of 28.3 and 31.3 μM, respectively, but exhibited no inhibition activities to CYP1A2, CYP2A6, CYP2C19, CYP2D6, and CYP2E1. CSA showed a weak effect on CYP450 enzymes in a time-dependent manner. CSA did not substantially induce CYP1A2, CYP2A6, CYP2B6, CYP2E1, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at concentrations up to 30 μM in primary human hepatocytes. The results of our experiments may be helpful to predict clinically significant food-drug interactions when other drugs are administered in combination with CSA.

  12. Concept: The Use of Targeted Immunoaffinity Proteomics for Routine Assessment of In Vitro Enzyme Induction.

    Science.gov (United States)

    MacLean, Caroline; Weiß, Frederik; Poetz, Oliver; Ebner, Thomas

    2017-12-01

    In vitro investigations on enzyme induction are indispensable for assessing drug-drug interactions of drug candidates. Regulatory bodies require measurement of changes of mRNA in cultured human hepatocytes. However, such data provide only indirect assessments of effects of enzyme induction in vivo. We describe the quantification of cytochrome P450 (CYP) enzyme protein levels by liquid chromatography-mass spectrometry for the routine assessment of enzyme induction. Protein concentration of CYP1A2, 2B6, 3A4, and 2C8 were measured in human hepatocytes after incubation with prototypical enzyme inducers and drug candidate BI-X using an antibody-based capturing method. In addition, CYP mRNA levels and CYP enzyme activities were determined. Except for CYP2B6, mRNA levels consistently showed more pronounced induction effects than CYP activity or CYP protein concentration. Induction of CYP activities was better reflected on the level of CYP protein. The described method requires small sample amounts and can be integrated in routine in vitro enzyme induction studies using tissue culture in 48- and 96-well plates. Assessment of changes of enzyme protein levels adds valuable information to conventional measurements of enzyme induction and can improve the use of in vitro data for the prediction of clinical outcomes. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. In vivo induction of tyrosylprotein sulfotransferase by ethanol: role of increased enzyme synthesis.

    Science.gov (United States)

    Ramaprasad, P; Kasinathan, C

    1998-08-01

    Tyrosine sulfation is a posttranslational modification involved in the synthesis, secretion, and biological activity of proteins and peptides. Our previous studies have demonstrated that the enzyme activity was induced by ethanol. In the present work, the induction was studied in detail. Initial experiments were conducted to examine the time course of tyrosylprotein sulfotransferase (TPST) induction in rats pair-fed liquid diets containing either ethanol or carbohydrate substitute (controls). Marked elevation of TPST activity (3-fold) was measured on day 10 in the liver and gastric mucosa of ethanol-fed rats. Ethanol-mediated enhancement was also noticed by Western-blot analysis with anti-TPST antibody in both the liver and gastric mucosa on days 5 and 10. We then determined the steady-state TPST protein turnover in ethanol-fed and control animals that were given 35S-methionine after 10 days of pair-feeding with liquid diet. The rates of TPST synthesis assessed by measuring initial rates of incorporation of 35S-methionine into TPST was increased in the liver and gastric mucosa of animals fed with ethanol. Monophasic exponential decay curves showed that TPST protein half-lives for liver (control: 34 hr, ethanol: 32 hr) and gastric mucosa (control: 52 hr, ethanol: 48 hr) did not differ between control and ethanol groups. Our overall results indicate that the in vivo induction of TPST by ethanol involves increased enzyme synthesis rather than decreased enzyme degradation.

  14. Thai Fruits Exhibit Antioxidant Activity and Induction of Antioxidant Enzymes in HEK-293 Cells.

    Science.gov (United States)

    Anantachoke, Natthinee; Lomarat, Pattamapan; Praserttirachai, Wasin; Khammanit, Ruksinee; Mangmool, Supachoke

    2016-01-01

    The cellular antioxidant enzymes play the important role of protecting the cells and organisms from the oxidative damage. Natural antioxidants contained in fruits have attracted considerable interest because of their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals contained in fruits on the induction of antioxidant enzymes in the cells have not been fully defined. In this study, we showed that extracts from Antidesma ghaesembilla , Averrhoa bilimbi , Malpighia glabra , Mangifera indica, Sandoricum koetjape , Syzygium malaccense, and Ziziphus jujuba inhibited H 2 O 2 -induced intracellular reactive oxygen species production in HEK-293 cells. Additionally, these Thai fruit extracts increased the mRNA and protein expressions of antioxidant enzymes, catalase, glutathione peroxidase-1, and manganese superoxide dismutase. The consumption of Thai fruits rich in phenolic compounds may reduce the risk of oxidative stress.

  15. Thai Fruits Exhibit Antioxidant Activity and Induction of Antioxidant Enzymes in HEK-293 Cells

    Directory of Open Access Journals (Sweden)

    Natthinee Anantachoke

    2016-01-01

    Full Text Available The cellular antioxidant enzymes play the important role of protecting the cells and organisms from the oxidative damage. Natural antioxidants contained in fruits have attracted considerable interest because of their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals contained in fruits on the induction of antioxidant enzymes in the cells have not been fully defined. In this study, we showed that extracts from Antidesma ghaesembilla, Averrhoa bilimbi, Malpighia glabra, Mangifera indica, Sandoricum koetjape, Syzygium malaccense, and Ziziphus jujuba inhibited H2O2-induced intracellular reactive oxygen species production in HEK-293 cells. Additionally, these Thai fruit extracts increased the mRNA and protein expressions of antioxidant enzymes, catalase, glutathione peroxidase-1, and manganese superoxide dismutase. The consumption of Thai fruits rich in phenolic compounds may reduce the risk of oxidative stress.

  16. In vivo induction of hepatic P4502E1 by ethanol: role of increased enzyme synthesis.

    Science.gov (United States)

    Tsutsumi, M; Lasker, J M; Takahashi, T; Lieber, C S

    1993-07-01

    P4502E1 (2E1), an ethanol-inducible P450 enzyme, plays an important role in the bioactivation of certain hepatotoxins and chemical carcinogens. Different mechanisms of 2E1 induction by ethanol and other agents (e.g., acetone) have been proposed, ranging from enhanced de novo enzyme synthesis caused by an increase in 2E1 mRNA and/or the efficiency with which it is translated to decreased enzyme degradation stemming from substrate stabilization. To evaluate these mechanisms, we first examined the time course of hepatic 2E1 protein induction in rats pair-fed liquid diets containing 36% of total calories as either ethanol or dextrin-maltose (controls) for 28 days. Western blot analysis with anti-2E1 immunoglobulins revealed that 2E1 reached a new steady-state level (eightfold greater than that found with controls) after ethanol feeding for 10 days and remained elevated for the duration of treatment. Microsomal p-nitrophenol hydroxylation, a 2E1-catalyzed reaction, exhibited a similar induction time course, with the maximal increase in enzyme activity also observed on Day 10 of ethanol administration. We then determined steady-state 2E1 protein turnover in ethanol-fed and control animals that were given [35S]methionine plus[3H]aminolevulinate to radiolabel 2E1 apoprotein and the prosthetic heme group, respectively. Monophasic exponential decay curves showed that hepatic 2E1 protein and heme half-lives (27-28 h and 17 h, respectively) did not differ between the treatment groups. However, rates of 2E1 synthesis, assessed by measuring initial rates of incorporation of [35S]methionine and [3H]aminolevulinate into 2E1 apoprotein and heme, were increased in animals fed ethanol. Our results indicate that the in vivo induction of hepatic 2E1 protein by ethanol involves increased enzyme synthesis rather than decreased enzyme degradation. This enhancement of de novo 2E1 synthesis most likely entails the ethanol-mediated increase of steady-state levels of 2E1 mRNA and/or the

  17. Modest induction of phase 2 enzyme activity in the F-344 rat prostate

    Directory of Open Access Journals (Sweden)

    Brooks James D

    2006-03-01

    Full Text Available Abstract Background Prostate cancer is the most commonly diagnosed malignancy in men and is thought to arise as a result of endogenous oxidative stress in the face of compromised carcinogen defenses. We tested whether carcinogen defense (phase 2 enzymes could be induced in the prostate tissues of rats after oral feeding of candidate phase 2 enzyme inducing compounds. Methods Male F344 rats were gavage fed sulforaphane, β-naphthoflavone, curcumin, dimethyl fumarate or vehicle control over five days, and on the sixth day, prostate, liver, kidney and bladder tissues were harvested. Cytosolic enzyme activities of nicotinamide quinone oxidoreductase (NQO1, total glutathione transferase (using DCNB and mu-class glutathione transferase (using CDNB were determined in the treated and control animals and compared. Results In prostatic tissues, sulforaphane produced modest but significant increases in the enzymatic activities of NQO1, total GST and GST-mu compared to control animals. β-naphthoflavone significantly increased NQO1 and GST-mu activities and curcumin increased total GST and GST-mu enzymatic activities. Dimethyl fumarate did not significantly increase prostatic phase 2 enzyme activity. Compared to control animals, sulforaphane also significantly induced NQO1 or total GST enzyme activity in the liver, kidney and, most significantly, in the bladder tissues. All compounds were well tolerated over the course of the gavage feedings. Conclusion Orally administered compounds will induce modestly phase 2 enzyme activity in the prostate although the significance of this degree of induction is unknown. The 4 different compounds also altered phase 2 enzyme activity to different degrees in different tissue types. Orally administered sulforaphane potently induces phase 2 enzymes in bladder tissues and should be investigated as a bladder cancer preventive agent.

  18. In vivo induction of phase II detoxifying enzymes, glutathione transferase and quinone reductase by citrus triterpenoids

    Directory of Open Access Journals (Sweden)

    Ahmad Hassan

    2010-09-01

    Full Text Available Abstract Background Several cell culture and animal studies demonstrated that citrus bioactive compounds have protective effects against certain types of cancer. Among several classes of citrus bioactive compounds, limonoids were reported to prevent different types of cancer. Furthermore, the structures of citrus limonoids were reported to influence the activity of phase II detoxifying enzymes. The purpose of the study was to evaluate how variations in the structures of citrus limonoids (namely nomilin, deacetyl nomilin, and isoobacunoic acid and a mixture of limonoids would influence phase II enzyme activity in excised tissues from a mouse model. Methods In the current study, defatted sour orange seed powder was extracted with ethyl acetate and subjected to silica gel chromatography. The HPLC, NMR and mass spectra were used to elucidate the purity and structure of compounds. Female A/J mice were treated with three limonoids and a mixture in order to evaluate their effect on phase II enzymes in four different tissues. Assays for glutathione S-transferase and NAD(PH: quinone reductase (QR were used to evaluate induction of phase II enzymatic activity. Results The highest induction of GST against 1-chloro-2,4-dinitrobenzene (CDNB was observed in stomach (whole, 58% by nomilin, followed by 25% isoobacunoic acid and 19% deacetyl nomilin. Deacetyl nomilin in intestine (small as well as liver significantly reduced GST activity against CDNB. Additionally isoobacunoic acid and the limonoid mixture in liver demonstrated a significant reduction of GST activity against CDNB. Nomilin significantly induced GST activity against 4-nitroquinoline 1-oxide (4NQO, intestine (280% and stomach (75% while deacetyl nomilin showed significant induction only in intestine (73%. Induction of GST activity was also observed in intestine (93% and stomach (45% treated with the limonoid mixture. Finally, a significant induction of NAD(PH: quinone reductase (QR activity was

  19. Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula, on the Main CYP450 Activities in Rats Using a Cocktail Method

    Directory of Open Access Journals (Sweden)

    Huan-Hua Xu

    2017-01-01

    Full Text Available The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs. Realgar, a toxic traditional Chinese medicine (TCM, does have curative effect on acute promyelocytic leukemia (APL. Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

  20. Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula, on the Main CYP450 Activities in Rats Using a Cocktail Method.

    Science.gov (United States)

    Xu, Huan-Hua; Hao, Fei-Ran; Wang, Mei-Xi; Ren, Si-Jia; Li, Ming; Tan, Hong-Ling; Wang, Yu-Guang; Tang, Xiang-Lin; Xiao, Cheng-Rong; Liang, Qian-De; Gao, Yue; Ma, Zeng-Chun

    2017-01-01

    The purpose of this work was to study the influences of Realgar- Indigo naturalis (RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM), does have curative effect on acute promyelocytic leukemia (APL). Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

  1. Biomass growth, micronucleus induction, and antioxidant stress enzyme responses in Vicia faba exposed to cadmium in solution.

    Science.gov (United States)

    Rosa, Edson V Cordova; Valgas, Cleidson; Souza-Sierra, Maria M; Corrêa, Albertina X R; Radetski, Claudemir Marcos

    2003-03-01

    Biomass growth, micronucleus induction, and antioxidative stress enzymes (superoxide dismutase, peroxidase, glutathione reductase, and catalase) were investigated simultaneously in the Vicia faba plant exposed to cadmium in solution. The biomass lowest-observed-effect concentration (LOEC) value was 2,000 microM Cd2+. In the shoots, enzymic activities increased without concentration-response relationships. In the roots, after an initial increase, activities of all enzymes showed negative concentration-response relationships. A significant increase in micronucleus induction was observed at 20 microM Cd2+. Regarding sensitivity, our results showed that biomass endpoint was less sensitive than micronucleus induction, which was less sensitive than antioxidative enzyme activities. The increase of antioxidant stress enzyme activities in response to cadmium exposure may be taken as evidence for an enhanced detoxification capacity of V. faba plants toward reactive oxygen species (and derivatives) that might be generated in the stressed plants. Concomitant micronucleus induction may be also interpreted as a consequence of oxidative stress, upholding the view that cadmium-induced DNA damage is, to some extent, via generation of reactive (intermediate) oxygen species.

  2. Nicotine infusion modulates immobilization stress-triggered induction of gene expression of rat catecholamine biosynthetic enzymes.

    Science.gov (United States)

    Serova, L; Danailov, E; Chamas, F; Sabban, E L

    1999-11-01

    The relationship between nicotine and stress is complex and paradoxical. Although people claim they smoke because it relaxes them, nicotine can trigger some of the effects observed with stress, including the release and synthesis of the catecholamines and their biosynthetic enzymes. This study examined one aspect of this confusing relationship between nicotine and stress. Multiple injections of nicotine bitartrate (5 mg/kg) elevated mRNA levels for the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase, and of preproneuropeptide Y in rat adrenal medulla more than did 1 mg/kg of nicotine bitartrate. In the locus ceruleus, substantia nigra, and ventral tegmental area both doses equally induced TH mRNA levels. Nicotine infusion (15 mg/kg/day) did not affect adrenal mRNA levels for any of the genes of interest and did not increase plasma corticosterone levels. However, in rats pre-exposed to nicotinic infusions, the response to a single immobilization (IMO) stress was markedly attenuated with respect to changes in adrenomedullary TH, DBH, and phenylethanolamine N-methyltransferase mRNA levels and in c-Fos protein levels. In the central nervous system, the chronic infusion of nicotine prevented the induction of TH mRNA by repeated IMO stress in the ventral tegmental area (but not in substantia nigra) and of DBH mRNA by single IMO in the locus ceruleus. These findings may explain some of the complex interactions between stress and exposure to nicotine.

  3. Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450

    Directory of Open Access Journals (Sweden)

    Christopher Trent Brewer

    2017-11-01

    Full Text Available Herbal supplements are a significant source of drug-drug interactions (DDIs, herb-drug interactions, and hepatotoxicity. Cytochrome P450 (CYP450 enzymes metabolize a large number of FDA-approved pharmaceuticals and herbal supplements. This metabolism of pharmaceuticals and supplements can be augmented by concomitant use of either pharmaceuticals or supplements. The xenobiotic receptors constitutive androstane receptor (CAR and the pregnane X receptor (PXR can respond to xenobiotics by increasing the expression of a large number of genes that are involved in the metabolism of xenobiotics, including CYP450s. Conversely, but not exclusively, many xenobiotics can inhibit the activity of CYP450s. Induction of the expression or inhibition of the activity of CYP450s can result in DDIs and toxicity. Currently, the United States (US Food and Drug Administration does not require the investigation of the interactions of herbal supplements and CYP450s. This review provides a summary of herbal supplements that inhibit CYP450s, induce the expression of CYP450s, and/or whose toxicity is mediated by CYP450s.

  4. Enhancing bioplastic-substrate interaction via pore induction and directed migration of enzyme location.

    Science.gov (United States)

    Lele, Bhalchandra S; Papworth, Glenn; Katsemi, Vicky; Rüterjans, Heinz; Martyano, Igor; Klabunde, Kenneth J; Russell, Alan J

    2004-06-20

    We demonstrate two novel approaches to enhance interactions of polymer-immobilized biomolecules with their substrates. In the first approach, diisopropylfluorophosphatase (DFPase) containing poly(urethane) (PU) coatings were made microporous by incorporating, then extracting, poly(ethylene glycol)-based diesters as porogens. Incorporation of 2% w/w porogen increased the effective diffusion coefficient of diisopropylfluorophosphate (DFP) through the coatings by 30% and increased the apparent turnover number of immobilized DFPase 3-fold. In the second approach, prior to immobilization, hydrophobic modification of DFPase was achieved through its conjugation with a dimer/trimer mixture of a uretdione based on 1,6-diisocyanatohexane. When the hydrophobically modified DFPase was immobilized in coatings, catalytic activity was 4-fold higher than that of the equivalent, immobilized, native DFPase. This activity enhancement was independent of the presence or absence of pores. Confocal microscopy images of coatings containing fluorescently labeled lysozyme show that the native enzyme is distributed uniformly over the entire thickness of the coatings. Hydrophobically modified and fluorescently labeled lysozyme is accumulated only in the upper 10 microm cross-sectional layer of a 100 microm-thick coating. Interactions of bioplastics with their substrates are tunable either by pore induction in a polymer or by directed migration of the hydrophobically modified biomolecule to the desired location. The latter approach has broad implications, including overcoming mass transfer limitations experienced by immobilized biocatalysts. Copyright 2004 Wiley Periodicals, Inc.

  5. Tyrosine Hydroxylation in Betalain Pigment Biosynthesis Is Performed by Cytochrome P450 Enzymes in Beets (Beta vulgaris.

    Directory of Open Access Journals (Sweden)

    Rasika Sunnadeniya

    Full Text Available Yellow and red-violet betalain plant pigments are restricted to several families in the order Caryophyllales, where betacyanins play analogous biological roles to anthocyanins. The initial step in betalain biosynthesis is the hydroxylation of tyrosine to form L-DOPA. Using gene expression experiments in beets, yeast, and Arabidopsis, along with HPLC/MS analysis, the present study shows that two novel cytochrome P450 (CYP450 enzymes, CYP76AD6 and CYP76AD5, and the previously described CYP76AD1 can perform this initial step. Co-expressing these CYP450s with DOPA 4,5-dioxygenase in yeast, and overexpression of these CYP450s in yellow beets show that CYP76AD1 efficiently uses L-DOPA leading to red betacyanins while CYP76AD6 and CYP76AD5 lack this activity. Furthermore, CYP76AD1 can complement yellow beetroots to red while CYP76AD6 and CYP76AD5 cannot. Therefore CYP76AD1 uniquely performs the beet R locus function and beets appear to be genetically redundant for tyrosine hydroxylation. These new functional data and ancestral character state reconstructions indicate that tyrosine hydroxylation alone was the most likely ancestral function of the CYP76AD alpha and beta groups and the ability to convert L-DOPA to cyclo-DOPA evolved later in the alpha group.

  6. Influence of dietary macronutrients on induction of hepatic drug metabolizing enzymes by Coleus forskohlii extract in mice.

    Science.gov (United States)

    Yokotani, Kaori; Chiba, Tsuyoshi; Sato, Yoko; Nakanishi, Tomoko; Murata, Masatsune; Umegaki, Keizo

    2013-01-01

    From studies in mice, we have reported that Coleus forskohlii extract (CFE), a popular herbal weight-loss ingredient, markedly induced hepatic drug metabolizing enzymes, especially cytochrome P450 (CYP), and interacted with co-administered drugs. This study was designed to examine how the induction of drug metabolizing enzymes by CFE was influenced by different levels of macronutrients in the diet. Mice were fed a non-purified diet or semi-purified diet with and without CFE (0.3-0.5%) for 14-18 d, and changes in the ratio of liver weight to body weight, an indicator of hepatic CYP induction, and hepatic drug metabolizing enzymes were analyzed. The ratio of liver weight to body weight, content and activities of CYPs, and activity of glutathione S-transferase were higher in a semi-purified standard diet (AIN93G formula) group than in high sucrose (62.9%) and high fat (29.9%) diet groups. Different levels of protein (7%, 20%, and 33%) in the diets did not influence CFE-induced CYP induction or increase the ratio of liver weight to body weight. The effect of CFE on the ratio of liver weight to body weight was higher with a semi-purified diet than with a non-purified diet, and was similar between dietary administration and intragastric gavage when the CFE dose and the diet were the same. There was a positive correlation between CFE-induced CYP induction and the content of starch in the diets, suggesting that dietary starch potentiates CFE-induced CYP induction in mice. The mechanism of enhanced CYP induction remains unclear.

  7. Natural variations in xenobiotic-metabolizing enzymes: developing tools for coral monitoring

    Science.gov (United States)

    Rougée, L. R. A.; Richmond, R. H.; Collier, A. C.

    2014-06-01

    The continued deterioration of coral reefs worldwide demonstrates the need to develop diagnostic tools for corals that go beyond general ecological monitoring and can identify specific stressors at sublethal levels. Cellular diagnostics present an approach to defining indicators (biomarkers) that have the potential to reflect the impact of stress at the cellular level, allowing for the detection of intracellular changes in corals prior to outright mortality. Detoxification enzymes, which may be readily induced or inhibited by environmental stressors, present such a set of indicators. However, in order to apply these diagnostic tools for the detection of stress, a detailed understanding of their normal, homeostatic levels within healthy corals must first be established. Herein, we present molecular and biochemical evidence for the expression and activity of major Phase I detoxification enzymes cytochrome P450 (CYP450), CYP2E1, and CYP450 reductase, as well as the Phase II enzymes UDP, glucuronosyltransferase (UGT), β-glucuronidase, glutathione- S-transferase (GST), and arylsulfatase C (ASC) in the coral Pocillopora damicornis. Additionally, we characterized enzyme expression and activity variations over a reproductive cycle within a coral's life history to determine natural endogenous changes devoid of stress exposure. Significant changes in enzyme activity over the coral's natural lunar reproductive cycle were observed for CYP2E1 and CYP450 reductase as well as UGT and GST, while β-glucuronidase and ASC did not fluctuate significantly. The data represent a baseline description of `health' for the expression and activity of these enzymes that can be used toward understanding the impact of environmental stressors on corals. Such knowledge can be applied to address causes of coral reef ecosystem decline and to monitor effectiveness of mitigation strategies. Achieving a better understanding of cause-and-effect relationships between putative stressors and biological

  8. Induction

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Elkjaer, Bente

    2010-01-01

    The purpose of this paper is to explore how induction of newcomers can be understood as both organizational renewal and the maintenance of status quo, and to develop ways of describing this in terms of learning.......The purpose of this paper is to explore how induction of newcomers can be understood as both organizational renewal and the maintenance of status quo, and to develop ways of describing this in terms of learning....

  9. Interaction of IBA and NAA with enzymes in root induction of Crocus ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-11

    Jan 11, 2010 ... cell wall peroxidases are required to generate H2O2 and monolignol ... xide is catalase. Catalase is one of the few enzymes that exhibit dual enzyme activity. This enzyme has a hyperoxidase activity when catalyzing the dismutation of hydrogen ... transport and decomposition, in experiments using intact.

  10. INDUCTION OF AUTOANTIBODIES TO HUMAN ENZYMES FOLLOWING VIRAL-INFECTION - A BIOLOGICALLY RELEVANT HYPOTHESIS

    NARCIS (Netherlands)

    WEIJERS, RNM; LAWSON, C; LEUNISSEN, J

    Macro enzymes, i. e. complexes of normal (iso-)enzymes with an immunoglobulin, may be due to immunological cross-reactions evoked by specific viral antigenic determinants that are homologous to regions in the target enzymes. A search of the National Biomedical Research Foundation protein databank

  11. Enzyme

    Science.gov (United States)

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  12. The role of carbon starvation in the induction of enzymes that degrade plant-derived carbohydrates in Aspergillus niger.

    Science.gov (United States)

    van Munster, Jolanda M; Daly, Paul; Delmas, Stéphane; Pullan, Steven T; Blythe, Martin J; Malla, Sunir; Kokolski, Matthew; Noltorp, Emelie C M; Wennberg, Kristin; Fetherston, Richard; Beniston, Richard; Yu, Xiaolan; Dupree, Paul; Archer, David B

    2014-11-01

    Fungi are an important source of enzymes for saccharification of plant polysaccharides and production of biofuels. Understanding of the regulation and induction of expression of genes encoding these enzymes is still incomplete. To explore the induction mechanism, we analysed the response of the industrially important fungus Aspergillus niger to wheat straw, with a focus on events occurring shortly after exposure to the substrate. RNA sequencing showed that the transcriptional response after 6h of exposure to wheat straw was very different from the response at 24h of exposure to the same substrate. For example, less than half of the genes encoding carbohydrate active enzymes that were induced after 24h of exposure to wheat straw, were also induced after 6h exposure. Importantly, over a third of the genes induced after 6h of exposure to wheat straw were also induced during 6h of carbon starvation, indicating that carbon starvation is probably an important factor in the early response to wheat straw. The up-regulation of the expression of a high number of genes encoding CAZymes that are active on plant-derived carbohydrates during early carbon starvation suggests that these enzymes could be involved in a scouting role during starvation, releasing inducing sugars from complex plant polysaccharides. We show, using proteomics, that carbon-starved cultures indeed release CAZymes with predicted activity on plant polysaccharides. Analysis of the enzymatic activity and the reaction products, indicates that these proteins are enzymes that can degrade various plant polysaccharides to generate both known, as well as potentially new, inducers of CAZymes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Identification of two Nereis virens [Annelida: Polychaeta] cytochrome P450 enzymes and induction by xenobiotics

    DEFF Research Database (Denmark)

    Rewitz, Kim; Kjellerup, C; Jørgensen, A

    2004-01-01

    Cytochrome P450 (CYP) enzyme catalysed metabolism of xenobiotics such as polycyclic aromatic hydrocarbons (PAHs) are known to occur in polychaetes. Yet specific polychaete CYP enzymes have so far not been identified. Here, we report two partial CYP cDNA sequences, both of 453 bp, characterised fr...

  14. Controlled biosynthesis of silver nanoparticles using nitrate reductase enzyme induction of filamentous fungus and their antibacterial evaluation.

    Science.gov (United States)

    Hamedi, Sepideh; Ghaseminezhad, Masumeh; Shokrollahzadeh, Soheila; Shojaosadati, Seyed Abbas

    2017-12-01

    The controlled synthesis of silver nanoparticles (AgNPs) using cell-free filtrate of Fusarium oxysporum fungus was investigated. The effect of fungal incubation period on nanoparticle formation and nitrate reductase enzyme activity was studied using UV-visible spectroscopy and Harley assay, respectively. The highest AgNP formation was observed in the cell-free filtrate of biomass harvested at the early stationary phase where the NR enzyme activity is the maximum. Mixing of the cell-free filtrates of fungal cultures obtained at 23, 28, and 33 °C with silver nitrate solution confirms the higher productivity of AgNP biosynthesis using the cell-free filtrate of fungus incubated at 28 °C. The effect of some factors such as carbon and nitrate sources and light in fungal incubation period on nitrate reductase induction and AgNP formation was also evaluated. In conclusion, increasing nitrate and carbon sources and presence of light induced NR enzyme and produced AgNPs with smaller size, higher monodispersity, and productivity. Results revealed that the presence of ammonium prevents the NR enzyme secretion and causes to the lower productivity of AgNPs.

  15. Induction of antioxidant enzyme activity and lipid peroxidation level in ion-beam-bombarded rice seeds

    Energy Technology Data Exchange (ETDEWEB)

    Semsang, Nuananong, E-mail: nsemsang@gmail.com [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, LiangDeng [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

    2013-07-15

    Highlights: ► Ion beam bombarded rice seeds in vacuum. ► Studied seed survival from the ion bombardment. ► Determined various antioxidant enzyme activities and lipid peroxidation level. ► Discussed vacuum, ion species and ion energy effects. ► Attributed the changes to free radical formation due to ion bombardment. -- Abstract: Low-energy ion beam bombardment has been used to mutate a wide variety of plant species. To explore the indirect effects of low-energy ion beam on biological damage due to the free radical production in plant cells, the increase in antioxidant enzyme activities and lipid peroxidation level was investigated in ion-bombarded rice seeds. Local rice seeds were bombarded with nitrogen or argon ion beams at energies of 29–60 keV and ion fluences of 1 × 10{sup 16} ions cm{sup −2}. The activities of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST) and lipid peroxidation level were assayed in the germinated rice seeds after ion bombardment. The results showed most of the enzyme activities and lipid peroxidation levels in both the argon and nitrogen bombarded samples were higher than those in the natural control. N-ion bombardment could induce higher levels of antioxidant enzyme activities in the rice samples than the Ar-ion bombardment. Additional effects due to the vacuum condition were found to affect activities of some antioxidant enzymes and lipid peroxidation level. This study demonstrates that ion beam bombardment and vacuum condition could induce the antioxidant enzyme activity and lipid peroxidation level which might be due to free radical production in the bombarded rice seeds.

  16. Induction of phase 2 antioxidant enzymes by broccoli sulforaphane: Perspectives in maintaining the antioxidant activity of vitamins A, C, and E

    Directory of Open Access Journals (Sweden)

    Sekhar s Boddupalli

    2012-01-01

    Full Text Available Consumption of fruits and vegetables is recognized as an important part of a healthy diet. Increased consumption of cruciferous vegetables in particular has been associated with a decreased risk of several degenerative and chronic diseases, including cardiovascular disease and certain cancers. Members of the cruciferous vegetable family, which includes broccoli, Brussels sprouts, cauliflower, and cabbage, accumulate significant concentrations of glucosinolates, which are metabolized in vivo to biologically active isothiocyanates (ITCs. The ITC sulforaphane, which is derived from glucoraphanin, has garnered particular interest due to its extraordinary ability to induce expression of several enzymes via the Keap1/Nrf2/ARE pathway. Nrf2/ARE gene products are typically characterized as Phase II detoxification enzymes and/or antioxidant (AO enzymes. Over the last decade, human clinical studies have begun to provide in vivo evidence of both Phase II and AO enzyme induction by SF. Many AO enzymes are redox cycling enzymes that maintain redox homeostasis and activity of free radical scavengers such as such as vitamins A, C and E. In this review, we present the existing evidence for induction of PII and AO enzymes by SF, the interactions of SF-induced AO enzymes and proposed maintenance of the essential vitamins A, C and E, and, finally, the current view of genotypic effects on ITC metabolism and AO enzyme induction and function.

  17. Alpha Adrenergic Induction of Transport of Lysosomal Enzyme across the Blood-Brain Barrier.

    Directory of Open Access Journals (Sweden)

    Akihiko Urayama

    Full Text Available The impermeability of the adult blood-brain barrier (BBB to lysosomal enzymes impedes the ability to treat the central nervous system manifestations of lysosomal storage diseases. Here, we found that simultaneous stimulation of the alpha1 and alpha2 adrenoreceptor restores in adult mice the high rate of transport for the lysosomal enzyme P-GUS that is seen in neonates but lost with development. Beta adrenergics, other monoamines, and acetylcholine did not restore this transport. A high dose (500 microg/mouse of clonidine, a strong alpha2 and weak alpha1 agonist, was able to act as monotherapy in the stimulation of P-GUS transport. Neither use of alpha1 plus alpha2 agonists nor the high dose clonidine disrupted the BBB to albumin. In situ brain perfusion and immunohistochemistry studies indicated that adrengerics act on transporters already at the luminal surface of brain endothelial cells. These results show that adrenergic stimulation, including monotherapy with clonidine, could be key for CNS enzyme replacement therapy.

  18. Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2.

    Directory of Open Access Journals (Sweden)

    Jian-Guo Ren

    2010-09-01

    Full Text Available Malic enzyme 2 (ME2 is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel

  19. Carbon source regulation of nicotinamide adenine dinucleotide (phosphate) glycohydrolase in Neurospora crassa: induction and repression of enzyme synthesis.

    Science.gov (United States)

    Jorge, J A; Terenzi, H F

    1984-06-01

    Synthesis and release of NAD(P)ase by Neurospora crassa wild type was studied in experiments in which mycelia grown in Vogel minimal medium were transferred to media containing protein as the only carbon source. Several results are presented suggesting that the NAD(P)ase may be induced by the presence of protein in the culture medium. Low concentrations of sucrose or glucose (0.1%), Casamino acids or some amino acids such as methionine, cysteine, phenylalanine and tryptophan strongly repressed the enzyme synthesis. Under induction conditions NAD(P)ase and alkaline protease appeared together in the culture medium. It would appear that NAD(P)ase and alkaline protease are coordinately regulated by a common control mechanism related to carbon catabolism.

  20. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Seiji [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813 (Japan); Kobayashi, Saori [Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813 (Japan); Tsubota, Kazuo [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ozawa, Yoko, E-mail: ozawa@a5.keio.jp [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2014-04-04

    Highlights: • Lutein reduced ROS levels in a PC12D neuronal cell line. • Lutein induced mRNAs of phase II antioxidative enzymes in PC12D neuronal cells. • Lutein increased protein levels of HO-1, SOD2, and NQO-1 in PC12D neuronal cells. • Lutein had no effect on intranuclear Nrf2 levels in PC12D neuronal cells. • Lutein did not activate potential upstream Nrf2 nuclear translocation pathways. - Abstract: The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.

  1. Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes

    Directory of Open Access Journals (Sweden)

    Cho YY

    2014-11-01

    Full Text Available Yong-Yeon Cho,1 Hyeon-Uk Jeong,1 Jeong-Han Kim,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon, Korea; 2Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea Abstract: Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP, UDP-glucuronosyltransferase (UGT, and sulfotransferase 2A1 (SULT2A1, were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 µM increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5–50 µM did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19 or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1 in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1'-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans. Keywords: honokiol, human hepatocytes, drug interactions, cytochrome P450, UDP-glucuronosyltransferases

  2. Metabolic activity and enzyme induction in rat fecal microflora maintained in continuous culture.

    Science.gov (United States)

    Mallett, A K; Bearne, C A; Rowland, I R

    1983-01-01

    The enzyme activity of the rat hindgut microflora maintained in an anaerobic two-stage continuous culture was compared with that of rat cecal contents. A qualitative comparison (API ZYM) showed a high degree of similarity between the two populations. Quantitative determinations showed that azoreductase, beta-glucosidase, nitrate reductase, and nitroreductase activities were comparable, and that beta-glucuronidase activity was very low in the culture. beta-Glucuronidase, beta-glucosidase, and nitrate reductase activities were induced within the culture by their respective substrates. Bile acids influenced microbial activity in vitro, with cholic acid inducing beta-glucosidase, azoreductase, and beta-glucuronidase activities and decreasing nitrate reductase activity. Chenodeoxycholic acid increased beta-glucosidase and beta-glucuronidase activities and decreased azoreductase, nitrate reductase, and nitroreductase activities in vitro. These studies demonstrate that the rat hindgut microflora may be successfully cultured in vitro and suggest control mechanisms that regulate the metabolic activity of these organisms in vivo. PMID:6416166

  3. [Involvement of microRNA in the induction of drug-metabolizing enzymes].

    Science.gov (United States)

    Shizu, Ryota; Numazawa, Satoshi; Yoshida, Takemi

    2012-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs of about 20 nucleotides in length and participate in the post-transcriptional regulation of gene expression. Accumulating evidence indicates that miRNA binds to 3'-UTR of its target mRNAs and thereby destabilizes the transcripts or suppresses the translation. It is expected that miRNAs could have diverse functions and therefore play a role in the gene expression caused by the drug treatment, which have yet to be determined. Demonstration of the participation of specific miRNA in the drug-mediated gene expression would make it a biomarker for the toxicological assessment and help an understanding of molecular machinery of the drug-drug interaction. Under these backgrounds, we investigated the change of miRNAs in the liver of mice treated with phenobarbital, a typical inducer for drug-metabolizing enzymes, and demonstrate the participation of miRNAs in the phenobarbital-regulated gene expression. We investigated the relationship between phenobarbital-mediated changes in miRNA and mRNA by using Agilent miRNA microarray and DNA microarray, followed by real time RT-PCR. From these experiments, it was suggested that the phenobarbital-induced changes in cyp2c29 and mrp3 are regulated by miR-30a and miR-29b, respectively. In addition, we obtained evidence that indicates a phenobarbital-mediated decrease in miR-122, a highly abundant liver-specific miRNA, leads to the activation of the transcription factor CAR and thereby induces drug-metabolizing enzymes.

  4. Kinetic determination of vitellogenin induction in the epidermis of cyprinid and perciform fishes: Evaluation of sensitive enzyme-linked immunosorbent assays.

    Science.gov (United States)

    Allner, Bernhard; Hennies, Mark; Lerche, Cristiano F; Schmidt, Thomas; Schneider, Klaus; Willner, Marco; Stahlschmidt-Allner, Petra

    2016-12-01

    Induction of vitellogenin (VTG) in male and immature fish is a standardized endpoint in endocrine-disruption testing. To establish a nondestructive swab sampling method, VTG induction in the epidermis of Cypriniformes and Perciformes species was investigated. Both VTG and estrogen receptor genes are expressed in epidermal cells. Immunoaffinity and mass fingerprint analyses show induction of identical VTG peptides in liver and epidermis. Induction of VTG by estradiol (E2) and bisphenol A (BPA) in the epidermis was quantified with homolog enzyme-linked immunosorbent assays. Initial values in juveniles and males were below 1 ng VTG/mL extraction buffer. Exposure to E2 led to values between 200 ng/mL and 4600 ng/mL in cyprinids and between 10 ng/mL and 81 ng/mL in perciforms. Exposure to BPA increased VTG amounts to 250 ng/mL in fathead minnows, 1360 ng/mL in goldfish, 100 ng/mL in zebrafish, and 12 ng/mL in bluegills. Serum VTG contents demonstrated a similar dose-response pattern in the epidermis and the blood. These results show that VTG induction may be reliably assessed in the skin mucus of fishes, demonstrating the suitability of this biological sample for investigating estrogenic activity in compliance with Organisation for Economic Co-operation and Development standard protocols. This broadens the perspectives in toxicological screening and environmental monitoring, reducing the number of tested animals and minimizing harmful effects for animals, allowing for follow-up of individual induction profiles. Environ Toxicol Chem 2016;35:2916-2930. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

  5. Phase I enzyme induction in Girardinichthys viviparus, an endangered goodeid fish, exposed to water from native localities enriched with polychlorinated biphenyls.

    Science.gov (United States)

    Vega-López, Armando; Jiménez-Orozco, F Alejandro; Jiménez-Zamudio, Luís A; García-Latorre, Ethel; Domínguez-López, M Lilia

    2009-10-01

    The present study examines the induction of mixed-function oxidase (MFO) enzymes, including CYP content CYP1A (EROD) activity and alcohol dehydrogenase activity (ADH), in an endemic Mexican fish species, the black-fin goodeid Girardinichthys viviparus, exposed to the water of two localities, Lake Texcoco (LTX) and Lake Zumpango, and to the same matrices enriched in polychlorinated biphenyls (PCBs) to simulate the potential toxic effects of sublethal increases in these xenobiotics. Fishes of both sexes born in the laboratory were exposed for 1, 2, 4, 8, and 16 days. Water from the two types of localities of the black-fin goodeid contains MFO inducers. Of the two, the most contaminated is LTX water, which also contains PCBs. EROD activity was higher in all treatments with female compared with male fish. This suggests greater metabolic compromise in female fish as a response to damage caused by these xenobiotics. In this species, CYP induction displayed two patterns that were not always concurrent with higher CYP1A activity. In the enriched matrix system, biotransformation processes were notably altered. Increased ADH may indicate that this enzyme is involved in the biotransformation of PCBs and their metabolites, particularly in male fish, and provides at least a part of reductive power required by the MFO enzymes; however, specific studies are needed to clarify this point.

  6. Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison).

    Science.gov (United States)

    Folland, William R; Newsted, John L; Fitzgerald, Scott D; Fuchsman, Phyllis C; Bradley, Patrick W; Kern, John; Kannan, Kurunthachalam; Zwiernik, Matthew J

    2016-03-01

    Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with

  7. Flavonoids as modulators of metabolic enzymes and drug transporters.

    Science.gov (United States)

    Miron, Anca; Aprotosoaie, Ana Clara; Trifan, Adriana; Xiao, Jianbo

    2017-06-01

    Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs)). Flavonoids have been reported to inhibit ATP-binding cassette (ABC) transporters (multidrug resistance (MDR)-associated proteins, breast cancer-resistance protein) that contribute to the development of MDR. P-glycoprotein, an ABC transporter that limits drug bioavailability and also induces MDR, was differently modulated by flavonoids. Flavonoids and their phase II metabolites (sulfates, glucuronides) inhibit organic anion transporters involved in the tubular uptake of nephrotoxic compounds. In vivo studies have partially confirmed in vitro findings, suggesting that the mechanisms underlying the modulatory effects of flavonoids are complex and difficult to predict in vivo. Data summarized in this review strongly support the view that flavonoids are promising candidates for the enhancement of oral drug bioavailability, chemoprevention, and reversal of MDR. © 2017 New York Academy of Sciences.

  8. Dipeptidyl peptidase IV is involved in the cellulose-responsive induction of cellulose biomass-degrading enzyme genes in Aspergillus aculeatus.

    Science.gov (United States)

    Tani, Shuji; Yuki, Shota; Kunitake, Emi; Sumitani, Jun-Ichi; Kawaguchi, Takashi

    2017-06-01

    We screened for factors involved in the cellulose-responsive induction of cellulose biomass-degrading enzyme genes from approximately 12,000 Aspergillus aculeatus T-DNA insertion mutants harboring a transcriptional fusion between the FIII-avicelase gene (cbhI) promoter and the orotidine 5'-monophosphate decarboxylase gene. Analysis of 5-fluoroorodic acid (5-FOA) sensitivity, cellulose utilization, and cbhI expression of the mutants revealed that a mutant harboring T-DNA at the dipeptidyl peptidase IV (dppIV) locus had acquired 5-FOA resistance and was deficient in cellulose utilization and cbhI expression. The deletion of dppIV resulted in a significant reduction in the cellulose-responsive expression of both cbhI as well as genes controlled by XlnR-independent and XlnR-dependent signaling pathways at an early phase in A. aculeatus. In contrast, the dppIV deletion did not affect the xylose-responsive expression of genes under the control of XlnR. These results demonstrate that DppIV participates in cellulose-responsive induction in A. aculeatus.

  9. Contributions of apoplasmic cadmium accumulation, antioxidative enzymes and induction of phytochelatins in cadmium tolerance of the cadmium-accumulating cultivar of black oat (Avena strigosa Schreb.).

    Science.gov (United States)

    Uraguchi, Shimpei; Kiyono, Masako; Sakamoto, Takuya; Watanabe, Izumi; Kuno, Katsuji

    2009-07-01

    The contributions of cadmium (Cd) accumulation in cell walls, antioxidative enzymes and induction of phytochelatins (PCs) to Cd tolerance were investigated in two distinctive genotypes of black oat (Avena strigosa Schreb.). One cultivar of black oat 'New oat' accumulated Cd in the leaves at the highest concentration compared to another black oat cultivar 'Soil saver' and other major graminaceous crops. The shoot:root Cd ratio also demonstrated that 'New oat' was the high Cd-accumulating cultivar, whereas 'Soil saver' was the low Cd-accumulating cultivar. Varied levels of Cd exposure demonstrated the strong Cd tolerance of 'New oat'. By contrast, low Cd-accumulating cultivar 'Soil saver' suffered Cd toxicity such as growth defects and increased lipid peroxidation, even though it accumulated less Cd in shoots than 'New oat'. Higher activities of ascorbate peroxidase (EC 1.11.1.11) and superoxide dismutase (EC 1. 15. 1. 1) were observed in the leaves of 'New oat' than in 'Soil saver'. No advantage of 'New oat' in PCs induction was observed in comparison to Cd-sensitive cultivar 'Soil saver', although Cd exposure increased the concentration of total PCs in both cultivars. Higher and increased Cd accumulation in cell wall fraction was observed in shoots of 'New oat'. On the other hand, in 'Soil saver', apoplasmic Cd accumulation showed saturation under higher Cd exposure. Overall, the present results suggest that cell wall Cd accumulation and antioxidative activities function in the tolerance against Cd stress possibly in combination with vacuolar Cd compartmentation.

  10. Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction.

    Science.gov (United States)

    Li, Chuan; Zhang, Wei-Jian; Frei, Balz

    2016-10-01

    Atherosclerosis, the underlying cause of ischemic heart disease and stroke, is an inflammatory disease of arteries in a hyperlipidemic milieu. Endothelial expression of cellular adhesion molecules, such as endothelial-leukocyte adhesion molecule-1 (E-selectin) and intercellular adhesion molecule-1 (ICAM-1), plays a critical role in the initiation and progression of atherosclerosis. The dietary flavonoid, quercetin, has been reported to inhibit expression of cellular adhesion molecules, but the underlying mechanisms are incompletely understood. In this study, we found that quercetin dose-dependently (5-20µM) inhibits lipopolysaccharide (LPS)-induced mRNA and protein expression of E-selectin and ICAM-1 in human aortic endothelial cells (HAEC). Incubation of HAEC with quercetin also significantly reduced LPS-induced oxidant production, but did not inhibit activation of the nuclear factor-kappaB (NF-κB). Furthermore, quercetin induced activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and subsequent mRNA and protein expression of the antioxidant enzymes, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase, quinone 1, and glutamate-cysteine ligase. The induction of Nrf2 and antioxidant enzymes was partly inhibited by the p38 mitogen-activated protein kinase (p38) inhibitor, SB203580. Our results suggest that quercetin suppresses LPS-induced oxidant production and adhesion molecule expression by inducing Nrf2 activation and antioxidant enzyme expression, which is partially mediated by p38; and the inhibitory effect of quercetin on adhesion molecule expression is not due to inhibition of NF-κB activation, but instead due to antioxidant-independent effects of HO-1. Copyright © 2016. Published by Elsevier B.V.

  11. C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

    Directory of Open Access Journals (Sweden)

    Haijian Sun

    2017-05-01

    Full Text Available Oxidized low-density lipoprotein (ox-LDL accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9 is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO production and oxidative stress in human umbilical vein endothelial cells (HUVECs exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1, nicotinamide adenine dinucleotide phosphate (NAD(PH dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL, as well as endothelial nitric oxide synthase (eNOS. Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK. Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation.

  12. Autotaxin, a synthetic enzyme of lysophosphatidic acid (LPA, mediates the induction of nerve-injured neuropathic pain

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    Chun Jerold

    2008-02-01

    Full Text Available Abstract Recently, we reported that lysophosphatidic acid (LPA induces long-lasting mechanical allodynia and thermal hyperalgesia as well as demyelination and upregulation of pain-related proteins through one of its cognate receptors, LPA1. In addition, mice lacking the LPA1 receptor gene (lpa1-/- mice lost these nerve injury-induced neuropathic pain behaviors and phenomena. However, since lpa1-/- mice did not exhibit any effects on the basal nociceptive threshold, it is possible that nerve injury-induced neuropathic pain and its machineries are initiated by LPA via defined biosynthetic pathways that involve multiple enzymes. Here, we attempted to clarify the involvement of a single synthetic enzyme of LPA known as autotaxin (ATX in nerve injury-induced neuropathic pain. Wild-type mice with partial sciatic nerve injury showed robust mechanical allodynia starting from day 3 after the nerve injury and persisting for at least 14 days, along with thermal hyperalgesia. On the other hand, heterozygous mutant mice for the autotaxin gene (atx+/-, which have 50% ATX protein and 50% lysophospholipase D activity compared with wild-type mice, showed approximately 50% recovery of nerve injury-induced neuropathic pain. In addition, hypersensitization of myelinated Aβ˜ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaGafqOSdiMbaGaaaaa@2D83@- or Aδ-fiber function following nerve injury was observed in electrical stimuli-induced paw withdrawal tests using a Neurometer®. The hyperalgesia was completely abolished in lpa1-/- mice, and reduced by 50% in atx+/- mice. Taken together, these findings suggest that LPA biosynthesis through ATX is the source of LPA for LPA1 receptor-mediated neuropathic pain. Therefore, targeted inhibition of ATX-mediated LPA biosynthesis as well as

  13. Silver coordination polymers for prevention of implant infection: thiol interaction, impact on respiratory chain enzymes, and hydroxyl radical induction.

    Science.gov (United States)

    Gordon, Oliver; Vig Slenters, Tünde; Brunetto, Priscilla S; Villaruz, Amer E; Sturdevant, Daniel E; Otto, Michael; Landmann, Regine; Fromm, Katharina M

    2010-10-01

    Prosthetic joint replacements are used increasingly to alleviate pain and improve mobility of the progressively older and more obese population. Implant infection occurs in about 5% of patients and entails significant morbidity and high social costs. It is most often caused by staphylococci, which are introduced perioperatively. They are a source of prolonged seeding and difficult to treat due to antibiotic resistance; therefore, infection prevention by prosthesis coating with nonantibiotic-type anti-infective substances is indicated. A renewed interest in topically used silver has fostered development of silver nanoparticles, which, however, present a potential health hazard. Here we present new silver coordination polymer networks with tailored physical and chemical properties as nanostructured coatings on metallic implant substrates. These compounds exhibited strong biofilm sugar-independent bactericidal activity on in vitro-grown biofilms and prevented murine Staphylococcus epidermidis implant infection in vivo with slow release of silver ions and limited transient leukocyte cytotoxicity. Furthermore, we describe the biochemical and molecular mechanisms of silver ion action by gene screening and by targeting cell metabolism of S. epidermidis at different levels. We demonstrate that silver ions inactivate enzymes by binding sulfhydryl (thiol) groups in amino acids and promote the release of iron with subsequent hydroxyl radical formation by an indirect mechanism likely mediated by reactive oxygen species. This is the first report investigating the global metabolic effects of silver in the context of a therapeutic application. We anticipate that the compounds presented here open a new treatment field with a high medical impact.

  14. Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes

    Science.gov (United States)

    Gonzalez-Carter, Daniel A.; Leo, Bey Fen; Ruenraroengsak, Pakatip; Chen, Shu; Goode, Angela E.; Theodorou, Ioannis G.; Chung, Kian Fan; Carzaniga, Raffaella; Shaffer, Milo S. P.; Dexter, David T.; Ryan, Mary P.; Porter, Alexandra E.

    2017-03-01

    Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson’s disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag2S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H2S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag2S formation, resulting from CSE-mediated H2S production in microglia, sequesters Ag+ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.

  15. Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure.

    Science.gov (United States)

    Ma, Huaxian; Wang, Jianling; Abdel-Rahman, Sherif Z; Boor, Paul J; Khan, M Firoze

    2013-03-15

    Mechanisms by which aniline exposure elicits splenotoxicity, especially a tumorigenic response, are not well-understood. Earlier, we have shown that aniline exposure leads to oxidative DNA damage and up-regulation of OGG1 and NEIL1/2 DNA glycosylases in rat spleen. However, the contribution of endonuclease III homolog 1 (NTH1) and apurinic/apyrimidinic endonuclease 1 (APE1) in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on examining whether NTH1 and APE1 contribute to the repair of oxidative DNA lesions in the spleen, in an experimental condition preceding tumorigenesis. To achieve this, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. By quantitating the cleavage products, the activities of NTH1 and APE1 were assayed using substrates containing thymine glycol (Tg) and tetrahydrofuran, respectively. Aniline treatment led to significant increases in NTH1- and APE1-mediated BER activity in the nuclear extracts of spleen of aniline-treated rats compared to the controls. NTH1 and APE1 mRNA expression in the spleen showed 2.9- and 3.2-fold increases, respectively, in aniline-treated rats compared to the controls. Likewise, Western blot analysis showed that protein expression of NTH1 and APE1 in the nuclear extracts of spleen from aniline-treated rats was 1.9- and 2.7-fold higher than the controls, respectively. Immunohistochemistry indicated that aniline treatment also led to stronger immunoreactivity for both NTH1 and APE1 in the spleens, confined to the red pulp areas. These results, thus, show that aniline exposure is associated with induction of NTH1 and APE1 in the spleen. The increased repair activity of NTH1 and APE1 could be an important mechanism for the removal of oxidative DNA lesions. These findings thus identify a novel mechanism through which NTH1 and APE1 may regulate the repair of

  16. Induction of deubiquitinating enzyme USP50 during erythropoiesis and its potential role in the regulation of Ku70 stability.

    Science.gov (United States)

    Cai, Junting; Wei, Jianxin; Schrott, Valerie; Zhao, Jing; Bullock, Grant; Zhao, Yutong

    2017-11-03

    Anemia is a very common blood disorder that affects the lives of billions of people worldwide. Anemia is caused by the loss of blood, increased destruction of red blood cells (RBCs), or reduced production of RBCs. Erythropoiesis is the complex process of RBC differentiation and maturation, in which protein degradation plays a crucial role. Protein ubiquitination regulates programmed protein degradation, which can be reversed by deubiquitinating enzymes (DUBs); however, the role of DUBs in erythropoiesis has not been well studied. We examined the expression of DUBs during erythropoiesis using an ex vivo human CD34+ hematopoietic progenitor cell culture system. Here we show that ubiquitin-specific protease 50 (USP50) levels are increased during erythropoiesis. USP50 mRNA levels are significantly increased on day 3 and protein levels are elevated on day 9 of erythroid differentiation. Coimmunoprecipitation and proteomics analyses reveal that Ku70, a DNA-binding protein, is associated with USP50. Overexpression of USP50 has no effect on Ku70 mRNA levels, while it reduces Ku70 protein levels by promoting Ku70 degradation, suggesting that USP50 may indirectly regulate Ku70 protein stability. USP50 protein is also not stable. USP50 protein degradation is independent of the proteasomal and the lysosomal degradation systems. This study suggests that DUBs like USP50 may regulate protein stability during erythropoiesis; however, more investigation is warranted. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate

    Science.gov (United States)

    Wimhurst, Janet M.; Manchester, K. L.

    1973-01-01

    1. Measurements were made of the activities of the four key enzymes involved in gluconeogenesis, pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxylase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), of serine dehydratase (EC 4.2.1.13) and of the four enzymes unique to glycolysis, glucokinase (EC 2.7.1.2), hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40), in livers from starved rats perfused with glucose, fructose or lactate. Changes in perfusate concentrations of glucose, fructose, lactate, pyruvate, urea and amino acid were monitored for each perfusion. 2. Addition of 15mm-glucose at the start of perfusion decreased the activity of pyruvate carboxylase. Constant infusion of glucose to maintain the concentration also decreased the activities of phosphoenolpyruvate carboxylase, fructose 1,6-diphosphatase and serine dehydratase. Addition of 2.2mm-glucose initially to give a perfusate sugar concentration similar to the blood sugar concentration of starved animals had no effect on the activities of the enzymes compared with zero-time controls. 3. Addition of 15mm-fructose initially decreased glucokinase activity. Constant infusion of fructose decreased activities of glucokinase, phosphofructokinase, pyruvate carboxylase, phosphoenolpyruvate carboxylase, glucose 6-phosphatase and serine dehydratase. 4. Addition of 7mm-lactate initially elevated the activity of pyruvate carboxylase, as also did constant infusion; maintenance of a perfusate lactate concentration of 18mm induced both pyruvate carboxylase and phosphoenolpyruvate carboxylase activities. 5. Addition of cycloheximide had no effect on the activities of the enzymes after 4h of perfusion at either low or high concentrations of glucose or at high lactate concentration. Cycloheximide also prevented the loss or induction of pyruvate carboxylase and phosphoenolpyruvate carboxylase activities with high substrate

  18. Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity.

    Science.gov (United States)

    Murayama, Norie; Kazuki, Yasuhiro; Satoh, Daisuke; Arata, Kazuya; Harada, Tasuku; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-01-01

    Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. Human placental BeWo cells, cultured in the recommended media, also indicated detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. To reduce any masking effects by endogenous hormones used in the recommended media, induction of P450 3A4/5 mRNA and oxidation activities were measured in placental BeWo cells cultured with a modified medium containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold, but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media conditions. Under these modified conditions, thalidomide also significantly induced midazolam 1´-hydroxylation and thalidomide 5-hydroxylaion activities 3-fold but not bupropion hydroxylation activity. Taken together, activation of thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in human placentas, as well as livers, is suggested in vivo.

  19. Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C.

    Science.gov (United States)

    Gupta, Samir K; Kolz, Karen; Cutler, David L

    2011-06-01

    To examine the effect of pegylated interferon (PEG-IFN) alfa-2b on the activity of major drug-metabolizing enzymes. This nonrandomized, open-label, multiple-dose study examined the effects of PEG-IFN alfa-2b on the activity of CYP450 1A2, 2 C8/9, 2D6, and 3A4 enzymes and N-acetyltransferase in subjects with chronic hepatitis C. Eligible subjects received PEG-IFN alfa-2b 1.5 μg/kg subcutaneously once weekly for 4 weeks (days 3, 10, 17, and 24). Oral probe substrates (dextromethorphan hydrobromide 45 mg, caffeine 200 mg, tolbutamide 500 mg, and dapsone 100 mg) were administered after a 10-h fast on days 1 and 25. Midazolam 4 mg was administered orally on days 2 and 26. Enzyme activity for each CYP450 isozyme and for N-acetyltransferase was estimated based on the ratios of the observed concentrations of the substrates and metabolites in plasma or urine samples. Twenty-six subjects enrolled in the study. Mean age was 44.3 years, mean weight was 78.9 kg, and mean body mass index was 26.3 kg/m(2). Multiple doses of PEG-IFN alfa-2b inhibited CYP1A2 activity to a limited extent (point estimate = 84.2%, 90% confidence interval [CI] 79-90), increased CYP2C8/9 activity to a limited extent (point estimate = 127.6%, 90% CI 115-142), increased CYP2D6 activity (point estimate = 167%, 90% CI 125-223), and had no effect on the activity of CYP3A4 or N-acetyltransferase. Weekly administration of PEG-IFN alfa-2b to subjects with chronic hepatitis C increased CYP2C8/9 and CYP2D6 activity in some individuals.

  20. The induction of salt stress tolerance by propyl gallate treatment in green microalga Dunaliella bardawil, through enhancing ascorbate pool and antioxidant enzymes activity.

    Science.gov (United States)

    Einali, Alireza

    2017-10-08

    The effect of propyl gallate (PG), a synthetic antioxidant, on antioxidant responses and salinity tolerance was investigated in the cells of the green microalga, Dunaliella bardawil. Algal suspensions grown at three salinity levels of 1, 2, and 3 M NaCl were incubated with 1 mM of PG. The number of cells was significantly lower in all PG-treated cells compared to untreated controls. Despite PG-induced cell death, the fresh weight of all PG-treated cells was considerably higher than controls. PG-treated cells had enhanced antioxidant capacity because of increased levels of Chlorophyll a, β-carotene, reduced ascorbate, protein, and enzymatic activities, but accumulated lower levels of malonyldialdehyde and hydrogen peroxide compared to untreated cells. The results suggest that PG acts as a signal molecule both directly by reducing of free radical oxidants and indirectly by augmenting ascorbate pool levels, β-carotene production, and antioxidant enzymes activity to boost the capacity of antioxidant systems and radical oxygen species scavenging. Therefore, induction of salt stress tolerance by PG in D. bardawil is associated with metabolic adjustments through activation or synthesis of both enzymatic and non-enzymatic molecules involved in antioxidant systems.

  1. Effect of Coleus forskohlii and its major constituents on cytochrome P450 induction.

    Science.gov (United States)

    Hebbani Nagarajappa, Shivaprasad; Pandit, Subrata; Divanji, Manohar; Mariyanna, Bhanumathy; Kumar, Pavan; Godavarthi, Ashok

    2016-01-01

    Coleus forskohlii Briq. has been used traditionally for the treatment of several ailments since antiquity in Ayurveda. In the present study, an approach has been made to evaluate the effect of C. forskohlii and its major constituents on cytochrome P450 (CYP3A, CYP2B, and CYP2C) mRNA expression in rat hepatocytes. To gain better understanding of the herb-drug interaction potential of the chemical constituents present in C. forskohlii, the extract was subjected to column chromatography followed by standardization with respect to forskolin, 1-deoxyforskolin, and 1,9-dideoxyforskolin using reversed-phase high-performance liquid chromatography (RP-HPLC). Hepatocytes were treated with extracts, fractions, and phytoconstituents, followed by extraction and purification of total mRNA. Study of mRNA expression was carried out through reverse transcription polymerase chain reaction, followed by agarose gel electrophoresis. Results revealed that the test substances did not show any significant mRNA expression compared to the control against CYP3A, CYP2B, and CYP2C. Positive controls such as dexamethasone and rifampin showed significantly high (p < 0.001) induction potential compared to the control. It can be concluded that C. forskohlii and its major constituents may not be involved in CYP450 induction-based drug interaction.

  2. Effect of Coleus forskohlii and its major constituents on cytochrome P450 induction

    Directory of Open Access Journals (Sweden)

    Shivaprasad Hebbani Nagarajappa

    2016-01-01

    Full Text Available Coleus forskohlii Briq. has been used traditionally for the treatment of several ailments since antiquity in Ayurveda. In the present study, an approach has been made to evaluate the effect of C. forskohlii and its major constituents on cytochrome P450 (CYP3A, CYP2B, and CYP2C mRNA expression in rat hepatocytes. To gain better understanding of the herb–drug interaction potential of the chemical constituents present in C. forskohlii, the extract was subjected to column chromatography followed by standardization with respect to forskolin, 1-deoxyforskolin, and 1,9-dideoxyforskolin using reversed-phase high-performance liquid chromatography (RP-HPLC. Hepatocytes were treated with extracts, fractions, and phytoconstituents, followed by extraction and purification of total mRNA. Study of mRNA expression was carried out through reverse transcription polymerase chain reaction, followed by agarose gel electrophoresis. Results revealed that the test substances did not show any significant mRNA expression compared to the control against CYP3A, CYP2B, and CYP2C. Positive controls such as dexamethasone and rifampin showed significantly high (p < 0.001 induction potential compared to the control. It can be concluded that C. forskohlii and its major constituents may not be involved in CYP450 induction-based drug interaction.

  3. Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults.

    OpenAIRE

    Niwa, Y; Iizawa, O.; Ishimoto, K.; AKAMATSU, H.; Kanoh, T.

    1993-01-01

    Several enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, and D-glucose-6-phosphate dehydrogenase are capable of scavenging reactive oxygen species in in vivo. We assessed both basal levels and the capacity of these enzyme activities to be induced in human leukocytes in response to a variety of agents. Basal activity of copper-zinc SOD, and manganese SOD showed little variation with age. In contrast, the basal activity of the three H2O2 scavenging enzymes, catal...

  4. [The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor].

    Science.gov (United States)

    Ceker, Zahit; Takmaz, Suna Akın; Baltaci, Bülent; Başar, Hülya

    2015-01-01

    The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500mcg/kg followed by a 100mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5min after esmolol and saline administration, 3min after the induction and 30s, 2min and 4min after intubation. The corrected-QT interval was shorter in the esmolol group (p=0.012), the corrected-QT interval dispersion interval was longer in the control group (p=0.034) and the mean heart rate was higher in the control group (p=0.022) 30s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p=0.038). Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin converting enzyme inhibitors. These effects were prevented with esmolol (500mcg/kg bolus, followed by

  5. The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor

    Directory of Open Access Journals (Sweden)

    Zahit Çeker

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. METHODS: 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500 mcg/kg followed by a 100 mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5 min after esmolol and saline administration, 3 min after the induction and 30 s, 2 min and 4 min after intubation. RESULTS: The corrected-QT interval was shorter in the esmolol group (p = 0.012, the corrected-QT interval dispersion interval was longer in the control group (p = 0.034 and the mean heart rate was higher in the control group (p = 0.022 30 s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p = 0.038. CONCLUSION: Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin converting

  6. Regulation of Porcine Hepatic Cytochrome P450 — Implication for Boar Taint

    Science.gov (United States)

    Rasmussen, Martin Krøyer; Zamaratskaia, Galia

    2014-01-01

    Cytochrome P450 (CYP450) is the major family of enzymes involved in the metabolism of several xenobiotic and endogenous compounds. Among substrates for CYP450 is the tryptophan metabolite skatole (3-methylindole), one of the major contributors to the off-odour associated with boar-tainted meat. The accumulation of skatole in pigs is highly dependent on the hepatic clearance by CYP450s. In recent years, the porcine CYP450 has attracted attention both in relation to meat quality and as a potential model for human CYP450. The molecular regulation of CYP450 mRNA expression is controlled by several nuclear receptors and transcription factors that are targets for numerous endogenously and exogenously produced agonists and antagonists. Moreover, CYP450 expression and activity are affected by factors such as age, gender and feeding. The regulation of porcine CYP450 has been suggested to have more similarities with human CYP450 than other animal models, including rodents. This article reviews the available data on porcine hepatic CYP450s and its implications for boar taint. PMID:25408844

  7. Regulation of Porcine Hepatic Cytochrome P450 — Implication for Boar Taint

    Directory of Open Access Journals (Sweden)

    Martin Krøyer Rasmussen

    2014-09-01

    Full Text Available Cytochrome P450 (CYP450 is the major family of enzymes involved in the metabolism of several xenobiotic and endogenous compounds. Among substrates for CYP450 is the tryptophan metabolite skatole (3-methylindole, one of the major contributors to the off-odour associated with boar-tainted meat. The accumulation of skatole in pigs is highly dependent on the hepatic clearance by CYP450s. In recent years, the porcine CYP450 has attracted attention both in relation to meat quality and as a potential model for human CYP450. The molecular regulation of CYP450 mRNA expression is controlled by several nuclear receptors and transcription factors that are targets for numerous endogenously and exogenously produced agonists and antagonists. Moreover, CYP450 expression and activity are affected by factors such as age, gender and feeding. The regulation of porcine CYP450 has been suggested to have more similarities with human CYP450 than other animal models, including rodents. This article reviews the available data on porcine hepatic CYP450s and its implications for boar taint.

  8. D-arabinose metabolism in Escherichia coli B: induction and cotransductional mapping of the L-fucose-D-arabinose pathway enzymes.

    Science.gov (United States)

    Elsinghorst, E A; Mortlock, R P

    1988-12-01

    D-Arabinose is degraded by Escherichia coli B via some of the L-fucose pathway enzymes and a D-ribulokinase which is distinct from the L-fuculokinase of the L-fucose pathway. We found that L-fucose and D-arabinose acted as the apparent inducers of the enzymes needed for their degradation. These enzymes, including D-ribulokinase, appeared to be coordinately regulated, and mutants which constitutively synthesized the L-fucose enzymes also constitutively synthesized D-ribulokinase. In contrast to D-arabinose-positive mutants of E. coli K-12, in which L-fuculose-1-phosphate and D-ribulose-1-phosphate act as inducers of the L-fucose pathway, we found that these intermediates did not act as inducers in E. coli B. To further characterize the E. coli B system, some of the L-fucose-D-arabinose genes were mapped by using bacteriophage P1 transduction. A transposon Tn10 insertion near the E. coli B L-fucose regulon was used in two- and three-factor reciprocal crosses. The gene encoding D-ribulokinase, designated darK, was found to map within the L-fucose regulon, and the partial gene order was found to be Tn10-fucA-darK-fucI-fucK-thyA.

  9. Phenotypic changes and the fate of digestive enzymes during induction of amber disease in larvae of the New Zealand grass grub (Costelytra zealandica).

    Science.gov (United States)

    Gatehouse, H S; Tan, B; Christeller, J T; Hurst, M R H; Marshall, S D G; Jackson, T A

    2009-07-01

    Amber disease of the New Zealand grass grub Costelytra zealandica (Coleoptera: Scarabaeidae) is caused by ingestion of pADAP plasmid carrying isolates of Serratia entomophila or Serratia proteamaculans (Enterobacteriaceae) and causes infected larvae to cease feeding and clear their midgut to a pale amber colour where midgut serine protease activities are virtually eliminated. Using bacterial strains and mutants expressing combinations of the anti-feeding (afp) and gut clearance (sep) gene clusters from pADAP, we manipulated the disease phenotype and demonstrated directly the relationship between gene clusters, phenotype and loss of enzyme activity. Treatment with afp-expressing strains caused cessation of feeding without gut clearance where midgut protease activity was maintained at levels similar to that of healthy larvae. Treatment with strains expressing sep-genes caused gut clearance followed by a virtual elimination of trypsin and chymotrypsin titre in the midgut indicating both the loss of pre-existing enzyme from the lumen and a failure to replenish enzyme levels in this region by secretion from the epithelium. Monitoring of enzymatic activity through the alimentary tract during expression of disease showed that loss of serine protease activity in the midgut was matched by a surge of protease activity in the hindgut and frass pellets, indicating a flushing and elimination of the midgut contents. The blocking of enzyme secretion through amber disease appears to be selective as leucine aminopeptidase and alpha-amylase were still detected in the midgut of diseased larvae.

  10. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  11. Solid bioprocess of tarbush (Flourensia cernua) leaves for β-glucosidase production by Aspergillus niger: initial approach to fiber-glycoside interaction for enzyme induction.

    Science.gov (United States)

    Lopez-Trujillo, Juan; Medina-Morales, Miguel A; Sanchez-Flores, Ariel; Arevalo, Carlos; Ascacio-Valdes, Juan A; Mellado, Miguel; Aguilar, Cristobal N; Aguilera-Carbo, Antonio F

    2017-08-01

    Commercial cellulase production has increased in recent years and consistent research has been carried out to improve levels of β-glucosidase. Bioprocesses have been successfully adapted to produce this enzyme, with solid-state fermentations as the best-suited technique involving fungi. The aim of this study was to use leaves of tarbush (Flourensia cernua), an abundant shrub of the Chihuahuan Desert, as a carbon source for β-glucosidase production by Aspergillus niger. During the solid bioprocess, this enzyme reached its peak production at 36 h of culture with 3876.6 U/L. There is a particular interest in the substrate composition because of the possibility of phenolic glycosides having an important role in β-glucosidase production. HPLC-MS analyses showed that glycosides were present with the highest accumulation at 36 h of fungal culture. Luteolin and apigenin glycosides [1.8 and 2.4 absorbance units, respectively] were also detected and showed their highest point of detection alongside the highest β-glucosidase activity. No apparent changes in cellulose were observed, while hemicellulose content decreased, which could be related to production and activity of β-glucosidase. This study shows that leaves of F. cernua are an important raw material for β-glucosidase production and give a source of compounds of added value which also may have an important role for β-glucosidase production.

  12. Labor Induction

    Science.gov (United States)

    ... QUESTIONS FAQ154 LABOR, DELIVERY, AND POSTPARTUM CARE Labor Induction • What is labor induction? • Why is labor induced? • What is the Bishop ... oxytocin? • What are the risks associated with labor induction? • Is labor induction always effective? •Glossary What is ...

  13. Neonicotinoid insecticides: reduction and cleavage of imidacloprid nitroimine substituent by liver microsomal and cytosolic enzymes.

    Science.gov (United States)

    Schulz-Jander, Daniel A; Leimkuehler, William M; Casida, John E

    2002-09-01

    The major insecticide imidacloprid (IMI) is known to be metabolized by human cytochrome P450 3A4 with NADPH by imidazolidine hydroxylation and dehydrogenation to give 5-hydroxy-imidacloprid and the olefin, respectively, and by nitroimine reduction and cleavage to yield the nitrosoimine, guanidine, and urea derivatives. More extensive metabolism by human or rabbit liver microsomes with NADPH or rabbit liver cytosol without added cofactor reduces the IMI N-nitro group to an N-amino substituent, i.e., the corresponding hydrazone. A major metabolite on incubation of IMI in the human microsome-NADPH system is tentatively assigned by LC/MS as a 1,2,4-triazol-3-one derived from the hydrazone; the same product is obtained on reaction of the hydrazone with ethyl chloroformate. The hydrazone and proposed triazolone are considered here together (referred to as the hydrazone) for quantitation. Only a portion of the microsomal reduction and cleavage of the nitroimine substituent is attributable to a CYP450 enzyme. The cytosolic enzyme conversion to the hydrazone is inhibited by added cofactors (NAD > NADH > NADP > NADPH) and enhanced by an argon instead of an air atmosphere. The responsible cytosolic enzyme(s) does not appear to be DT-diaphorase (which is inhibited by several neonicotinoids), aldose reductase, aldehyde reductase, or xanthine oxidase. However, the cytosolic metabolism of IMI is inhibited by several aldo-keto-reductase inhibitors (i.e., alrestatin, EBPC, Ponalrestat, phenobarbital, and quercetin). Other neonicotinoids with nitroimine, nitrosoimine, and nitromethylene substituents are probably also metabolized by "neonicotinoid nitro reductase(s)" since they serve as competitive substrates for [(3)H]IMI metabolism.

  14. cis-Terpin Hydrate Metabolism by a Brevibacterium: Patterns of Enzyme Induction, and Accumulation of α-Terpineol in Growth Media

    Science.gov (United States)

    Baum, Robert H.; Marr, Eleanor K.

    1972-01-01

    A brevibacterium, strain TH-4, previously isolated by aerobic enrichment on the monocyclic monoterpenoid cis-terpin hydrate as a sole carbon and energy source, was found to grow on α-terpineol and on a number of common sugars and organic acids. Oxidation of these terpenoids was shown to occur via an induced enzyme system, as measured manometrically by oxygen uptake and prevention of protein synthesis with chloramphenicol or puromycin. Oxidation of terpin hydrate by cell suspensions appeared to be coincidentally induced by growth on α-terpineol, and oxidation of α-terpineol similarly appeared to be induced by growth on terpin hydrate. Culture fluids in which the TH-4 organism was grown at the expense of cis-terpin hydrate were found to contain (−)-α-terpineol in combined butanol-ether extracts. The isolated compound was shown to be chromatographically and spectrophotometrically identical to an authentic sample of α-terpineol. The stereospecificity of an enzymatic dehydration of terpin hydrate to α-terpineol is considered. PMID:4336108

  15. Changes in CYP2D enzyme activity following induction of type 2 diabetes, and administration of cinnamon and metformin: an experimental animal study.

    Science.gov (United States)

    Taheri, Ali; Lavasani, Hoda; Kasirzadeh, Sara; Sheikholeslami, Behjat; Ardakani, Yalda H; Rouini, Mohammad-Reza

    2017-11-02

    1. Alterations in the activity of hepatic cytochrome P-450 isoenzymes result in changes in the pharmacokinetic behavior of drugs. This study was designed to explore the impact of type II diabetes, metformin and cinnamon on the activity of CYP2D isoenzyme. 2. Streptozotocin-nicotinamide-induced diabetic and normal rats were gavaged by cinnamon and/or metformin for 14 days. Using isolated perfusion of rat livers, the metabolic activity of CYP2D in the study groups was evaluated based on the oxidative biotransformation of tramadol hydrochloride. 3. The metabolic ratios of O-desmethyltramadol, the product of CYP2D-mediated metabolism of tramadol, in normal and diabetic control rats were found to be 0.33 ± 0.12 and 0.29 ± 0.07, respectively. Cinnamon significantly reduced the mentioned ratio in both normal and diabetic rats (0.13 ± 0.05 and 0.15 ± 0.04) and metformin increased the reduced activity in diabetic rats (0.37 ± 0.09 versus 0.29 ± 0.07). 4. In conclusion, it is evident that this study has shown the significant inhibitory effect of cinnamon on CYP2D. This finding suggests that it should be taken into consideration the possible metabolism-related pharmacokinetic drug-cinnamon interactions. 5. Additionally, type 2 diabetes condition reduced the enzyme activity and metformin consumption reversed this reduction; however, the significance of the latest is not clear.

  16. Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

    Science.gov (United States)

    Topletz, Ariel R.; Tripathy, Sasmita; Foti, Robert S.; Shimshoni, Jakob A.; Nelson, Wendel L.

    2015-01-01

    All-trans-retinoic acid (atRA), the active metabolite of vitamin A, induces gene transcription via binding to nuclear retinoic acid receptors (RARs). The primary hydroxylated metabolites formed from atRA by CYP26A1, and the subsequent metabolite 4-oxo-atRA, bind to RARs and potentially have biologic activity. Hence, CYP26A1, the main atRA hydroxylase, may function either to deplete bioactive retinoids or to form active metabolites. This study aimed to determine the role of CYP26A1 in modulating RAR activation via formation and elimination of active retinoids. After treatment of HepG2 cells with atRA, (4S)-OH-atRA, (4R)-OH-atRA, 4-oxo-atRA, and 18-OH-atRA, mRNAs of CYP26A1 and RARβ were increased 300- to 3000-fold, with 4-oxo-atRA and atRA being the most potent inducers. However, >60% of the 4-OH-atRA enantiomers were converted to 4-oxo-atRA in the first 12 hours of treatment, suggesting that the activity of the 4-OH-atRA was due to 4-oxo-atRA. In human hepatocytes, atRA, 4-OH-atRA, and 4-oxo-atRA induced CYP26A1 and 4-oxo-atRA formation was observed from 4-OH-atRA. In HepG2 cells, 4-oxo-atRA formation was observed even in the absence of CYP26A1 activity and this formation was not inhibited by ketoconazole. In human liver microsomes, 4-oxo-atRA formation was supported by NAD+, suggesting that 4-oxo-atRA formation is mediated by a microsomal alcohol dehydrogenase. Although 4-oxo-atRA was not formed by CYP26A1, it was depleted by CYP26A1 (Km = 63 nM and intrinsic clearance = 90 μl/min per pmol). Similarly, CYP26A1 depleted 18-OH-atRA and the 4-OH-atRA enantiomers. These data support the role of CYP26A1 to clear bioactive retinoids, and suggest that the enzyme forming active 4-oxo-atRA may be important in modulating retinoid action. PMID:25492813

  17. Pungent ginger components modulates human cytochrome P450 enzymes in vitro

    Science.gov (United States)

    Li, Mian; Chen, Pei-zhan; Yue, Qing-xi; Li, Jing-quan; Chu, Rui-ai; Zhang, Wei; Wang, Hui

    2013-01-01

    Aim: Ginger rhizome is used worldwide as a spicy flavor agent. This study was designed to explore the potential effects of pungent ginger components, 6-, 8-, and 10-gingerol, on human cytochrome P450 (CYP450) enzymes that are responsible for the metabolism of many prescription drugs. Methods: The activities of human CYP2C9, CYP2C19, CYP2D6, and CYP3A4 were analyzed using Vivid P450 assay kits. The mRNA expression of CYP3A4 in human hepatocellular carcinoma cell line HepG2 was measured using quantitative real-time PCR assay. Results: All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4, and weak inhibion on CYP2D6. 8-Gingerol was the most potent in inhibition of P450 enzymes with IC50 values of 6.8, 12.5, 8.7, and 42.7 μmol/L for CYP2C9, CYP2C19, CYP3A4, and CYP2D6, respectively. By comparing the effects of gingerols on CYP3A4 with three different fluorescent substrate probes, it was demonstrated that the inhibition of gingerols on CYP3A4 had no substrate-dependence. In HepG2 cells, 8-gingerol and 10-gingerol inhibited, but 6-gingerol induced mRNA expression of CYP3A4. Conclusion: 6-, 8-, and 10-gingerol suppress human cytochrome P450 activity, while 8- and 10-gingerol inhibit CYP3A4 expression. The results may have an implication for the use of ginger or ginger products when combined with therapeutic drugs that are metabolized by cytochrome P450 enzymes. PMID:23770984

  18. In vitro activity of Lycium barbarum (Goji) against major human phase I metabolism enzymes.

    Science.gov (United States)

    Liu, Rui; Tam, Teresa W; Mao, Jingqin; Salem, Ammar; Arnason, John T; Krantis, Anthony; Foster, Brian C

    2016-09-01

    Goji berry (Lycium barbarum) has been used as traditional Chinese medicine and a functional food in China. Goji tea may interact with drugs such as warfarin by inhibiting the cytochrome P450 (CYP) 2C9, and this study was undertaken to characterize the effect of Goji products on CYP2C9/19-, CYP2D6 *1/*10-, CYP3A4/5/7-, CYP19-, and flavin-containing monooxygenase (FMO) 3-mediated metabolism. Goji juice, water, and ethanol extracts were examined for their effect on CYP2C9/19-, 2D6-, 3A4/5/7-, 4A11-, CYP19-, and FMO3-mediated metabolism by using in vitro bioassay. The mechanism-based inactivation (MBI) of Goji juice on CYP3A4 was also examined. Data indicates that both fresh juice and commercially available juice caused strong inhibition (over 75 %) of most of the major CYP450 enzymes and moderate inhibition of FMO3 (30-60 %). Compared to juice, the Goji cold/hot water extracts effected low inhibition (below 30 %) of these enzymes. Ethanol (80 %) extracts exhibit the strongest inhibition on CYP2C9 and 2C19 (over 90 %). The inhibition pattern of dried and fresh berry extract and high-performance liquid chromatography (HPLC)-UV fingerprints were similar. These findings suggest that Goji products (berries, tea, tincture, and juice) can inhibit phase I drug metabolism enzymes and have the potential to affect the safety and efficacy of therapeutic products.

  19. The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method

    National Research Council Canada - National Science Library

    Cai, Jinzhang; Zhang, Qingwei; Lin, Kezhi; Hu, Lufeng; Zheng, Yuancai

    2015-01-01

      MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi), has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents...

  20. The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method

    National Research Council Canada - National Science Library

    Cai, Jinzhang; Zhang, Qingwei; Lin, Kezhi; Hu, Lufeng; Zheng, Yuancai

    2015-01-01

    MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi), has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents...

  1. Effect of Fruit/Vegetable-Drug Interactions on CYP450, OATP and p ...

    African Journals Online (AJOL)

    Purpose: To review the concomitant use of certain drugs with fruit/vegetable juices that may lead to drug-juice interactions resulting in medication-related problems. Method: In this systematic review, online databases (PubMed, Google Scholar and Science Direct) were searched for information on juices derived from fruits ...

  2. Analysis of Genetic Variation in CYP450 Genes for Clinical Implementation.

    Science.gov (United States)

    Goh, Liuh Ling; Lim, Chia Wei; Sim, Wey Cheng; Toh, Li Xian; Leong, Khai Pang

    2017-01-01

    Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. We designed a 32-SNP panel for PGx testing in clinical laboratories. The variants were selected using the clinical annotations of the Pharmacogenomics Knowledgebase (PharmGKB) and include polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A5 and VKORC1 genes. The CYP2D6 gene allele quantification was determined simultaneously with TaqMan copy number assays targeting intron 2 and exon 9 regions. The genotyping results showed high call rate accuracy according to concordance with genotypes identified by independent analyses on Sequenome massarray and droplet digital PCR. Furthermore, 506 genomic samples across three major ethnic groups of Singapore (Malay, Indian and Chinese) were analysed on our workflow. We found that 98% of our study subjects carry one or more CPIC actionable variants. The major alleles detected include CYP2C9*3, CYP2C19*2, CYP2D6*10, CYP2D6*36, CYP2D6*41, CYP3A5*3 and VKORC1*2. These translate into a high percentage of intermediate (IM) and poor metabolizer (PM) phenotypes for these genes in our population. Genotyping may be useful to identify patients who are prone to drug toxicity with standard doses of drug therapy in our population. The simplicity and robustness of this PGx panel is highly suitable for use in a clinical laboratory.

  3. Analysis of Genetic Variation in CYP450 Genes for Clinical Implementation.

    Directory of Open Access Journals (Sweden)

    Liuh Ling Goh

    Full Text Available Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories.We designed a 32-SNP panel for PGx testing in clinical laboratories. The variants were selected using the clinical annotations of the Pharmacogenomics Knowledgebase (PharmGKB and include polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A5 and VKORC1 genes. The CYP2D6 gene allele quantification was determined simultaneously with TaqMan copy number assays targeting intron 2 and exon 9 regions. The genotyping results showed high call rate accuracy according to concordance with genotypes identified by independent analyses on Sequenome massarray and droplet digital PCR. Furthermore, 506 genomic samples across three major ethnic groups of Singapore (Malay, Indian and Chinese were analysed on our workflow.We found that 98% of our study subjects carry one or more CPIC actionable variants. The major alleles detected include CYP2C9*3, CYP2C19*2, CYP2D6*10, CYP2D6*36, CYP2D6*41, CYP3A5*3 and VKORC1*2. These translate into a high percentage of intermediate (IM and poor metabolizer (PM phenotypes for these genes in our population.Genotyping may be useful to identify patients who are prone to drug toxicity with standard doses of drug therapy in our population. The simplicity and robustness of this PGx panel is highly suitable for use in a clinical laboratory.

  4. Bush mint (Hyptis suaveolens) and spreading hogweed (Boerhavia diffusa) medicinal plant extracts differentially affect activities of CYP1A2, CYP2D6 and CYP3A4 enzymes.

    Science.gov (United States)

    Ekow Thomford, Nicholas; Dzobo, Kevin; Adu, Faustina; Chirikure, Shadreck; Wonkam, Ambroise; Dandara, Collet

    2018-01-30

    Hyptis suaveolens (L) Poit and Boerhavia diffusa Linn are medicinal herbal plants commonly found in the tropics and sub-tropics. They are used to treat various conditions among them boils, dyslipidaemia, eczema, malaria, jaundice and gonorrhoea. Thus, the herbal medicinal extracts are now found as part of some commercial herbal formulations. There has not been adequate characterization of these medicinal herbs on their effects on drug metabolising enzymes. To investigate the effects of extracts of Hyptis suaveolens (HS) and Boerhavia diffusa (BD) on activity of drug metabolising enzymes, CYP1A2, CYP2D6 and CYP3A4, as well predict their potential for herb-drug interaction. A secondary aim was to identify constituent compounds such as polyphenolics, in the crude extract preparations of Hyptis suaveolens and Boerhavia diffusa and measure them for activity. CYP450 inhibition assays using recombinant CYP450 (rCYP) and fluorescence screening employing individual isozymes (CYP1A2, CYP2D6 and CYP3A4) were used to determine reversible- and time-dependent inhibition (TDI) profiles of extracts of Hyptis suaveolens and Boerhavia diffusa. Inhibition kinetic parameters, Ki and Kinact were also estimated. UPLC-MS employing a Synapt G2 (ESI negative) coupled to a PDA detector was used to identify polyphenolic compounds in crude extracts of Hyptis suaveolens and Boerhavia diffusa. The inhibitory potency of Hyptis suaveolens and Boerhavia diffusa extracts varied among the different enzymes, with CYP1A2 (3.68 ± 0.10µg/mL) being the least inhibited by HS compared to CYP2D6 (1.39 ± 0.01µg/mL) and CYP3A4 (2.36 ± 0.57µg/mL). BD was most potent on CYP3A4 (7.36 ± 0.94µg/mL) compared to both CYP2D6 (17.79 ± 1.02µg/mL) and CYP1A2 (9.48 ± 0.78µg/mL). Extracts of Hyptis suaveolens and Boerhavia diffusa exhibited TDIs on all CYPs. The most prominent phenolic candidates identified in both medicinal herbs using UPLC-MS analysis included caffeic acid, rutin, quercetin, citric acid

  5. Pancreatic Enzymes

    Science.gov (United States)

    ... NOW HONOR/MEMORIAL GENERAL DONATION MONTHLY PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  6. Pectic enzymes

    NARCIS (Netherlands)

    Benen, J.A.E.; Voragen, A.G.J.; Visser, J.

    2003-01-01

    The pectic enzymes comprise a diverse group of enzymes. They consist of main-chain depolymerases and esterases active on methyl- and acetylesters of galacturonosyl uronic acid residues. The depolymerizing enzymes comprise hydrolases as wel as lyases

  7. Detection of EETs and HETE-generating cytochrome P-450 enzymes and the effects of their metabolites on myometrial and vascular function.

    Science.gov (United States)

    Pearson, Timothy; Warren, Averil Y; Barrett, David A; Khan, Raheela N

    2009-09-01

    Cytochrome P-450 (CYP450) enzymes of the CYP2 and -4 family in humans metabolize arachidonic acid to generate bioactive epoxyeicosatrienenoic acids (EETs) and hydroxyeicosatetrenoic acids (HETEs). We report significantly higher levels of CYP 2J2 protein expression following the onset of labor (n = 6, P vascular reactivity (n = 6). Both 12- and 20-HETE (n = 5-6) caused vasoconstriction of partially depolarized blood vessels, with glibenclamide (n = 5) enhancing the effect of 12-HETE alone. Our findings signify a role for CYP2C9/19, -2J2, and -4A11/22 in late pregnancy, possibly related to the synthesis of lipid metabolites and downstream effects on vascular remodeling in the term pregnant uterus. The presence of CYP4A11/22 and their resultant procontractile metabolites could argue either a role in the control and initiation of labor and/or modification of the vascular delivery system to influence blood flow to the laboring uterus. The differential effects of the EETs and HETEs in the pregnant human uterus identify the CYP pathway as a novel modulator of myometrial and vascular physiology during late pregnancy.

  8. Practicing induction:

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Rohde, Nicolas

    2009-01-01

    We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning....

  9. Kunstige Enzymer

    DEFF Research Database (Denmark)

    Bols, Mikael; Bjerre, Jeannette; Marinescu, Lavinia

    2007-01-01

    Enzymer har en enestående evne til at accelerere kemiske processer. Der forskes målrettet i at optimere enzymer baseret på cyclodextrin.......Enzymer har en enestående evne til at accelerere kemiske processer. Der forskes målrettet i at optimere enzymer baseret på cyclodextrin....

  10. Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes

    Directory of Open Access Journals (Sweden)

    Barbara Pavan

    2018-01-01

    Full Text Available Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg, its concentration in whole blood (detected via HPLC decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

  11. Induction Brazing

    DEFF Research Database (Denmark)

    Henningsen, Poul

    Induction brazing is a fast and appropriate method for industrial joining of complex geometries and metal combinations. In all types of brazing processes it is important to heat the joint interface of the two materials to the same, high temperature. If one of the specimens is warmer than the other...... materials has large influence on the heating time and temperature distribution in induction heating. In order to ensure high and uniform temperature distribution near the interface of a joint between dissimilar materials the precise coil geometry and position is of great importance. The present report...... presents a combined numerical and experimental method for determination of appropriate/optimiged coil geometry and position in induction brazing tube-to-plate joints of different ratios between tube and plate thickness and different combinations of the materials stainless steel, brass and copper...

  12. Induction accelerators

    CERN Document Server

    Takayama, Ken

    2011-01-01

    A broad class of accelerators rests on the induction principle whereby the accelerating electrical fields are generated by time-varying magnetic fluxes. Particularly suitable for the transport of bright and high-intensity beams of electrons, protons or heavy ions in any geometry (linear or circular) the research and development of induction accelerators is a thriving subfield of accelerator physics. This text is the first comprehensive account of both the fundamentals and the state of the art about the modern conceptual design and implementation of such devices. Accordingly, the first part of the book is devoted to the essential features of and key technologies used for induction accelerators at a level suitable for postgraduate students and newcomers to the field. Subsequent chapters deal with more specialized and advanced topics.

  13. Enzyme assays

    OpenAIRE

    Bisswanger, Hans

    2014-01-01

    The essential requirements for enzyme assays are described and frequently occurring errors and pitfalls as well as their avoidance are discussed. The main factors, which must be considered for assaying enzymes, are temperature, pH, ionic strength and the proper concentrations of the essential components like substrates and enzymes. Standardization of these parameters would be desirable, but the diversity of the features of different enzymes prevents unification of assay conditions. Neverthele...

  14. Induction practice -

    DEFF Research Database (Denmark)

    Rohde, Nicolas; Sprogøe, Jonas

    2007-01-01

    of learning. We focus on and describe the interplay that takes place in particular induction events and analyze the "dance" through the lens of learning. The paper concludes with a brief discussion about the implications for practitioners and the challenges and future research prospects we have encountered....... We draw on an empirical enquiry in two organizational settings, a Danish management consulting company and a German retail bank....

  15. Enzyme Informatics

    Science.gov (United States)

    Alderson, Rosanna G.; Ferrari, Luna De; Mavridis, Lazaros; McDonagh, James L.; Mitchell, John B. O.; Nath, Neetika

    2012-01-01

    Over the last 50 years, sequencing, structural biology and bioinformatics have completely revolutionised biomolecular science, with millions of sequences and tens of thousands of three dimensional structures becoming available. The bioinformatics of enzymes is well served by, mostly free, online databases. BRENDA describes the chemistry, substrate specificity, kinetics, preparation and biological sources of enzymes, while KEGG is valuable for understanding enzymes and metabolic pathways. EzCatDB, SFLD and MACiE are key repositories for data on the chemical mechanisms by which enzymes operate. At the current rate of genome sequencing and manual annotation, human curation will never finish the functional annotation of the ever-expanding list of known enzymes. Hence there is an increasing need for automated annotation, though it is not yet widespread for enzyme data. In contrast, functional ontologies such as the Gene Ontology already profit from automation. Despite our growing understanding of enzyme structure and dynamics, we are only beginning to be able to design novel enzymes. One can now begin to trace the functional evolution of enzymes using phylogenetics. The ability of enzymes to perform secondary functions, albeit relatively inefficiently, gives clues as to how enzyme function evolves. Substrate promiscuity in enzymes is one example of imperfect specificity in protein-ligand interactions. Similarly, most drugs bind to more than one protein target. This may sometimes result in helpful polypharmacology as a drug modulates plural targets, but also often leads to adverse side-effects. Many cheminformatics approaches can be used to model the interactions between druglike molecules and proteins in silico. We can even use quantum chemical techniques like DFT and QM/MM to compute the structural and energetic course of enzyme catalysed chemical reaction mechanisms, including a full description of bond making and breaking. PMID:23116471

  16. Enzyme Informatics

    OpenAIRE

    Alderson, Rosanna G.; De Ferrari, Luna; Mavridis, Lazaros; McDonagh, James L.; Mitchell, John B O; Nath, Neetika

    2012-01-01

    Over the last 50 years, sequencing, structural biology and bioinformatics have completely revolutionised biomolecular science, with millions of sequences and tens of thousands of three dimensional structures becoming available. The bioinformatics of enzymes is well served by, mostly free, online databases. BRENDA describes the chemistry, substrate specificity, kinetics, preparation and biological sources of enzymes, while KEGG is valuable for understanding enzymes and metabolic pathways. EzCa...

  17. Influence of amino acid residues near the active site of cytochrome P450 from Bacillus megaterium on the selectivity of n-octane oxidation to octanol regioisomers

    Science.gov (United States)

    Miyaji, Akimitsu; Baba, Toshihide

    2017-09-01

    A mutant of cytochrome P450 from Bacillus megaterium (CYP450BM-3) was prepared by replacing two alanine residues around active site of the enzyme, alanine 328 and alanine 82, with leucine and tryptophan, respectively. The CYP450BM-3 mutant produced 2-octanol selectively from n-octane under atmospheric temperature and pressure; its selectivity was 74%. Furthermore, the mutant produced 1-octanol, which is not produced by wild-type enzyme.

  18. Lexicographic Path Induction

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Sarnat, Jeffrey

    2009-01-01

    an induction principle that combines the comfort of structural induction with the expressive strength of transfinite induction. Using lexicographic path induction, we give a consistency proof of Martin-Löf’s intuitionistic theory of inductive definitions. The consistency of Heyting arithmetic follows directly...

  19. Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2013-05-01

    Full Text Available Background/Aims: The components of cigarette smoke (CS have been implicated in the development of cancer as well as in cardiopulmonary diseases. We have previously reported increased oxidative stress in rat tissues induced by tobacco-specific toxins nicotine and 4-(N-methyl-N-nitrosamino-1-(3-pyridyl-1-butanone (NNK. Recently, we have also shown increased oxidative stress and associated inflammatory responses in various tissues after exposure to cigarette smoke. Methods: In this study, we have further investigated the effects of nose-only cigarette smoke exposure on mitochondrial functions and glutathione-dependent redox metabolism in tissues of BALB/C mice. Liver, kidney, heart and lung tissues were analyzed for oxidative stress, glutathione (GSH and cytochrome P450 dependent enzyme activities and mitochondrial functions after exposure to smoke generated by 9 cigarettes/day for 4 days. Control mice were exposed to air only. Results: An increase in oxidative stress as observed by increased production of reactive oxygen species (ROS and altered GSH metabolism was apparent in all the tissues, but lung and heart appeared to be the main targets. Increased expression and activity of CYP450 1A1 and 1A2 were also observed in the tissues after exposure to cigarette smoke. Mitochondrial respiratory dysfunction in the tissues, as observed by alterations in the activities of Complex I and IV enzymes, was also observed after exposure to cigarette smoke. SDS-PAGE and Western blot results also indicate that alterations in the expression of enzyme proteins were in accordance with the changes in their catalytic functions. Conclusion: These results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking.

  20. Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity.

    Science.gov (United States)

    Quintanilha, Júlia Coelho França; de Sousa, Vanessa Marcilio; Visacri, Marília Berlofa; Amaral, Laís Sampaio; Santos, Roseane Maria Maia; Zambrano, Tomás; Salazar, Luis Antonio; Moriel, Patricia

    2017-08-01

    The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure. We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.

  1. Enzyme immunoassay

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Dinesen, B; Deckert, M

    1985-01-01

    An enzyme linked immunoadsorbent assay for urinary albumin using commercially available reagents is described. The assay range is 2.5-120 micrograms/l. When samples are analysed in two standard dilutions, the assayable albumin concentration range is 2.5-240 mg/l, covering the clinical range from...

  2. Food Enzymes

    Science.gov (United States)

    McBroom, Rachel; Oliver-Hoyo, Maria T.

    2007-01-01

    Many students view biology and chemistry as two unrelated, separate sciences; how these courses are generally taught in high schools may do little to change that impression. The study of enzymes provide a great opportunity for both biology and chemistry teachers to share with students the interdisciplinary nature of science. This article describes…

  3. CYP-450 isoenzymes catalyze the generation of hazardous aromatic amines after reaction with the azo dye Sudan III.

    Science.gov (United States)

    Zanoni, Thalita Boldrin; Lizier, Thiago M; Assis, Marilda das Dores; Zanoni, Maria Valnice B; de Oliveira, Danielle Palma

    2013-07-01

    This work describes the mutagenic response of Sudan III, an adulterant food dye, using Salmonella typhimurium assay and the generation of hazardous aromatic amines after different oxidation methods of this azo dye. For that, we used metabolic activation by S9, catalytic oxidation by ironporphyrin and electrochemistry oxidation in order to simulate endogenous oxidation conditions. The oxidation reactions promoted discoloration from 65% to 95% of Sudan III at 1 × 10(-4)molL(-1) and generation of 7.6 × 10(-7)molL(-1) to 0.31 × 10(-4)molL(-1) of aniline, o-anisidine, 2-methoxi-5-methylaniline, 4-aminobiphenyl, 4,4'-oxydianiline; 4,4'-diaminodiphenylmethane and 2,6-dimethylaniline. The results were confirmed by LC-MS-MS experiments. We also correlate the mutagenic effects of Sudan III using S. typhimurium with the strain TA1535 in the presence of exogenous metabolic activation (S9) with the metabolization products of this compound. Our findings clearly indicate that aromatic amines are formed due to oxidative reactions that can be promoted by hepatic cells, after the ingestion of Sudan III. Considering that, the use of azo compounds as food dyestuffs should be carefully controlled. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. An extensive cocktail approach for rapid risk assessment of in vitro CYP450 direct reversible inhibition by xenobiotic exposure.

    Science.gov (United States)

    Spaggiari, Dany; Daali, Youssef; Rudaz, Serge

    2016-07-01

    Acute exposure to environmental factors strongly affects the metabolic activity of cytochrome P450 (P450). As a consequence, the risk of interaction could be increased, modifying the clinical outcomes of a medication. Because toxic agents cannot be administered to humans for ethical reasons, in vitro approaches are therefore essential to evaluate their impact on P450 activities. In this work, an extensive cocktail mixture was developed and validated for in vitro P450 inhibition studies using human liver microsomes (HLM). The cocktail comprised eleven P450-specific probe substrates to simultaneously assess the activities of the following isoforms: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and subfamily 3A. The high selectivity and sensitivity of the developed UHPLC-MS/MS method were critical for the success of this methodology, whose main advantages are: (i) the use of eleven probe substrates with minimized interactions, (ii) a low HLM concentration, (iii) fast incubation (5min) and (iv) the use of metabolic ratios as microsomal P450 activities markers. This cocktail approach was successfully validated by comparing the obtained IC50 values for model inhibitors with those generated with the conventional single probe methods. Accordingly, reliable inhibition values could be generated 10-fold faster using a 10-fold smaller amount of HLM compared to individual assays. This approach was applied to assess the P450 inhibition potential of widespread insecticides, namely, chlorpyrifos, fenitrothion, methylparathion and profenofos. In all cases, P450 2B6 was the most affected with IC50 values in the nanomolar range. For the first time, mixtures of these four insecticides incubated at low concentrations showed a cumulative inhibitory in vitro effect on P450 2B6. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A computational approach predicting CYP450 metabolism and estrogenic activity of an endocrine disrupting compound (PCB-30).

    Science.gov (United States)

    Harris, Jason B; Eldridge, Melanie L; Sayler, Gary; Menn, Fu-Min; Layton, Alice C; Baudry, Jerome

    2014-07-01

    Endocrine disrupting chemicals influence growth and development through interactions with the hormone system, often through binding to hormone receptors such as the estrogen receptor. Computational methods can predict endocrine disrupting chemical activity of unmodified compounds, but approaches predicting activity following metabolism are lacking. The present study uses a well-known environmental contaminant, PCB-30 (2,4,6-trichlorobiphenyl), as a prototype endocrine disrupting chemical and integrates predictive (computational) and experimental methods to determine its metabolic transformation by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) into estrogenic byproducts. Computational predictions suggest that hydroxylation of PCB-30 occurs at the 3- or 4-phenol positions and leads to metabolites that bind more strongly than the parent molecule to the human estrogen receptor alpha (hER-α). Gas chromatography-mass spectrometry experiments confirmed that the primary metabolite for CYP3A4 and CYP2D6 is 4-hydroxy-PCB-30, and the secondary metabolite is 3-hydroxy-PCB-30. Cell-based bioassays (bioluminescent yeast expressing hER-α) confirmed that hydroxylated metabolites are more estrogenic than PCB-30. These experimental results support the applied model's ability to predict the metabolic and estrogenic fate of PCB-30, which could be used to identify other endocrine disrupting chemicals involved in similar pathways. © 2014 SETAC.

  6. Polymorphisms in the Human Cytochrome P450 and Arylamine N-Acetyltransferase: Susceptibility to Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Rim Khlifi

    2013-01-01

    Full Text Available The occurrence of head and neck cancer (HNC is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s, such as CYP1A1, CYP1B1, and CYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, via CYP450 (CYP2E1 oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, two N-acetyltransferase isozymes (NATs, NAT1 and NAT2, are polymorphic and catalyze both N-acetylation and O-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochrome P450 enzymes (CYP1A1, CYP1BA1, CYP2D6, and CYP2E1, and two N-acetyltransferase isozymes (NAT1 and NAT2 in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i the interaction between these genes and the environment, (ii the impact of genetic defect on protein activity and/or expression, and (iii the eventual involvement of race in such associations.

  7. Enzyme Nanorings

    OpenAIRE

    Chou, Tsui-Fen; So, Christopher; White, Brian R.; Carlson, Jonathan C.T.; Sarikaya, Mehmet; Wagner, Carston

    2008-01-01

    We have demonstrated that nanostructures, and in particular nanorings incorporating a homodimeric enzyme, can be prepared by chemically induced self-assembly of dihydrofolate reductase (DHFR)-histidine triad nucleotide binding 1(Hint1) fusion proteins. The dimensions of the nanorings were found by static light scattering and atomic force microscopy studies to be dependent on the length and composition of the peptide linking the fusion proteins, ranging in size from 10 to 70 nm in diameter and...

  8. Screening for the optimal induction parameters for periplasmic ...

    African Journals Online (AJOL)

    ONOS

    2010-09-20

    Sep 20, 2010 ... 2Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra. Malaysia ... induction temperature and the length of induction) were analyzed to find the suitable range to be used ...... restriction enzyme EcoRI from recombinant Escherichia coli 294. Turk.

  9. Callus induction and growth in transgenic potato genotypes | Turhan ...

    African Journals Online (AJOL)

    The aim of this study was to establish an effective protocol for callus induction from the potato genotypes (Solanum tuberosum L.) used and to investigate whether the transferred oxalate oxidase enzyme or transformation procedure has any effect on callus induction of transgenic lines of cultivar Desiree and Maris Bard.

  10. Effect of Yajieshaba, a preparation of Dai indigenous medicine, on enhanced liver detoxification.

    Science.gov (United States)

    Xiaohua, Duan; Jin, Zheng; Hui, Wang; Haifeng, Cheng; Chao, Zhang; Zepu, Yu

    2015-04-01

    To explore the mechanistic effects of Yajieshaba (YJSB) on enhanced liver detoxification. The effects of YJSB on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in five acute chemical liver injury models [carbon tetrachloride (CCl4), D-galactosamine (D-Glan), 4-acetamidophenol (AAP), thioacetamide (TAA) and 1-naphthyl isothiocyanate (ANIT)]. Sleep latency and sleep time of pentobarbital sodium were tested in control mice and CCl4 model miceafter oral YJSB administration. The effects of YJSB on drug metabolism enzymes of liver microsomes were tested in control rats and CCl4 model rats. The levels of cytochrome P450 (CYP450) and Cyt b5 in liver microsomes were assayed using the method by Omura and Sato, and activities of erythromycin N-demethylase (ERD) and aminopyrine N-demethyl (ADM) were evaluated by Nash colorimetry. Probe substrate-based high performance liquid chromatography (HPLC) methods were established for CYP3A4 and CYP1A2. The level of serum ALT was reduced by YJSB at 3.51 g/kg in the five models as follows: CCl4 > D-Glan, AAP, ANIT > TAA. YJSB treatment did not reduce the level of serum AST. YJSB at 3.51 g/kg prolonged the sleep latency in control mice and shortened the sleep time of control mice and CCl4 model mice. For control rats, YJSB at 2.43 g/kg increased the levels of CYP450 and Cyt b5 and induced the activities of ERD and ADM; for liver injuries induced by CCl4 in rats, YJSB at 2.43 g/kg increased the levels of CYP450 and Cyt b5. These results suggest that YJSB at 2.43 g/kg induces CYP3A4 and CYP1A2. These results suggest that YJSB enhanced liver detoxification and the mechanisms may be partially related to CYP3A4 and CYP1A2 induction.

  11. Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

    Science.gov (United States)

    Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

    2016-06-01

    The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

  12. Storage stability study of porcine hepatic and intestinal cytochrome P450 isoenzymes by use of a newly developed and fully validated highly sensitive HPLC-MS/MS method.

    Science.gov (United States)

    Schelstraete, Wim; Devreese, Mathias; Croubels, Siska

    2018-01-11

    Microsomes are an ideal medium to investigate cytochrome P450 (CYP450) enzyme-mediated drug metabolism. However, before microsomes are prepared, tissues can be stored for a long time. Studies about the stability of these enzymes in porcine hepatic and intestinal tissues upon storage are lacking. To be able to investigate CYP450 stability in microsomes prepared from these tissues, a highly sensitive and rapid HPLC-MS/MS method for the simultaneous determination of six CYP450 metabolites in incubation medium was developed and validated. The metabolites, paracetamol (CYP1A), 7-hydroxy-coumarin (CYP2A), 1-hydroxy-midazolam (CYP3A), 4-hydroxy-tolbutamide (CYP2C), dextrorphan (CYP2D), and 6-hydroxy-chlorzoxazone (CYP2E) were extracted with ethyl acetate at pH 1.0, followed by evaporation and separation on an Agilent Zorbax Eclipse Plus C18 column. The method was fully validated in a GLP-compliant laboratory according to European guidelines and was highly sensitive (LOQ = 0.25-2.5 ng/mL), selective, had good precision (RSD-within, 1.0-9.1%; RSD-between, 1.0-18.4%) and accuracy (within-run, 83.3-102%; between-run, 78.5-102%), and showed no relative signal suppression and enhancement. Consequently, this method was applied to study the stability of porcine hepatic and intestinal CYP450 isoenzymes when tissues were stored at - 80 °C. The results indicate that porcine CYP450 isoenzymes are stable in tissues at least up to 4 months when snap frozen and stored at - 80 °C. Moreover, the results indicate differences in porcine CYP450 stability compared to rat, rabbit, and fish CYP450, as observed by other research groups, hence stressing the importance to investigate the CYP450 stability of a specific species.

  13. Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

    Directory of Open Access Journals (Sweden)

    Ganesan Anuradha

    2011-05-01

    Full Text Available Abstract Background To evaluate the efficacy of highly-active antiretroviral therapy (HAART in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs, we evaluated the virologic response to HAART with or without concurrent antiepileptic use. Methods Participants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group as well as to a matched group of individuals not taking AEDs (non-AED group. For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied. Results EI-AED participants (n = 19 had greater virologic failure (62.5% compared to NEI-AED participants (n = 85; 26.7% for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009. Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006. Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005. Compared to the non-AED group (n = 190, EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134, however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046. Conclusions Consistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.

  14. Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study.

    Science.gov (United States)

    Okulicz, Jason F; Grandits, Greg A; French, Jacqueline A; George, Jomy M; Simpson, David M; Birbeck, Gretchen L; Ganesan, Anuradha; Weintrob, Amy C; Crum-Cianflone, Nancy; Lalani, Tahaniyat; Landrum, Michael L

    2011-05-16

    To evaluate the efficacy of highly-active antiretroviral therapy (HAART) in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs), we evaluated the virologic response to HAART with or without concurrent antiepileptic use. Participants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group) as well as to a matched group of individuals not taking AEDs (non-AED group). For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied. EI-AED participants (n = 19) had greater virologic failure (62.5%) compared to NEI-AED participants (n = 85; 26.7%) for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009). Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006). Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005). Compared to the non-AED group (n = 190), EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134), however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046). Consistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.

  15. Inductive Monitoring System (IMS)

    Data.gov (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  16. Induction machine handbook

    CERN Document Server

    Boldea, Ion

    2002-01-01

    Often called the workhorse of industry, the advent of power electronics and advances in digital control are transforming the induction motor into the racehorse of industrial motion control. Now, the classic texts on induction machines are nearly three decades old, while more recent books on electric motors lack the necessary depth and detail on induction machines.The Induction Machine Handbook fills industry's long-standing need for a comprehensive treatise embracing the many intricate facets of induction machine analysis and design. Moving gradually from simple to complex and from standard to

  17. Involvement of methyltransferases enzymes during the energy ...

    African Journals Online (AJOL)

    The methyl group transfer from dimethylsulfide (DMS), trimethylamine and methanol to 2-mercaptoethanesulfonic acid (coenzyme M) were investigated from cell extracts of Methanosarcina semesiae sp. nov. to evaluate whether the enzyme systems involved were constitutive or inductive. The extracts from cells grown on ...

  18. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted by that enzyme......Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...

  19. Induction of morphological aberrations by enzyme inhibition in Drosophila melanogaster

    NARCIS (Netherlands)

    Bos, M.; Scharloo, W.; Bijlsma, R.; de Boer, I.M.; den Hollander, J.

    1969-01-01

    Zusatz zum Futter vonDrosophila melanogaster von 5-Fluoro-2-deoxyuridin oder Aminopterin induziert überzählige Skutellar- und Dorsozentralborsten sowie gekerbte Flügel. Diese Modifikationen wurden als Konsequenz von Enzymhemmung interpretiert.

  20. Induction of phenolics, lignin and key defense enzymes in eggplant ...

    African Journals Online (AJOL)

    The increase in total phenolic content of eggplant roots by the elicitors was significantly higher. Lignin deposition in the cell wall of eggplant roots was increased 5, 4, 3 and 3 times by SA, CHT, MeJA and MeSA at 96 h of elicitation, respectively. Phenylalanine ammonia-lyase (PAL) activity showed an increase of 4.7, 3.7, 3.5 ...

  1. Induction Therapy for Mesothelioma.

    Science.gov (United States)

    Opitz, Isabelle; Weder, Walter

    2015-01-01

    One particular approach of multimodality treatment for mesothelioma is induction therapy followed by surgery. Among its several advantages, the most important is downstaging of the tumor into a resectable stage, although morbidity and mortality might be increased. In this article we review the principles and outcome of different modalities for induction treatment of mesothelioma. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  3. Progress in Induction Linacs

    Energy Technology Data Exchange (ETDEWEB)

    Caporaso, G J

    2000-09-27

    This presentation will be a broad survey of progress in induction technology over the past four years. Much work has been done on accelerators for hydrodynamic test radiography and other applications. Solid-state pulsers have been developed which can provide unprecedented flexibility and precision in pulse format and accelerating voltage for both ion and electron induction machines. Induction linacs can now be built which can operate with MHz repetition rates. Solid-state technology has also made possible the development of fast kickers for precision control of high current beams. New insulator technology has been developed which will improve conventional induction linacs in addition to enabling a new class of high gradient induction linacs.

  4. Tryptophan catabolizing enzymes – party of three

    Directory of Open Access Journals (Sweden)

    Helen J Ball

    2014-10-01

    Full Text Available Indoleamine 2,3-dioxygenase (IDO and tryptophan 2,3-dioxygenase (TDO are tryptophan-degrading enzymes that have independently evolved to catalyze the first step in tryptophan catabolism via the kynurenine pathway. The depletion of tryptophan and formation of kynurenine pathway metabolites modulates the activity of the mammalian immune, reproductive and central nervous systems. IDO and TDO enzymes can have overlapping or distinct functions depending on their expression patterns. The expression of TDO and IDO enzymes in mammals differs not only by tissue/cellular localization but also by their induction by distinct stimuli. To add to the complexity, these genes also have undergone duplications in some organisms leading to multiple isoforms of IDO or TDO. For example, many vertebrates, including all mammals, have acquired two IDO genes via gene duplication, although the IDO1-like gene has been lost in some lower vertebrate lineages. Gene duplications can allow the homologs to diverge and acquire different properties to the original gene. There is evidence for IDO enzymes having differing enzymatic characteristics, signaling properties and biological functions. This review analyses the evolutionary convergence of IDO and TDO enzymes as tryptophan-catabolizing enzymes and the divergent evolution of IDO homologs to generate an enzyme family with diverse characteristics not possessed by TDO enzymes, with an emphasis on the immune system.

  5. Induction melter apparatus

    Science.gov (United States)

    Roach, Jay A [Idaho Falls, ID; Richardson, John G [Idaho Falls, ID; Raivo, Brian D [Idaho Falls, ID; Soelberg, Nicholas R [Idaho Falls, ID

    2008-06-17

    Apparatus and methods of operation are provided for a cold-crucible-induction melter for vitrifying waste wherein a single induction power supply may be used to effect a selected thermal distribution by independently energizing at least two inductors. Also, a bottom drain assembly may be heated by an inductor and may include an electrically resistive heater. The bottom drain assembly may be cooled to solidify molten material passing therethrough to prevent discharge of molten material therefrom. Configurations are provided wherein the induction flux skin depth substantially corresponds with the central longitudinal axis of the crucible. Further, the drain tube may be positioned within the induction flux skin depth in relation to material within the crucible or may be substantially aligned with a direction of flow of molten material within the crucible. An improved head design including four shells forming thermal radiation shields and at least two gas-cooled plenums is also disclosed.

  6. Thermal kinetic inductance detector

    Science.gov (United States)

    Cecil, Thomas; Gades, Lisa; Miceli, Antonio; Quaranta, Orlando

    2016-12-20

    A microcalorimeter for radiation detection that uses superconducting kinetic inductance resonators as the thermometers. The detector is frequency-multiplexed which enables detector systems with a large number of pixels.

  7. The use and value of in vitro technologies in metabolism studies.

    Science.gov (United States)

    Doehmer, Johannes

    2009-09-01

    The detailed investigation of the metabolism of drugs is one of the key issues in drug development. Several in vitro metabolism assays have been developed over the last two decades, to replace time-consuming and expensive animal studies. These have the potential to speed up drug development and increase drug safety, as they can be used to improve the prediction of the effects of drugs on humans. The key factors to be identified in metabolism are: a) the enzymes involved, and b) the metabolites produced by these enzymes. Cytochromes P450 (CYP-450s) are the key enzymes in drug metabolism. Cloning the genes encoding the CYP-450s, and the genetic engineering of suitable cells for heterologous expression, have provided new cell lines for studies on drug metabolism in vitro, under highly defined conditions. The V79 cell line, derived from Chinese hamster lung fibroblasts, was found to be suitable for heterologous expression, as these cells themselves do not express CYP-450s, thus providing a clean background for genetically engineering for the stable expression of any cloned CYP-450. In this way, V79 cell lines were created which specifically express CYP-450s from human, mouse, rat, and fish. These recombinant V79 cells have been applied in several drug metabolism and toxicity studies. 2009 FRAME.

  8. Fundamentals of enzyme kinetics.

    Science.gov (United States)

    Seibert, Eleanore; Tracy, Timothy S

    2014-01-01

    This chapter provides a general introduction to the kinetics of enzyme-catalyzed reactions, with a focus on drug-metabolizing enzymes. A prerequisite to understanding enzyme kinetics is having a clear grasp of the meanings of "enzyme" and "catalysis." Catalysts are reagents that can increase the rate of a chemical reaction without being consumed in the reaction. Enzymes are proteins that form a subset of catalysts. These concepts are further explored below.

  9. Industrial enzyme applications.

    Science.gov (United States)

    Kirk, Ole; Borchert, Torben Vedel; Fuglsang, Claus Crone

    2002-08-01

    The effective catalytic properties of enzymes have already promoted their introduction into several industrial products and processes. Recent developments in biotechnology, particularly in areas such as protein engineering and directed evolution, have provided important tools for the efficient development of new enzymes. This has resulted in the development of enzymes with improved properties for established technical applications and in the production of new enzymes tailor-made for entirely new areas of application where enzymes have not previously been used.

  10. Cloning and nitrate induction of nitrate reductase mRNA

    OpenAIRE

    Cheng, Chi-Lien; Dewdney, Julia; Kleinhofs, Andris; Goodman, Howard M.

    1986-01-01

    Nitrate is the major source of nitrogen taken from the soil by higher plants but requires reduction to ammonia prior to incorporation into amino acids. The first enzyme in the reducing pathway is a nitrate-inducible enzyme, nitrate reductase (EC 1.6.6.1). A specific polyclonal antiserum raised against purified barley nitrate reductase has been used to immunoprecipitate in vivo labeled protein and in vitro translation products, demonstrating that nitrate induction increases nitrate reductase p...

  11. Induction in a Modular Learner.

    Science.gov (United States)

    Carroll, Susanne E.

    2002-01-01

    Presents a theory of inductive learning--Autonomous Induction Theory--a form of induction that takes place within the autonomous and modular representational systems of the language faculty. Argues that Autonomous Induction Theory is constrained enough to be taken seriously as a plausible approach to explaining second language acquisition.…

  12. Transcriptome Assembly and Systematic Identification of Novel Cytochrome P450s in Taxus chinensis

    Directory of Open Access Journals (Sweden)

    Weifang Liao

    2017-08-01

    Full Text Available Taxus spp. is a highly valuable medicinal plant with multiple pharmacological effects on various cancers. Cytochrome P450s (CYP450s play important roles in the biosynthesis of active compounds in Taxus spp., such as the famous diterpenoid, Taxol. However, some specific CYP450 enzymes involved in the biosynthesis of Taxol remain unknown, and the systematic identification of CYP450s in Taxus has not been reported. In this study, 118 full-length and 175 partial CYP450 genes were identified in Taxus chinensis transcriptomes. The 118 full-length genes were divided into 8 clans and 29 families. The CYP71 clan included all A-type genes (52 belonging to 11 families. The other seven clans possessed 18 families containing 66 non-A-type genes. Two new gymnosperm-specific families were discovered, and were named CYP864 and CYP947 respectively. Protein sequence alignments revealed that all of the T. chinensis CYP450s hold distinct conserved domains. The expression patterns of all 118 CYP450 genes during the long-time subculture and MeJA elicitation were analyzed. Additionally, the expression levels of 15 novel CYP725 genes in different Taxus species were explored. Considering all the evidence, 6 CYP725s were identified to be candidates for Taxol biosynthesis. The cis-regulatory elements involved in the transcriptional regulation were also identified in the promoter regions of CYP725s. This study presents a comprehensive overview of the CYP450 gene family in T. chinensis and can provide important insights into the functional gene studies of Taxol biosynthesis.

  13. The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

    Science.gov (United States)

    Daneshmend, T K; Roberts, C J

    1984-01-01

    The oral and intravenous pharmacokinetics of labetalol were determined in five subjects before and after a 3 week course of glutethimide 500 mg/day. After glutethimide there was a significant reduction in the AUC after the oral dose of labetalol, from 40,596 +/- 11,534 (mean +/- s.e. mean) to 22,057 +/- 6,276 ng ml-1 min (2P less than 0.05), and systemic bioavailability was reduced from 30.3 +/- 2.8 to 17.0 +/- 3.5% (2P less than 0.001). There was no significant change in labetalol plasma concentration-time curve (AUC) following an intravenous dose, half-life, volume of distribution, and plasma clearance. The oral and intravenous pharmacokinetics of labetalol were determined in six subjects before and after a 3 day course of cimetidine 1.6 g/day. After cimetidine there was a significant reduction in the volume of distribution of labetalol, from 520 +/- 51 to 445 +/- 24 1 (2P less than 0.05). The AUC of labetalol after the oral dose increased by 66%, from 51,029 +/- 7,950 to 84,772 +/- 19,444 ng ml-1 min (2P = 0.06). The systemic bioavailability of labetalol increased from 25.1 +/- 2.4 to 39.0 +/- 7.6% (2P = 0.06). There was no significant change in labetalol AUC after the intravenous dose, half life, and plasma clearance. There were no significant changes in resting heart rate and supine systolic and diastolic blood pressure following labetalol plus glutethimide, or labetalol plus cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6487478

  14. Mutation induction in synchronous hamster cells

    Energy Technology Data Exchange (ETDEWEB)

    Aebersold, P.M.

    1975-11-01

    Mutagenesis of synchronous Mutahinese hamster cells by 5-bromodeoxyuridine (BUdR) shows pronounced cell cycle dependency. Resistance to 6-thioguanine (6-TG) and ouabain are induced maximally by BUdR at different times early in the DNA synthesis period, suggesting that the genes coding for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and the (Na/sup +/K/sup +/)-associated ATPase of the plasma membrane are replicated early in the DNA synthesis period. Although BUdR induces mutations in specific genes only when present during their replication, the rate of mutation induction is not linearly related to the amount of BUdR incorporated into DNA. The data show a BUdR concentration threshold for mutation induction, suggesting that BUdR exerts some deterimental allosteric effect on DNA synthesis enzymes.

  15. Induction and Natural Kinds

    Directory of Open Access Journals (Sweden)

    Howard Sankey

    1997-12-01

    Full Text Available The paper sketches an ontological solution to an epistemological problem in the philosophy of science. Taking the work of Hilary Kornblith and Brian Ellis as a point of departure, it presents a realist solution to the Humean problem of induction, which is based on a scientific essentialist interpretation of the principle of the uniformity of nature. More specifically, it is argued that use of inductive inference in science is rationally justified because of the existence of real, natural kinds of things, which are characterized as such by the essential properties which all members of a kind necessarily possess in common. The proposed response to inductive scepticism combines the insights of epistemic naturalism with a metaphysical outlook that is due to s cientific realism.

  16. Inductive dielectric analyzer

    Science.gov (United States)

    Agranovich, Daniel; Polygalov, Eugene; Popov, Ivan; Ben Ishai, Paul; Feldman, Yuri

    2017-03-01

    One of the approaches to bypass the problem of electrode polarization in dielectric measurements is the free electrode method. The advantage of this technique is that, the probing electric field in the material is not supplied by contact electrodes, but rather by electromagnetic induction. We have designed an inductive dielectric analyzer based on a sensor comprising two concentric toroidal coils. In this work, we present an analytic derivation of the relationship between the impedance measured by the sensor and the complex dielectric permittivity of the sample. The obtained relationship was successfully employed to measure the dielectric permittivity and conductivity of various alcohols and aqueous salt solutions.

  17. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  18. AmpC β-lactamase induction by avibactam and relebactam.

    Science.gov (United States)

    Livermore, David M; Jamrozy, Dorota; Mushtaq, Shazad; Nichols, Wright W; Young, Katherine; Woodford, Neil

    2017-12-01

    Diazabicyclooctanes, e.g. avibactam and relebactam, are a new class of β-lactamase inhibitors. Their spectrum includes AmpC enzymes, but it is important to understand whether they also induce these enzymes. Levels of ampC mRNA were measured by RT-PCR during 4 h of exposure of Enterobacter cloacae, Citrobacter freundii and Pseudomonas aeruginosa (n = 5 strains per species) to avibactam, relebactam and cefoxitin at 0, 1, 4 and 32 mg/L. The method had low precision compared with conventional specific-activity-based induction assays, which are impracticable for inhibitors. Accordingly, induction was only considered to be significant if induction ratios >10 were found at two consecutive time intervals, with 'strong induction' if one or more of these ratios was >100. Cefoxitin, as expected, gave concentration-dependent induction for all strains, with strong induction for 13/15. At the other extreme, relebactam caused no significant induction for any strain. Avibactam gave strain-variable results, with strong concentration-dependent induction for 2/5 E. cloacae and 2/5 P. aeruginosa, but little or no induction for the other strains, including all the C. freundii strains. Avibactam, but not relebactam, had some strain-variable ability to induce AmpC enzymes, though at concentrations (32 mg/L) above those reached in the patient.

  19. Ultraregular inductive limits

    Directory of Open Access Journals (Sweden)

    Jan Kucera

    1990-01-01

    Full Text Available An inductive limit E=indlim En is ultraregular if it is regular and each set B⊂En, which is bounded in E, is also bounded in En. A necessary and sufficient condition for ultraregularity of E is given provided each En is an LF-space which is closed in En+1.

  20. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system...

  1. Using Continuity Induction

    Science.gov (United States)

    Hathaway, Dan

    2011-01-01

    Here is a technique for proving the fundamental theorems of analysis that provides a unified way to pass from local properties to global properties on the real line, just as ordinary induction passes from local implication (if true for "k", the theorem is true for "k" + 1) to a global conclusion in the natural numbers.

  2. Xylanolytic enzyme systems in Arthrobacter sp MTCC 5214 and Lactobacillus sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Khandeparker, R.; Jalal, T.

    The production of extracellular xylanolytic enzymes such as xylanase, alfa-L-arabinofuranosidase (alfa-l-AFase), and acetyl xylan esterase (Axe) by marine Arthrobacter sp and Lactobacillus sp was investigated using different carbon sources Induction...

  3. Rapid birth-death evolution specific to xenobiotic cytochrome P450 genes in vertebrates.

    Directory of Open Access Journals (Sweden)

    James H Thomas

    2007-05-01

    Full Text Available Genes vary greatly in their long-term phylogenetic stability and there exists no general explanation for these differences. The cytochrome P450 (CYP450 gene superfamily is well suited to investigating this problem because it is large and well studied, and it includes both stable and unstable genes. CYP450 genes encode oxidase enzymes that function in metabolism of endogenous small molecules and in detoxification of xenobiotic compounds. Both types of enzymes have been intensively studied. My analysis of ten nearly complete vertebrate genomes indicates that each genome contains 50-80 CYP450 genes, which are about evenly divided between phylogenetically stable and unstable genes. The stable genes are characterized by few or no gene duplications or losses in species ranging from bony fish to mammals, whereas unstable genes are characterized by frequent gene duplications and losses (birth-death evolution even among closely related species. All of the CYP450 genes that encode enzymes with known endogenous substrates are phylogenetically stable. In contrast, most of the unstable genes encode enzymes that function as xenobiotic detoxifiers. Nearly all unstable CYP450 genes in the mouse and human genomes reside in a few dense gene clusters, forming unstable gene islands that arose by recurrent local gene duplication. Evidence for positive selection in amino acid sequence is restricted to these unstable CYP450 genes, and sites of selection are associated with substrate-binding regions in the protein structure. These results can be explained by a general model in which phylogenetically stable genes have core functions in development and physiology, whereas unstable genes have accessory functions associated with unstable environmental interactions such as toxin and pathogen exposure. Unstable gene islands in vertebrates share some functional properties with bacterial genomic islands, though they arise by local gene duplication rather than horizontal gene

  4. Inductive Communication System Design Summary

    Science.gov (United States)

    1978-09-01

    The report documents the experience obtained during the design and development of the Inductive Communications System used in the Morgantown People Mover. The Inductive Communications System is used to provide wayside-to-vehicle and vehicle-to-waysid...

  5. Enzymes and muscle diseases

    Directory of Open Access Journals (Sweden)

    M. Plebani

    2011-09-01

    Full Text Available Skeletal muscle disorders may result in release of muscle enzymes into the circulation and give increased serum enzyme activity. A variety of enzymes routinely determined in the clinical laboratory may be elevated, but creatine kinase is the enzyme present in the highest concentration in muscle, and in every variety of muscle disease is the serum enzyme which shows the greatest incidence and degree of elevation. Aspartate aminotransferase is the enzyme associated most significantly with inflammation. A diagnostic algorithm based on the combined measurement of creatine kinase, aspartate aminotransferase and aldolase has been found to discriminate muscular distrophies from polymyositis and other myopathies. This combination of laboratory tests has diagnostic application and thus allows the clinician to better select patients who need to have a skeletal muscle biopsy as a diagnostic procedure.

  6. Inductive Supervised Quantum Learning

    Science.gov (United States)

    Monràs, Alex; Sentís, Gael; Wittek, Peter

    2017-05-01

    In supervised learning, an inductive learning algorithm extracts general rules from observed training instances, then the rules are applied to test instances. We show that this splitting of training and application arises naturally, in the classical setting, from a simple independence requirement with a physical interpretation of being nonsignaling. Thus, two seemingly different definitions of inductive learning happen to coincide. This follows from the properties of classical information that break down in the quantum setup. We prove a quantum de Finetti theorem for quantum channels, which shows that in the quantum case, the equivalence holds in the asymptotic setting, that is, for large numbers of test instances. This reveals a natural analogy between classical learning protocols and their quantum counterparts, justifying a similar treatment, and allowing us to inquire about standard elements in computational learning theory, such as structural risk minimization and sample complexity.

  7. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    1990-01-01

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  8. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  9. Catabolite repression and nitrogen control of allantoin-degrading enzymes in Pseudomonas aeruginosa

    NARCIS (Netherlands)

    Janssen, D.B.; Drift, C. van der

    1983-01-01

    The formation of the allantoin-degrading enzymes allantoinase, allantoicase and ureidoglycolase in Pseudomonas aeruginosa was found to be regulated by induction, catabolite repression and nitrogen control. Induction was observed when urate, allantoin or allantoate were included in the growth medium,

  10. Enzymes for improved biomass conversion

    Science.gov (United States)

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  11. Inductive Temporal Logic Programming

    OpenAIRE

    Kolter, Robert

    2009-01-01

    We study the extension of techniques from Inductive Logic Programming (ILP) to temporal logic programming languages. Therefore we present two temporal logic programming languages and analyse the learnability of programs from these languages from finite sets of examples. In first order temporal logic the following topics are analysed: - How can we characterize the denotational semantics of programs? - Which proof techniques are best suited? - How complex is the learning task? In propositional ...

  12. Inductive Pulse Generation

    OpenAIRE

    Lindblom, Adam

    2006-01-01

    Pulsed power generators are a key component in compact systems for generation of high-power microwaves (HPM). HPM generation by virtual cathode devices such as Vircators put high demands on the source. The rise time and the pulse length of the source voltage are two key issues in the generation of HPM radiation. This thesis describes the construction and tests of several inductive high power pulse generators. The pulse generators were designed with the intent to deliver a pulse with fast rise...

  13. Profiling the orphan enzymes

    Science.gov (United States)

    2014-01-01

    The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new

  14. Enzymes in animal nutrition

    OpenAIRE

    Scientific Committee on Animal Nutrition

    2011-01-01

    This report brings overview of endogenous as well as exogenous enzymes and their role and importance in animal nutrition. Enzymes for animal nutrition have been systematically developed since 1980´s. Phytase, xylanase and β-glucanase are used in poultry-rising, pig breeding, aquaculture and begin to push to the ruminant nutrition. Phytase increase availability of P, Ca, Zn, digestibility of proteins and fats. Its positive effect on the environment is well described – enzymes decrease the cont...

  15. Enzyme catalysed tandem reactions

    OpenAIRE

    Oroz-Guinea, Isabel; García-Junceda, Eduardo

    2013-01-01

    To transfer to the laboratory, the excellent efficiency shown by enzymes in Nature, biocatalysis, had to mimic several synthetic strategies used by the living organisms. Biosynthetic pathways are examples of tandem catalysis and may be assimilated in the biocatalysis field for the use of isolated multi-enzyme systems in the homogeneous phase. The concurrent action of several enzymes that work sequentially presents extraordinary advantages from the synthetic point of view, since it permits a r...

  16. Food and feed enzymes.

    Science.gov (United States)

    Fraatz, Marco Alexander; Rühl, Martin; Zorn, Holger

    2014-01-01

    Humans have benefited from the unique catalytic properties of enzymes, in particular for food production, for thousands of years. Prominent examples include the production of fermented alcoholic beverages, such as beer and wine, as well as bakery and dairy products. The chapter reviews the historic background of the development of modern enzyme technology and provides an overview of the industrial food and feed enzymes currently available on the world market. The chapter highlights enzyme applications for the improvement of resource efficiency, the biopreservation of food, and the treatment of food intolerances. Further topics address the improvement of food safety and food quality.

  17. Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

    NARCIS (Netherlands)

    Price, R.J.; Scott, M.P.; Walters, D.G.; Stierum, R.H.; Groten, J.P.; Meredith, C.; Lake, B.G.

    2004-01-01

    The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets

  18. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    However, one of the proposed mechanisms for induction of acute pancreatitis is auto-digestion of pancreatic tissues by unwanted activation of pancreatic digestive enzymes. The main objective of this review is to describe the pathogenesis mechanism of acute pancreatitis that are related to various inflammatory and ...

  19. Acute but not chronic angiotensin-converting enzyme inhibition induces enzyme synthesis in the glomerulus of the spontaneously hypertensive rat.

    Science.gov (United States)

    Hodge, G; Makarious, M M; Charlesworth, J A; Duggan, K A

    1997-06-01

    1. Treatment with angiotensin-converting enzyme (ACE) inhibitors slows the rate of progression of nephropathy in the spontaneously hypertensive rat (SHR) with streptozotocin-induced diabetes. Paradoxically, however, chronic ACE inhibitor therapy has been reported to be associated with induction of ACE in the plasma. We sought to determine whether induction also occurred in the glomerulus. 2. Seven days after induction of diabetes rats were randomized to receive perindopril (4 mg/kg per day) in the drinking water or water alone. Blood glucoses were maintained 6-10 mmol/L by daily ultralente insulin. Rats were killed after 1 and 12 weeks of ACE inhibitor therapy and the kidneys were harvested. Angiotensin-converting enzyme activity was determined in isolated glomeruli before and after removal of perindopril and reconstitution with zinc sulphate. 3. After 1 week of ACE inhibitor therapy, glomerular ACE was significantly greater after removal of perindopril than either before its removal (P < 0.025) or in the untreated controls (P < 0.025). After 12 weeks of therapy, ACE activity was significantly lower in the perindopril-treated group than in the untreated controls (P < 0.025). There was no increase in ACE activity following removal of perindopril. 4. These studies suggest that short-term ACE inhibition is associated with induction of ACE in the glomerulus. However, there was no increase in ACE activity after removal of perindopril, suggesting that induction of synthesis of this enzyme in the glomerulus does not occur during chronic ACE inhibition.

  20. Acute porphyria: The drug demon etiology

    Directory of Open Access Journals (Sweden)

    Sridharan Kannan

    2015-01-01

    Full Text Available Drugs are one of the important factors that precipitate acute attacks in patients with porphyria. Various in vitro and preclinical animal models exist for determining porphyrogenicity of a drug, but these predictions are not very reliable. Ambiguities still remain with many drugs as to whether they are safe in patients with porphyria. An algorithm for determining the porphyrogenic potential using evidence from anectodotal reports, lipophilicity, affinity of a drug to the Cytochrome enzymes (CYP450, ability to induce or irreversibly inhibit either CYP450 2C9 or CYP450 3A4 and the ability to induce hepatic 5-aminolevulinate synthase has been devised. Management of an acute attack of porphyria involves symptomatic treatment and administration of haem arginate. Several international networks have been initiated that serve as good sources of information for the safe use of drugs to be used in porphyria.

  1. [Current aspects of labor induction].

    Science.gov (United States)

    Surbek, D V; Hösli, I; Holzgreve, W

    2002-12-01

    Induction of labor is one of the most important means for therapeutic intervention in modern obstetrics. The aim of labor induction is to achieve a better perinatal result for mother and baby as compared to expectative management. Different methods for induction include administration of oxytocin or prostaglandins, amniotomy, and mechanical means of cervical dilatation. The success of the labor induction depends primarily on the readiness of the uterus to go into labor, and the method used for induction. If the cervical ripeness is very advanced, induction with amniotomy and oxytocin seems beneficial. However if the cervix is not yet ready, intravaginal or intracervical prostaglandins are more promising. Until recently, prostaglandins E2 are used in the first line. Now, the prostaglandin E1-analogon misoprostol is also increasingly used. As a rule, induction of labor should be performed as an inpatient procedure in order to be able to provide the surveillance for maternal and fetal safety.

  2. Enzymes in Fermented Fish.

    Science.gov (United States)

    Giyatmi; Irianto, H E

    Fermented fish products are very popular particularly in Southeast Asian countries. These products have unique characteristics, especially in terms of aroma, flavor, and texture developing during fermentation process. Proteolytic enzymes have a main role in hydrolyzing protein into simpler compounds. Fermentation process of fish relies both on naturally occurring enzymes (in the muscle or the intestinal tract) as well as bacteria. Fermented fish products processed using the whole fish show a different characteristic compared to those prepared from headed and gutted fish. Endogenous enzymes like trypsin, chymotrypsin, elastase, and aminopeptidase are the most involved in the fermentation process. Muscle tissue enzymes like cathepsins, peptidases, transaminases, amidases, amino acid decarboxylases, glutamic dehydrogenases, and related enzymes may also play a role in fish fermentation. Due to the decreased bacterial number during fermentation, contribution of microbial enzymes to proteolysis may be expected prior to salting of fish. Commercial enzymes are supplemented during processing for specific purposes, such as quality improvement and process acceleration. In the case of fish sauce, efforts to accelerate fermentation process and to improve product quality have been studied by addition of enzymes such as papain, bromelain, trypsin, pepsin, and chymotrypsin. © 2017 Elsevier Inc. All rights reserved.

  3. Amperometric enzyme electrodes

    OpenAIRE

    Calvo,E.J.; Danilowicz, C.

    1997-01-01

    Recent advances on amperometric enzyme electrodes are reviewed with particular emphasis on biosensors based on Glucose Oxidase and Horseradish Peroxidase. Redox mediation by artificial soluble and polymer attached redox mediators is discussed in terms of recent theoretical developments and experimental verification. The dependence of the amperometric response on substrate and mediator concentration, enzyme concentration, electrode potential and film thickness are analyzed. Possible applicatio...

  4. Enzyme Vs. Extremozyme -32 ...

    Indian Academy of Sciences (India)

    industries, while Taq polymerase T 4 lysozyme, ribonuclease and malate dehydrogenase are enzymes used in research laboratories. A major limitation of most enzymes used in the industries/ research .... pol 1 , (8) Small domain of Klentaq 1 and (C) Superimposed cluster of aromatic residues in K1entaq1. (thick lines) ...

  5. ON-COLUMN ENRICHMENT OF HYDROPHOBIC CYP450 PROTEINS IN HPLC FRACTIONATION OF MOUSE MICROSOMES PRIOR TO PROTEIN DIGESTION AND NANOSPRAY-LC/MSMS ANALYSIS

    Science.gov (United States)

    IntroductionMembrane proteins play crucial role in many cellular processes and are promising candidates for biomarker discovery but are under-represented in the field of proteomics due to their hydrophobic nature. Although standard reversed-phase LC methods often exhibit ...

  6. CYP450-Dependent Biotransformation of the Insecticide Fipronil into Fipronil Sulfone Can Mediate Fipronil-Induced Thyroid Disruption in Rats (Full paper and erratum)

    OpenAIRE

    ROQUES, Beatrice; Lacroix, Marlène; Puel, Sylvie; Gayrard-Troy, Véronique; Hagen-Picard, Nicole; Jouanin, Isabelle; Perdu, Elisabeth; Martin, Pascal; Viguie, Catherine

    2012-01-01

    In rats, the widely used insecticide fipronil increases the clearance of thyroxine (T-4). This effect is associated with a high plasma concentration of fipronil sulfone, the fipronil main metabolite in several species including rats and humans. In sheep, following fipronil treatment, fipronil sulfone plasma concentration and thyroid disruption are much lower than in rats. We postulated that fipronil biotransformation into fipronil sulfone by hepatic cytochromes P450 (CYP) could act as a pote...

  7. E. coli infection modulates the pharmacokinetics of oral enrofloxacin by targeting P-glycoprotein in small intestine and CYP450 3A in liver and kidney of broilers.

    Science.gov (United States)

    Guo, Mengjie; Sun, Yong; Zhang, Yu; Bughio, Shamsuddin; Dai, Xiaohua; Ren, Weilong; Wang, Liping

    2014-01-01

    P-glycoprotein (P-gp) expression determines the absorption, distribution, metabolism and excretion of many drugs in the body. Also, up-regulation of P-gp acts as a defense mechanism against acute inflammation. This study examined expression levels of abcb1 mRNA and localization of P-gp protein in the liver, kidney, duodenum, jejunum and ileum in healthy and E. coli infected broilers by real time RT-PCR and immunohistochemistry. Meanwhile, pharmacokinetics of orally administered enrofloxacin was also investigated in healthy and infected broilers by HPLC. The results indicated that E. coli infection up-regulated expression of abcb1 mRNA levels significantly in the kidney, jejunum and ileum (P0.05). However, the expression level of CYP 3A37 mRNA were observed significantly decreased only in liver and kidney of E. coli infected broilers (Pinfection reduced absorption of orally administered enrofloxacin, significantly decreased Cmax (0.34 vs 0.98 µg mL(-1), P = 0.000) and AUC0-12h (4.37 vs 8.88 µg mL(-1) h, P = 0.042) of enrofloxacin, but increased Tmax (8.32 vs 3.28 h, P = 0.040), T1/2a(2.66 vs 1.64 h(-1), P = 0.050) and V/F (26.7 vs 5.2 L, P = 0.040). Treatment with verapamil, an inhibitor of P-gp, significantly improved the absorption of enrofloxacin in both healthy and infected broilers. The results suggest that the E. coli infection induces intestine P-gp expression, altering the absorption of orally administered enrofloxacin in broilers.

  8. Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of Tanzanian plant extracts traditionally used for treatment of fungal infections.

    Science.gov (United States)

    van den Bout-van den Beukel, Carolien J P; Hamza, Omar J M; Moshi, Mainen J; Matee, Mecky I N; Mikx, Frans; Burger, David M; Koopmans, Peter P; Verweij, Paul E; Schoonen, Willem G E J; van der Ven, André J A M

    2008-06-01

    HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.

  9. 17β Estradiol Modulates Perfusion Pressure and Expression of 5-LOX and CYP450 4A in the Isolated Kidney of Metabolic Syndrome Female Rats

    Directory of Open Access Journals (Sweden)

    A. M. Zúñiga-Muñoz

    2015-01-01

    Full Text Available Prevalence of metabolic syndrome and progression of nephropathy depend on sex. We examined a protective effect of estradiol against nephropathy in metabolic syndrome through the modulation of the arachidonic acid metabolism by activating the 5-lipoxygenase and cytochrome p450 4A pathways. 28 female Wistar rats were divided into four groups of seven animals each: control, intact metabolic syndrome, ovariectomized metabolic syndrome, and metabolic syndrome ovariectomized plus estradiol. Blood pressure, body weight, body fat, triglycerides, insulin, HOMA-index, albuminuria, and TNF-α were increased in ovariectomized metabolic syndrome rats (p<0.001. The perfusion pressure in isolated kidneys of ovariectomized metabolic syndrome rats in presence of 4 μg of arachidonic acid was increased. The inhibitors of the arachidonic acid metabolism Baicalein, Miconazole, and Indomethacin in these rats decreased the perfusion pressure by 57.62%, 99.83%, and 108.5%, respectively and they decreased creatinine clearance and the arachidonic acid percentage. Phospholipase A2 expression in the kidney of ovariectomized metabolic syndrome rats was not modified. 5-lipoxygenase was increased in metabolic syndrome ovariectomized rats while cytochrome p450 4A was decreased. In conclusion, the loss of estradiol increases renal damage while the treatment with estradiol benefits renal function by modulating arachidonic acid metabolism through the 5-lipoxygenase and cytochrome p450 4A pathways.

  10. NQO1 and CYP450 reductase decrease the systemic exposure of rifampicin-quinone and mediate its redox cycle in rats.

    Science.gov (United States)

    Shi, Fuguo; Li, Xiaobing; Pan, Hong; Ding, Li

    2017-01-05

    Rifampicin (RIF) is used in regimens for infections caused by Mycobacteria accompanied by serious adverse reactions. Rifampicin-quinone (RIF-Q) is a major autoxidation product of RIF. It is not clear whether RIF-Q plays a role in RIF induced adverse reactions. Investigation of the systemic exposure of RIF-Q is helpful to better understand the role of RIF-Q in RIF induced adverse reactions. In this study, a simple and reproducible high performance liquid chromatography-mass spectrometry (LC-MS) method involving a procedure to prevent the RIF from oxidation for simultaneous quantification of RIF and RIF-Q in rat plasma has been developed and validated, and applied to elucidate the systemic exposure of RIF-Q in rats. The pharmacokinetics data showed that the systemic exposure of RIF-Q was very low (0.67% of RIF, AUC0-24) in rats after oral administration of RIF. However, RIF-Q may undergo the redox cycle in vivo by the evidence that the majority of RIF-Q was reduced to RIF after an oral dose of RIF-Q. Pretreatment with the NAD(P)H: quinone oxidoreductase 1 (NQO1) specific inhibitor dicoumarol and/or cytochrome P450 reductase (CPR) inhibitor diphenyleneiodonium suppressed the redox cycle and significantly increased the systemic exposure of RIF-Q. The inhibitors also attenuated the redox cycle induced reactive oxygen species formation and cytotoxicity in RIF-Q-treated HepG2 cells. These results indicate that NQO1 and CPR play an important role in redox cycle of RIF-Q and may thus contribute to RIF-induced adverse reactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Low inductance gas switching.

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Ray; Harjes, Henry Charles III; Wallace, Zachariah; Elizondo, Juan E.

    2007-10-01

    The laser trigger switch (LTS) is a key component in ZR-type pulsed power systems. In ZR, the pulse rise time through the LTS is > 200 ns and additional stages of pulse compression are required to achieve the desired <100 ns rise time. The inductance of the LTS ({approx}500nH) in large part determines the energy transfer time through the switch and there is much to be gained in improving system performance and reducing system costs by reducing this inductance. The current path through the cascade section of the ZR LTS is at a diameter of {approx} 6-inches which is certainly not optimal from an inductance point of view. The LTS connects components of much greater diameter (typically 4-5 feet). In this LDRD the viability of switch concepts in which the diameter of cascade section is greatly increased have been investigated. The key technical question to be answered was, will the desired multi-channel behavior be maintained in a cascade section of larger diameter. This LDRD proceeded in 2 distinct phases. The original plan for the LDRD was to develop a promising switch concept and then design, build, and test a moderate scale switch which would demonstrate the key features of the concept. In phase I, a switch concept which meet all electrical design criteria and had a calculated inductance of 150 nH was developed. A 1.5 MV test switch was designed and fabrication was initiated. The LDRD was then redirected due to budgetary concerns. The fabrication of the switch was halted and the focus of the LDRD was shifted to small scale experiments designed to answer the key technical question concerning multi-channel behavior. In phase II, the Multi-channel switch test bed (MCST) was designed and constructed. The purpose of MCST was to provide a versatile, fast turn around facility for the study the multi-channel electrical breakdown behavior of a ZR type cascade switch gap in a parameter space near that of a ZR LTS. Parameter scans on source impedance, gap tilt, gap spacing and

  12. [Regulation of alpha-amylase biosynthesis in Bacillus diastaticus mutants with various levels of enzyme synthesis].

    Science.gov (United States)

    Murygina, V P

    1988-01-01

    The regulation of alpha-amylase biosynthesis was studied in Bacillus diastaticus mutants with different levels of the enzyme synthesis (by two orders of magnitude). The enzyme biosynthesis was shown to be regulated by induction and catabolite repression. Maltose, starch and methyl-alpha,D-glucoside (which cannot be metabolised) induced the synthesis while glucose and fructose acted as catabolite repressors.

  13. Regulation of malic enzyme synthesis by thyroid hormone and glucagon: inhibitor and kinetic experiments.

    Science.gov (United States)

    Goodridge, A G

    1978-06-01

    Synthesis of malic enzyme was rapidly and markedly stimulated by the addition of triiodothyronine to chick embryo liver cells in culture. Alpha-Amanitin, an inhibitor of DNA-dependent RNA polymerase II, blocked induction. The kinetics of induction and de-induction of malic enzyme synthesis suggested that the most stable event in triiodothyronine induction had a half-life of 18 to 20 h. However, malic enzyme synthesis decayed with a half-life of 2,4 h when transcription was inhibited with alpha-amanitin. Thus a long-lived event in thyroid hormone stimulation of malic enzyme synthesis occurred prior to transcription of a specific messenger RNA (mRNA), presumably malic enzyme mRNA. Malic enzyme synthesis decayed with a half-life of about 2 h when glucagon was added to pre-induced liver cells. The similarity of decay rates after inhibition of transcription with alpha-amanitin or inhibition of malic enzyme synthesis by glucagon suggests that glucagon may inhibit the transcription or processing of a specific mRNA required for malic enzyme synthesis.

  14. Indicators: Sediment Enzymes

    Science.gov (United States)

    Sediment enzymes are proteins that are produced by microorganisms living in the sediment or soil. They are indicators of key ecosystem processes and can help determine which nutrients are affecting the biological community of a waterbody.

  15. Enzyme catalysed tandem reactions.

    Science.gov (United States)

    Oroz-Guinea, Isabel; García-Junceda, Eduardo

    2013-04-01

    To transfer to the laboratory, the excellent efficiency shown by enzymes in Nature, biocatalysis, had to mimic several synthetic strategies used by the living organisms. Biosynthetic pathways are examples of tandem catalysis and may be assimilated in the biocatalysis field for the use of isolated multi-enzyme systems in the homogeneous phase. The concurrent action of several enzymes that work sequentially presents extraordinary advantages from the synthetic point of view, since it permits a reversible process to become irreversible, to shift the equilibrium reaction in such a way that enantiopure compounds can be obtained from prochiral or racemic substrates, reduce or eliminate problems due to product inhibition or prevent the shortage of substrates by dilution or degradation in the bulk media, etc. In this review we want to illustrate the developments of recent studies involving in vitro multi-enzyme reactions for the synthesis of different classes of organic compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Starch Biorefinery Enzymes.

    Science.gov (United States)

    Läufer, Albrecht

    2017-03-07

    Nature uses enzymes to build and convert biomass; mankind uses the same enzymes and produces them on a large scale to make optimum use of biomass in biorefineries. Bacterial α-amylases and fungal glucoamylases have been the workhorses of starch biorefineries for many decades. Pullulanases were introduced in the 1980s. Proteases, cellulases, hemicellulases, and phytases have been on the market for a few years as process aids, improving yields, performance, and costs. Detailed studies of the complex chemical structures of biomass and of the physicochemical limitations of industrial biorefineries have led enzyme developers to produce novel tailor-made solutions for improving yield and profitability in the industry. This chapter reviews the development of enzyme applications in the major starch biorefining processes.

  17. Vector control of induction machines

    CERN Document Server

    Robyns, Benoit

    2012-01-01

    After a brief introduction to the main law of physics and fundamental concepts inherent in electromechanical conversion, ""Vector Control of Induction Machines"" introduces the standard mathematical models for induction machines - whichever rotor technology is used - as well as several squirrel-cage induction machine vector-control strategies. The use of causal ordering graphs allows systematization of the design stage, as well as standardization of the structure of control devices. ""Vector Control of Induction Machines"" suggests a unique approach aimed at reducing parameter sensitivity for

  18. Technological inductive power transfer systems

    National Research Council Canada - National Science Library

    Nikolay D. Madzharov; Valentin S. Nemkov

    2017-01-01

    Inductive power transfer is a very fast expanding technology with multiple design principles and practical implementations ranging from charging phones and computers to bionic systems, car chargers...

  19. Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model

    NARCIS (Netherlands)

    Taher, Yousef A.; Piavaux, Benoit J. A.; Gras, Renee; van Esch, Betty C. A. M.; Hofman, Gerard A.; Bloksma, Nanne; Henricks, Paul A. J.; van Oosterhout, Antoon J. M.

    Background: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. Objective: We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive

  20. Regulation of the cellulolytic system in Trichoderma reesei by sophorose: induction of cellulase and repression of beta-glucosidase.

    OpenAIRE

    Sternberg, D; Mandels, G. R.

    1980-01-01

    Sophorose has two regulatory roles in the production of cellulase enzymes in Trichoderma reesei: beta-glucosidase repression and cellulase induction. Sophorose also is hydrolyzed by the mycelial-associated beta-glucosidase. Repression of beta-glucosidase reduces sophorose hydrolysis and thus may increase cellulase induction.

  1. Advances in enzyme immobilisation

    CSIR Research Space (South Africa)

    Brady, D

    2009-07-10

    Full Text Available substrate to fix the structure of cyclodextrin glycosyltransferases during rigidification by immobilisation, thereby enhancing the synthetic capability of the enzyme relative to its hydrolytic activity. In particular, modulation of enzyme... aggregates for enantioselective nitrile hydrolysis. Adv Synth Catal 349:2167- 2176 Kaulpiboon J, Pongsawasdi P, Zimmermann W (2007) Molecular imprinting of cyclodextrin glycosyltransferases from Paenibacillus sp. A11 and Bacillus macerans with γ-cyclodextrin...

  2. Overproduction of ligninolytic enzymes

    Science.gov (United States)

    Elisashvili, Vladimir; Kachlishvili, Eva; Torok, Tamas

    2014-06-17

    Methods, compositions, and systems for overproducing ligninolytic enzymes from the basidiomycetous fungus are described herein. As described, the method can include incubating a fungal strain of Cerrena unicolor IBB 303 in a fermentation system having growth medium which includes lignocellulosic material and then cultivating the fungal strain in the fermentation system under conditions wherein the fungus expresses the ligninolytic enzymes. In some cases, the lignocellulosic material is mandarin peel, ethanol production residue, walnut pericarp, wheat bran, wheat straw, or banana peel.

  3. Comprehensive Teacher Induction: Linking Teacher Induction to Theory

    Science.gov (United States)

    Keilwitz, Heather A.

    2014-01-01

    Teacher retention is a wide concern in education and in response school districts throughout the United States are developing more comprehensive teacher induction programs. Components of teacher induction programs that have assisted with successful teacher development include release time for teacher observation, assignment of a knowledgeable…

  4. Pre-Induction and Intrapartum Correlates of Successful Induction Of ...

    African Journals Online (AJOL)

    Context: Induction of labour (IOL) is a therapeutic challenge and an alternative to Caesarean section. Objectives: To evaluate the success rate of IOL and its determinants at the Ebonyi State University Teaching Hospital (EBSUTH), Abakaliki. Methods: A retrospective study involving 251 parturients who had induction of ...

  5. Induction heating using induction coils in series-parallel circuits

    Energy Technology Data Exchange (ETDEWEB)

    Matsen, Marc Rollo; Geren, William Preston; Miller, Robert James; Negley, Mark Alan; Dykstra, William Chet

    2017-11-14

    A part is inductively heated by multiple, self-regulating induction coil circuits having susceptors, coupled together in parallel and in series with an AC power supply. Each of the circuits includes a tuning capacitor that tunes the circuit to resonate at the frequency of AC power supply.

  6. The effect of inflammation on drug metabolism: A focus on pediatrics

    NARCIS (Netherlands)

    N.J. Vet (Nienke); M. de Hoog (Matthijs); D. Tibboel (Dick); S.N. de Wildt (Saskia)

    2011-01-01

    textabstractInflammation is associated with downregulation of the expression and activity of cytochrome P450 enzymes (CYP450) involved in hepatic drug metabolism. Elevated plasma drug levels and increased toxicity might be the consequences of this downregulation. Few clinical studies have

  7. Surface-modified electrodes in the mimicry of oxidative drug metabolism

    NARCIS (Netherlands)

    Yuan, Tao; Permentier, Hjalmar; Bischoff, Rainer

    2015-01-01

    This review discusses different approaches that have been taken to mimic oxidative drug metabolism as executed by members of the Cytochrome P450 (CYP450) family of enzymes in humans. Non-modified electrodes can be used to produce some of the oxidative drug metabolites observed in vivo but their

  8. Sampling Assumptions in Inductive Generalization

    Science.gov (United States)

    Navarro, Daniel J.; Dry, Matthew J.; Lee, Michael D.

    2012-01-01

    Inductive generalization, where people go beyond the data provided, is a basic cognitive capability, and it underpins theoretical accounts of learning, categorization, and decision making. To complete the inductive leap needed for generalization, people must make a key "sampling" assumption about how the available data were generated.…

  9. Regularity of conservative inductive limits

    Directory of Open Access Journals (Sweden)

    Jan Kucera

    1999-01-01

    Full Text Available A sequentially complete inductive limit of Fréchet spaces is regular, see [3]. With a minor modification, this property can be extended to inductive limits of arbitrary locally convex spaces under an additional assumption of conservativeness.

  10. Random-walk enzymes

    Science.gov (United States)

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C →U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  11. Enzyme recycling in lignocellulosic biorefineries

    DEFF Research Database (Denmark)

    Jørgensen, Henning; Pinelo, Manuel

    2017-01-01

    platform. Cellulases are the most important enzymes required in this process, but the complex nature of lignocellulose requires several other enzymes (hemicellulases and auxiliary enzymes) for efficient hydrolysis. Enzyme recycling increases the catalytic productivity of the enzymes by reusing them...... upscaled and tested in industrial settings, mainly because of many difficulties with recycling of enzymes from the complex lignocellulose hydrolyzate at industrially relevant conditions, i.e., high solids loadings. The challenges are associated with the large number of different enzymes required...... for efficient hydrolysis, enzyme stability, and the detrimental interaction between enzyme and lignin. This review provides a comprehensive overview of the various methods for enzyme recovery and recycling, for example recycling of free enzymes, readsorption to fresh material, recycling of solids, membrane...

  12. Detoxication enzymes as indicators of environmental stress on fish

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez, B.D. (Oak Ridge National Laboratory, TN (United States)); Stegeman, J.J. (Woods Hole Oceanographic Institution, MA (United States))

    1990-01-01

    Organisms possess several genetically mechanisms that cope with exposure to toxic contaminants in the environment. Two systems involved in the defense against xenobiotic compounds are the immune response and the induction of drug-metabolizing enzymes. Fish can metabolize foreign chemicals mainly by oxidation, reduction, hydrolysis, and conjugation reactions catalyzed by various enzymes, which are mainly localized in the liver but are also found in lower concentrations in other tissues. Metal-binding proteins (methallothioneins) also are induced by high concentrations of heavy metals. A major advantage of using the activity and quantity of these enzymes as indicators of stress instead of other biochemical measures is their sensitivity to specific types of pollutants. Efforts are being made to use enzyme activities in conjunction with other biological indicators, such as the immune response and histopathology of certain tissues, to evaluate integrated responses of organisms to chronic stress.

  13. Artificial Enzymes, "Chemzymes"

    DEFF Research Database (Denmark)

    Bjerre, Jeannette; Rousseau, Cyril Andre Raphaël; Pedersen, Lavinia Georgeta M

    2008-01-01

    that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called...... "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well...

  14. Induction of mixed-function oxidases in mouse liver by psoralens.

    Science.gov (United States)

    Mandula, B B; Pathak, M A; Nakayama, Y; Davidson, S J

    1978-12-01

    8-methoxypsoralen, the most widely used psoralen in photochemotherapy, was shown to induce mixed-function oxidases. Induction of mixed-function oxidases in mouse liver was examined after mice were given a single dose of one of three psoralens. 8-methoxypsoralen clearly induced p-nitroanisole O-demethylase and slightly induced aryl hydrocarbon hydroxylase. Psoralen and 4,5',8-trimethylpsoralen failed to induce either enzyme. These results represent the first enzyme induction studies on these clinically useful compounds. The studies may have relevance in understanding the clinical differences in skin photosensitizing activity and photochemotherapeutic effectiveness of the compounds in such diseases as psoriasis and vitiligo.

  15. Antibody induction versus corticosteroid induction for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, André; Wilson, Colin H

    2014-01-01

    BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation....... OBJECTIVES: To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register...... of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 September 2013 together with reference checking, citation searching, contact with trial authors and pharmaceutical companies...

  16. The surface science of enzymes

    DEFF Research Database (Denmark)

    Rod, Thomas Holm; Nørskov, Jens Kehlet

    2002-01-01

    One of the largest challenges to science in the coming years is to find the relation between enzyme structure and function. Can we predict which reactions an enzyme catalyzes from knowledge of its structure-or from its amino acid sequence? Can we use that knowledge to modify enzyme function......? To solve these problems we must understand in some detail how enzymes interact with reactants from its surroundings. These interactions take place at the surface of the enzyme and the question of enzyme function can be viewed as the surface science of enzymes. In this article we discuss how to describe...... catalysis by enzymes, and in particular the analogies between enzyme catalyzed reactions and surface catalyzed reactions. We do this by discussing two concrete examples of reactions catalyzed both in nature (by enzymes) and in industrial reactors (by inorganic materials), and show that although analogies...

  17. enzyme-linked

    African Journals Online (AJOL)

    SA MEDIESE TYDSKRIF DEEL 63 29 JANUARIE 1983. B surface antigen in donated screening and confirmation by immunosorbent assay. Hepatitis blood - enzyme-linked. M. O. BUBB, T. ... weeks at weekly intervals. After 6 weeks test blood samples were ... This assay normally takes 3 hours. Results. Fig. 1. Frequency ...

  18. Implantable enzyme amperometric biosensors.

    Science.gov (United States)

    Kotanen, Christian N; Moussy, Francis Gabriel; Carrara, Sandro; Guiseppi-Elie, Anthony

    2012-05-15

    The implantable enzyme amperometric biosensor continues as the dominant in vivo format for the detection, monitoring and reporting of biochemical analytes related to a wide range of pathologies. Widely used in animal studies, there is increasing emphasis on their use in diabetes care and management, the management of trauma-associated hemorrhage and in critical care monitoring by intensivists in the ICU. These frontier opportunities demand continuous indwelling performance for up to several years, well in excess of the currently approved seven days. This review outlines the many challenges to successful deployment of chronically implantable amperometric enzyme biosensors and emphasizes the emerging technological approaches in their continued development. The foreign body response plays a prominent role in implantable biotransducer failure. Topics considering the approaches to mitigate the inflammatory response, use of biomimetic chemistries, nanostructured topographies, drug eluting constructs, and tissue-to-device interface modulus matching are reviewed. Similarly, factors that influence biotransducer performance such as enzyme stability, substrate interference, mediator selection and calibration are reviewed. For the biosensor system, the opportunities and challenges of integration, guided by footprint requirements, the limitations of mixed signal electronics, and power requirements, has produced three systems approaches. The potential is great. However, integration along the multiple length scales needed to address fundamental issues and integration across the diverse disciplines needed to achieve success of these highly integrated systems, continues to be a challenge in the development and deployment of implantable amperometric enzyme biosensor systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Angiotensin-converting enzyme

    DEFF Research Database (Denmark)

    Sørensen, P G; Rømer, F K; Cortes, D

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog...

  20. Enzymes and fungal virulence

    African Journals Online (AJOL)

    may be common across a variety of fungal pathogens. Most fungal pathogens and ... Fungi utilize the food substances in their immediate vicinity to .... digestion of the fungal secreted enzymes thereby denying access to the host cell. For a pathogen to be successful, it mttst be able to circumvent or overcome these antifungal ...

  1. [Elevated liver enzymes].

    Science.gov (United States)

    Holstege, Axel

    2016-10-01

    Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients necessitating further evaluation to clarify the underlying disease. Three different patterns of increased liver enzymes can be defined to allow for a more precise and rational further diagnostic approach. A predominant increase in transaminase activities reflects a disturbance of hepatocellular integrity which can be found in patients with viral hepatitis, genetic liver diseases like Wilson`s disease or hemochromatosis, and drug-induced liver diseases. A second pattern is characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities indicating cholestatic liver diseases. The next important diagnostic measure in this group is an ultrasound study discerning intra- from extrahepatic cholestasis. Intrahepatic cholestatic diseases include primary and secondary sclerosing cholangitis, genetic disturbances of canalicular membrane transporters or drug-induced liver dieseases. Extrahepatic cholestasis involves obstruction of the large bile ducts by gall stones or tumors. The third enzym pattern is defined by a predominant rise in γ-glutamyl transpeptidase which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases. A rise in liver enzymes is not necessarily indicative of a primary hepatic origin. Extrahepatic diseases often cause similarly increased serum activities. In addition even higher values can be observed under normal conditions during pregnancy or in adolescens. Lower values in asymptomatic patients should only be controlled since more than 30% of elevated transaminases spontaneously normalize during follow-up. © Georg Thieme Verlag KG Stuttgart · New York.

  2. ISFET based enzyme sensors

    NARCIS (Netherlands)

    van der Schoot, Bart H.; Bergveld, Piet

    1987-01-01

    This paper reviews the results that have been reported on ISFET based enzyme sensors. The most important improvement that results from the application of ISFETs instead of glass membrane electrodes is in the method of fabrication. Problems with regard to the pH dependence of the response and the

  3. Enzymes and fungal virulence

    African Journals Online (AJOL)

    Plant pathogenic fungi secrete extracellular enlymes that are capable of degrading the cell walls of their host plants. These CWDES may be necessary for penetration ofthc cell wall harricr. as well as for generation of simple molecules that can he assimilated for growth. Most of these enzymes are substrawinducible and both ...

  4. Induction, complexity, and economic methodology

    OpenAIRE

    Smith, Peter

    2009-01-01

    This paper focuses on induction, because the supposed weaknesses of that process are the main reason for favouring falsificationism, which plays an important part in scientific methodology generally; the paper is part of a wider study of economic methodology. The standard objections to, and paradoxes of, induction are reviewed, and this leads to the conclusion that the supposed ‘problem’ or ‘riddle’ of induction is a false one. It is an artefact of two assumptions: that the classic two-valued...

  5. Overview of Bearingless Induction Motors

    Directory of Open Access Journals (Sweden)

    Xiaodong Sun

    2014-01-01

    Full Text Available Bearingless induction motors combining functions of both torque generation and noncontact magnetic suspension together have attracted more and more attention in the past decades due to their definite advantages of compactness, simple structure, less maintenance, no wear particles, high rotational speed, and so forth. This paper overviews the key technologies of the bearingless induction motors, with emphasis on motor topologies, mathematical models, and control strategies. Particularly, in the control issues, the vector control, independent control, direct torque control, nonlinear decoupling control, sensorless control, and so forth are investigated. In addition, several possible development trends of the bearingless induction motors are also discussed.

  6. The Enzyme Function Initiative†

    Science.gov (United States)

    Gerlt, John A.; Allen, Karen N.; Almo, Steven C.; Armstrong, Richard N.; Babbitt, Patricia C.; Cronan, John E.; Dunaway-Mariano, Debra; Imker, Heidi J.; Jacobson, Matthew P.; Minor, Wladek; Poulter, C. Dale; Raushel, Frank M.; Sali, Andrej; Shoichet, Brian K.; Sweedler, Jonathan V.

    2011-01-01

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily-specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include: 1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation); 2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia; 3) computational and bioinformatic tools for using the strategy; 4) provision of experimental protocols and/or reagents for enzyme production and characterization; and 5) dissemination of data via the EFI’s website, enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal and pharmaceutical efforts. PMID

  7. Monitoring enzyme kinetic behavior of enzyme-quantum dot bioconjugates

    Science.gov (United States)

    Claussen, Jonathan C.; Walper, Scott A.; Susumu, Kimihiro; Ancona, Mario G.; Medintz, Igor L.

    2014-05-01

    Luminescent semiconductor nanocrystals or quantum dots (QDs) hold tremendous promise for in vivo biosensing, cellular imaging, theranostics, and smart molecular sensing probes due to their small size and favorable photonic properties such as resistance to photobleaching, size-tunable PL, and large effective Stokes shifts. Herein, we demonstrate how QD-based bioconjugates can be used to enhance enzyme kinetics. Enzyme-substrate kinetics are analyzed for solutions containing both alkaline phosphatase enzymes and QDs with enzyme-to- QD molar ratios of 2, 12, and 24 as well as for a solution containing the same concentration of enzymes but without QDs. The enzyme kinetic paramters Vmax, KM, and Kcat/KM are extracted from the enzyme progress curves via the Lineweaver-Burk plot. Results demonstrate an approximate increase in enzyme efficiency of 5 - 8% for enzymes immobilized on the QD versus free in solution without QD immobilization.

  8. Survey of Inductive Communication Systems

    Science.gov (United States)

    1975-04-01

    A survey is made of various inductive systems proposed for low frequency train communication. It is found that thick dielectric jackets or coaxial and metallic shields may be required to reduce the environmental effects that lead to high attenuation....

  9. Fault diagnosis of induction motors

    CERN Document Server

    Faiz, Jawad; Joksimović, Gojko

    2017-01-01

    This book is a comprehensive, structural approach to fault diagnosis strategy. The different fault types, signal processing techniques, and loss characterisation are addressed in the book. This is essential reading for work with induction motors for transportation and energy.

  10. ORGANIZATIONAL DEVELOPMENT ACTION: INDUCTION PROGRAM

    National Research Council Canada - National Science Library

    José G. VARGAS-HERNÁNDEZ

    2016-01-01

    .... Also, an induction program is presented as an intervention proposal of organization development, on the premise that this program is a first step in the solving of the existing low productivity problem...

  11. Timing of enzyme synthesis during outgrowth of spores of Bacillus cereus. I. Ordered enzyme synthesis.

    Science.gov (United States)

    Steinberg, W; Halvorson, H O

    1968-02-01

    During outgrowth of spores of Bacillus cereus T, the pattern of enzymes synthesized varied with respect to time. The periods of synthesis of alpha-glucosidase, l-alanine dehydrogenase, and histidase were ordered; each began at a specific time and synthesis continued for only a brief period. An examination of the timing of induced alpha-glucosidase and induced histidase was made to determine whether specific regions of the genome were continually available for transcription and regulation during this period. Several observations indicated that inducers could function during outgrowth, but for only a limited time interval. The period of induced enzyme synthesis occurred over the same interval as that observed for uninduced and catabolically repressed cultures. When inducer was added partway through the period of gene expression, the level of enzyme induction was diminished. Addition of inducer at a time after the period of gene expression had no significant effect. Since messenger ribonucleic acid formed during outgrowth had a half-life of only a few minutes, it was concluded that ordered enzyme synthesis was a result of ordered transcription of the corresponding portion of the genome. An examination of the timing of induced alpha-glucosidase and histidase synthesized in the presence of actinomycin D supported this conclusion.

  12. Inductance and hypergeometric functions. II

    DEFF Research Database (Denmark)

    Karlsson, Per W.

    2000-01-01

    A previously obtained integral for the self-inductance of a solenoid is further transformed. The resulting formula involves double Kampé de Fériet functions which are analytic continuations rather than power series.......A previously obtained integral for the self-inductance of a solenoid is further transformed. The resulting formula involves double Kampé de Fériet functions which are analytic continuations rather than power series....

  13. On-Site Enzyme Production by Trichoderma asperellum for the Degradation of Duckweed

    DEFF Research Database (Denmark)

    Bech, Lasse; Herbst, Florian-Alexander; Grell, Morten Nedergaard

    2015-01-01

    was performed on T. asperellum growing on PDA agar, wheat bran and duckweed, respectively. T. asperellum proved to be able to produce a wide enzyme profile, including both depolymerization and debranching enzymes, mainly consisting of hemi-cellulases. The secretome analysis showed specific glycoside hydrolase......-induction on duckweed compared with growth on wheat bran and PDA, including a GH62 $-L-arabinofuranosidase, a promising candidate enzyme for the degradation of duckweed. The enzyme cocktail from T. asperellum proved capable of degrading pretreated duckweed, obtaining up to 60% of the theoretical glucose yield, making...

  14. Regulation mechanisms of enzymes in ontogenesis. Mekhanizmy regulyatsii fermentov v ontogeneze

    Energy Technology Data Exchange (ETDEWEB)

    Parina, E.V.; Kaliman, P.A.

    1978-01-01

    An examination is made of the basic principles underlying the regulation of enzyme activity in tissues, its changes in connection with metabolic characteristics at various periods of ontogenesis as well as contemporary concepts on the mechanisms of age changes in enzyme activity. Considerable attention is given to features of enzyme induction and adaptation with respect to the organism's age. The book is intended for biochemists, physiologists, biologists, and specialists in medicine and animal husbandary engaged in problems of ontogenesis, gerontology, geriatrics, and enzyme regulation. 475 references, 39 figures, 15 tables.

  15. Purinergic agonist induction of metallothionein.

    Science.gov (United States)

    Xiong, X; Garrett, S H; Arizono, K; Brady, F O

    1992-10-01

    Metallothionein (MT) protein is readily induced in vivo in rat liver by adenosine and adenosine agonists (2-chloroadenosine, 5-(N-ethyl) carboxamido adenosine, and 5-chloro-5-deoxyadenosine). These presumably operate via AMP/adenosine receptors of the P1 (A2) type, which use the cAMP pathway. ATP was ineffective as an inducer for MT. 2-Chloroadenosine was the most effective inducer (7.27-fold at 11 hr). This induction was blockable by the adenosine antagonists, caffeine and theophylline. MT protein induction by 2-chloroadenosine in primary cultured rat hepatocytes was modest (1.55-fold), but this was also blocked by theophylline. MT mRNA induction was assessed using dot blot and Northern gel assays. Large inductions by 2-chloroadenosine (5.1- to 41-fold) were seen, and these were detectable as early as 2 hr in vivo. Two rat hepatoma cell lines (EC3 and 2M) were studied in vitro. Modest inductions of MT mRNA were seen: 2.10-fold for EC3 and 4.12-fold for 2M. Our studies implicate the potential role of the purinergic system in the modulation of transcription of MT genes in rat liver. The sources of adenosine in vivo that might cause induction of MT mRNA and protein are not well defined, but adenosine may be important as a signal in stress response situations involving tissue damage, such as ischemia, hypoxia, and hemorrhagic shock.

  16. Special Issue: Retroviral Enzymes

    Directory of Open Access Journals (Sweden)

    Luis Menéndez-Arias

    2010-05-01

    Full Text Available The retroviral RNA genome encodes for three enzymes essential for virus replication: (i the viral protease (PR, that converts the immature virion into a mature virus through the cleavage of precursor polypeptides; (ii the reverse transcriptase (RT, responsible for the conversion of the single-stranded genomic RNA into double-stranded proviral DNA; and (iii the integrase (IN that inserts the proviral DNA into the host cell genome. All of them are important targets for therapeutic intervention. This Special Issue provides authoritative reviews on the most recent research towards a better understanding of structure-function relationships in retroviral enzymes. The Issue includes three reviews on retroviral PRs, seven on RT and reverse transcription, and four dedicated to viral integration. [...

  17. Halophilic adaptation of enzymes.

    Science.gov (United States)

    Madern, D; Ebel, C; Zaccai, G

    2000-04-01

    It is now clear that the understanding of halophilic adaptation at a molecular level requires a strategy of complementary experiments, combining molecular biology, biochemistry, and cellular approaches with physical chemistry and thermodynamics. In this review, after a discussion of the definition and composition of halophilic enzymes, the effects of salt on their activity, solubility, and stability are reviewed. We then describe how thermodynamic observations, such as parameters pertaining to solvent-protein interactions or enzyme-unfolding kinetics, depend strongly on solvent composition and reveal the important role played by water and ion binding to halophilic proteins. The three high-resolution crystal structures now available for halophilic proteins are analyzed in terms of haloadaptation, and finally cellular response to salt stress is discussed briefly.

  18. Membrane Assisted Enzyme Fractionation

    DEFF Research Database (Denmark)

    Yuan, Linfeng

    Purification of proteins is an increasingly important process for the biotechnology industry. Separation of the desired high value protein from other proteins produced by the cell is usually attempted using a combination of different chromatographic techniques. These techniques separate mixtures...... of proteins on the basis of their charge, degree of hydrophobicity, affinity or size. Adequate purity is often not achieved unless several purification steps are combined thereby increasing cost and reducing product yield. Conventional fractionation of proteins using ultrafiltration membranes is limited....... In this thesis, separations using crossflow elecro-membrane filtration (EMF) of amino acids, bovine serum albumin (BSA) and industrial enzymes from Novozymes were performed. The main objective of this study was to investigate the technological feasibility of EMF in the application of industrial enzyme...

  19. Quorum quenching enzymes.

    Science.gov (United States)

    Fetzner, Susanne

    2015-05-10

    Bacteria use cell-to-cell communication systems based on chemical signal molecules to coordinate their behavior within the population. These quorum sensing systems are potential targets for antivirulence therapies, because many bacterial pathogens control the expression of virulence factors via quorum sensing networks. Since biofilm maturation is also usually influenced by quorum sensing, quenching these systems may contribute to combat biofouling. One possibility to interfere with quorum sensing is signal inactivation by enzymatic degradation or modification. Such quorum quenching enzymes are wide-spread in the bacterial world and have also been found in eukaryotes. Lactonases and acylases that hydrolyze N-acyl homoserine lactone (AHL) signaling molecules have been investigated most intensively, however, different oxidoreductases active toward AHLs or 2-alkyl-4(1H)-quinolone signals as well as other signal-converting enzymes have been described. Several approaches have been assessed which aim at alleviating virulence, or biofilm formation, by reducing the signal concentration in the bacterial environment. These involve the application or stimulation of signal-degrading bacteria as biocontrol agents in the protection of crop plants against soft-rot disease, the use of signal-degrading bacteria as probiotics in aquaculture, and the immobilization or entrapment of quorum quenching enzymes or bacteria to control biofouling in membrane bioreactors. While most approaches to use quorum quenching as antivirulence strategy are still in the research phase, the growing number of organisms and enzymes known to interfere with quorum sensing opens up new perspectives for the development of innovative antibacterial strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Uronic polysaccharide degrading enzymes.

    Science.gov (United States)

    Garron, Marie-Line; Cygler, Miroslaw

    2014-10-01

    In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Modulation of radical pairs dynamics immersed in an ELF-EMF: The effect on hepatocarcinogenesis

    Science.gov (United States)

    López-Riquelme, G. O.; López-Sandoval, E.; Vera-Aguilar, E.; Godina-Nava, J. J.

    2015-01-01

    The most suitable mechanism of action of electromagnetic fields (EMF) on biological systems is the effect on the radical pair (RP) recombination through the Zeeman effect and hyperfine interaction, which changes the rate of reactions or the product distribution. Enzyme reactions with RP intermediates can be altered by EMF, like those catalyzed by cytochrome P450 enzymes (CYP450), a heme-thiolate family protein that detoxifies xenobiotics and involved in chemical carcinogenesis. CYP450 activate chemical carcinogens producing an enormous amount of free radicals, which damage the DNA resulting in the malignant transformation of cells. During the activation, CYP450 produce spin-correlated RP intermediates that can either go to recombination or to continue the catalytic process. As CYP450 are electron carrier proteins, it is possible that RP intermediates may be affected by EMF. It was previously found that periodic treatment with extremely low frequency electromagnetic fields (ELF-EMF) inhibits more than 50% the number and area of preneoplastic lesions in rats with chemically induced hepatocarcinogenesis through reduction of cell proliferation. In this work, we developed a quantum mechanical model based on RP mechanism in order to explain the experimental effects of ELF-EMF on the free radicals produced in the early stages of chemical carcinogenesis.

  2. Hypnosis for induction of labour.

    Science.gov (United States)

    Nishi, Daisuke; Shirakawa, Miyako N; Ota, Erika; Hanada, Nobutsugu; Mori, Rintaro

    2014-08-14

    Induction of labour using pharmacological and mechanical methods can increase complications. Complementary and alternative medicine methods including hypnosis may have the potential to provide a safe alternative option for the induction of labour. However, the effectiveness of hypnosis for inducing labour has not yet been fully evaluated. To assess the effect of hypnosis for induction of labour compared with no intervention or any other interventions. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014), handsearched relevant conference proceedings, contacted key personnel and organisations in the field for published and unpublished references. All published and unpublished randomised controlled trials (RCTs) and cluster-RCTs of acceptable quality comparing hypnosis with no intervention or any other interventions, in which the primary outcome is to assess whether labour was induced. Two review authors assessed the one trial report that was identified (but was subsequently excluded). No RCTs or cluster-RCTs were identified from the search strategy. There was no evidence available from RCTs to assess the effect of hypnosis for induction of labour. Evidence from RCTs is required to evaluate the effectiveness and safety of this intervention for labour induction. As hypnosis may delay standard care (in case standard care is withheld during hypnosis), its use in induction of labour should be considered on a case-by-case basis.Future RCTs are required to examine the effectiveness and safety of hypnotic relaxation for induction of labour among pregnant women who have anxiety above a certain level. The length and timing of the intervention, as well as the staff training required, should be taken into consideration. Moreover, the views and experiences of women and staff should also be included in future RCTs.

  3. Enzyme synthesis in the regulation of hepatic `malic' enzyme activity

    Science.gov (United States)

    Murphy, Gillian; Walker, Deryck G.

    1974-01-01

    A homogeneous preparation of `malic' enzyme (EC 1.1.1.40) from livers of thyroxine-treated rats was used to prepare in rabbits an antiserum to the enzyme that reacts monospecifically with the `malic' enzyme in livers of rats in several physiological states. Changes in enzyme activity resulting from modification of the state of the animal are hence due to an altered amount of enzyme protein. The antiserum has been used to precipitate out `malic' enzyme from heat-treated supernatant preparations of livers from both adult and neonatal rats, in a number of physiological conditions, that had been injected 30min earlier with l-[4,5-3H]leucine. The low incorporations of radioactivity into the immunoprecipitable enzyme have permitted the qualitative conclusion that changed enzyme activity in adult rats arises mainly from alterations in the rate of enzyme synthesis. The marked increase in `malic' enzyme activity that occurs naturally or as a result of thyroxine treatment of the weanling rat is likewise due to a marked increase in the rate of enzyme synthesis possibly associated with a concurrent diminished rate of enzyme degradation. PMID:4462568

  4. Enzyme synthesis in the regulation of hepatic "malic" enzyme activity.

    Science.gov (United States)

    Murphy, G; Walker, D G

    1974-10-01

    A homogeneous preparation of ;malic' enzyme (EC 1.1.1.40) from livers of thyroxine-treated rats was used to prepare in rabbits an antiserum to the enzyme that reacts monospecifically with the ;malic' enzyme in livers of rats in several physiological states. Changes in enzyme activity resulting from modification of the state of the animal are hence due to an altered amount of enzyme protein. The antiserum has been used to precipitate out ;malic' enzyme from heat-treated supernatant preparations of livers from both adult and neonatal rats, in a number of physiological conditions, that had been injected 30min earlier with l-[4,5-(3)H]leucine. The low incorporations of radioactivity into the immunoprecipitable enzyme have permitted the qualitative conclusion that changed enzyme activity in adult rats arises mainly from alterations in the rate of enzyme synthesis. The marked increase in ;malic' enzyme activity that occurs naturally or as a result of thyroxine treatment of the weanling rat is likewise due to a marked increase in the rate of enzyme synthesis possibly associated with a concurrent diminished rate of enzyme degradation.

  5. Estimation of physical parameters in induction motors

    DEFF Research Database (Denmark)

    Børsting, H.; Knudsen, Morten; Rasmussen, Henrik

    1994-01-01

    Parameter estimation in induction motors is a field of great interest, because accurate models are needed for robust dynamic control of induction motors......Parameter estimation in induction motors is a field of great interest, because accurate models are needed for robust dynamic control of induction motors...

  6. 14 CFR 25.1091 - Air induction.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Air induction. 25.1091 Section 25.1091... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Induction System § 25.1091 Air induction. (a) The air induction system for each engine and auxiliary power unit must supply— (1) The air required by that engine...

  7. 14 CFR 27.1091 - Air induction.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Air induction. 27.1091 Section 27.1091... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Induction System § 27.1091 Air induction. (a) The air induction system for each engine must supply the air required by that engine under the operating conditions...

  8. 14 CFR 29.1091 - Air induction.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Air induction. 29.1091 Section 29.1091... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Induction System § 29.1091 Air induction. (a) The air induction system for each engine and auxiliary power unit must supply the air required by that engine and...

  9. NRSA enzyme decomposition model data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme activities measured at more than 2000 US streams and rivers. These enzyme data were then used to predict organic matter decomposition and microbial...

  10. Induction of formaldehyde contact sensitivity

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Boman, A; Vølund, A

    1985-01-01

    The sensitizing potential of aqueous formaldehyde was evaluated with the guinea pig maximization test (GPMT) in two laboratories (Copenhagen and Stockholm) using different guinea pig strains. Six intradermal (0.01%-3%), and 6 topical (0.5%-20%) concentrations were used for induction, and formalde......The sensitizing potential of aqueous formaldehyde was evaluated with the guinea pig maximization test (GPMT) in two laboratories (Copenhagen and Stockholm) using different guinea pig strains. Six intradermal (0.01%-3%), and 6 topical (0.5%-20%) concentrations were used for induction......, and formaldehyde 1% and 0.1% was used for challenge. The incidence of contact sensitivity depended on the intradermal, but not on the topical induction dose. Statistical analyses showed a non-monotonous (non-linear) dose response relationship. The estimated maximal sensitization rate in Copenhagen was 80% after...... intradermal induction with 0.65% formaldehyde; in Stockholm it was 84% after induction with 0.34%. The data from the two laboratories could be described by parallel displaced dose response curves suggesting that the guinea pig strain used in Stockholm was significantly more susceptible to formaldehyde than...

  11. The Catalytic Function of Enzymes.

    Science.gov (United States)

    Splittgerber, Allan G.

    1985-01-01

    Discusses: structure of the enzyme molecule; active site; reaction mechanism; transition state; factors affecting enzyme reaction rates, concentration of enzyme; concentration of substrate; product concentration; temperature effects and pH effects; factors causing a lowering of activation energy; proximity and orientation effects; substrate strain…

  12. Simple Laboratory Exercise for Induction of Beta-Mannanase from "Aspergillus niger"

    Science.gov (United States)

    Mulimani, V. H.; Naganagouda, K.

    2010-01-01

    This laboratory experiment was designed for Biochemistry, Biotechnology, Microbiology, and Food Technology students of undergraduate and postgraduate courses. The experiment shows the advantages of using agricultural waste, copra mannan as potent inducer of [beta]-mannanase. The students were able to compare the enzyme induction by commercial…

  13. INDUCTION OF CYTOCHROME P450 ISOFORMS IN RAT LIVER BY TWO CONAZOLES, TRIADIMEFON AND MYCLOBUTANIL

    Science.gov (United States)

    1. This study was undertaken to examine the inductive effects of two triazole antifungal agents, myclobutanil and triadimefon on the expression of hepatic cytochrome P450 (CYP) genes and on the activities of CYP enzymes in male Sprague-Dawley rats. Rats were dosed by gavage for 1...

  14. 38 CFR 21.282 - Effective date of induction into a rehabilitation program; retroactive induction.

    Science.gov (United States)

    2010-07-01

    ... induction into a rehabilitation program; retroactive induction. 21.282 Section 21.282 Pensions, Bonuses, and... Vocational Rehabilitation and Employment Under 38 U.S.C. Chapter 31 Induction into A Rehabilitation Program § 21.282 Effective date of induction into a rehabilitation program; retroactive induction. (a) Entering...

  15. Induction brazing of complex joints

    DEFF Research Database (Denmark)

    Henningsen, Poul; Zhang, Wenqi; Bay, Niels

    2003-01-01

    Induction brazing is a fast and appropriate method for industrial joining of complex geometries and metal combinations. In all types of brazing processes it is important to heat the joint interface of the two materials to the same, high temperature. If one of the specimens is warmer than the other...... materials has large influence on the heating time and temperature distribution in induction heating. In order to ensure high and uniform temperature distribution near the interface of a joint between dissimilar materials the precise coil geometry and position is of great importance. The present paper...... presents a combined numerical and experimental method for fast determination of appropriate coil geometry and position in induction brazing tube-to-plate joints of different ratios between tube and plate thickness and different combinations of the materials stainless steel, brass and copper. The method has...

  16. Induction interview form in EDH

    CERN Multimedia

    Information technology Department, AIS (Administrative Information Services) Group,

    2007-01-01

    As part of the efforts to rationalise administrative procedures, the IT and HR Departments have developed a new EDH form for induction interviews, which can be accessed using the link below. In accordance with Administrative Circular No. 2 ('Recruitment, Appointment and possible developments regarding the contractual position of Staff Members', Rev. 3), the work and training objectives to be achieved during the probation period shall be specified in writing to all new staff members during an induction interview. The interview shall take place between the new staff member and his supervisor within six weeks of him taking up his duties at the latest. https://edh.cern.ch/Document/MAPS/Induction (or from the EDH desktop, by clicking on 'Other Tasks' and going to the 'HR & Training' heading) Please note that this form is to be used exclusively for new staff members. A separate EDH form will be developed for fellows. Information technology Department, AIS (Administrative Information Services) Group Human...

  17. Induction interview form in EDH

    CERN Multimedia

    Information technology Department, AIS (Administrative Information Services) Group

    2007-01-01

    As part of the efforts to rationalise administrative procedures, the IT and HR Departments have developed a new EDH form for induction interviews, which can be accessed using the link below. In accordance with Administrative Circular No. 2 ('Recruitment, Appointment and possible developments regarding the contractual position of Staff Members', Rev. 3), the work and training objectives to be achieved during the probation period shall be specified in writing to all new staff members during an induction interview. The interview shall take place between the new staff member and his supervisor within six weeks of his taking up his duties at the latest. https://edh.cern.ch/Document/MAPS/Induction1) (or from the EDH desktop, by clicking on 'Other Tasks' and going to the 'HR & Training' heading) Please note that this form is to be used exclusively for new staff members. A separate EDH form will be developed for fellows.Information technology Department, AIS (Administrative Information Services) Group Human Re...

  18. THE INDUCTION PERIOD IN PHOTOSYNTHESIS.

    Science.gov (United States)

    Smith, E L

    1937-11-20

    1. Measurements on the photosynthesis of Cabomba caroliniana show an induction period at low and high light intensities and CO(2) concentrations. 2. The equation which describes the data for Cabomba also describes the data obtained by other investigators on different species. The phenomenon is thus shown to be similar in plants representative of three phyla. 3. A derivation of the induction period equation is made from a consideration of the cycle of light and dark processes known to occur in photosynthesis. The equation indicates that light intensity enters as the square, and that the same light reactions are involved as those which affect the stationary state rates. However, a different dark reaction appears to limit photosynthesis during the induction period.

  19. Polycyclic Aromatic Hydrocarbons (PAHs) Mediate Transcriptional Activation of the ATP Binding Cassette Transporter ABCB6 Gene via the Aryl Hydrocarbon Receptor (AhR)*

    Science.gov (United States)

    Chavan, Hemantkumar; Krishnamurthy, Partha

    2012-01-01

    Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics. PMID:22761424

  20. Polycyclic aromatic hydrocarbons (PAHs) mediate transcriptional activation of the ATP binding cassette transporter ABCB6 gene via the aryl hydrocarbon receptor (AhR).

    Science.gov (United States)

    Chavan, Hemantkumar; Krishnamurthy, Partha

    2012-09-14

    Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics.

  1. Technological inductive power transfer systems

    Science.gov (United States)

    Madzharov, Nikolay D.; Nemkov, Valentin S.

    2017-05-01

    Inductive power transfer is a very fast expanding technology with multiple design principles and practical implementations ranging from charging phones and computers to bionic systems, car chargers and continuous power transfer in technological lines. Only a group of devices working in near magnetic field is considered. This article is devoted to overview of different inductive power transfer (IPT) devices. The review of literature in this area showed that industrial IPT are not much discussed and examined. The authors have experience in design and implementation of several types of IPTs belonging to wireless automotive chargers and to industrial application group. Main attention in the article is paid to principles and design of technological IPTs

  2. Plant Growth-Promoting Rhizobacteria Enhance Salinity Stress Tolerance in Okra through ROS-Scavenging Enzymes

    OpenAIRE

    Habib, Sheikh Hasna; Kausar, Hossain; Saud, Halimi Mohd

    2016-01-01

    Salinity is a major environmental stress that limits crop production worldwide. In this study, we characterized plant growth-promoting rhizobacteria (PGPR) containing 1-aminocyclopropane-1-carboxylate (ACC) deaminase and examined their effect on salinity stress tolerance in okra through the induction of ROS-scavenging enzyme activity. PGPR inoculated okra plants exhibited higher germination percentage, growth parameters, and chlorophyll content than control plants. Increased antioxidant enzym...

  3. Propionic acidemia in a parturient presenting for induction of labor.

    Science.gov (United States)

    Schmeck, Alison; Beilin, Yaakov

    2014-11-01

    Propionic acidemia is a congenital disorder of metabolism where the enzyme propionyl-CoA carboxylase is nonfunctional, resulting in an accumulation of propionic acid in the blood. It is important to avoid excess protein intake and a catabolic state to prevent acidemia. Additionally, it may be wise to avoid anesthetic drugs metabolized by propionyl-CoA carboxylase because use of these drugs may lead to acidosis. We present a case of a parturient with propionic acidemia who presented for induction of labor.

  4. Single Enzyme Studies Reveal the Existence of Discrete Functional States for Monomeric Enzymes and How They Are “Selected” upon Allosteric Regulation

    DEFF Research Database (Denmark)

    Hatzakis, Nikos S.; Wei, Li; Jørgensen, Sune Klamer

    2012-01-01

    Allosteric regulation of enzymatic activity forms the basis for controlling a plethora of vital cellular processes. While the mechanism underlying regulation of multimeric enzymes is generally well understood and proposed to primarily operate via conformational selection, the mechanism underlying...... with the enzyme’s major conformational states and are redistributed in the presence of the regulatory effector. Thus, our data support allosteric regulation of monomeric enzymes to operate via selection of preexisting functional states and not via induction of ones.......Allosteric regulation of enzymatic activity forms the basis for controlling a plethora of vital cellular processes. While the mechanism underlying regulation of multimeric enzymes is generally well understood and proposed to primarily operate via conformational selection, the mechanism underlying...... allosteric regulation of monomeric enzymes is poorly understood. Here we monitored for the first time allosteric regulation of enzymatic activity at the single molecule level. We measured single stochastic catalytic turnovers of a monomeric metabolic enzyme (Thermomyces lanuginosus Lipase) while titrating...

  5. Dirac Induction for loop groups

    NARCIS (Netherlands)

    Posthuma, H.

    2011-01-01

    Using a coset version of the cubic Dirac operators for affine Lie algebras, we give an algebraic construction of the Dirac induction homomorphism for loop group representations. With this, we prove a homogeneous generalization of the Weyl-Kac character formula and show compatibility with Dirac

  6. Mathematical Induction: Deductive Logic Perspective

    Science.gov (United States)

    Dogan, Hamide

    2016-01-01

    Many studies mentioned the deductive nature of Mathematical Induction (MI) proofs but almost all fell short in explaining its potential role in the formation of the misconceptions reported in the literature. This paper is the first of its kind looking at the misconceptions from the perspective of the abstract of the deductive logic from one's…

  7. Inductive logic on conceptual spaces

    NARCIS (Netherlands)

    Sznajder, Marta

    2017-01-01

    This thesis investigates the question of how conceptual frameworks influence inductive reasoning. A conceptual framework is a collection of concepts used for a particular purpose; we can think of it as a semantic environment in which observations, or evidence, are recorded, and beliefs are formed

  8. Phonotactics in inductive logic programming

    NARCIS (Netherlands)

    Nerbonne, J.; Konstantopoulos, S.; Klopotek, M.A.; Wierzchon, S.T.; Trojanowski, K.

    2004-01-01

    We examine the results of applying inductive logic programming (ILP) to a relatively simple linguistic task, that of recognizing monosyllables in one language. ILP is suited to linguistic problems given linguists' preference for formulating their theories in discrete rules, and because of ILP's

  9. Teaching the Photoelectric Effect Inductively

    Science.gov (United States)

    Sokolowski, Andrzej

    2013-01-01

    Research has shown that students have difficulty understanding the underlying process of the photoelectric effect. Thus, this study sought to utilize an inductively situated lesson for teaching the photoelectric effect, hypothesizing that this type of enquiry would help learners delve deeper into the principles of the phenomenon and provide a…

  10. Induction studies with satellite data

    DEFF Research Database (Denmark)

    Olsen, Nils

    1999-01-01

    satellites. The results of several induction studies with scalar satellite data (from the POGO satellites) and with vector data (from the Magsat mission) demonstrate the ability to probe the Earth's conductivity from space. However, compared to the results obtained with ground data the satellite results...

  11. Enzyme changes associated with mitochondrial malic enzyme deficiency in mice

    Energy Technology Data Exchange (ETDEWEB)

    Mohrenweiser, H.W.; Erickson, R.P.

    1979-01-01

    A genetically determined absence of mitochondrial malic enzyme (EC 1.1.1.40) in c/sup 3H//c/sup 6H/ mice is accompanied by a four-fold increase in liver glucose-6-phosphate dehydrogenase and a two-fold increase for 6-phosphogluconate dehydrogenase activity. Smaller increases in the activity of serine dehydratase and glutamic oxaloacetic transaminase are observed while the level of glutamic pyruvate transaminase activity is reduced in the liver of deficient mice. Unexpectedly, the level of activity of total malic enzyme in the livers of mitochrondrial malic enzyme-deficient mice is increased approximately 50% compared to littermate controls. No similar increase in solublle malic enzyme activity is observed in heart of kidney tissue of mutant mice and the levels of total malic enzyme in these tissues are in accord with expected levels of activity in mitochondrial malic enzyme-deficient mice. The divergence in levels of enzyme activity between mutant and wild-type mice begins at 19 to 21 days of age. Immunoinactivation experiments with monospecific antisera to the soluble malic enzyme and glucose-6-phosphate dehydrogenase demonstrate that the activity increases represent increases in the amount of enzyme protein. The alterations are not consistent with a single hormonal response.

  12. Induction generator-induction motor wind-powered pumping system

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, M.S.; Lyra, R.O.C.; Silva, S.R. [CPDEE - UFMG, Belo Horizonte (Brazil)

    1997-12-31

    The energy storage matter plays an important role in wind-electric conversion systems for isolated applications. Having that in mind, two different approaches can be basically considered: either the immediate conversion of the generated electric energy, as in a water pumping system or electric energy storage for later use, as in a battery charging system. Due to some features such as no need of an external reactive power source and, sometimes, a gearbox, permanent-magnet synchronous generators have been broadly used in low rated power isolated systems. Despite that, system performance can be affected when the generator is feeding an inductive load (e.g., an induction motor) under variable-speed-variable-frequency operational conditions. Since there is no effective flux control, motor overload may occur at high wind speeds. Thus, good system performance can be obtained through additional control devices which may increase system cost. Although being rugged and cheap, induction machines always work as a reactive power drain; therefore, they demand an external reactive power source. Considering that, reactive static compensators appear as an attractive alternative to the cost x performance problem. In addition to that, different control strategies can be used so that system performance can be improved.

  13. Imposex induction in laboratory reared juvenile Buccinum undatum by tributyltin (TBT).

    Science.gov (United States)

    Mensink, Berend P; Kralt, Hans; Vethaak, A Dick; Ten Hallers-Tjabbes, Cato C; Koeman, Jan H; van Hattum, Bert; Boon, Jan P

    2002-01-01

    Here we report a series of experiments on the development and occurrence of imposex in the common whelk, Buccinum undatum, under the influence of (chronic) exposure to butyltin compounds. The main objective of the experiments was to obtain more information about the effects of organotin compounds in the marine environment, which possibly relate to the reported decline of B. undatum in Dutch coastal waters. In these studies tributyltin (TBT) dose-dependently induced the development of male sexual organs in juvenile whelks. A TBT concentration >7 ng Sn/l induced imposex in juvenile whelks. Growth in TBT-exposed juvenile whelks was significantly reduced compared to the reference group at a nominal TBT dose ≥ 4 ng Sn/l in one of the exposure studies. After 5 years in the laboratory, egg-laying was only observed in reference aquaria. Thus, TBT might impair whelk reproduction through growth reduction. The results showed a sensitivity towards imposex development in different life-stages. Juveniles were the most sensitive, adolescent females also responded, but adult females did not respond to TBT exposure, although they dose-dependently increased their organotin (OT) body-burden when exposed. Environmental TBT during only the in ovo stage, did not result in an increased masculinisation compared to non-exposed developing whelks. Histological studies showed no sterilisation due to mechanical blockage of the (adult) female genital opening by sperm-duct tissue. Gonadal development in 2-year old juveniles was not observed. This implies that the differentiation of a penis and a vas deferens, which already occurred in the first few months after hatching, was not controlled by gonadal factors. No other sexual characteristics than those already visible with the eye were found. TBT inactivated CYP450 to its inactive form CYP420 in in vitro exposure studies with microsomal fractions of whelks. The studies have shown TBT to disrupt sexual development dose dependently in juvenile

  14. Enzyme actuated bioresponsive hydrogels

    Science.gov (United States)

    Wilson, Andrew Nolan

    Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors and regenerative medicine. Conferred with the ability to respond to specific biologically derived stimuli, the design challenge is in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range and limit of detection. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide the sensing, transduction, and the actuation response of hydrogels. To investigate the dynamics of these materials, model systems may be used which seek to interrogate the system dynamics by uni-variable experimentation and limit confounding phenomena such as: polymer-solute interactions, polymer swelling dynamics and biomolecular reaction-diffusion concerns. To this end, a model system, alpha-chymotrypsin (Cht) (a protease) and a cleavable peptide-chromogen (pro-drug) covalently incorporated into a hydrogel, was investigated to understand the mechanisms of covalent loading and release by enzymatic cleavage in bio-responsive delivery systems. Using EDC and Sulfo-NHS, terminal carboxyl groups of N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, a cleavable chromogen, were conjugated to primary amines of a hydrated poly(HEMA)-based hydrogel. Hydrogel discs were incubated in buffered Cht causing enzyme-mediated cleavage of the peptide and concomitant release of the chromophore for monitoring. To investigate substrate loading and the effects of hydrogel morphology on the system, the concentration of the amino groups (5, 10, 20, and 30 mol%) and the cross-linked density (1, 5, 7, 9 and 12 mol%) were independently varied. Loading-Release Efficiency of the chromogen was shown to exhibit a positive relation to increasing amino groups (AEMA). The release rates demonstrated a

  15. Hydrolytic enzymes of "Streptococcus milleri".

    Science.gov (United States)

    Ruoff, K L; Ferraro, M J

    1987-01-01

    Seventy-two isolates classified as "Streptococcus milleri" were examined for the presence of various hydrolytic enzymes. While no protein or lipid-degrading activities were demonstrated, some isolates showed DNase and mucopolysaccharide-degrading activities. Beta-hemolytic isolates were more likely to produce these enzymes than were nonhemolytic strains. Isolates of one "S. milleri" biotype (mannitol fermentation positive) were uniformly devoid of all enzyme activities tested. PMID:2958496

  16. Defining failed induction of labor.

    Science.gov (United States)

    Grobman, William A; Bailit, Jennifer; Lai, Yinglei; Reddy, Uma M; Wapner, Ronald J; Varner, Michael W; Thorp, John M; Leveno, Kenneth J; Caritis, Steve N; Prasad, Mona; Tita, Alan T N; Saade, George; Sorokin, Yoram; Rouse, Dwight J; Blackwell, Sean C; Tolosa, Jorge E

    2018-01-01

    While there are well-accepted standards for the diagnosis of arrested active-phase labor, the definition of a "failed" induction of labor remains less certain. One approach to diagnosing a failed induction is based on the duration of the latent phase. However, a standard for the minimum duration that the latent phase of a labor induction should continue, absent acute maternal or fetal indications for cesarean delivery, remains lacking. The objective of this study was to determine the frequency of adverse maternal and perinatal outcomes as a function of the duration of the latent phase among nulliparous women undergoing labor induction. This study is based on data from an obstetric cohort of women delivering at 25 US hospitals from 2008 through 2011. Nulliparous women who had a term singleton gestation in the cephalic presentation were eligible for this analysis if they underwent a labor induction. Consistent with prior studies, the latent phase was determined to begin once cervical ripening had ended, oxytocin was initiated, and rupture of membranes had occurred, and was determined to end once 5-cm dilation was achieved. The frequencies of cesarean delivery, as well as of adverse maternal (eg, postpartum hemorrhage, chorioamnionitis) and perinatal (eg, a composite frequency of seizures, sepsis, bone or nerve injury, encephalopathy, or death) outcomes, were compared as a function of the duration of the latent phase (analyzed with time both as a continuous measure and categorized in 3-hour increments). A total of 10,677 women were available for analysis. In the vast majority (96.4%) of women, the active phase had been reached by 15 hours. The longer the duration of a woman's latent phase, the greater her chance of ultimately undergoing a cesarean delivery (P 40% of women whose latent phase lasted ≥18 hours still had a vaginal delivery. Several maternal morbidities, such as postpartum hemorrhage (P induction will have entered the active phase by 15 hours

  17. Enzymes From Rare Actinobacterial Strains.

    Science.gov (United States)

    Suriya, J; Bharathiraja, S; Manivasagan, P; Kim, S-K

    Actinobacteria constitute rich sources of novel biocatalysts and novel natural products for medical and industrial utilization. Although actinobacteria are potential source of economically important enzymes, the isolation and culturing are somewhat tough because of its extreme habitats. But now-a-days, the rate of discovery of novel compounds producing actinomycetes from soil, freshwater, and marine ecosystem has increased much through the developed culturing and genetic engineering techniques. Actinobacteria are well-known source of their bioactive compounds and they are the promising source of broad range of industrially important enzymes. The bacteria have the capability to degrade a range of pesticides, hydrocarbons, aromatic, and aliphatic compounds (Sambasiva Rao, Tripathy, Mahalaxmi, & Prakasham, 2012). Most of the enzymes are mainly derived from microorganisms because of their easy of growth, minimal nutritional requirements, and low-cost for downstream processing. The focus of this review is about the new, commercially useful enzymes from rare actinobacterial strains. Industrial requirements are now fulfilled by the novel actinobacterial enzymes which assist the effective production. Oxidative enzymes, lignocellulolytic enzymes, extremozymes, and clinically useful enzymes are often utilized in many industrial processes because of their ability to catalyze numerous reactions. Novel, extremophilic, oxidative, lignocellulolytic, and industrially important enzymes from rare Actinobacterial population are discussed in this chapter. © 2016 Elsevier Inc. All rights reserved.

  18. Enzyme Mimics: Advances and Applications.

    Science.gov (United States)

    Kuah, Evelyn; Toh, Seraphina; Yee, Jessica; Ma, Qian; Gao, Zhiqiang

    2016-06-13

    Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. ADAPTIVE ENZYME SYNTHESIS: ITS INHIBITION AS A POSSIBLE ANALOGUE OF IMMUOLOGICAL TOLERANCE.

    Science.gov (United States)

    VAN BEKKUMD; NIEUWERKERK, H T

    1965-07-30

    Substrate induction of tryptophan pyrrolase in the liver of rats is inhibited by prior treatment of very young rats with tryptophan. This inhibition seems analogous to immunological tolerance, which can be produced by prior treatment with the antigen. The findings prowide support for an analogy between mechanisms of adaptive enzyme synthesis and those involved in adaptive immunity.

  20. Induction brazing at the Kennedy Space Center

    Science.gov (United States)

    Clautice, W. E.

    1974-01-01

    A description of the joint design, materials, equipment, qualification testing, inspection methods, and applications involved in performing induction brazing on hyperbolic propellants tubing at Kennedy Space Center. Induction brazing is a form of brazing in which the energy is transmitted to the workpiece by electrical induction; the eddy currents generated in the metal produce heat by resistance losses. Since induction heating is fast and highly localized, undesirable heat effects are minimized and the resulting braze is of high quality.

  1. Enzyme structure, enzyme function and allozyme diversity in ...

    African Journals Online (AJOL)

    In estimates of population genetic diversity based on allozyme heterozygosity, some enzymes are regularly more variable than others. Evolutionary theory suggests that functionally less important molecules, or parts of molecules, evolve more rapidly than more important ones; the latter enzymes should then theoretically be ...

  2. [The rise of enzyme engineering in China].

    Science.gov (United States)

    Li, Gaoxiang

    2015-06-01

    Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China.

  3. Online Monitoring of Induction Motors

    Energy Technology Data Exchange (ETDEWEB)

    McJunkin, Timothy R. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Lybeck, Nancy Jean [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-01-01

    The online monitoring of active components project, under the Advanced Instrumentation, Information, and Control Technologies Pathway of the Light Water Reactor Sustainability Program, researched diagnostic and prognostic models for alternating current induction motors (IM). Idaho National Laboratory (INL) worked with the Electric Power Research Institute (EPRI) to augment and revise the fault signatures previously implemented in the Asset Fault Signature Database of EPRI’s Fleet Wide Prognostic and Health Management (FW PHM) Suite software. Induction Motor diagnostic models were researched using the experimental data collected by Idaho State University. Prognostic models were explored in the set of literature and through a limited experiment with 40HP to seek the Remaining Useful Life Database of the FW PHM Suite.

  4. Device for side induction sensing

    Energy Technology Data Exchange (ETDEWEB)

    Bilibin, S.I.; Byalyy, Yu.V.; Malyshev, D.A.; Orlov, V.N.; Ovchinnikov, A.Ye.; Plyusnin, N.I.

    1982-01-01

    The device can be used to determine geophysical parameters of the beds at the zone of penetration of the drilling mud filtrate. Improvement in information content of sensing is attained by increasing the quantity of induction probes formed by the coils, and improvement in sensing accuracy by conducting measurements on one fixed part with time separation of the signals from different induction probes. The system of separation of the measurable signals is done in the form of a group of commutators and a block of cyclic control of commutation. The controlling outlets of it are connected to the controllable inlets of the commutators and the inlet of the remote measurement system for transmission of information to the surface.

  5. Computational enzyme design: transitioning from catalytic proteins to enzymes.

    Science.gov (United States)

    Mak, Wai Shun; Siegel, Justin B

    2014-08-01

    The widespread interest in enzymes stem from their ability to catalyze chemical reactions under mild and ecologically friendly conditions with unparalleled catalytic proficiencies. While thousands of naturally occurring enzymes have been identified and characterized, there are still numerous important applications for which there are no biological catalysts capable of performing the desired chemical transformation. In order to engineer enzymes for which there is no natural starting point, efforts using a combination of quantum chemistry and force-field based protein molecular modeling have led to the design of novel proteins capable of catalyzing chemical reactions not catalyzed by naturally occurring enzymes. Here we discuss the current status and potential avenues to pursue as the field of computational enzyme design moves forward. Published by Elsevier Ltd.

  6. On generic representation of implicit induction procedures

    NARCIS (Netherlands)

    D. Naidich

    1996-01-01

    textabstractWe develop a generic representation of implicit induction proof procedures within the cover set induction framework. Our work further develops the approach of cover set induction on propositional orderings. We show that in order to represent a substantially wide range of implicit

  7. Propofol Induction's Effect on Cardiac Function

    Science.gov (United States)

    2015-03-31

    This Study Was Focused to Evaluate Feasibility of Doppler Tissue Monitoring During the Induction Anesthesia,; and Evaluate Routine Propofol Induction's Effect on Myocardial Tissue Motion, Using Non-invasive Doppler Tissue and 2D Speckle Tracking Imaging.; This is the First Study, to Our Knowledge, Which Has Evaluated the Possible Impact of Propofol Induction on LV Function.

  8. A Retrospective Appraisal of Teacher Induction

    Science.gov (United States)

    Nasser-Abu Alhija, Fadia M.; Fresko, Barbara

    2016-01-01

    Examination of an induction program for new teachers was undertaken from the viewpoint of induction graduates three years after participation. Their retrospective perspectives were investigated as to their satisfaction with assimilation in school in the induction year, their attitudes towards organizational aspects of the program, and the…

  9. Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats

    Directory of Open Access Journals (Sweden)

    Alan F. Sasso

    2012-01-01

    Full Text Available A lipid-based physiologically based toxicokinetic (PBTK model has been developed for a mixture of six polychlorinated biphenyls (PCBs in rats. The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate. Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients. A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied to in vivo data. A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses. The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles.

  10. Blackout cloth for dormancy induction

    Science.gov (United States)

    Tom Jopson

    2007-01-01

    The use of blackout cloth to create long night photoperiods for the induction of dormancy in certain conifer species has been an established practice for a long time. Its use was suggested by Tinus and McDonald (1979) as an effective technique, and the practice has been commonly used in Canadian forest nurseries for a number of years. Cal-Forest Nursery installed its...

  11. The law of electromagnetic induction

    Directory of Open Access Journals (Sweden)

    V.J. Kutkovetskyy

    2014-09-01

    Full Text Available Mathematical models of the electromagnetic induction law which do not take into account Faraday’s restrictions are not in full accordance with the physical phenomenon and so they are not laws. Their incomplete correspondence with real devices results in such "paradoxes" as unlimited magnetic field of unipolar generators, infinite sizes of inductors for DC and AC machines modeled, and so on.

  12. Two fluxes multistage induction coilgun

    Science.gov (United States)

    Gherman, L.; Pearsica, M.; Circiu, I.; Rotaru, C.

    2017-05-01

    This paper presents a brand new induction electromagnetic launcher, which uses two magnetic fluxes in order to accelerate a projectile. One magnetic flux induce a current in the armature and the second magnetic flux is creating a radial magnetic field. This aproach offer multiple advantages over single flux designs. First we are able to control the induced current in armature because we use the coil just to induce current inside the ring with a great efficiency. Second advantage is the angle of 900 between magnetic field density B and the ring. We used the induction to avoid contact between armature and accelerator. In order to create the magnetic field radial we used four coils perpendicular on armature. This approach alove us to control the phase difference between induced current in armature and current in magnetic field coils for a maximum force. The phase difference is obtained by changing the frequency of magnetic field coils power source. We used simulation software to analyze, and simulate a multistage induction coilgun design with two fluxes. The simulation results demonstrated the theoretical results.

  13. Quality Teacher Induction: "Fourth-Wave" (1997-2006) Induction Programs

    Science.gov (United States)

    Wood, Ann L.; Stanulis, Randi Nevins

    2009-01-01

    The purpose of this essay is to describe quality teacher induction that has evolved from "fourth-wave" (1997-2006) teacher induction program development and research. A definition of quality induction is proposed, and a set of induction goals and components are outlined. Understandings gained from fourth-wave programs are described, including ways…

  14. Enzyme Kinetics? Elementary, my dear

    Indian Academy of Sciences (India)

    Suppose that, in the absence of an enzyme, the. Desirazu N Rao is at the. Department of. Biochemistry, Indian. Institute of Science,. Bangalore. His main research interests are in the ateas of protein-DNA interactions using restriction enzymes as model systems and in. DNA methylation. 1 When a carbon atom has four.

  15. Cellulase enzyme and biomass utilization

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... Key words: Cellulose, cellulase enzyme, fuel ethanol, biomass. ... nearly all fuel ethanol is produced by fermentation of corn ... efficiency. This review will introduce some background knowledge of cellulase enzyme and its hydrolyzation mechanism, focus on its current status in research and application,.

  16. Biocatalytic induction of supramolecular order

    Science.gov (United States)

    Hirst, Andrew R.; Roy, Sangita; Arora, Meenakshi; Das, Apurba K.; Hodson, Nigel; Murray, Paul; Marshall, Stephen; Javid, Nadeem; Sefcik, Jan; Boekhoven, Job; van Esch, Jan H.; Santabarbara, Stefano; Hunt, Neil T.; Ulijn, Rein V.

    2010-12-01

    Supramolecular gels, which demonstrate tunable functionalities, have attracted much interest in a range of areas, including healthcare, environmental protection and energy-related technologies. Preparing these materials in a reliable manner is challenging, with an increased level of kinetic defects observed at higher self-assembly rates. Here, by combining biocatalysis and molecular self-assembly, we have shown the ability to more quickly access higher-ordered structures. By simply increasing enzyme concentration, supramolecular order expressed at molecular, nano- and micro-levels is dramatically enhanced, and, importantly, the gelator concentrations remain identical. Amphiphile molecules were prepared by attaching an aromatic moiety to a dipeptide backbone capped with a methyl ester. Their self-assembly was induced by an enzyme that hydrolysed the ester. Different enzyme concentrations altered the catalytic activity and size of the enzyme clusters, affecting their mobility. This allowed structurally diverse materials that represent local minima in the free energy landscape to be accessed based on a single gelator structure.

  17. Positron emitter labeled enzyme inhibitors

    Science.gov (United States)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1987-05-22

    This invention involved a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide in activators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  18. Engineering Cellulase Enzymes for Bioenergy

    Science.gov (United States)

    Atreya, Meera Elizabeth

    Sustainable energy sources, such as biofuels, offer increasingly important alternatives to fossil fuels that contribute less to global climate change. The energy contained within cellulosic biofuels derives from sunlight energy stored in the form of carbon-carbon bonds comprising sugars such as glucose. Second-generation biofuels are produced from lignocellulosic biomass feedstocks, including agricultural waste products and non-food crops like Miscanthus, that contain lignin and the polysaccharides hemicellulose and cellulose. Cellulose is the most abundant biological material on Earth; it is a polymer of glucose and a structural component of plant cell walls. Accessing the sugar is challenging, as the crystalline structure of cellulose resists degradation; biochemical and thermochemical means can be used to depolymerize cellulose. Cellulase enzymes catalyze the biochemical depolymerization of cellulose into glucose. Glucose can be used as a carbon source for growth of a biofuel-producing microorganism. When it converts glucose to a hydrocarbon fuel, this microbe completes the biofuels process of transforming sunlight energy into accessible, chemical energy capable of replacing non-renewable transportation fuels. Due to strong intermolecular interactions between polymer chains, cellulose is significantly more challenging to depolymerize than starch, a more accessible polymer of glucose utilized in first-generation biofuels processes (often derived from corn). While most mammals cannot digest cellulose (dietary fiber), certain fungi and bacteria produce cellulase enzymes capable of hydrolyzing it. These organisms secrete a wide variety of glycoside hydrolase and other classes of enzymes that work in concert. Because cellulase enzymes are slow-acting and expensive to produce, my aim has been to improve the properties of these enzymes as a means to make a cellulosic biofuels process possible that is more efficient and, consequently, more economical than current

  19. A study of overproduction and enhanced secretion of enzymes. Quarterly report

    Energy Technology Data Exchange (ETDEWEB)

    Dashek, W.V.

    1993-09-01

    Wood decay within forests, a significant renewable photosynthetic energy resource, is caused primarily by Basidiomycetous fungi, e.g., white rot fungi. These organisms possess the ability to degrade lignin, cellulose and hemicellulose, the main organic polymers of wood. In the case of the white rot fungi, e.g., Coriolus versicolor, the capacity results from the fungus` ability to elaborate extracellular cellulolytic and ligninolytic enzymes. With regard to the latter, at least one of the enzymes, polyphenol oxidase (PPO) appears within a defined growth medium. This proposal focuses on the over-production and enhanced secretion of PPO, cellulase and lignin peroxidase. There are two major sections to the proposal: (1) overproduction of lignocellulolytic enzymes by genetic engineering methodologies and hyper-production and enhanced secretion of these enzymes by biochemical/electro microscopical techniques and (2) the biochemical/electron microscopical method involves substrate induction and the time-dependent addition of respiration and PPO enzymes.

  20. Increased exposure of vitamin A by Chrysanthemum morifolium Ramat extract in rat was not via induction of CYP1A1, CYP1A2, and CYP2B1.

    Science.gov (United States)

    Wang, Ping; Pan, Xian; Chen, Guanming; Li, Jia; Liu, Li; Liu, Xiaodong; Jin, Shi; Xie, Lin; Wang, Guangji

    2012-06-01

    The aim of this study was to investigate the effect of Chrysanthemum morifolium Ramat (CM) extract on the pharmacokinetics of retinol and activities of cytochrome P450s (CYP450s) related to retinoid metabolism. Rats were treated with CM extract for 15 d. Plasma concentrations of retinol were measured following oral administration of retinol (45 mg/kg). Basal levels of retinol and retinoic acid in serum and liver were also measured. 7-Ethoxyresorufin-O-deethylase activity, phenacetin-O-deethylase activity, and 7-pentoxyresorufin-O-deethylase activities were used to assay the activities of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats, respectively. Protein expressions of the 3 CYP450s were measured by western blot. Our studies demonstrated that CM extract dose-dependently increased basal level of retinol in serum. In pharmacokinetic experiment, CM extract dose-dependently increased plasma concentrations of retinol after oral administration of retinol to rats treated with CM extract. But activities and expressions of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats were also induced by CM extract. © 2012 Institute of Food Technologists®

  1. Regulation of methylamine and formaldehyde metabolism in Arthrobacter P1. Formaldehyde is the inducing signal for the synthesis of the RuMP cycle enzyme hexulose phosphate synthase

    NARCIS (Netherlands)

    Croes, L.M.; Dijkhuizen, L.

    The inducing potential of formaldehyde on the synthesis of hexulose phosphate synthase, a key enzyme of the RuMP cycle in Arthrobacter P1, was investigated in resting cell suspensions. Induction of this enzyme only occurred at formaldehyde concentrations of 0.5 mM and below. No evidence was obtained

  2. BAKERY ENZYMES IN CEREAL TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    Václav Koman

    2012-10-01

    Full Text Available Normal 0 21 false false false SK X-NONE X-NONE Bread is the most common and traditional food in the world. For years, enzymes such as malt and fungal alpha-amylase have been used in bread making. Due to the changes in the baking industry and the ever-increasing demand for more natural products, enzymes have gained real importance in bread-making. If an enzyme is added, it is often destroyed by the heat during the baking process. For generations, enzymes have been used for the improvement of texture and appearance, enhancement of nutritional values and generation of appealing flavours and aromas. Enzymes used in bakery industry constitute nearly one third of the market. The bakery products have undergone radical improvements in quality over the past years in terms of flavour, texture and shelf-life. The the biggest contributor for these improvementsis the usage of enzymes. Present work seeks to systematically describe bakery enzymes, their classification, benefits, usage and chemical reactions in the bread making process.doi:10.5219/193

  3. Mathematical model of induction heating

    Science.gov (United States)

    Rak, Josef

    2017-07-01

    One of mathematical models of induction heating can be described by a parabolic differential equation with the specific Joule looses in the body. Advantage of this method is that the detailed knowledge of the 3D-magnetic field is not necessary and move of the body or the inductor can be easily implemented. The specific Joule looses can computed by solving the Fredholm integral equation of the second kind for the eddy current of density by the Nyström method with the singularity subtraction.

  4. An Induction Linac Test Stand

    CERN Document Server

    De Hope, William; Kihara, Ron; Ong, Mike; Vogtlin, George; Zentler, Jan-Mark

    2005-01-01

    A single-cell test stand has been constructed to facilitate study and guide improvements of the induction electron linac at the FXR radiographic facility at LLNL.* This paper will discuss how modifications in pulse compression and shaping, pulse power transmission, initial ferrite state, and accelerator cell loading have been performed on the test stand and can be applied to the entire accelerator. Some of the specialized diagnostics being used will be described. Finally, the paper will discuss how computer modeling and judicious timing control can be used to optimize accelerator performance by making only selective changes that can be accomplished at minimal cost.

  5. Elementary induction on abstract structures

    CERN Document Server

    Moschovakis, Yiannis N

    2008-01-01

    Hailed by the Bulletin of the American Mathematical Society as ""easy to use and a pleasure to read,"" this research monograph is recommended for students and professionals interested in model theory and definability theory. The sole prerequisite is a familiarity with the basics of logic, model theory, and set theory.The author, Professor of Mathematics at UCLA and Emeritus Professor of Mathematics,University of Athens, Greece, begins with a focus on the theory of inductive and hyperelementary sets. Subsequent chapters advance to acceptable structures and countable acceptable structures, concl

  6. The regulation of urea-biosynthesis enzymes in vertebrates

    Science.gov (United States)

    Mora, J.; Martuscelli, J.; Ortiz-Pineda, Juana; Soberón, G.

    1965-01-01

    1. Carbamoyl phosphate synthetase, ornithine transcarbamoylase, the arginine-synthetase system and arginase were measured in the livers of ammoniotelic, ureotelic and uricotelic animals. The chelonian reptiles, whose nitrogen excretory patterns vary according to the habitat, and the Mexican axolotl, a neotenic species, were also studied. 2. The levels of the activities of the first three enzymes mentioned correlate with the amount of nitrogen excreted as urea. 3. The terrestrial turtle, which excretes mainly uric acid, maintains a high arginase activity but has very low levels of the activities of the other three enzymes. 4. The first three enzymes of the urea cycle vary in the phylogenic scale in a co-ordinated manner, which suggests that they are under the same regulatory mechanism. 5. Urea formation from endogenous arginine in vitro has a low efficiency in the Mexican axolotl. 6. The induction of metamorphosis in the Mexican axolotl by the administration of l-tri-iodothyronine, which causes a shift from ammonio-ureotelism to complete ureotelism, is accompanied by an increase mainly in carbamoyl phosphate synthetase and also by an improvement in the efficiency of hydrolysis of endogenous arginine in vitro to give urea. 7. The results obtained by differential centrifugation of the urea-cycle enzymes in rat and Mexican-axolotl livers are presented. The location requirements for the integration of a metabolic cycle are discussed. PMID:14343146

  7. Autophagy induction by tetrahydrobiopterin deficiency

    Science.gov (United States)

    Kwak, Sang Su; Suk, Jinkyu; Choi, Ji Hye; Yang, Seungkyung; Kim, Jin Woo; Sohn, Seonghyang; Chung, Jae Hoon; Hong, Yong Hee; Lee, Dong Hwan; Ahn, Jeong Keun; Min, Hyesun; Fu, Ya-Min; Meadows, Gary G

    2011-01-01

    Tetrahydrobiopterin (BH4) deficiency is a genetic disorder associated with a variety of metabolic syndromes such as phenylketonuria (PKU). In this article, the signaling pathway by which BH4 deficiency inactivates mTORC1 leading to the activation of the autophagic pathway was studied utilizing BH4-deficient Spr-/- mice generated by the knockout of the gene encoding sepiapterin reductase (SR) catalyzing BH4 synthesis. We found that mTORC1 signaling was inactivated and autophagic pathway was activated in tissues from Spr-/- mice. This study demonstrates that tyrosine deficiency causes mTORC1 inactivation and subsequent activation of autophagic pathway in Spr-/- mice. Therapeutic tyrosine diet completely rescued dwarfism and mTORC1 inhibition but inactivated autophagic pathway in Spr-/- mice. Tyrosine-dependent inactivation of mTORC1 was further supported by mTORC1 inactivation in Pahenu2 mouse model lacking phenylalanine hydroxylase (Pah). NIH3T3 cells grown under the condition of tyrosine restriction exhibited autophagy induction. However, mTORC1 activation by RhebQ64L, a positive regulator of mTORC1, inactivated autophagic pathway in NIH3T3 cells under tyrosine-deficient conditions. In addition, this study first documents mTORC1 inactivation and autophagy induction in PKU patients with BH4 deficiency. PMID:21795851

  8. Induction and inactivation of catalase and superoxide dismutase of Escherichia coli by ozone

    Energy Technology Data Exchange (ETDEWEB)

    Whiteside, C.; Hassan, H.M.

    1987-09-01

    Oxyradicals have been implicated in ozone (O/sub 3/) toxicity and in other oxidant stress. In this study, we investigated the effects of O/sub 3/ on the biosynthesis of the antioxidant enzymes catalase and superoxide dismutase in Escherichia coli to determine their role in the defense against ozone toxicity. Inhibition of growth and loss of viability were observed in cultures exposed to ozone. Results also showed an increase in the activities of catalase and superoxide dismutase in cultures exposed to ozone, which was shown to be due to true induction rather than activation of preexisting apoproteins. Cessation of O/sub 3/ exposure resulted in 30 min of continual high rate of catalase biosynthesis followed by a gradual decrease in the level of the enzyme approaching that of control cultures. This decrease was attributed to a concomitant cessation of de novo enzyme synthesis and dilution of preexisting enzyme by cellular growth. Ozonation of cell-free extracts showed that superoxide dismutase and catalase are subject to oxidative inactivation by ozone. In vivo induction of these enzymes may represent an adaptive response evolved to protect cells against ozone toxicity.

  9. Induction of hexanol dehydrogenase in Geotrichum spp. by the addition of hexanol.

    Science.gov (United States)

    Zhang, Jinhua; Shi, Junling; Lv, Hongliang; Liu, Yanlin

    2013-02-01

    Excessive hexanol content distorts the flavor of foods and is harmful to human health. Previously, two strains of fungi were found capable of producing hexanol-degrading enzymes. The current study identified these strains as Galactomyces geotrichum according to the gene sequence of the 26 S rDNA D1/D2 region (strain S12) and genus Geotrichum according to the gene sequence of ITS region (strain S13). Parallel analysis of extracellular and intracellular enzyme activities showed that the enzymes mainly accumulated intracellularly. Native polyacrylamide gel electrophoresis with reactive dyes showed the enzymes were alcohol dehydrogenases induced by the addition of hexanol. Hexanol was catalyzed into hexanoic acid and hexanal by strain S12 and into hexanoic acid by strain S13. The optimum conditions for the induction of enzymes were determined to be 6-9 h in the presence of 0.7 g/l hexanol. The identification of two strains capable of enzymatically degrading hexanol and optimum conditions for their induction will facilitate their use in industrial applications.

  10. Enzymes of inorganic polyphosphate metabolism.

    Science.gov (United States)

    Kulakovskaya, Tatyana; Kulaev, Igor

    2013-01-01

    Inorganic polyphosphate (PolyP) is a linear polymer containing a few to several hundred orthophosphate residues linked by energy-rich phosphoanhydride bonds. Investigation of PolyP-metabolizing enzymes is important for medicine, because PolyPs perform numerous functions in the cells. In human organism, PolyPs are involved in the regulation of Ca(2+) uptake in mitochondria, bone tissue development, and blood coagulation. The essentiality of polyphosphate kinases in the virulence of pathogenic bacteria is a basis for the discovery of new antibiotics. The properties of the major enzymes of PolyP metabolism, first of all polyphosphate kinases and exopolyphosphatases, are described in the review. The main differences between the enzymes of PolyP biosynthesis and utilization of prokaryotic and eukaryotic cells, as well as the multiple functions of some enzymes of PolyP metabolism, are considered.

  11. Photosynthetic fuel for heterologous enzymes

    DEFF Research Database (Denmark)

    Mellor, Silas Busck; Vavitsas, Konstantinos; Nielsen, Agnieszka Janina Zygadlo

    2017-01-01

    of reducing power. Recent work on the metabolic engineering of photosynthetic organisms has shown that the electron carriers such as ferredoxin and flavodoxin can be used to couple heterologous enzymes to photosynthetic reducing power. Because these proteins have a plethora of interaction partners and rely...... on electrostatically steered complex formation, they form productive electron transfer complexes with non-native enzymes. A handful of examples demonstrate channeling of photosynthetic electrons to drive the activity of heterologous enzymes, and these focus mainly on hydrogenases and cytochrome P450s. However......, competition from native pathways and inefficient electron transfer rates present major obstacles, which limit the productivity of heterologous reactions coupled to photosynthesis. We discuss specific approaches to address these bottlenecks and ensure high productivity of such enzymes in a photosynthetic...

  12. GRE Enzymes for Vector Analysis

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme data that were collected during the 2004-2006 EMAP-GRE program. These data were then used by Moorhead et al (2016) in their ecoenzyme vector...

  13. Enzymes: principles and biotechnological applications

    Science.gov (United States)

    Robinson, Peter K.

    2015-01-01

    Enzymes are biological catalysts (also known as biocatalysts) that speed up biochemical reactions in living organisms, and which can be extracted from cells and then used to catalyse a wide range of commercially important processes. This chapter covers the basic principles of enzymology, such as classification, structure, kinetics and inhibition, and also provides an overview of industrial applications. In addition, techniques for the purification of enzymes are discussed. PMID:26504249

  14. Multi-enzyme Process Modeling

    DEFF Research Database (Denmark)

    Andrade Santacoloma, Paloma de Gracia

    or potential process configurations operated under different conditions. In these cases, process engineering, enzyme immobilization and protein engineering are presented as fields that can offer feasible solutions for better process configurations or biocatalyst modification to enhance actual process...... proven to be useful for a fast model formulation of multi-enzyme processes. Additionally, programming codes were developed using MATLAB (The Mathworks, Natick, MA) which were also used as computational tools to support the implementation, solution and analysis of all the mathematical problems faced...

  15. Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults

    DEFF Research Database (Denmark)

    Petersen, Maria Skaalum; Halling, Jónrit; Damkier, Per

    2007-01-01

    A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18-60 years, the CYP3A4 activity was determined based on the urinary 6beta-hydroxycortisol/cortisol (6beta...... analysis showed significant associations between 6beta-OHC/FC ratios and summation PCB, PCB-TEQ and p,p'-DDE, o,p'-DDT and HCB, respectively, but the associations were statistically significant for men only....

  16. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of CYP1 enzymes

    Science.gov (United States)

    Smoking is a major risk factor for osteoporosis and fracture. Here, we show that smoke toxins and environmental chemicals such as benzo[a]pyrene (BaP), 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and 3-methyl cholanthrene, which are well known aryl hydrocarbon receptor (AHR) agonists, induce osteocla...

  17. Alprazolam as an in vivo probe for studying induction of CYP3A in cynomolgus monkeys.

    Science.gov (United States)

    Ohtsuka, Tatsuyuki; Yoshikawa, Takahiro; Kozakai, Kazumasa; Tsuneto, Yumi; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi; Kume, Toshiyuki

    2010-10-01

    Induction of the cytochrome P450 (P450) enzyme is a major concern in the drug discovery processes. To predict the clinical significance of enzyme induction, it is helpful to investigate pharmacokinetic alterations of a coadministered drug in a suitable animal model. In this study, we focus on the induction of CYP3A, which is involved in the metabolism of approximately 50% of marketed drugs and is inducible in both the liver and intestine. As a marker substrate for CYP3A activity, alprazolam (APZ) was selected and characterized using recombinant CYP3A enzymes expressed in Escherichia coli. Both human CYP3A4 and its cynomolgus P450 ortholog predominantly catalyzed APZ 4-hydroxylation with sigmoidal kinetics. When administered intravenously and orally to cynomolgus monkeys, APZ had moderate clearance; its first-pass extraction ratio after oral dosing was estimated to be 0.09 in the liver and 0.45 in the intestine. Pretreatment with multiple doses of rifampicin (20 mg/kg p.o. for 5 days), a known CYP3A inducer, significantly decreased plasma concentrations of APZ after intravenous and oral administrations (0.5 mg/kg), and first-pass extraction ratios were increased to 0.39 in the liver and 0.63 in the intestine. The results were comparable to those obtained in clinical drug-drug interaction (DDI) reports related to CYP3A induction, although the rate of recovery of CYP3A activity seemed to be slower than rates estimated in clinical studies. In conclusion, pharmacokinetic studies using APZ as a probe in monkeys may provide useful information regarding the prediction of clinical DDIs due to CYP3A induction.

  18. A High-Throughput (HTS) Assay for Enzyme Reaction Phenotyping in Human Recombinant P450 Enzymes Using LC-MS/MS.

    Science.gov (United States)

    Li, Xiaofeng; Suhar, Tom; Glass, Lateca; Rajaraman, Ganesh

    2014-03-03

    Enzyme reaction phenotyping is employed extensively during the early stages of drug discovery to identify the enzymes responsible for the metabolism of new chemical entities (NCEs). Early identification of metabolic pathways facilitates prediction of potential drug-drug interactions associated with enzyme polymorphism, induction, or inhibition, and aids in the design of clinical trials. Incubation of NCEs with human recombinant enzymes is a popular method for such work because of the specificity, simplicity, and high-throughput nature of this approach for phenotyping studies. The availability of a relative abundance factor and calculated intersystem extrapolation factor for the expressed recombinant enzymes facilitates easy scaling of in vitro data, enabling in vitro-in vivo extrapolation. Described in this unit is a high-throughput screen for identifying enzymes involved in the metabolism of NCEs. Emphasis is placed on the analysis of the human recombinant enzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2B6, and CYP3A4, including the calculation of the intrinsic clearance for each. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

  19. Selective Induction of Optical Magnetism.

    Science.gov (United States)

    Manna, Uttam; Lee, Jung-Hoon; Deng, Tian-Song; Parker, John; Shepherd, Nolan; Weizmann, Yossi; Scherer, Norbert F

    2017-12-13

    An extension of the Maxwell-Faraday law of electromagnetic induction to optical frequencies requires spatially appropriate materials and optical beams to create resonances and excitations with curl. Here we employ cylindrical vector beams with azimuthal polarization to create electric fields that selectively drive magnetic responses in dielectric core-metal nanoparticle "satellite" nanostructures. These optical frequency magnetic resonances are induced in materials that do not possess spin or orbital angular momentum. Multipole expansion analysis of the scattered fields obtained from electrodynamics simulations show that the excitation with azimuthally polarized beams selectively enhances magnetic vs electric dipole resonances by nearly 100-fold in experiments. Multipolar resonances (e.g., quadrupole and octupole) are enhanced 5-fold by focused azimuthally versus linearly polarized beams. We also selectively excite electric multipolar resonances in the same identical nanostructures with radially polarized light. This work opens new opportunities for spectroscopic investigation and control of "dark modes", Fano resonances, and magnetic modes in nanomaterials and engineered metamaterials.

  20. BACKWARD INDUCTION: MERITS AND FLAWS

    Directory of Open Access Journals (Sweden)

    Kamiński Marek M.

    2017-06-01

    Full Text Available Backward induction (BI was one of the earliest methods developed for solving finite sequential games with perfect information. It proved to be especially useful in the context of Tom Schelling’s ideas of credible versus incredible threats. BI can be also extended to solve complex games that include an infinite number of actions or an infinite number of periods. However, some more complex empirical or experimental predictions remain dramatically at odds with theoretical predictions obtained by BI. The primary example of such a troublesome game is Centipede. The problems appear in other long games with sufficiently complex structure. BI also shares the problems of subgame perfect equilibrium and fails to eliminate certain unreasonable Nash equilibria.

  1. Induction Magnetometers – Design Peculiarities

    Directory of Open Access Journals (Sweden)

    Valeriy KOREPANOV

    2010-09-01

    Full Text Available Induction or search-coil magnetometers (IM are widely used in many branches of science and industry. The frequency range and dynamic range of IMs are probably the widest of all existing magnetometers: they are used for the measurement of magnetic field variations in the frequency band from ~10-4 till ~106 Hz with the intensities from fractions of femtotesla till tens of tesla. This explains the permanent interest to IM design and the attempts to construct the IMs with best possible parameters. The present paper deals with the peculiarities of IM design. An attempt to re-establish the correctness of priorities in the field is made and the approaches to the IM optimization and their quality estimation are described.

  2. Enzymes and Enzyme Activity Encoded by Nonenveloped Viruses.

    Science.gov (United States)

    Azad, Kimi; Banerjee, Manidipa; Johnson, John E

    2017-09-29

    Viruses are obligate intracellular parasites that rely on host cell machineries for their replication and survival. Although viruses tend to make optimal use of the host cell protein repertoire, they need to encode essential enzymatic or effector functions that may not be available or accessible in the host cellular milieu. The enzymes encoded by nonenveloped viruses-a group of viruses that lack any lipid coating or envelope-play vital roles in all the stages of the viral life cycle. This review summarizes the structural, biochemical, and mechanistic information available for several classes of enzymes and autocatalytic activity encoded by nonenveloped viruses. Advances in research and development of antiviral inhibitors targeting specific viral enzymes are also highlighted.

  3. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    DEFF Research Database (Denmark)

    Biran, Suzan; Bach, Poul; Simonsen, Ole

    with previously reported H2O2-induced oxidation studies of Savinase® in solutions. Preliminary formulation studies were conducted and application of the designed setup on stability measurements of commercial granulates was illustrated. Addition of salts resulted in a considerable conservation of enzyme activity...... stability was significantly conserved, while at multilayer hydration level, especially when samples were exposed to 100% RH, the activity was reduced by 80% in a one week period. Since no auto-proteolytic activity and covalently-bound aggregate formation were detected, humidity possibly induced formation...... with the enzyme provided better protection than coating the salt as a separate layer. The effect of site-directed mutagenesis on Savinase® stability was illustrated and possible stability enhancing additives for enzyme granulates were proposed. The present study is the first to report the solid-state inactivation...

  4. Mineral induction by immobilized phosphoproteins

    Science.gov (United States)

    Saito, T.; Arsenault, A. L.; Yamauchi, M.; Kuboki, Y.; Crenshaw, M. A.

    1997-01-01

    Dentin phosphoproteins are thought to have a primary role in the deposition of mineral on the collagen of dentin. In this study we determined the type of binding between collagen and phosphoproteins necessary for mineral formation onto collagen fibrils and whether the phosphate esters are required. Bovine dentin phosphophoryn or phosvitin from egg yolk were immobilized on reconstituted skin type I collagen fibrils by adsorption or by covalent cross-linking. In some samples the ester phosphate was removed from the covalently cross-linked phosphoproteins by treatment with acid phosphatase. All samples were incubated at 37 degrees C in metastable solutions that do not spontaneously precipitate. Reconstituted collagen fibrils alone did not induce mineral formation. The phosphoproteins adsorbed to the collagen fibrils desorbed when the mineralization medium was added, and mineral was not induced. The mineral induced by the cross-linked phosphoproteins was apatite, and the crystals were confined to the surface of the collagen fibrils. With decreasing medium saturation the time required for mineral induction increased. The interfacial tensions calculated for apatite formation by either phosphoprotein cross-linked to collagen were about the same as that for phosphatidic acid liposomes and hydroxyapatite. This similarity in values indicates that the nucleation potential of these highly phosphorylated surfaces is about the same. It is concluded that phosphoproteins must be irreversibly bound to collagen fibrils for the mineralization of the collagen network in solutions that do not spontaneously precipitate. The phosphate esters of phosphoproteins are required for mineral induction, and the carboxylate groups are not sufficient.

  5. Inductance identification of an induction machine taking load-dependent saturation into account

    OpenAIRE

    Ranta, Mikaela; Hinkkanen, Marko; Luomi, Jorma

    2008-01-01

    The paper proposes an identification method for the inductances of induction machines, based on signal injection. Due to magnetic saturation, a saturation-induced saliency appears in the induction motor, and the total leakage inductance estimate depends on the angle of the excitation signal. The proposed identification method is based on a small-signal model that includes the saturation-induced saliency. Because of the saturation, the load also affects the estimate, and measurements are neede...

  6. Induction of Laccase, Lignin Peroxidase and Manganese Peroxidase Activities in White-Rot Fungi Using Copper Complexes

    Directory of Open Access Journals (Sweden)

    Martina Vrsanska

    2016-11-01

    Full Text Available Ligninolytic enzymes, such as laccase, lignin peroxidase and manganese peroxidase, are biotechnologically-important enzymes. The ability of five white-rot fungal strains Daedaleopsis confragosa, Fomes fomentarius, Trametes gibbosa, Trametes suaveolens and Trametes versicolor to produce these enzymes has been studied. Three different copper(II complexes have been prepared ((Him[Cu(im4(H2O2](btc·3H2O, where im = imidazole, H3btc = 1,3,5-benzenetricarboxylic acid, [Cu3(pmdien3(btc](ClO43·6H2O and [Cu3(mdpta3(btc](ClO43·4H2O, where pmdien = N,N,N′,N′′,N′′-pentamethyl-diethylenetriamine and mdpta = N,N-bis-(3-aminopropylmethyl- amine, and their potential application for laccase and peroxidases induction have been tested. The enzyme-inducing activities of the complexes were compared with that of copper sulfate, and it has been found that all of the complexes are suitable for the induction of laccase and peroxidase activities in white-rot fungi; however, the newly-synthesized complex M1 showed the greatest potential for the induction. With respect to the different copper inducers, this parameter seems to be important for enzyme activity, which depends also on the fungal strains.

  7. Human cytosolic thymidine kinase: purification and physical characterization of the enzyme from HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Sherley, J.L.; Kelly, T.J.

    1988-01-05

    The mammalian cytosolic thymidine kinase is one of a number of enzymes involved in DNA replication whose activities increase dramatically during S phase of the cell cycle. As a first step in defining the mechanisms that control the S phase induction of thymidine kinase activity, the authors have purified the human enzyme from HeLa cells and raised a specific immune serum against the purified protein. The enzyme was isolated from cells arrested in S phase by treatment with methotrexate and purified to near homogeneity by ion-exchange and affinity chromatography. Stabilization of the purified enzyme was achieved by the addition of digitonin. An electrophoretic R/sub m/ of 0.2 in nondenaturing gels characterizes the purified enzyme activity as cytosolic thymidine kinase. The enzyme has a Stoke's radius of 40 A determined by gel filtration and a sedimentation coefficient of 5.5 S determined by glycerol gradient sedimentation. Based on these hydrodynamic values, a native molecular weight of 96,000 was calculated for the purified enzyme. When electrophoresed in denaturing sodium dodecyl sulfate-polyacrylamide gels under reducing conditions, the most purified enzyme fraction was found to contain one predominant polypeptide of M/sub r/ = 24,000. Several lines of evidence indicate that this polypeptide is responsible for thymidine kinase enzymatic activity.

  8. Resistance induction in wheat plants by silicon and aphids

    Directory of Open Access Journals (Sweden)

    Gomes Flávia Batista

    2005-01-01

    Full Text Available The pest greenbug Schizaphis graminum (Rondani (Hemiptera: Aphididae stands out among the factors limiting Brazilian wheat production. Chemical control is predominant in aphid management making the production dependent on insecticides. The effect of silicon and previous infestation with aphids on the induction of resistance to the greenbug was evaluated in wheat plants. Treatments consisted of control; fertilization with calcium silicate; plant infestation with aphids; fertilization with calcium silicate + plant infestation with aphids. A free-choice preference test was performed 35 days after seedling emergence; the aphid's intrinsic rate of population increase (r m was also determined, and the activities of three enzymes (peroxidase, polyphenoloxidase, and phenylalanine ammonia-lyase involved in plant defense were quantified. Silicon fertilization and the previous infestation with aphids induced wheat plant resistance to the greenbug.

  9. Cancer-selective induction of apotosis by leczyme

    Directory of Open Access Journals (Sweden)

    Takeo eTatsuta

    2014-06-01

    Full Text Available Sialic acid-binding lectin (SBL is a multifunctional protein that is isolated from oocytes of Rana catesbeiana. It has both lectin and ribonuclease (enzyme properties, and therefore is called leczyme. We examined the antitumor effects of SBL and discovered that SBL has potential as a new type of anticancer drug. SBL causes a cancer-selective induction of apoptosis by multiple signaling pathways whereby RNA is its target. It is suggested that the mitochondrial pathway and endoplasmic reticulum stress-mediated pathway participate in SBL-induced signaling. The synergistic antitumor effects with other molecules, such as tumor necrosis factor-related apoptosis ligand (TRAIL and interferon γ (IFN-γ, have been reported. In this study, we summarize the effects of SBL and focus on its cancer-selective apoptotic properties. In addition, we present a possible explanation its cancer specificity.

  10. Nonclassical Kinetics of Clonal yet Heterogeneous Enzymes.

    Science.gov (United States)

    Park, Seong Jun; Song, Sanggeun; Jeong, In-Chun; Koh, Hye Ran; Kim, Ji-Hyun; Sung, Jaeyoung

    2017-07-06

    Enzyme-to-enzyme variation in the catalytic rate is ubiquitous among single enzymes created from the same genetic information, which persists over the lifetimes of living cells. Despite advances in single-enzyme technologies, the lack of an enzyme reaction model accounting for the heterogeneous activity of single enzymes has hindered a quantitative understanding of the nonclassical stochastic outcome of single enzyme systems. Here we present a new statistical kinetics and exactly solvable models for clonal yet heterogeneous enzymes with possibly nonergodic state dynamics and state-dependent reactivity, which enable a quantitative understanding of modern single-enzyme experimental results for the mean and fluctuation in the number of product molecules created by single enzymes. We also propose a new experimental measure of the heterogeneity and nonergodicity for a system of enzymes.

  11. Enzymes in CO2 Capture

    DEFF Research Database (Denmark)

    Fosbøl, Philip Loldrup; Gladis, Arne; Thomsen, Kaj

    The enzyme Carbonic Anhydrase (CA) can accelerate the absorption rate of CO2 into aqueous solutions by several-fold. It exist in almost all living organisms and catalyses different important processes like CO2 transport, respiration and the acid-base balances. A new technology in the field...... of carbon capture is the application of enzymes for acceleration of typically slow ternary amines or inorganic carbonates. There is a hidden potential to revive currently infeasible amines which have an interesting low energy consumption for regeneration but too slow kinetics for viable CO2 capture. The aim...... of this work is to discuss the measurements of kinetic properties for CA promoted CO2 capture solvent systems. The development of a rate-based model for enzymes will be discussed showing the principles of implementation and the results on using a well-known ternary amine for CO2 capture. Conclusions...

  12. Electric Fields and Enzyme Catalysis.

    Science.gov (United States)

    Fried, Stephen D; Boxer, Steven G

    2017-06-20

    What happens inside an enzyme's active site to allow slow and difficult chemical reactions to occur so rapidly? This question has occupied biochemists' attention for a long time. Computer models of increasing sophistication have predicted an important role for electrostatic interactions in enzymatic reactions, yet this hypothesis has proved vexingly difficult to test experimentally. Recent experiments utilizing the vibrational Stark effect make it possible to measure the electric field a substrate molecule experiences when bound inside its enzyme's active site. These experiments have provided compelling evidence supporting a major electrostatic contribution to enzymatic catalysis. Here, we review these results and develop a simple model for electrostatic catalysis that enables us to incorporate disparate concepts introduced by many investigators to describe how enzymes work into a more unified framework stressing the importance of electric fields at the active site.

  13. Enzyme-Based Listericidal Nanocomposites

    Science.gov (United States)

    Solanki, Kusum; Grover, Navdeep; Downs, Patrick; Paskaleva, Elena E.; Mehta, Krunal K.; Lee, Lillian; Schadler, Linda S.; Kane, Ravi S.; Dordick, Jonathan S.

    2013-01-01

    Cell lytic enzymes represent an alternative to chemical decontamination or use of antibiotics to kill pathogenic bacteria, such as listeria. A number of phage cell lytic enzymes against listeria have been isolated and possess listericidal activity; however, there has been no attempt to incorporate these enzymes onto surfaces. We report three facile routes for the surface incorporation of the listeria bacteriophage endolysin Ply500: covalent attachment onto FDA approved silica nanoparticles (SNPs), incorporation of SNP-Ply500 conjugates into a thin poly(hydroxyethyl methacrylate) film; and affinity binding to edible crosslinked starch nanoparticles via construction of a maltose binding protein fusion. These Ply500 formulations were effective in killing L. innocua (a reduced pathogenic surrogate) at challenges up to 105 CFU/ml both in non-growth sustaining PBS as well as under growth conditions on lettuce. This strategy represents a new route toward achieving highly selective and efficient pathogen decontamination and prevention in public infrastructure. PMID:23545700

  14. impedance calculations of induction machine rotor conductors.

    African Journals Online (AJOL)

    Dr Obe

    desired steady-state or transient performances of induction machines. INTRODUCTION. For the past 30 years, the dynamic behaviour of induction machines has received a considerable attention in most researched works [1.2, 3.4.5.6]. However, the analysis is based on the simple idealised machine model without deep-bar ...

  15. Examining the Effects of New Teacher Induction

    Science.gov (United States)

    Wechsler, Marjorie E.; Caspary, Kyra; Humphrey, Daniel C.; Matsko, Kavita Kapadia

    2012-01-01

    The objective of this research is to explore comprehensively the effect of induction on new teachers. Through a mixed-method design, the authors examine both the inputs of induction (i.e., the types of support provided for new teachers, its content, and frequency) and a variety of outcomes (i.e., teacher efficacy, teacher-reported growth, teacher…

  16. Designing Induction as Professional Learning Community

    Science.gov (United States)

    O'Malley, Gary S.

    2010-01-01

    This study describes the professional development experience in one high school in which participants worked over a four-year period to share responsibility in the design of a teacher induction program. The article explores the salient features of an ideal induction program by examining purpose, organization, and delivery. The author concludes…

  17. Organogenesis induction in rice callus by cyanobacterial ...

    African Journals Online (AJOL)

    The endosperm of three rice varieties, IR 50, ASD 16 and ADT 36, were used as explants. IR 50 showed earlier and good callus induction response in MS medium. For root induction, cyanobaterial extracellular product was added instead of 2,4-D. The result showed that the number of days taken for root initiation and root ...

  18. Characterization of human cytochrome P450 induction by pesticides.

    Science.gov (United States)

    Abass, Khaled; Lämsä, Virpi; Reponen, Petri; Küblbeck, Jenni; Honkakoski, Paavo; Mattila, Sampo; Pelkonen, Olavi; Hakkola, Jukka

    2012-03-29

    Pesticides are a large group of structurally diverse toxic chemicals. The toxicity may be modified by cytochrome P450 (CYP) enzyme activity. In the current study, we have investigated effects and mechanisms of 24 structurally varying pesticides on human CYP expression. Many pesticides were found to efficiently activate human pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR). Out of the 24 compounds tested, 14 increased PXR- and 15 CAR-mediated luciferase activities at least 2-fold. While PXR was predominantly activated by pyrethroids, CAR was, in addition to pyrethroids, well activated by organophosphates and several carbamates. Induction of CYP mRNAs and catalytic activities was studied in the metabolically competent, human derived HepaRG cell line. CYP3A4 mRNA was induced most powerfully by pyrethroids; 50 μM cypermethrin increased CYP3A4 mRNA 35-fold. CYP2B6 was induced fairly equally by organophosphate, carbamate and pyrethroid compounds. Induction of CYP3A4 and CYP2B6 by these compound classes paralleled their effects on PXR and CAR. The urea herbicide diuron and the triazine herbicide atrazine induced CYP2B6 mRNA more than 10-fold, but did not activate CAR indicating that some pesticides may induce CYP2B6 via CAR-independent mechanisms. CYP catalyzed activities were induced much less than the corresponding mRNAs. At least in some cases, this is probably due to significant inhibition of CYP enzymes by the studied pesticides. Compared with human CAR activation and CYP2B6 expression, pesticides had much less effect on mouse CAR and CYP2B10 mRNA. Altogether, pesticides were found to be powerful human CYP inducers acting through both PXR and CAR. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Modeling and analysis with induction generators

    CERN Document Server

    Simões, M Godoy

    2014-01-01

    ForewordPrefaceAcknowledgmentsAuthorsPrinciples of Alternative Sources of Energy and Electric GenerationScope of This ChapterLegal DefinitionsPrinciples of Electrical ConversionBasic Definitions of Electrical PowerCharacteristics of Primary SourcesCharacteristics of Remote Industrial, Commercial, and Residential Sites and Rural EnergySelection of the Electric GeneratorInterfacing Primary Source, Generator, and LoadExample of a Simple Integrated Generating and Energy-Storing SystemSolved ProblemsSuggested ProblemsReferencesSteady-State Model of Induction GeneratorsScope of This ChapterInterconnection and Disconnection of the Electric Distribution NetworkRobustness of Induction GeneratorsClassical Steady-State Representation of the Asynchronous MachineGenerated PowerInduced TorqueRepresentation of Induction Generator LossesMeasurement of Induction Generator ParametersBlocked Rotor Test (s = 1)No-Load Test (s = 0)Features of Induction Machines Working as Generators Interconnected to the Distribution NetworkHigh-...

  20. Phase rotation channel design with induction linacs

    CERN Document Server

    Fukui, Y

    2001-01-01

    Two models of the phase rotation channels of the neutrino factory were designed with a solenoid transport system and the induction linac acceleration system. One model has the one stage induction linac channel, and another model has two stages of the induction linac channels and an absorber and drift space in between them. Major figure of merits of the channel are the particle ratio of muons over primary protons, the momentum spread and the muon polarization correlation to the arrival time at the end of the phase rotation channel. The mu/proton ratios were 0.25 and 0.13 for the single stage and the double stage induction linac channels, respectively. The effective muon polarization, radicalradical, was 0.16 and the muon polarization correlation was 0.23/(100 ns) for the single stage induction linac model.

  1. Reasoning about modular datatypes with Mendler induction

    Directory of Open Access Journals (Sweden)

    Paolo Torrini

    2015-09-01

    Full Text Available In functional programming, datatypes a la carte provide a convenient modular representation of recursive datatypes, based on their initial algebra semantics. Unfortunately it is highly challenging to implement this technique in proof assistants that are based on type theory, like Coq. The reason is that it involves type definitions, such as those of type-level fixpoint operators, that are not strictly positive. The known work-around of impredicative encodings is problematic, insofar as it impedes conventional inductive reasoning. Weak induction principles can be used instead, but they considerably complicate proofs. This paper proposes a novel and simpler technique to reason inductively about impredicative encodings, based on Mendler-style induction. This technique involves dispensing with dependent induction, ensuring that datatypes can be lifted to predicates and relying on relational formulations. A case study on proving subject reduction for structural operational semantics illustrates that the approach enables modular proofs, and that these proofs are essentially similar to conventional ones.

  2. Enzyme and biochemical producing fungi

    DEFF Research Database (Denmark)

    Lübeck, Peter Stephensen; Lübeck, Mette; Nilsson, Lena

    2010-01-01

    We are developing a biorefinery concept for biological production of chemicals, drugs, feed and fuels using plant biomass as raw material in well-defined cell-factories. Among the important goals is the discovery of new biocatalysts for production of enzymes, biochemicals and fuels and already our...... screening of a large collection of fungal strains isolated from natural habitats have resulted in identification of strains with high production of hydrolytic enzymes and excretion of organic acids. Our research focuses on creating a fungal platform based on synthetic biology for developing new cell...

  3. Replication-independent MCB gene induction and deoxyribonucleotide accumulation at G1/S in Saccharomyces cerevisiae.

    Science.gov (United States)

    Koç, Ahmet; Wheeler, Linda J; Mathews, Christopher K; Merrill, Gary F

    2003-03-14

    In Saccharomyces cerevisiae, many genes encoding enzymes involved in deoxyribonucleotide synthesis are expressed preferentially near the G1/S boundary of the cell cycle. The relationship between the induction of deoxyribonucleotide-synthesizing genes, deoxyribonucleoside triphosphate levels, and replication initiation was investigated using factor-synchronized wild-type yeast or dbf4 yeast that are temperature-sensitive for replication initiation. Neither the timing nor extent of gene induction was inhibited when factor-arrested dbf4 cells were released into medium containing the ribonucleotide reductase inhibitor hydroxyurea, which blocks replication fork progression, or were released at 37 degrees C, which blocks replication origin firing. Thus, the induction of deoxyribonucleotide-synthesizing genes at G1/S was fully independent of DNA chain elongation or initiation. Deoxyribonucleoside triphosphate levels increased severalfold at G1/S in wild-type cells and in dbf4 mutants incubated at the non-permissive temperature. Thus, deoxyribonucleoside triphosphate accumulation, like the induction of deoxyribonucleotide-synthesizing genes, was not dependent on replication initiation. Deoxyribonucleoside triphosphate accumulation at G1/S was suppressed in cells lacking Swi6, a transcription factor required for normal cell cycle regulation of deoxyribonucleotide-synthesizing genes. The results suggest that cells use gene induction at G1/S as a mechanism to pre-emptively, rather than reflexively, increase the synthesis of DNA precursors to meet the demand of the replication forks for deoxyribonucleotides.

  4. Cryogenic pulsed inductive microwave magnetometer

    Science.gov (United States)

    Kos, A. B.; Nibarger, J. P.; Lopusnik, R.; Silva, T. J.; Celinski, Z.

    2003-05-01

    A cryogenic pulsed inductive microwave magnetometer is used to characterize the switching dynamics in thin-film magnetic materials at low temperatures and microwave frequencies. The system is contained inside a 20-cm-diam ultrahigh vacuum chamber and cooled by a cryopump that allows measurements between 20 and 350 K. A temperature controller regulates the sample temperature using two silicon diodes as sensors. Applied magnetic fields of up to 36 kA/m (450 Oe) are generated by a four-pole, water-cooled electromagnet with independent control of each axis. Magnetic switching in the sample is driven by high-speed current step pulses in a coplanar waveguide structure with the sample placed in a flip-chip configuration. A 20 GHz sampling oscilloscope is used to record the dynamics of the magnetic reorientation. The switching dynamics are given for a 10-nm-thick Ni-Fe film at 30 K in response to a 1 kA/m field step.

  5. Induction technique in manufacturing preforms

    Science.gov (United States)

    Frauenhofer, M.; Ströhlein, T.; Fabig, S.; Böhm, S.; Herbeck, L.; Dilger, K.

    2008-09-01

    The prepreg technology is a state-of-the-art method to produce high-performance CFRP parts. Due to the high material prices, the restricted process rate, and limitations to the component complexity, in future, more and more parts will be assembled by using liquid composite moulding. Especially in the case of series larger than 100 parts per year, the LCM technology offers the best cost-effectiveness. This technology is based on resin injection into dry multilayer fibre textiles (preforms). The Institute of Joining and Welding (TU, Braunschweig), together with the Institute of Composite Structures and Adaptive Systems (DLR), has elaborated a new technology to speed up the preform process, which is the most labour-intensive step within the LCM process chain. A novel concept to consolidate binder-coated fabrics is under development. By applying the high energy transfer rate of induction technology, it is possible to heat up a preform with rates up to 50 K/s to melt the binder and consolidate the preform.

  6. Organoclay-enzyme film electrodes.

    Science.gov (United States)

    Mbouguen, Justin Kemmegne; Ngameni, Emmanuel; Walcarius, Alain

    2006-09-25

    This paper aims at showing the interest of organoclays (clay minerals containing organic groups covalently attached to the inorganic particles) as suitable host matrices likely to immobilize enzymes onto electrode surfaces for biosensing applications. The organoclays used in this work were natural Cameroonian smectites grafted with either aminopropyl (AP) or trimethylpropylammonium (TMPA) groups. The first ones were exploited for their ability to anchor biomolecules by covalent bonding while the second category exhibited favorable electrostatic interactions with negatively charged enzymes due to ion exchange properties that were pointed out here by means of multisweep cyclic voltammetry. AP-clay materials were applied to the immobilization of glucose oxidase (GOD) and TMPA-clays for polyphenol oxidase (PPO) anchoring. When deposited onto the surface of platinum or glassy carbon electrodes as enzyme/organoclay films, these systems were evaluated as biosensing electrochemical devices for detection of glucose and catechol chosen as model analytes. The advantageous features of these organoclays were discussed by comparison to the performance of related film electrodes made of non-functionalized clays. It appeared that organoclays provide a favorable environment to enzymes activity, as highlighted from the biosensors characteristics and determination of Michaelis-Menten constants.

  7. Cellulase enzyme and biomass utilization

    African Journals Online (AJOL)

    In recent years, fundamental and applied researches on cellulase enzyme have not only generated significant scientific knowledge but also have revealed their enormous potential in biotechnology. Growing attention has been devoted to its bioconversion of biomass into fuel ethanol, considered the cleanest liquid fuel ...

  8. Udfordringer ved undervisning i enzymer

    DEFF Research Database (Denmark)

    Skriver, Karen; Dandanell, Gert; von Stemann, Jakob Hjorth

    2015-01-01

    Enzymer er et centralt emne i biokemiundervisning. Det forudsætter og anvender grundlæggende viden inden for og kompetencer i kemi og matematik. Artiklen undersøger hvilke forståelsesvanskeligheder og udfordringer der er knyttet til dette område, såvel som virtuelle øvelsers potentiale i denne ko...

  9. Immobilized Enzymes for Automated Analyses.

    Science.gov (United States)

    1979-12-01

    more sensitive than either UV absorption at 2780 R or the biuret method . We evaluated the effect of complete protein denaturation on absorbance by... Methods were developed for analyzing enzyme immobilization pro- cesses applicable to carrier materials suitable for automated cliical chemistry...carrier. The methods were applied to study of immobilization of glycerol dehydrogenase (GD). Three distinct types of immobilization pro- cesses were

  10. Enzymes with activity toward Xyloglucan

    NARCIS (Netherlands)

    Vincken, J.P.

    2003-01-01

    Xyloglucans are plant cell wall polysaccharides, which belong to the hemicellulose class. Here the structural variations of xyloglucans will be reviewed. Subsequently, the anchoring of xyloglucan in the plant cell wall will be discussed. Enzymes involved in degradation or modification of xyloglucan

  11. Enzyme recovery using reversed micelles

    NARCIS (Netherlands)

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.

    Reversed micelles are aggregates of surfactant

  12. Phage lytic enzymes targeting streptococci

    Science.gov (United States)

    Streptococcal pathogens contribute to a wide variety of human and livestock diseases. There is a need for new antimicrobials to replace over-used conventional antibiotics. Bacteriophage (viruses that infect bacteria) endolysins (enzymes that help degrade the bacterial cell wall) are ideal candidat...

  13. Kathepsine C : Een allosterisch enzyme

    NARCIS (Netherlands)

    Gorter, Jeannette

    1969-01-01

    In chapter I an introduction into allosteric systems is given. In chapter II is a detailed method is described for the applica of Gly-Phe--p. nitroanilide (GPNA) as a substrate for the activity assay of the lysosomal enzyme cathepsin C. It is an allosteric which is activated by Cl-, Br-, 1-, CNS-,

  14. The enzymes associated with denitrification

    Science.gov (United States)

    Hochstein, L. I.; Tomlinson, G. A.

    1988-01-01

    The enzymes involved in the reduction of nitrogenous oxides are thought to be intermediates in denitrification processes. This review examines the roles of nitrate reductase, nitrite reductases, nitric oxide reductase, mechanisms of N-N bond formation, and nitrous oxide reductases.

  15. Effects of Cyclamen trochopteranthum on hepatic drug-metabolizing enzymes

    Directory of Open Access Journals (Sweden)

    Arslan Sevki

    2011-01-01

    Full Text Available The modulatory effects of the Cyclamen trochopterantum tuber extract on hepatic drug-metabolizing enzymes, including aniline 4-hydroxylase (A4H; CYP2E1, ethoxyresorufin O-deethylase (EROD; CYP1A, methoxyresorufin O-demethylase (MROD; CYP1A, caffeine N-demethylase (C3ND; CYP1A2 aminopyrene N-demethylase (APND; CYP2C6, and erythromycin N-demethylase (ERND; CYP3A1, were examined in vivo in rats. The activities of all of these enzymes were induced by the cyclamen extract. In addition, Western-blot and RT-PCR results clearly showed that CYP2E1, CYP1A1/CYP1A2 and CYP2C6 protein and mRNA levels were substantially increased by four different doses of cyclamen. Although, the CYP3A1 protein level was increased significantly, the mRNA level was not changed. These results indicate that cyclamen tuber extract might have a potential not only to inhibit and/or induce the metabolism of certain co-administered drugs but also influence the development of toxicity and carcinogenesis due to the induction of the cytochrome P450-dependent drug-metabolizing enzymes.

  16. Thermodynamics of Enzyme-Catalyzed Reactions Database

    Science.gov (United States)

    SRD 74 Thermodynamics of Enzyme-Catalyzed Reactions Database (Web, free access)   The Thermodynamics of Enzyme-Catalyzed Reactions Database contains thermodynamic data on enzyme-catalyzed reactions that have been recently published in the Journal of Physical and Chemical Reference Data (JPCRD). For each reaction the following information is provided: the reference for the data, the reaction studied, the name of the enzyme used and its Enzyme Commission number, the method of measurement, the data and an evaluation thereof.

  17. Oral Misoprostol Solution for Induction of Labour.

    Science.gov (United States)

    Deshmukh, Varsha L; Rajamanya, Apurva V; Yelikar, K A

    2017-04-01

    To determine the effects of oral misoprostol solution for induction of labour. This is a prospective observational study. This study was conducted in Government Medical College, Aurangabad. Patients undergoing induction of labour after 36 weeks of pregnancy were allocated by randomization to induction of labour with oral misoprostol solution administered 2 h apart. Delivery within 24 h after induction with oral misoprostol solution was the primary outcome on which the sample size was based. The data were analysed by Statistical Software for Social Sciences software. Two hundred patients were randomly selected for induction with oral misoprostol solution. There were no significant differences in substantive outcomes. Vaginal delivery within 24 h was achieved in 80.5 % of patients. The caesarean section rate was 19.5 %. Uterine hyperactivity occurred in 4 % of patients. The response to induction of labour in women with unfavourable cervices (modified Bishop's score induction to delivery interval was more, oxytocin requirement was more, and vaginal delivery rate was less. This new approach to oral misoprostol solution administration was successful in achieving vaginal delivery rate in 24 h in 80.5 % of patients; rate of LSCS was less 19.5 %.

  18. Postterm with favorable cervix: is induction necessary?

    Science.gov (United States)

    Chanrachakul, Boonsri; Herabutya, Yongyoth

    2003-02-10

    To study the cesarean rate between expectant management and immediate induction in the otherwise uncomplicated postterm pregnancy with favorable cervix. A total of 249 women with uncomplicated pregnancies at 41 weeks plus 3 days (290 days) with favorable cervix (Bishop score > or =6) were randomized to either expectant management (n=125) or immediate induction of labor (n=124). The women in the induction group were sent to labor ward for induction by artificial rupture of membranes (ARM) and/or oxytocin infusion. The women with expectant management had nonstress test (NST) and amniotic fluid index (AFI) performed once a week and twice a week after 43 weeks of gestation until spontaneous labor. The cesarean rate was not different between expectant management and immediate induction (21.6% versus 26.6%; P=0.36). Ninety-five percent of the expectant group delivered within 1 week after enrollment, and all of them delivered within 9 days after randomization. Maternal and fetal complications in both groups were not different. There was also no difference in the mean birth weight (P=0.24) and the frequency of macrosomia (birth weight > or = 4000 g) between the two groups (P=0.23). Cesarean section rate between expectant management and immediate induction in the otherwise uncomplicated postterm pregnancy with favorable cervix was not different. Due to the very low adverse perinatal outcome, both expectant management and immediate induction are acceptable.

  19. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

    Science.gov (United States)

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-08-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

  20. Heavy enzymes--experimental and computational insights in enzyme dynamics.

    Science.gov (United States)

    Swiderek, Katarzyna; Ruiz-Pernía, J Javier; Moliner, Vicent; Tuñón, Iñaki

    2014-08-01

    The role of protein motions in the chemical step of enzyme-catalyzed reactions is the subject of an open debate in the scientific literature. The systematic use of isotopically substituted enzymes has been revealed as a useful tool to quantify the role of these motions. According to the Born-Oppenheimer approximation, changing the mass of the protein does not change the forces acting on the system but alters the frequencies of the protein motions, which in turn can affect the rate constant. Experimental and theoretical studies carried out in this field are presented in this article and discussed in the framework of Transition State Theory. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Applied intelligent control of induction motor drives

    CERN Document Server

    Chan, Tze Fun

    2011-01-01

    Induction motors are the most important workhorses in industry. They are mostly used as constant-speed drives when fed from a voltage source of fixed frequency. Advent of advanced power electronic converters and powerful digital signal processors, however, has made possible the development of high performance, adjustable speed AC motor drives.This book aims to explore new areas of induction motor control based on artificial intelligence (AI) techniques in order to make the controller less sensitive to parameter changes. Selected AI techniques are applied for different induction motor control s.

  2. On Resistance and Inductance of Solid Conductors

    Directory of Open Access Journals (Sweden)

    Oldřich Coufal

    2013-01-01

    Full Text Available The concepts of resistance and inductance are strewn with misunderstanding and errors that result from inaccurate terminology, mistakes in their definitions, and from the fact that they are quantities that characterize elements of ideal electrical circuits as well as real solid conductors. This is shown unfavourably not only in the respective field of the theory of electrical engineering, but also in the calculation of resistance and inductance. In this paper, a brief theoretical analysis of the state of the art is given, and its results are applied in the calculation of the current density, resistance, and inductance of two coaxial solid tubular conductors.

  3. Labor Induction Techniques: Which Is the Best?

    Science.gov (United States)

    Penfield, Christina A; Wing, Deborah A

    2017-12-01

    Induction of labor is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Cervical assessment is essential to determine the optimal approach. Indication for induction, clinical presentation and history, safety, cost, and patient preference may factor into the selection of methods. For the unfavorable cervix, several pharmacologic and mechanical methods are available, each with associated advantages and disadvantages. In women with a favorable cervix, combined use of amniotomy and intravenous oxytocin is generally the most effective approach. The goal of labor induction is to ensure the best possible outcome for mother and newborn. Published by Elsevier Inc.

  4. Linear Parameter Varying Control of Induction Motors

    DEFF Research Database (Denmark)

    Trangbæk, Klaus

    The subject of this thesis is the development of linear parameter varying (LPV) controllers and observers for control of induction motors. The induction motor is one of the most common machines in industrial applications. Being a highly nonlinear system, it poses challenging control problems...... for high performance applications. This thesis demonstrates how LPV control theory provides a systematic way to achieve good performance for these problems. The main contributions of this thesis are the application of the LPV control theory to induction motor control as well as various contributions...

  5. CYP4 enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid ω-hydroxylase activities.

    Science.gov (United States)

    Edson, Katheryne Z; Rettie, Allan E

    2013-01-01

    The Cytochrome P450 4 (CYP4) family of enzymes in humans is comprised of thirteen isozymes that typically catalyze the ω-oxidation of endogenous fatty acids and eicosanoids. Several CYP4 enzymes can biosynthesize 20- hydroxyeicosatetraenoic acid, or 20-HETE, an important signaling eicosanoid involved in regulation of vascular tone and kidney reabsorption. Additionally, accumulation of certain fatty acids is a hallmark of the rare genetic disorders, Refsum disease and X-ALD. Therefore, modulation of CYP4 enzyme activity, either by inhibition or induction, is a potential strategy for drug discovery. Here we review the substrate specificities, sites of expression, genetic regulation, and inhibition by exogenous chemicals of the human CYP4 enzymes, and discuss the targeting of CYP4 enzymes in the development of new treatments for hypertension, stroke, certain cancers and the fatty acid-linked orphan diseases.

  6. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Pauline Byakika-Kibwika

    2011-01-01

    Full Text Available Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART poses significant challenges. Artemether-lumefantrine (AL is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450 enzymes which metabolize the protease inhibitors (PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.

  7. 7 CFR 58.436 - Rennet, pepsin, other milk clotting enzymes and flavor enzymes.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rennet, pepsin, other milk clotting enzymes and flavor enzymes. 58.436 Section 58.436 Agriculture Regulations of the Department of Agriculture (Continued... clotting enzymes and flavor enzymes. Enzyme preparations used in the manufacture of cheese shall be safe...

  8. Hepatic Cytochrome P450 as Biomarkers of Cypermethrin Toxicity in Freshwater Teleost, Channa punctatus (Bloch

    Directory of Open Access Journals (Sweden)

    Dawa Bhutia

    2015-02-01

    Full Text Available In this study, Channa punctatus was treated with sub-lethal concentration of cypermethrin (6.6 µg/L for 5, 10 and 15 days and its effect on total CYP 450 and the activity of hepatic CYP450 isoforms measured. Total CYP450 content and CYP1A mediated EROD activity was significantly induced (p<0.05 in all three treated groups compared to control whereas only 15 days treated group showed significant induction in CYP2B mediated N,Ndimethylaniline demethylase activity. CYP2E1 mediated aniline hydroxylase activity showed only a marginal increase while there was inhibition of CYP3A4 mediated erythromycin demethylase activity. Liver somatic index (LSI also showed a marginal increase in all the treated groups. Results showed differential induction of CYP1A, CYP2B, CYP2E1 and inhibition of CYP3A4 isoform due to cypermethrin treatment in C. punctatus. The study clearly showed CYP1A isoform as the most responsive and important biomarker for monitoring the aquatic pollution.

  9. Callus induction and regeneration via shoot tips of Dendrocalamus hamiltonii

    National Research Council Canada - National Science Library

    Zang, Qiaolu; Zhou, Ling; Zhuge, Fei; Yang, Haiyun; Wang, Xiaoqin; Lin, Xinchun

    2016-01-01

    By using shoot tips as explants, various media and culture conditions for callus induction and proliferation, shoot differentiation, root induction and plantlet transplantation to develop an efficient...

  10. Transient repression of catabolite-sensitive enzyme synthesis elicited by 2,4-dinitrophenol.

    Science.gov (United States)

    Oki, R

    1975-09-01

    Transient inhibition of catabolic enzyme synthesis in Escherichia coli occurred when a low concentration of 2,4-dinitrophenol (DNP) was simultaneously added with inducer. Using mutant strains defective for gamma-gene product or constitutive for lac enzymes, it was found that the inhibition is not due to the exclusion of inducer by uncoupling. The addition of cyclic adenosine 3',5'-monophosphate overcame repression. The components of the lac operon coordinately responded to DNP inhibition. From deoxyribonucleic acid-ribonucleic acid hybridization experiments, it was found that the inhibition of beta-galactosidase induction occurred at the level of messenger ribonucleic acid synthesis specific for the lac operon. It seems probable that DNP represses induction in a similar manner to that of transient repression observed upon the addition of glucose. Furthermore, it was found that transient repression disappeared if cells were preincubated with DNP before induction. This indicates that new contact of cells with DNP is obligatory for transient repression. From these results, it is suggested that the cell membrane may be responsible for regulation of catabolite-sensitive enzyme synthesis.

  11. Enzyme technology: Key to selective biorefining

    DEFF Research Database (Denmark)

    Meyer, Anne S.

    2014-01-01

    their rational use in biorefinery processes requires an understanding of the basic features of enzymes and reaction traits with respect to specificity, kinetics, reaction optima, stability and structure-function relations – we are now at a stage where it is possible to use nature’s enzyme structures as starting...... point and then improve the functional traits by targeted mutation of the protein. The talk will display some of our recent hypotheses related to enzyme action, recently obtained results within knowledge-based enzyme improvements as well as cast light on research methods used in optimizing enzyme...... to the reaction is a unique trait of enzyme catalysis. Since enzyme selectivity means that a specific reaction is catalysed between particular species to produce definite products, enzymes are particularly fit for converting specific compounds in mixed biomass streams. Since enzymes are protein molecules...

  12. Controlled enzyme catalyzed heteropolysaccharide degradation

    DEFF Research Database (Denmark)

    Rasmussen, Louise Enggaard

    of the progress of enzymatic hydrolysis of different xylan substrates was developed. The method relies on dividing the HPSEC elution profiles into fixed time intervals and utilizing the linear refractive index response (area under the curve) of defined standard compounds. In order to obtain optimal high......-performance size exclusion chromatography profiles, the method was designed using 0.1 M CH3COONa in both the mobile phase and as the sample solution. This was based on the systematic evaluation of the influence of the mobile phase, including the type, ionic strength and pH, on the refractive index detector...... response. A time study of the enzyme catalyzed hydrolysis of birchwood xylan and wheat bran by BsX was used as an example to demonstrate the workability of the new HPSEC method for obtaining progress curves describing the evolution in the product profile during enzyme catalysis. Flaxseed mucilage (FM) has...

  13. Failed labor induction: toward an objective diagnosis.

    LENUS (Irish Health Repository)

    Rouse, Dwight J

    2011-02-01

    To evaluate maternal and perinatal outcomes in women undergoing labor induction with an unfavorable cervix according to duration of oxytocin administration in the latent phase of labor after ruptured membranes.

  14. Superconducting Resonant Inductive Power Coupling Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed effort will develop a technology to wirelessly and efficiently transfer power over hundreds of meters via resonant inductive coupling. The key...

  15. Progress in antenna coupled kinetic inductance detectors

    NARCIS (Netherlands)

    Baryshev, A.; Baselmans, J.J.A.; Freni, A.; Gerini, G.; Hoevers, H.; Iacono, A.; Neto, A.

    2011-01-01

    This paper describes the combined Dutch efforts toward the development of large wideband focal plane array receivers based on kinetic inductance detectors (KIDs). Taking into account strict electromagnetic and detector sensitivity requirements for future ground and space based observatories, this

  16. [Induction of general anesthesia in pediatric patients].

    Science.gov (United States)

    Ota, Chiharu; Taniguchi, Akihiro

    2007-05-01

    The induction of general anesthesia is one of the most stressful procedures during the perioperative period for pediatric patients. Postoperative negative behavioral changes, such as nightmares or separation anxiety are reported in the children undergoing general anesthesia. To avoid these problems, the anesthesiologists have to pay more attention to the psychological needs of young patients as well as the technical aspects. Preoperative interview is important to identify the child who has extreme fear and anxiety. Premedication with sedatives and psychological preparation are effective for the smooth induction. In this article, preparation for the induction and practical skills of the induction in children, newborns, as well as patients with difficult airway and with full stomach are summarized.

  17. Inductive tuners for microwave driven discharge lamps

    Science.gov (United States)

    Simpson, James E.

    1999-01-01

    An RF powered electrodeless lamp utilizing an inductive tuner in the waveguide which couples the RF power to the lamp cavity, for reducing reflected RF power and causing the lamp to operate efficiently.

  18. Validity of a frustration-induction procedure.

    Science.gov (United States)

    Henna, Elaine; Zilberman, Monica L; Gentil, Valentim; Gorenstein, Clarice

    2008-03-01

    To test a reliable and easily administered frustration-induction procedure for experimental research. One hundred volunteers (81 women, mean age +/- SD 34.2 +/- 8 years) physically and psychiatrically healthy submitted to the frustration induction procedure were prevented from reaching reward level scores. Subjective aggressiveness feelings related to frustration were self-rated in a 13-item visual analogue scale before and after the procedure. Significant increases in aggressiveness-related feelings were detected in 12 of the 13 items. This was consistent with the observed overt behavior of the subjects during the task. The frustration-induction procedure is a simple, easy to administer frustration-induction procedure that can be used in experimental studies in normal subjects.

  19. Malolactic enzyme from Oenococcus oeni

    Science.gov (United States)

    Schümann, Christina; Michlmayr, Herbert; del Hierro, Andrés M.; Kulbe, Klaus D.; Jiranek, Vladimir; Eder, Reinhard; Nguyen, Thu-Ha

    2013-01-01

    Malolactic enzymes (MLE) are known to directly convert L-malic acid into L-lactic acid with a catalytical requirement of nicotinamide adenine dinucleotide (NAD+) and Mn2+; however, the reaction mechanism is still unclear. To study a MLE, the structural gene from Oenococcus oeni strain DSM 20255 was heterologously expressed in Escherichia coli, yielding 22.9 kU l−1 fermentation broth. After affinity chromatography and removal of apparently inactive protein by precipitation, purified recombinant MLE had a specific activity of 280 U mg−1 protein with a recovery of approximately 61%. The enzyme appears to be a homodimer with a molecular mass of 128 kDa consisting of two 64 kDa subunits. Characterization of the recombinant enzyme showed optimum activity at pH 6.0 and 45°C, and Km, Vmax and kcat values of 4.9 mM, 427 U mg−1 and 456 sec−1 for L-malic acid, 91.4 µM, 295 U mg−1 and 315 sec−1 for NAD+ and 4.6 µM, 229 U mg−1 and 244 sec−1 for Mn2+, respectively. The recombinant MLE retained 95% of its activity after 3 mo at room temperature and 7 mo at 4°C. When using pyruvic acid as substrate, the enzyme showed the conversion of pyruvic acid with detectable L-lactate dehydrogenase (L-LDH) activity and oxidation of NADH. This interesting observation might explain that MLE catalyzes a redox reaction and hence, the requirements for NAD+ and Mn2+ during the conversion of L-malic to L-lactic acid. PMID:23196745

  20. Localization of enzymes within microbodies.

    Science.gov (United States)

    Huang, A H; Beevers, H

    1973-08-01

    Microbodies from rat liver and a variety of plant tissues were osmotically shocked and subsequently centrifuged at 40,000 g for 30 min to yield supernatant and pellet fractions. From rat liver microbodies, all of the uricase activity but little glycolate oxidase or catalase activity were recovered in the pellet, which probably contained the crystalline cores as many other reports had shown. All the measured enzymes in spinach leaf microbodies were solubilized. With microbodies from potato tuber, further sucrose gradient centrifugation of the pellet yielded a fraction at density 1.28 g/cm(3) which, presumably representing the crystalline cores, contained 7% of the total catalase activity but no uricase or glycolate oxidase activity. Using microbodies from castor bean endosperm (glyoxysomes), 50-60% of the malate dehydrogenase, fatty acyl CoA dehydrogenase, and crotonase and 90% of the malate synthetase and citrate synthetase were recovered in the pellet, which also contained 96% of the radioactivity when lecithin in the glyoxysomal membrane had been labeled by previous treatment of the tissue with [(14)C]choline. When the labeled pellet was centrifuged to equilibrium on a sucrose gradient, all the radioactivity, protein, and enzyme activities were recovered together at peak density 1.21-1.22 g/cm(3), whereas the original glyoxysomes appeared at density 1.24 g/cm(3). Electron microscopy showed that the fraction at 1.21-1.22 g/cm(3) was comprised of intact glyoxysomal membranes. All of the membrane-bound enzymes were stripped off with 0.15 M KCl, leaving the "ghosts" still intact as revealed by electron microscopy and sucrose gradient centrifugation. It is concluded that the crystalline cores of plant microbodies contain no uricase and are not particularly enriched with catalase. Some of the enzymes in glyoxysomes are associated with the membranes and this probably has functional significance.

  1. The Synthesis of Artificial Enzymes

    Science.gov (United States)

    1993-01-01

    21] describe an interesting model (4) of these processes in which vitamin B-12 is attached to cyclodextrin . The cyclodextrin simultaneously plays the...rotation to permit the second step leading to product. In a cyclodextrin enzyme mimic we had very effective imitation of the first step : , • when...been done on the cyclodextrin dimers that were proposed for this contract period. The previously reported paper with Greenspoon et. al.(5) described

  2. Integrating Decision Tree Learning into Inductive Databases

    OpenAIRE

    Fromont, Elisa; Blockeel, Hendrik; Struyf, Jan

    2006-01-01

    In inductive databases, there is no conceptual difference between data and the models describing the data: both can be stored and queried using some query language. The approach that adheres most strictly to this philosophy is probably the one proposed by Calders et al. (2006): in this approach, models are stored in relational tables and queried using standard SQL. The approach has been described in detail for association rule discovery. In this work, we study how decision tree induction can ...

  3. Physic basis of electromagnetic induction low

    Directory of Open Access Journals (Sweden)

    V.J. Kutkovetskyy

    2015-03-01

    Full Text Available The statement on the macro level of EMF dependence on change in magnetic flux in time wrong reflects the physical phenomenon of electromagnetic induction low by Faraday, because EMF can be inducted if the magnetic flux of the circuit does not change. Changing magnetic flux of the circuit when the electromotive force arises is only a result of crossing the magnetic field lines by conductor and is an exception, which applies only to certain classes of electric machines.

  4. Inductively Shorted Bicone Fed Tapered Dipole Antenna

    Science.gov (United States)

    2012-05-23

    DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Inductively Shorted Bicone Fed Tapered Dipole Antenna 5a. CONTRACT NUMBER 5b. GRANT...Attorney Docket No. 84449 1 INDUCTIVELY SHORTED BICONE FED TAPERED DIPOLE ANTENNA STATEMENT OF GOVERNMENT INTEREST [0001] The invention described...Invention [0003] The invention generally relates to RF antennas and more specifically to bicone and dipole antennas. (2) Description of the Prior Art

  5. The Inductive Logic of Information Systems

    OpenAIRE

    Dalkey, Norman C.

    2013-01-01

    An inductive logic can be formulated in which the elements are not propositions or probability distributions, but information systems. The logic is complete for information systems with binary hypotheses, i.e., it applies to all such systems. It is not complete for information systems with more than two hypotheses, but applies to a subset of such systems. The logic is inductive in that conclusions are more informative than premises. Inferences using the formalism have a strong justification i...

  6. Substrate mediated enzyme prodrug therapy.

    Directory of Open Access Journals (Sweden)

    Betina Fejerskov

    Full Text Available In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol, β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose - dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.

  7. Research progress of nanoparticles as enzyme mimetics

    Science.gov (United States)

    Hu, XiaoNa; Liu, JianBo; Hou, Shuai; Wen, Tao; Liu, WenQi; Zhang, Ke; He, WeiWei; Ji, YingLu; Ren, HongXuan; Wang, Qi; Wu, XiaoChun

    2011-10-01

    Natural enzymes as biological catalysts possess remarkable advantages, especially their highly efficient and selective catalysis under mild conditions. However, most natural enzymes are proteins, thus exhibiting an inherent low durability to harsh reaction conditions. Artificial enzyme mimetics have been pursued extensively to avoid this drawback. Quite recently, some inorganic nanoparticles (NPs) have been found to exhibit unique enzyme mimetics. In addition, their much higher stability overcomes the inherent disadvantage of natural enzymes. Furthermore, easy mass-production and low cost endow them more benefits. As a new member of artificial enzyme mimetics, they have received intense attention. In this review article, major progress in this field is summarized and future perspectives are highlighted.

  8. Consumer attitudes to enzymes in food production

    DEFF Research Database (Denmark)

    Søndergaard, Helle Alsted; Grunert, Klaus G.; Scholderer, Joachim

    2005-01-01

    The use of enzymes in food production has potential benefits for both food manufacturers and consumers. A central question is how consumers react to new ways of producing foods with enzymes. This study investigates the formation of consumer attitudes to different enzyme production methods in three...... European countries. Results show that consumers are most positive towards non-GM enzyme production methods. The enzyme production method is by far the most important factor for the formation of buying intentions compared to price and benefits. Results also show that environmental concern and attitudes...... to technological progress are the socio-political attitudes that have the highest predictive value regarding attitudes to enzyme production methods....

  9. Allosteric regulation of epigenetic modifying enzymes.

    Science.gov (United States)

    Zucconi, Beth E; Cole, Philip A

    2017-08-01

    Epigenetic enzymes including histone modifying enzymes are key regulators of gene expression in normal and disease processes. Many drug development strategies to target histone modifying enzymes have focused on ligands that bind to enzyme active sites, but allosteric pockets offer potentially attractive opportunities for therapeutic development. Recent biochemical studies have revealed roles for small molecule and peptide ligands binding outside of the active sites in modulating the catalytic activities of histone modifying enzymes. Here we highlight several examples of allosteric regulation of epigenetic enzymes and discuss the biological significance of these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Relationships among Ergot Alkaloids, Cytochrome P450 Activity, and Beef Steer Growth

    Directory of Open Access Journals (Sweden)

    Charles F. Rosenkrans

    2015-03-01

    Full Text Available Determining a grazing animal’s susceptibility to ergot alkaloids has been a research topic for decades. Our objective was to determine if the Promega™ P450-Glo assay could be used to indirectly detect ergot alkaloids or their metabolites in urine of steers. The first experiment validated the effects of ergot alkaloids [0, 20, and 40 μM of ergotamine (ET, dihydroergotamine (DHET, and ergonovine (EN] on human CYP3A4 using the P450-Glo assay (Promega™ V9800. With this assay, luminescence is directly proportional to CYP450 activity. Relative inhibition of in vitro cytochrome P450 activity was affected (P < 0.001 by an interaction between alkaloids and concentration. That interaction resulted in no concentration effect of EN, but within ET and DHET 20 and 40 µM concentrations inhibited CYP450 activity when compared with controls. In experiment 2, urine was collected from Angus-sired crossbred steers (n = 39; 216 ± 2.6 d of age; 203 ± 1.7 kg after grazing tall fescue pastures for 105 d. Non-diluted urine was added to the Promega™ P450-Glo assay, and observed inhibition (3.7 % ± 2.7 of control. Urine content of total ergot alkaloids (331.1 ng/mg of creatinine ± 325.7 was determined using enzyme linked immunosorbent assay. Urine inhibition of CYP450 activity and total alkaloids were correlated (r = -0.31; P < 0.05. Steers were genotyped at CYP450 single nucleotide polymorphism, C994G. Steer genotype affected (P < 0.03 inhibition of CYP450 activity by urine; heterozygous steers had the least amount of CYP450 inhibition suggesting that genotyping cattle may be a method of identifying animals that are susceptible to ergot alkaloids. Although, additional research is needed, we demonstrate that the Promega™ P450-Glo assay is sensitive to ergot alkaloids and urine from steers grazing tall fescue. With some refinement the P450-Glo assay has potential as a tool for screening cattle for their exposure to fescue toxins.

  11. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    Directory of Open Access Journals (Sweden)

    R. Chris Rathbun

    2011-10-01

    Full Text Available Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450 and uridine diphosphate glucuronosyltransferase (UGT enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide. The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed.

  12. Opioid pharmacokinetic drug-drug interactions.

    Science.gov (United States)

    Overholser, Brian R; Foster, David R

    2011-09-01

    Pharmacokinetic drug-drug interactions (DDIs) involving opioid analgesics can be problematic. Opioids are widely used, have a narrow therapeutic index, and can be associated with severe toxicity. The purpose of this review is to describe pharmacokinetic DDIs associated with opioids frequently encountered in managed care settings (morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, tramadol, and methadone). An introduction to the pharmacokinetic basis of DDIs is provided, and potential DDIs associated with opioids are reviewed. Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects. Conversely, opioids that are not metabolized by that system (morphine, oxymorphone, and hydromorphone) tend to be involved in fewer CYP450-associated pharmacokinetic DDIs.

  13. Precision genome engineering with programmable DNA-nicking enzymes

    Science.gov (United States)

    Kim, Eunji; Kim, Sojung; Kim, Duk Hyoung; Choi, Beom-Soon; Choi, Ik-Young; Kim, Jin-Soo

    2012-01-01

    Zinc finger nucleases (ZFNs) are powerful tools of genome engineering but are limited by their inevitable reliance on error-prone nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs), which gives rise to randomly generated, unwanted small insertions or deletions (indels) at both on-target and off-target sites. Here, we present programmable DNA-nicking enzymes (nickases) that produce single-strand breaks (SSBs) or nicks, instead of DSBs, which are repaired by error-free homologous recombination (HR) rather than mutagenic NHEJ. Unlike their corresponding nucleases, zinc finger nickases allow site-specific genome modifications only at the on-target site, without the induction of unwanted indels. We propose that programmable nickases will be of broad utility in research, medicine, and biotechnology, enabling precision genome engineering in any cell or organism. PMID:22522391

  14. Organic Pollutant Contamination of the River Tichá Orlice as Assessed by Biochemical Markers

    Directory of Open Access Journals (Sweden)

    M. Havelková

    2008-01-01

    Full Text Available This study used biochemical markers to assess contamination at two contaminated sites (Králíky and Lichkov and one control site (Červená Voda on the River Tichá Orlice, a left-side tributary of the River Elbe. The brown trout (Salmo trutta fario was selected as an indicator species. Enzymes of the first stage of xenobiotic conversion, namely cytochrome P450 (CYP 450 and ethoxyresorufin-O-deethylase (EROD in the liver were selected as biochemical markers. Blood plasma vitellogenin concentrations were used to evaluate xenoestrogenic effects of contamination. Results were compared with the most important inductors of these markers, i.e. with organic pollutants (PCB, HCH, HCB, OCS and DDT and their metabolites in fish muscle and with PAH concentrations in bottom sediments. The highest contamination with organic pollutants was at Králíky, and this was reflected in increased cytochrome P450, EROD activity and vitellogenin concentrations. Significant differences were demonstrated in EROD activity and vitellogenin concentrations between Králíky and Červená Voda (P s = -0.964 between EROD activity and vitellogenin concentrations was demonstrated. This relationship was discussed from the point of view of a possible induction or inhibition of the assessed biomarkers at persistently highly contaminated sites.

  15. Castor Oil Transesterification Catalysed by Liquid Enzymes

    DEFF Research Database (Denmark)

    Andrade, Thalles; Errico, Massimiliano; Christensen, Knud Villy

    2017-01-01

    In the present work, biodiesel production by reaction of non-edible castor oil with methanol under enzymatic catalysis is investigated. Two liquid enzymes were tested: Eversa Transform and Resinase HT. Reactions were performed at 35 °C and with a molar ratio of methanol to oil of 6:1. The reaction...... time was 8 hours. Stepwise addition of methanol was necessary to avoid enzyme inhibition by methanol. In order to minimize the enzyme costs, the influence of enzyme activity loss during reuse of both enzymes was evaluated under two distinct conditions. In the former, the enzymes were recovered...... and fully reused; in the latter, a mixture of 50 % reused and 50 % fresh enzymes was tested. In the case of total reuse after three cycles, both enzymes achieved only low conversions. The biodiesel content in the oil-phase using Eversa Transform was 94.21 % for the first cycle, 68.39 % in the second, and 33...

  16. The regulatory process in the de-repression of enzyme synthesis. Alkaline phosphatase of Bacillus subtilis.

    Science.gov (United States)

    Moses, V

    1967-06-01

    1. The kinetics of de-repression of alkaline phosphatase in Bacillus subtilis were studied after the removal of P(i). Enzyme activity appeared about 10min. after removal of P(i), whereas ;enzyme-forming potential' appeared after 6min. 2. Protein synthesis is not impaired for at least 20min. on removal of P(i), but RNA synthesis is considerably diminished. 3. Adding chloramphenicol to cells without P(i), just at the time they start to make enzyme-forming potential, does not affect the differential rate of enzyme synthesis compared with total protein. Enzyme-forming potential accumulates to about normal levels in the presence of chloramphenicol, even though peptide-bond formation is inhibited by more than 95%. 4. Similar experiments performed with actinomycin C show more complex effects. Actinomycin initially prevents RNA synthesis and also the synthesis of enzyme-forming potential. After some minutes RNA synthesis resumes at a low rate, to be followed 4min. later by enzyme synthesis. Enzyme-forming potential can accumulate in the presence of actinomycin after the resumption of RNA synthesis. Protein synthesis, initially inhibited by actinomycin as a consequence of the effect on RNA synthesis, is later directly inhibited by actinomycin. 5. Adding actinomycin to de-repressed cells already making enzyme stops enzyme synthesis within 4-5min. Enzyme synthesis resumes, as before, 4min. after the resumption of RNA synthesis. 6. Adding P(i) together with actinomycin to de-repressed cells synthesizing enzyme does not result in a lower yield of enzyme compared with actinomycin alone. 7. Actinomycin is less effective an inhibitor of RNA and protein synthesis in P(i)-starved cells if P(i) is also added. 8. These results are discussed in view of the three main models for the regulation of enzyme induction: regulation at the level of transcription only, at translation only, or a coupled model in which transcription requires concomitant translation. It is concluded that the

  17. The regulatory process in the de-repression of enzyme synthesis

    Science.gov (United States)

    Moses, V.

    1967-01-01

    1. The kinetics of de-repression of alkaline phosphatase in Bacillus subtilis were studied after the removal of Pi. Enzyme activity appeared about 10min. after removal of Pi, whereas `enzyme-forming potential' appeared after 6min. 2. Protein synthesis is not impaired for at least 20min. on removal of Pi, but RNA synthesis is considerably diminished. 3. Adding chloramphenicol to cells without Pi, just at the time they start to make enzyme-forming potential, does not affect the differential rate of enzyme synthesis compared with total protein. Enzyme-forming potential accumulates to about normal levels in the presence of chloramphenicol, even though peptide-bond formation is inhibited by more than 95%. 4. Similar experiments performed with actinomycin C show more complex effects. Actinomycin initially prevents RNA synthesis and also the synthesis of enzyme-forming potential. After some minutes RNA synthesis resumes at a low rate, to be followed 4min. later by enzyme synthesis. Enzyme-forming potential can accumulate in the presence of actinomycin after the resumption of RNA synthesis. Protein synthesis, initially inhibited by actinomycin as a consequence of the effect on RNA synthesis, is later directly inhibited by actinomycin. 5. Adding actinomycin to de-repressed cells already making enzyme stops enzyme synthesis within 4–5min. Enzyme synthesis resumes, as before, 4min. after the resumption of RNA synthesis. 6. Adding Pi together with actinomycin to de-repressed cells synthesizing enzyme does not result in a lower yield of enzyme compared with actinomycin alone. 7. Actinomycin is less effective an inhibitor of RNA and protein synthesis in Pi-starved cells if Pi is also added. 8. These results are discussed in view of the three main models for the regulation of enzyme induction: regulation at the level of transcription only, at translation only, or a coupled model in which transcription requires concomitant translation. It is concluded that the present evidence

  18. Laboratory and field studies on biotransformation enzymes in sunfish (Lepomis sp. )

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez, B.D.; Oikari, A.; Adams, S.M.; Esau, B.D.; Morrissey, C.M.; Petanen, T.I. (Oak Ridge National Lab., TN (USA))

    1988-09-01

    To cope with pollutants, organisms synthesize enzymes that detoxify organic compounds (mixed function oxidases or MFOs). A series of these enzymes are presently being employed as indicators of pollution at Oak Ridge National laboratory in the Y-12 Biological Monitoring and Abatement Program. The quantities and activities of several hepatic enzymes, as well as the liver somatic indices, were measured in redbreast sunfish, Leopomis auritus, sampled from several stations along a stream receiving large inputs of industrial and municipal effluents and a stream in a non-industrialized, rural drainage area. Fish collected close to the industrial and municipal outfalls exhibited high quantities and activities of these enzymes, as well as elevated somatic indices, compared to those from the rural stream and from other locations along the polluted stream. Laboratory experiments were conducted using Bluegill-green sunfish hybrid which were exposed to approximately 0.5 g Benzo(a)pyrene (BaP) per liter under 24 h static renewal conditions. The time course of induction for MFO activity was obtained. Induction of MFO activity occurred a week after BaP exposure.

  19. Biomedical Applications of Enzymes From Marine Actinobacteria.

    Science.gov (United States)

    Kamala, K; Sivaperumal, P

    Marine microbial enzyme technologies have progressed significantly in the last few decades for different applications. Among the various microorganisms, marine actinobacterial enzymes have significant active properties, which could allow them to be biocatalysts with tremendous bioactive metabolites. Moreover, marine actinobacteria have been considered as biofactories, since their enzymes fulfill biomedical and industrial needs. In this chapter, the marine actinobacteria and their enzymes' uses in biological activities and biomedical applications are described. © 2017 Elsevier Inc. All rights reserved.

  20. Interplay of transporters and enzymes in drug and metabolite processing.

    Science.gov (United States)

    Pang, K Sandy; Maeng, Han-Joo; Fan, Jianghong

    2009-01-01

    This review highlights the "interplay" between enzymes and transporters, essential components of eliminating organs for drug removal. The understanding of the interplay is important in terms of deciphering the change of one eliminatory pathway on compensatory mechanisms in drug disposal, and, ultimately, their importance in drug-drug interactions. Controversy existed on the explanation underlying the interplay between transporters and enzymes in the Caco-2 cell monolayer or cell culture systems, but less so on eliminating organs such as the intestine and liver. For the Caco-2 system, the increase in the mean residence time (MRT) accompanying increased secretion had been construed as the basis for increased metabolism. We hold the opposite view and assert that increased secretion should evoke a decrease in metabolism due to the competition between the enzyme and apical efflux transporter for the drug within the cell. To illustrate this point, simulations on the MRT, fraction of dose metabolized (f(met)) and the extraction ratio (ER) as defined by various investigators under linear and nonlinear metabolic conditions were compared to observed data and the trends upon induction/inhibition of secretion. The conclusion is that the f(met) is the more appropriate index to reflect the extent of metabolism in transporter-enzyme interplay, since the parameter captures drug metabolism in the cell when its contents in the apical, cell, and basolateral compartments or the entire dose is considered to be available for metabolism. This parameter for metabolism (f(met)) bears a reciprocal relationship to the secretory intrinsic clearance and is in concordance with the notion that both the enzyme and apical transporter compete for the cellular substrate within. For the liver and intestine, several physiologically based pharmacokinetic (PBPK) models that contain transporters and enzymes were utilized, together with the solved equations for the area under the curve (AUC), metabolic

  1. [Mood induction procedures: a critical review].

    Science.gov (United States)

    Gilet, A-L

    2008-06-01

    For a long period in the history of psychological research, emotion and cognition have been studied independently, as if one were irrelevant to the other. The renewed interest of researchers for the study of the relations between cognition and emotion has led to the development of a range of laboratory methods for inducing temporary mood states. This paper aims to review the main mood induction procedures allowing the induction of a negative mood as well as a positive mood, developed since the pioneer study of Schachter and Singer [Psychol Rev 69 (1962) 379-399] and to account for the usefulness and problems related to the use of such techniques. The first part of this paper deals with the detailed presentation of some of the most popular mood induction procedures according to their type: simple (use of only one mood induction technique) or combined (association of two or more techniques at once). The earliest of the modern techniques is the Velten Mood Induction Procedure [Behav Res Ther 6 (1968) 473-482], which involves reading aloud sixty self-referent statements progressing from relative neutral mood to negative mood or dysphoria. Some researchers have varied the procedure slightly by changing the number of the statements [Behav Res Ther 21 (1983) 233-239, Br J Clin Psychol 21 (1982) 111-117, J Pers Soc Psychol 35 (1977) 625-636]. Various other mood induction procedures have been developed including music induction [Cogn Emotion 11 (1997) 403-432, Br J Med Psychol 55 (1982) 127-138], film clip induction [J Pers Soc Psychol 20 (1971) 37-43, Cogn Emotion 7 (1993) 171-193, Rottenberg J, Ray RR, Gross JJ. Emotion elicitation using films. In: Coan JA, Allen JJB, editors. The handbook of emotion elicitation and assessment. New York: Oxford University Press, 2007], autobiographical recall [J Clin Psychol 36 (1980) 215-226, Jallais C. Effets des humeurs positives et négatives sur les structures de connaissances de type script. Thèse de doctorat non publi

  2. 32 CFR 1624.1 - Random selection procedures for induction.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Random selection procedures for induction. 1624... SYSTEM INDUCTIONS § 1624.1 Random selection procedures for induction. (a) The Director of Selective Service shall from time to time establish a random selection sequence for induction by a drawing to be...

  3. 32 CFR 1624.5 - Order to report for induction.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Order to report for induction. 1624.5 Section... INDUCTIONS § 1624.5 Order to report for induction. (a) Immediately upon determining which persons are to be ordered for induction, the Director of Selective Service shall issue to each person selected an Order to...

  4. 32 CFR 1624.9 - Induction into the Armed Forces.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Induction into the Armed Forces. 1624.9 Section... INDUCTIONS § 1624.9 Induction into the Armed Forces. Registrants in classes 1-A and 1-A-0, who have been... inducted at the MEPS into the Armed Forces. ...

  5. 14 CFR 23.1093 - Induction system icing protection.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Induction system icing protection. 23.1093... Induction System § 23.1093 Induction system icing protection. (a) Reciprocating engines. Each reciprocating engine air induction system must have means to prevent and eliminate icing. Unless this is done by other...

  6. Screening for the optimal induction parameters for periplasmic ...

    African Journals Online (AJOL)

    Recombinant E. coli Rosetta-gami 2(DE3) harboring the plasmid pET26b containing IFN-α2b gene under the control of the T7lac promoter was used, where the induction was accomplished by isopropyl β-D-1- thiogalactopyranoside (IPTG). The induction parameters (inducer concentration, point of induction, induction ...

  7. Enzyme Technology for Shipboard Waste Management

    Science.gov (United States)

    1976-12-01

    APPLICATIONS OF ENZYMES Ezm Type I Applications Soluble Enzymes Amylase Starch degradation; conversion of starch to glucose; liquefac- tion of grain...manufac- turing; chillproofing beer in brewing. Cellulase Clarification of fruit juices. Oxidase Removal of glucose or oxygen. Immobilized Enzymes

  8. Purification and characterization of extracellular amylolytic enzyme ...

    African Journals Online (AJOL)

    In the present study, the amylase enzyme producing potential of four different Aspergillus species was analyzed. The extracted amylase enzyme was purified by diethyl amino ethyl (DEAE) cellulose and Sephadex G-50 column chromatography and the enzyme activity was measured by using synthetic substrate starch.

  9. Immobilization of Enzymes in Polymer Supports.

    Science.gov (United States)

    Conlon, Hugh D.; Walt, David R.

    1986-01-01

    Two experiments in which an enzyme is immobilized onto a polymeric support are described. The experiments (which also demonstrate two different polymer preparations) involve: (1) entrapping an enzyme in an acrylamide polymer; and (2) reacting the amino groups on the enzyme's (esterase) lysine residues with an activated polymer. (JN)

  10. Activation of interfacial enzymes at membrane surfaces

    DEFF Research Database (Denmark)

    Mouritsen, Ole G.; Andresen, Thomas Lars; Halperin, Avi

    2006-01-01

    A host of water-soluble enzymes are active at membrane surfaces and in association with membranes. Some of these enzymes are involved in signalling and in modification and remodelling of the membranes. A special class of enzymes, the phospholipases, and in particular secretory phospholipase A2 (s...

  11. Purification and characterization of extracellular amylolytic enzyme ...

    African Journals Online (AJOL)

    DOSS

    2012-10-16

    Oct 16, 2012 ... In the present study, the amylase enzyme producing potential of four different Aspergillus species was analyzed. The extracted amylase enzyme was purified by diethyl amino ethyl (DEAE) cellulose and. Sephadex G-50 column chromatography and the enzyme activity was measured by using synthetic.

  12. Cellulolytic enzyme compositions and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Iyer, Prashant; Gaspar, Armindo Ribiero; Croonenberghs, James; Binder, Thomas P.

    2017-07-25

    The present invention relates enzyme composition comprising a cellulolytic preparation and an acetylxylan esterase (AXE); and the used of cellulolytic enzyme compositions for hydrolyzing acetylated cellulosic material. Finally the invention also relates to processes of producing fermentation products from acetylated cellulosic materials using a cellulolytic enzyme composition of the invention.

  13. 21 CFR 864.4400 - Enzyme preparations.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Enzyme preparations. 864.4400 Section 864.4400...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Specimen Preparation Reagents § 864.4400 Enzyme preparations. (a) Identification. Enzyme preparations are products that are used in the histopathology...

  14. Monitoring enzyme synthesis as a means of studying peptide transport and utilization in Escherichia coli.

    Science.gov (United States)

    Bell, G; Payne, G M; Payne, J W

    1977-02-01

    A new method has been developed for measuring peptide transport in aminoacid auxotrophs of Escherichia coli by following induction of beta-galactosidase. Appearance of the enzyme was determined after addition of inducer and peptides to amino-acid starved bacteria. For a given number of lysine equivalents, the rate and the extent of enzyme synthesis were the same for lysine and lysyl peptides; similar results were found for glycine and glycl peptides. Saturation constants for peptide transport were determined from the exogenous peptide concentration that gave half maximal rates of enzyme synthesis. The saturation constants, studies with mutants defective in peptide transport, and detection of competition between peptides for uptake, all endorsed earlier conclusions from growth tests about the structural specificities for peptide transport. The new method is quicker, more sensitive and more informative than growth tests.

  15. [Enzyme replacement therapy for hypophosphatasia].

    Science.gov (United States)

    Ozono, Keiichi

    2014-02-01

    Hypophosphatasia is caused by abnormal tissue-nonspecific alkaline phosphatase (ALP), leading to impaired calcification in bone. Patients with severe hypophosphatasia have difficulties in respiratory function from early days after birth and the rate of lethality is extremely high. Enzyme replacement therapy using bone-targeting recombinant ALP, which has 10 aspartic acids in the C-terminal tail has developed. The efficacy of ERT was firstly observed in model mice of hypophosphatasia. In clinical trial including perinatal and infantile types of hypophosphatasia, efficacy and safety have been reported. Expanded clinical trial is underway and the results of the clinical trial might be reported by the end of the next year.

  16. Enhanced cellulase production by Trichoderma harzianum by cultivation on glycerol followed by induction on cellulosic substrates.

    Science.gov (United States)

    Delabona, Priscila da Silva; Lima, Deise Juliana; Robl, Diogo; Rabelo, Sarita Cândida; Farinas, Cristiane Sanchez; Pradella, José Geraldo da Cruz

    2016-05-01

    The use of glycerol obtained as an intermediate of the biodiesel manufacturing process as carbon source for microbial growth is a potential alternative strategy for the production of enzymes and other high-value bioproducts. This work evaluates the production of cellulase enzymes using glycerol for high cell density growth of Trichoderma harzianum followed by induction with a cellulosic material. Firstly, the influence of the carbon source used in the pre-culture step was investigated in terms of total protein secretion and fungal morphology. Enzymatic productivity was then determined for cultivation strategies using different types and concentrations of carbon source, as well as different feeding procedures (batch and fed-batch). The best strategy for cellulase production was then further studied on a larger scale using a stirred tank bioreactor. The proposed strategy for cellulase production, using glycerol to achieve high cell density growth followed by induction with pretreated sugarcane bagasse, achieved enzymatic activities up to 2.27 ± 0.37 FPU/mL, 106.40 ± 8.87 IU/mL, and 9.04 ± 0.39 IU/mL of cellulase, xylanase, and β-glucosidase, respectively. These values were 2 times higher when compared to the control experiments using glucose instead of glycerol. This novel strategy proved to be a promising approach for improving cellulolytic enzymes production, and could potentially contribute to adding value to biomass within the biofuels sector.

  17. Sex-dependent behavioral changes in rat offspring after in utero administration of a single low dose PBDE 47

    Energy Technology Data Exchange (ETDEWEB)

    Kuriyama, S.N.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

    2004-09-15

    Increasing levels of polybrominated diphenyl ethers (PBDEs) in environmental and human samples has resulted in intensive discussion regarding possible hazard identification and risk assessment in the last years. In rodents, exposure to PBDE mixtures or single congeners has resulted in a mixed induction of CYP450- dependent enzymes, showing increased activity of hepatic EROD and PROD. In addition, genotoxicity has been observed in recombination assays, and neurotoxicity has been reported in mice exposed during development. Acute and sub-chronic exposures of mice and rats to a PBDE mixture (DE-71) cause dose-dependent reductions in serum concentrations of thyroxin (T4), and stressinduced elevations in plasma corticosterone. Further, some hydroxylated metabolites of PBDE congeners exhibit a higher potency in vivo than T4 in competitive binding to human transthyretin (TTR), the transport protein mediating transfer of thyroid hormones across the placenta and into the brain. The available information in the literature clearly indicates that PBDEs are potent neurotoxicants, causing effects at doses lower than that able to disrupt thyroid hormone profiles and change CYP 450 activities. Neurobehavior effects, which includes defects in learning and memory, and changes in nicotinic receptors were found at doses starting at 0.45 ppm in mouse (9). The congeners, PBDE 47 and PBDE 99, have also been shown to cause permanent aberrations in spontaneous behavior in mice which was more pronounced with increasing age. PBDE 47 is the most predominant congener found in environmental and human samples, including human breast milk. Its presence in breast milk highlights the importance of evaluating possible effects following early developmental exposure and because this period represents a critical time which an organism is extremely susceptible to minor changes in hormonal milieu. Variances in terms of time point and concentration of exposure to steroids can lead to an organizational

  18. Screening of Enzyme Biomarker for Nanotoxicity of Zinc Oxide in OREOCHROMIS MOSSAMBICUS

    Science.gov (United States)

    Subramanian, Periasamy; Bupesh, Giridharan

    2011-06-01

    Experiments were conducted to determine the effects of Zinc oxide (ZnO) nanoparticles (NPs) on fish models. Oreochromis mossambicus was orally administered with ZnO NPs (50-100 nm) once and its effects at five different concentrations (60 ppm-100 ppm) were observed for 12 days. Enzymatic assays were performed at every three days interval in the vital tissues of liver, gill, muscle and kidney. The defense enzymes, ethoxyresorufin O-deethylase (EROD) and glutathione S transferase (GST) exerted a dose dependent elevation up to 6 days. This hike then declines in higher concentrations and extended duration. Whereas the tissue damaging enzymes, glutamate oxaloacetic transaminase (GOT), glutamate pyruvic transaminase (GPT) and alkaline phosphatase (ALP) as well as the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) exhibited a dose and duration dependent increase until the end of the experiment. Among these enzymes, the antioxidant enzymes response to ZnO NP toxicity on fish showed notable continuous induction. This study demonstrates that antioxidant enzymes responses in O. mossambicus could be used as a biomarker for the early detection of nanotoxicity.

  19. Catechins Variously Affect Activities of Conjugation Enzymes in Proliferating and Differentiated Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Kateřina Lněničková

    2016-09-01

    Full Text Available The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and their modulation by green tea extract (GTE and epigallocatechin gallate (EGCG using both proliferating (P and differentiated (D caco-2 cells. The mRNA levels of the main conjugation enzymes were significantly elevated after the differentiation of Caco-2 cells. However, no increase in conjugation enzymes’ activities in differentiated cells was detected in comparison to proliferating ones. GTE/EGCG treatment did not affect the mRNA levels of any of the conjugation enzymes tested in either type of cells. Concerning conjugation enzymes activities, GTE/EGCG treatment elevated glutathione S-transferase (GST activity by approx. 30% and inhibited catechol-O-methyltransferase (COMT activity by approx. 20% in differentiated cells. On the other hand, GTE as well as EGCG treatment did not significantly affect the activities of conjugation enzymes in proliferating cells. Administration of GTE/EGCG mediated only mild changes of GST and COMT activities in enterocyte-like cells, indicating a low risk of GTE/EGCG interactions with concomitantly administered drugs. However, a considerable chemo-protective effect of GTE via the pronounced induction of detoxifying enzymes cannot be expected as well.

  20. Quality Induction: The Effects of Comprehensive Induction on New Teacher Retention and Job Satisfaction

    Science.gov (United States)

    Hendricks-Harris, Mary Therese

    2012-01-01

    This investigation examined the effect of a comprehensive new teacher induction program on teacher retention and job satisfaction in one suburban school district. New teachers are retained at low rates, and districts are spending resources in an attempt to decrease this number. New teacher induction includes supports for new teachers in their…

  1. Beta-lactamase induction and cell wall metabolism in Gram-negative bacteria

    Directory of Open Access Journals (Sweden)

    Ximin eZeng

    2013-05-01

    Full Text Available Production of beta-lactamases, the enzymes that degrade beta-lactam antibiotics, is the most widespread and threatening mechanism of antibiotic resistance. In the past, extensive research has focused on the structure, function, and ecology of beta-lactamases while limited efforts were placed on the regulatory mechanisms of beta-lactamases. Recently, increasing evidence demonstrate a direct link between beta-lactamase induction and cell wall metabolism in Gram-negative bacteria. Specifically, expression of beta-lactamase could be induced by the liberated murein fragments, such as muropeptides. This article summarizes current knowledge on cell wall metabolism, beta-lactam, and beta lactamases. In particular, we comprehensively reviewed recent studies on the beta-lactamase induction by muropeptides via two major molecular mechanisms (the AmpG-AmpR-AmpC pathway and BlrAB-like two-component regulatory system in Gram-negative bacteria. The signaling pathways for beta-lactamase induction offer a broad array of promising targets for the discovery of new antibacterial drugs used for combination therapies. Therefore, to develop effective mitigation strategies against the widespread beta-lactam resistance, examination of the molecular basis of beta-lactamase induction by cell wall fragment is highly warranted.

  2. Two-Phase Induction Motor Drives

    Directory of Open Access Journals (Sweden)

    Gholam Reza Arab Markadeh

    2010-10-01

    Full Text Available The lack of variable-speed drives for two (single induction motor is a reality. This article attempts mainly to investigate the reasons for this lack of variable – speed drives. This paper deals with literature survey of various existing converter topologies, which have been proposed for adjustable speed single phase induction motor drives. Various converter topologies have been compared in this paper. Among these converter topologies, the adjustable frequency PWM inverter is the best choice for single-phase induction motor drives. However, adjustable-frequency drives have not been widely used with single-phase Induction motors. The open-loop constant V/F control law cannot be used with the single-phase induction motor drives as it is used with three phase motors. The variation of the operating frequency at lower speed range with constant load torque causes variation in motor's slip. A constant V/F control is suitable only over the upper speed range.

  3. A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus standard-of-care office-based inductions.

    Science.gov (United States)

    Cunningham, Chinazo O; Giovanniello, Angela; Li, Xuan; Kunins, Hillary V; Roose, Robert J; Sohler, Nancy L

    2011-06-01

    Although novel buprenorphine induction strategies are emerging, they have been inadequately studied. To examine our newly developed patient-centered home-based inductions, we conducted a subgroup analysis of 79 opioid-dependent individuals who had buprenorphine inductions at an urban community health center. Participants chose their induction strategy. Standard-of-care office-based inductions were physician driven, with multiple assessments, and observed, and the patient-centered home-based inductions emphasized patient self-management and included a "kit" for induction at home. We conducted interviews and extracted medical records. Using mixed nonlinear models, we examined associations between induction strategy and opioid use and any drug use. Compared with those with standard-of-care office-based inductions, participants with patient-centered home-based inductions had no significant differences in opioid use (adjusted odds ratio [AOR] = 0.63, 95% confidence interval [CI] = 0.13-2.97) but greater reductions in any drug use (AOR = 0.05, 95% CI = 0.01-0.37). Taking into account the limitations of our observational cohort study design, we conclude that participants with patient-centered home-based inductions had similar reductions in opioid use and greater reductions in any drug use than those with standard-of-care office-based inductions. It is essential that new induction strategies be based on existing models or theories and be well studied. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Induction of Mannanase, Xylanase, and Endoglucanase Activities in Sclerotium rolfsii.

    Science.gov (United States)

    Sachslehner, A; Nidetzky, B; Kulbe, K D; Haltrich, D

    1998-02-01

    Induction of mannanase, xylanase, and cellulase (endoglucanase) synthesis in the plant-pathogenic basidiomycete Sclerotium rolfsii was studied by incubating noninduced, resting mycelia with a number of mono-, oligo-, and polysaccharides. The simultaneous formation of these three endoglycanases could be provoked by several polysaccharides structurally resembling the carbohydrate constituents of lignocellulose (e.g., mannan and cellulose), by various disaccharide catabolites of these lignocellulose constituents (e.g., cellobiose, mannobiose, and xylobiose), or by structurally related disaccharides (e.g., lactose, sophorose, and galactosyl-beta-1,4-mannose), as well as by l-sorbose. Synthesis of mannanase, xylanase, and endoglucanase always occurred concomitantly and could not be separated by selecting an appropriate inducer. Various structurally different inducing carbohydrates promoted the excretion of the same multiple isoforms of endoglycanases, as judged from the similar banding patterns obtained in zymogram analyses of enzyme preparations obtained in response to these different inducers and resolved by analytical isoelectric focusing. Whereas enhanced xylanase and endoglucanase formation is strictly dependent on the presence of suitable inducers, increased levels of mannanase are excreted by S. rolfsii even under noninducing, derepressed conditions, as shown in growth experiments with glucose as the substrate. Significant mannanase formation commenced only when glucose was exhausted from the medium. Under these conditions, only very low, presumably constitutive levels of xylanase and endoglucanase were formed. Although the induction of the three endoglycanases is very closely related in S. rolfsii, it was concluded that there is no common, coordinated regulatory mechanism that controls the synthesis of mannanase, xylanase, and endoglucanase.

  5. Induction of taxol metabolism in the rat by dexamethasone

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, C.D.; Gondi, K.N.; Walle, T.

    1994-12-31

    The antitumor drug taxol was metabolized to two major metabolites (RM1 and RM2) in adult male and female rat liver microsomes. The male rats produced RM1 2.6 fold faster than the females, and they produced RM2 3 fold faster than the females. This correlated well with the sex differences noticed in liver microsomal cytochrome P450 (CYP) 3A content (4.4 fold greater in male) and 6{beta}-hydroxylation of testosterone (2.4 fold greater in male). Taxol was metabolized to three major metabolites (RM1, RM2, and RM3) in adult male and female rat liver microsomes from rats pretreated with dexamethasone. Production of RM1 and RM2 was increased in these rats (2.3 and 3.3 fold respectively in males; 6.5 and 8.7 fold respectively in females) as compared to the untreated rats. These results compared well with the induction of CYP 3A proteins (3.5 fold in male, 10 fold in female) and induction of 6{beta}-hydroxylation (1.9 fold in males, 3.8 fold in females). RM3, which was produced only by the rats pretreated with dexamethasone, had a retention time of 0.58 relative to taxol which corresponds to 6{alpha}- hydroxytaxol, the major human metabolite of taxol. This study indicates that taxol metabolism in the rat is likely due to CYP 3A enzymes. Although the evidence points toward CYP 3A1 as the major isoform involved, it does not rule out others. The findings also suggest that CYP 3A1 is responsible for the induced metabolite, RM3.

  6. Mutational remodeling of enzyme specificity.

    Science.gov (United States)

    Bone, R; Agard, D A

    1991-01-01

    With the advent of genetic engineering techniques has come the ability to modify proteins as desired. Given this stunning capability, the question remains what residues should be altered, and how should they be changed to achieve a particular specificity pattern. The goals of such modifications are likely to fall into either of two categories: probing the function of a protein or attempting to alter its properties. In either case, our understanding of the consequences of a mutation, as ascertained by our ability to predict the results, is currently quite limited. The problem is extraordinarily complex; our understanding of how to calculate the energetics involved is still incomplete, and we are just beginning to accumulate experimental data which may help guide us. On the positive side, theoretical methods are now being developed and refined that should prove useful in the drive to engineer enzyme specificity. What may be most important at this juncture is to expand the experimental database interrelating sequence, function, and structure. That is, there should be a concerted effort to combine functional analysis of mutant proteins with structural analysis. Only from this combined examination of the effects of mutations can sufficient data be accumulated to test and improve both qualitative and quantitative approaches or methods for remodeling enzyme specificity.

  7. Impact of enzalutamide and its main metabolite N-desmethyl enzalutamide on pharmacokinetically important drug metabolizing enzymes and drug transporters.

    Science.gov (United States)

    Weiss, Johanna; Kocher, Jutta; Mueller, Corina; Rosenzweig, Stephanie; Theile, Dirk

    2017-12-01

    Enzalutamide is a new drug against castration-resistant prostate cancer. Recent data indicate profound induction of drug metabolizing enzymes (e.g. cytochrome P450 isoenzyme (CYP) 3A4) but comprehensive in vitro data on other CYP enzymes, drug conjugating enzymes or drug transporters is scarce. Moreover, the mechanisms of induction are poorly investigated and the effects of the active metabolite N-desmethyl enzalutamide are unknown. Using LS180 cells as an induction model and quantitative real-time reverse transcription polymerase chain reaction, our study demonstrated a concentration-dependent induction of CYP1A1, CYP1A2, CYP3A5, CYP3A4, UGT1A3, UGT1A9, ABCB1, ABCC2 and ABCG2 mRNA. Induction of CYP3A4 and ABCB1 was confirmed by Western blot analysis and is likely mediated by activation of the nuclear receptor pregnane x receptor, elucidated by a luciferase-based reporter gene assay. Enzalutamide's main active metabolite N-desmethyl enzalutamide exhibited only weak induction properties. mRNA expression of UGT2B7 was suppressed by enzalutamide and its metabolite. Both compounds are apparently not transported by P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP). N-desmethyl enzalutamide more potently inhibited important drug transporters (P-gp, BCRP, OATPs) than enzalutamide. Taken together, the pharmacokinetics of concurrently administered drugs is likely altered during enzalutamide therapy. Levels of metabolically (mainly CYP3A4) eliminated drugs are expected to be decreased, whereas the abundance of compounds with solely transporter-determined pharmacokinetics (P-gp, OATPs) is likely enhanced. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Stator Fault Modelling of Induction Motors

    DEFF Research Database (Denmark)

    Thomsen, Jesper Sandberg; Kallesøe, Carsten

    2006-01-01

    In this paper a model of an induction motor affected by stator faults is presented. Two different types of faults are considered, these are; disconnection of a supply phase, and inter-turn and turn-turn short circuits inside the stator. The output of the derived model is compared to real measurem......In this paper a model of an induction motor affected by stator faults is presented. Two different types of faults are considered, these are; disconnection of a supply phase, and inter-turn and turn-turn short circuits inside the stator. The output of the derived model is compared to real...... measurements from a specially designed induction motor. With this motor it is possible to simulate both terminal disconnections, inter-turn and turn-turn short circuits. The results show good agreement between the measurements and the simulated signals obtained from the model. In the tests focus...

  9. Induction surface hardening of hard coated steels

    DEFF Research Database (Denmark)

    Pantleon, Karen; Kessler, Olaf; Hoffmann, Franz

    1999-01-01

    -process is the high deposition temperature, consequently the properties of steel substrates are negatively influenced. Therefore, a subsequent heat treatment of the coated steels is necessary to restore the properties of steels ready for operation. Induction surface hardening is used as a method of heat treatment......, the scratch test is used to estimate critical loads for cohesive and adhesive failure of the coatings. Additionally, distortion measurements are carried out. The results emphasize the advantage of induction surface hardening as a method of subsequent heat treatment of CVD-coated steels....... after the deposition of TiN hard coatings on steel substrates. Influences of both the coating properties and the substrate properties are discussed in dependence on the parameters of induction heating. Thereby the heating time, heating atmosphere and the power input into the specimen are changed...

  10. Entropy generation analysis of magnetohydrodynamic induction devices

    Energy Technology Data Exchange (ETDEWEB)

    Salas, Hugo [UAEMor., Facultad de Ciencias, Cuernavaca (Mexico); Cuevas, Sergio; Haro, Mariano Lopez de [UNAM, Centro de Investigacion en Energia, Temixco (Mexico)

    1999-10-21

    Magnetohydrodynamic (MHD) induction devices such as electromagnetic pumps or electric generators are analysed within the approach of entropy generation. The flow of an electrically-conducting incompressible fluid in an MHD induction machine is described through the well known Hartmann model. Irreversibilities in the system due to ohmic dissipation, flow friction and heat flow are included in the entropy-generation rate. This quantity is used to define an overall efficiency for the induction machine that considers the total loss caused by process irreversibility. For an MHD generator working at maximum power output with walls at constant temperature, an optimum magnetic field strength (i.e., Hartmann number) is found based on the maximum overall efficiency. (Author)

  11. Application and Perspectives of Multiphase Induction Motors

    Directory of Open Access Journals (Sweden)

    Benas Kundrotas

    2012-04-01

    Full Text Available The article considers the areas of applying multiphase induction motors. Their advantages against three phase motors have become the main reason for employing them in multiphase drives. The paper deals with the six-phase induction motor having two similar three phase windings in the stator shifted by 30 degrees in space and three phase windings in the rotor. Differential equations for this motor are presented and transformed to dq synchronous reference frame. The transformed equations are expressed in a matrix form and solved by MATLAB software using the Dormand-Prince (ode45 method. The transient characteristics of the torque, speed and current of the six-phase induction motor are calculated and discussed.Article in Lithuanian

  12. Hybrid-secondary uncluttered induction machine

    Science.gov (United States)

    Hsu, John S.

    2001-01-01

    An uncluttered secondary induction machine (100) includes an uncluttered rotating transformer (66) which is mounted on the same shaft as the rotor (73) of the induction machine. Current in the rotor (73) is electrically connected to current in the rotor winding (67) of the transformer, which is not electrically connected to, but is magnetically coupled to, a stator secondary winding (40). The stator secondary winding (40) is alternately connected to an effective resistance (41), an AC source inverter (42) or a magnetic switch (43) to provide a cost effective slip-energy-controlled, adjustable speed, induction motor that operates over a wide speed range from below synchronous speed to above synchronous speed based on the AC line frequency fed to the stator.

  13. Determination of Coil Inductances Cylindrical Iron Nucleus

    Directory of Open Access Journals (Sweden)

    Azeddine Mazouz

    2014-03-01

    Full Text Available The paper describes the investigation and development of a structure and performance characteristics of a coil iron nucleus cylindrical (C.I.N.C. The coil iron nucleus cylindrical is a nonlinear electro radio in which the moving of the nucleus in a sense or in other causes change in inductance and can reach extreme values at the superposition of nucleus and coil centers. The variation of the inductance and the degree of freedom of movement of the nucleus can lead to a device with electromechanical conversion The aim of this paper is the determination and visualization of self inductance and mutual of the (C.I.N.C based on geometric dimensions and the displacement of the nucleus.  

  14. Pulmonary Hypertensive Crisis on Induction of Anesthesia.

    Science.gov (United States)

    Schisler, Travis; Marquez, Jose M; Hilmi, Ibtesam; Subramaniam, Kathirvel

    2017-03-01

    Anesthesia for lung transplantation remains one of the highest risk surgeries in the domain of the cardiothoracic anesthesiologist. End-stage lung disease, pulmonary hypertension, and right heart dysfunction as well as other comorbid disease factors predispose the patient to cardiovascular, respiratory and metabolic dysfunction during general anesthesia. Perhaps the highest risk phase of surgery in the patient with severe pulmonary hypertension is during the induction of anesthesia when the removal of intrinsic sympathetic tone and onset of positive pressure ventilation can decompensate a severely compromised cardiovascular system. Severe hypotension, cardiac arrest, and death have been reported previously. Here we present 2 high-risk patients for lung transplantation, their anesthetic induction course, and outcomes. We offer suggestions for the safe management of anesthetic induction to mitigate against hemodynamic and respiratory complications.

  15. Evaluation of thermostable enzymes for bioethanol processing

    DEFF Research Database (Denmark)

    Skovgaard, Pernille Anastasia

    for the ioethanol production, but the expenses can be reduced by using thermostable enzymes, which are known for their increased stability and inhibitor olerance. However, the advantage of using thermostable enzymes has not been studied thoroughly and more knowledge is needed for development of bioethanol processes...... concentration reduced the stability of the enzymes, while addition of polyethylene glycol (PEG) had the opposite effect. In addition, thermostable enzymes retained more activity when tested in a pilot distillation setup, where the enzymes were exposed to increasing temperature and air-liquid interfaces (chapter......, thermostable enzymes were shown to be more efficient than mesophilic enzymes when it came to temperature, inhibitor tolerance and stability against air-liquid forces....

  16. DNA-Based Enzyme Reactors and Systems

    Directory of Open Access Journals (Sweden)

    Veikko Linko

    2016-07-01

    Full Text Available During recent years, the possibility to create custom biocompatible nanoshapes using DNA as a building material has rapidly emerged. Further, these rationally designed DNA structures could be exploited in positioning pivotal molecules, such as enzymes, with nanometer-level precision. This feature could be used in the fabrication of artificial biochemical machinery that is able to mimic the complex reactions found in living cells. Currently, DNA-enzyme hybrids can be used to control (multi-enzyme cascade reactions and to regulate the enzyme functions and the reaction pathways. Moreover, sophisticated DNA structures can be utilized in encapsulating active enzymes and delivering the molecular cargo into cells. In this review, we focus on the latest enzyme systems based on novel DNA nanostructures: enzyme reactors, regulatory devices and carriers that can find uses in various biotechnological and nanomedical applications.

  17. Pathway and enzyme redundancy in putrescine catabolism in Escherichia coli.

    Science.gov (United States)

    Schneider, Barbara L; Reitzer, Larry

    2012-08-01

    Putrescine as the sole carbon source requires a novel catabolic pathway with glutamylated intermediates. Nitrogen limitation does not induce genes of this glutamylated putrescine (GP) pathway but instead induces genes for a putrescine catabolic pathway that starts with a transaminase-dependent deamination. We determined pathway utilization with putrescine as the sole nitrogen source by examining mutants with defects in both pathways. Blocks in both the GP and transaminase pathways were required to prevent growth with putrescine as the sole nitrogen source. Genetic and biochemical analyses showed redundant enzymes for γ-aminobutyraldehyde dehydrogenase (PatD/YdcW and PuuC), γ-aminobutyrate transaminase (GabT and PuuE), and succinic semialdehyde dehydrogenase (GabD and PuuC). PuuC is a nonspecific aldehyde dehydrogenase that oxidizes all the aldehydes in putrescine catabolism. A puuP mutant failed to use putrescine as the nitrogen source, which implies one major transporter for putrescine as the sole nitrogen source. Analysis of regulation of the GP pathway shows induction by putrescine and not by a product of putrescine catabolism and shows that putrescine accumulates in puuA, puuB, and puuC mutants but not in any other mutant. We conclude that two independent sets of enzymes can completely degrade putrescine to succinate and that their relative importance depends on the environment.

  18. A theory evaluation of an induction programme

    Directory of Open Access Journals (Sweden)

    Kenrick Hendricks

    2012-07-01

    Full Text Available Orientation: An induction programme is commonly used to help new employees understand their job within the organisation. Research purpose: The main aim of this study was to examine whether or not the programme theory of an induction programme was plausible and would lead to the intended outcomes as described by the programme manager.Motivation for the study: Induction training is one of the most common training programmes in an organisation. However, there is little research to evaluate whether or not the activities of an induction programme will lead to the intended outcomes of such a programme.Research design, approach and method: This theory evaluation used a descriptive design. One hundred and thirteen employees of a media company completed a ten-item, five-point Likert scale which measured their perceptions of the programme’s outcome, identification with the organisation and intentions to stay with the organisation.Main findings: From this theory evaluation it was apparent that an induction programme based on an implausible programme theory could be problematic. An implausible programme theory affects the design of the programme activities and unsuitable activities may not deliver the desired outcomes.Practical/managerial implications: The intention of the evaluation is to guide human resource managers through a process of replacing an implausible programme theory with one that is plausible, and which ensures better alignment of programme activities and outcomes.Contribution/value-add: The evaluators showed how a plausible programme theory could improve programme design. This redesigned induction programme may lead to benefits, such as staff retention and company identification, rather than the vague assumption that it has been conforming to a legal obligation.

  19. Modelling imperfect adherence to HIV induction therapy

    Directory of Open Access Journals (Sweden)

    Smith? Robert J

    2010-01-01

    Full Text Available Abstract Background Induction-maintenance therapy is a treatment regime where patients are prescribed an intense course of treatment for a short period of time (the induction phase, followed by a simplified long-term regimen (maintenance. Since induction therapy has a significantly higher chance of pill fatigue than maintenance therapy, patients might take drug holidays during this period. Without guidance, patients who choose to stop therapy will each be making individual decisions, with no scientific basis. Methods We use mathematical modelling to investigate the effect of imperfect adherence during the inductive phase. We address the following research questions: 1. Can we theoretically determine the maximal length of a possible drug holiday and the minimal number of doses that must subsequently be taken while still avoiding resistance? 2. How many drug holidays can be taken during the induction phase? Results For a 180 day therapeutic program, a patient can take several drug holidays, but then has to follow each drug holiday with a strict, but fairly straightforward, drug-taking regimen. Since the results are dependent upon the drug regimen, we calculated the length and number of drug holidays for all fifteen protease-sparing triple-drug cocktails that have been approved by the US Food and Drug Administration. Conclusions Induction therapy with partial adherence is tolerable, but the outcome depends on the drug cocktail. Our theoretical predictions are in line with recent results from pilot studies of short-cycle treatment interruption strategies and may be useful in guiding the design of future clinical trials.

  20. Automatic design of decision-tree induction algorithms tailored to flexible-receptor docking data.

    Science.gov (United States)

    Barros, Rodrigo C; Winck, Ana T; Machado, Karina S; Basgalupp, Márcio P; de Carvalho, André C P L F; Ruiz, Duncan D; de Souza, Osmar Norberto

    2012-11-21

    This paper addresses the prediction of the free energy of binding of a drug candidate with enzyme InhA associated with Mycobacterium tuberculosis. This problem is found within rational drug design, where interactions between drug candidates and target proteins are verified through molecular docking simulations. In this application, it is important not only to correctly predict the free energy of binding, but also to provide a comprehensible model that could be validated by a domain specialist. Decision-tree induction algorithms have been successfully used in drug-design related applications, specially considering that decision trees are simple to understand, interpret, and validate. There are several decision-tree induction algorithms available for general-use, but each one has a bias that makes it more suitable for a particular data distribution. In this article, we propose and investigate the automatic design of decision-tree induction algorithms tailored to particular drug-enzyme binding data sets. We investigate the performance of our new method for evaluating binding conformations of different drug candidates to InhA, and we analyze our findings with respect to decision tree accuracy, comprehensibility, and biological relevance. The empirical analysis indicates that our method is capable of automatically generating decision-tree induction algorithms that significantly outperform the traditional C4.5 algorithm with respect to both accuracy and comprehensibility. In addition, we provide the biological interpretation of the rules generated by our approach, reinforcing the importance of comprehensible predictive models in this particular bioinformatics application. We conclude that automatically designing a decision-tree algorithm tailored to molecular docking data is a promising alternative for the prediction of the free energy from the binding of a drug candidate with a flexible-receptor.

  1. Factors affecting the induction of 11 alpha-hydroxylase of progesterone in the filamentous fungus Rhizopus nigricans.

    Science.gov (United States)

    Hudnik-Plevnik, T; Cresnar, B

    1990-05-01

    The 11 alpha-hydroxylase of progesterone was induced in the filamentous fungus Rhizopus nigricans ATCC 6227b with different steroids as inducers and the induction process was optimized in regard to the age of the mycelium, to the concentration of the inducer and to the time of induction. Deoxycorticosterone and testosterone, steroids with higher polarity of the side-chain than progesterone, although poorer substrates for in vivo hydroxylation than progesterone, induced more enzyme compared to progesterone. Other alterations in the steroidal ring system examined diminished the induction capability of the inducing steroid to different extent. The highest 11 alpha-hydroxylating activity, if expressed on the basis of mycelial wet weight, was achieved with 18 h old mycelium which was induced for 2 h with 0.30 mM deoxycorticosterone.

  2. Inductive-storage pulse-circuit device

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, W.M.; Honig, E.M.

    1982-01-21

    Inductive storage pulse circuit device is disclosed which is capable of delivering a series of electrical pulses to a load in a sequential manner. Silicon controlled rectifiers as well as spark gap switches can be utilized in accordance with the present invention. A commutation switching array is utilized to produce a reverse current to turn-off the main opening switch. A commutation capacitor produces the reverse current and is initially charged to a predetermined voltage and subsequently charged in alternating directions by the inductive storage current.

  3. Induction generator models in dynamic simulation tools

    DEFF Research Database (Denmark)

    Knudsen, Hans; Akhmatov, Vladislav

    1999-01-01

    For AC network with large amount of induction generators (windmills) the paper demonstrates a significant discrepancy in the simulated voltage recovery after fault in weak networks when comparing dynamic and transient stability descriptions and the reasons of discrepancies are explained. It is fo......For AC network with large amount of induction generators (windmills) the paper demonstrates a significant discrepancy in the simulated voltage recovery after fault in weak networks when comparing dynamic and transient stability descriptions and the reasons of discrepancies are explained...

  4. About Eddy Currents in Induction Melting Processes

    Directory of Open Access Journals (Sweden)

    Gafiţa Nicolae-Bogdan

    2008-05-01

    Full Text Available In this paper we present a method forcomputing the eddy currents in induction meltingprocesses for non-ferrous alloys. We take intoconsideration the situation when only the crucible ismoving, inside the coils. This fact makes differentialcomputation methods to be hard to apply, because isnecessary to generate a new mesh and a new systemmatrix for every for every new position of the cruciblerelated to the coils. Integral methods cancel thisdrawback because the mesh is generated only for thedomains with eddy currents. For integral methods, themesh and the inductance matrix remain unchangedduring the movement of the crucible; only the free termsof the equation system will change.

  5. Ethanologenic Enzymes of Zymomonas mobilis

    Energy Technology Data Exchange (ETDEWEB)

    Ingram, Lonnie O' Neal

    1999-03-01

    Zymomonas mobilis is a unique microorganism in being both obligately fermentative and utilizing a Entner-Doudoroff pathway for glycolysis. Glycolytic flux in this organism is readily measured as evolved carbon dioxide, ethanol, or glucose consumed and exceeds 1 {micro}mole glucose/min per mg cell protein. To support this rapid glycolysis, approximately 50% of cytoplasmic protein is devoted to the 13 glycolytic and fermentative enzymes which constitute this central catabolic pathway. Only 1 ATP (net) is produced from each glucose metabolized. During the past grant period, we have completed the characterization of 11 of the 13 glycolytic genes from Z. mobilis together with complementary but separate DOE-fimded research by a former post-dot and collaborator, Dr. Tyrrell Conway. Research funded in my lab by DOE, Division of Energy Biosciences can be divided into three sections: A. Fundamental studies; B. Applied studies and utility; and C. Miscellaneous investigations.

  6. CELLULOSE DEGRADATION BY OXIDATIVE ENZYMES

    Directory of Open Access Journals (Sweden)

    Maria Dimarogona

    2012-09-01

    Full Text Available Enzymatic degradation of plant biomass has attracted intensive research interest for the production of economically viable biofuels. Here we present an overview of the recent findings on biocatalysts implicated in the oxidative cleavage of cellulose, including polysaccharide monooxygenases (PMOs or LPMOs which stands for lytic PMOs, cellobiose dehydrogenases (CDHs and members of carbohydrate-binding module family 33 (CBM33. PMOs, a novel class of enzymes previously termed GH61s, boost the efficiency of common cellulases resulting in increased hydrolysis yields while lowering the protein loading needed. They act on the crystalline part of cellulose by generating oxidized and non-oxidized chain ends. An external electron donor is required for boosting the activity of PMOs. We discuss recent findings concerning their mechanism of action and identify issues and questions to be addressed in the future.

  7. Cellulose degradation by oxidative enzymes

    Directory of Open Access Journals (Sweden)

    Maria Dimarogona

    2012-09-01

    Full Text Available Enzymatic degradation of plant biomass has attracted intensive research interest for the production of economically viable biofuels. Here we present an overview of the recent findings on biocatalysts implicated in the oxidative cleavage of cellulose, including polysaccharide monooxygenases (PMOs or LPMOs which stands for lytic PMOs, cellobiose dehydrogenases (CDHs and members of carbohydrate-binding module family 33 (CBM33. PMOs, a novel class of enzymes previously termed GH61s, boost the efficiency of common cellulases resulting in increased hydrolysis yields while lowering the protein loading needed. They act on the crystalline part of cellulose by generating oxidized and non-oxidized chain ends. An external electron donor is required for boosting the activity of PMOs. We discuss recent findings concerning their mechanism of action and identify issues and questions to be addressed in the future.

  8. Effects of induction starting time and Ca2+ on expression of active penicillin G acylase in Escherichia coli.

    Science.gov (United States)

    Jiang, Yong Mei; Tong, Wang Yu; Wei, Dong Zhi

    2007-01-01

    Formation of inclusion bodies is an important obstacle to the production of active recombinant protein in Escherichia coli. Thus, soluble expression of penicillin G acylase from Kluyvera citrophila was investigated in BL21(DE3). In this study, the yield of active enzyme was significantly enhanced by the composition of the medium and induction opportunity. When 0.5 mmol/L IPTG was added to complex medium at 15 h after incubation, the volumetric and specific activities of penicillin G acylase both achieved the highest values, respectively. However, aggravation of intracellular proteolysis and decline of enzyme expression were also observed if induction occurred too much later. Ca2+ ion was another critical factor in cell growth and protein expression. When 24 mmol/L Ca2+ ion was adding to the medium at the beginning of fermentation, a greater than 2-fold increase in cell density and a 7-fold increase in volumetric activity of penicillin G acylase were reached. Nevertheless, no significant benefit for recombination protein expression was found when excess Ca2+ was added after induction time. This study demonstrates that the induction starting time and Ca2+ ion are two critical factors for the expression of active penicillin G acylase.

  9. Amniotomy alone for induction of labour.

    Science.gov (United States)

    Bricker, L; Luckas, M

    2000-01-01

    Amniotomy (deliberate rupture of the membranes) is a simple procedure which can be used alone for induction of labour if the membranes are accessible, thus avoiding the need for pharmacological intervention. However, the time interval from amniotomy to established labour may not be acceptable to clinicians and women, and in a number of cases labour may not ensue. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. To determine the effects of amniotomy alone for third trimester labour induction in women with a live fetus. The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled trials register and bibliographies of relevant papers. The criteria for inclusion included the following: (1) clinical trials comparing amniotomy alone for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random or pseudo-random allocation to the treatment or control group; (3) ideally adequate allocation concealment (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into the series of primary reviews arranged by methods of induction of labour. The data from the primary reviews will be incorporated into a series of secondary reviews, arranged by category of woman to reflect clinical scenarios. To avoid duplication

  10. Intestinal Phospholipase, a Novel Enzyme

    Science.gov (United States)

    Mansbach, Charles M.; Pieroni, Gerard; Verger, Robert

    1982-01-01

    We evaluated phospholipase activity in the intestine of rats and other species. Phospholipase activity was assayed by a surface barostat technique or an egg yolk titration system. Mucosal activity was found only by the surface barostat technique with phosphatidylglycerol as substrate; it was not found with phosphatidylcholine as substrate in assays by either technique. In gut luminal fluid activity was found when both phosphatidylcholine and phosphatidylglycerol were used as substrate in assays by the surface barostat technique, and phosphatidylcholine as substrate yielded activity in egg yolk titration. In rats in which pancreatic juice had been diverted, mucosal and gut luminal phospholipase activity was greater than in controls, thus demonstrating that enzyme activity was not due to pancreatic phospholipase. Bacterial origin of phospholipase activity was excluded in that phospholipase activity was found in germ-free rats; gastric and salivary gland origins were excluded in that continued phospholipase activity was found in rats with gastric fistula. The physiological importance of the enzyme was established by the finding that rats with pancreatic fistula absorbed 111 μmol of phosphatidylcholine and that controls absorbed 119 μmol of a 135-μmol load. Activity was found to be three times greater in the distal than in the proximal intestine; in cryptal cells it was 10 times greater than in villus tip cells. 65% of the activity in the gut lumen was tightly bound to particulate matter. We propose that intestinal phospholipase may be important in gut bacterial control, in the digestion of vegetable matter (phosphatidylglycerol is a major phospholipid in both plants and bacteria), and in the digestion of phospholipids in the gut lumen. PMID:7056853

  11. Changes in activity of extracellular enzymes in dual cultures of Lentinula edodes and mycoparasitic Trichoderma strains.

    Science.gov (United States)

    Hatvani, N; Kredics, L; Antal, Z; Mécs, I

    2002-01-01

    The main problem that arises during the cultivation of Lentinula edodes, the Asian Shiitake mushroom, is that the logs on which the cultivation is performed are contaminated by competing micro-organisms, especially Trichoderma spp. The aim of this study was to examine the changes in activity of extracellular enzymes in dual cultures of Trichoderma spp. and L. edodes. Extracellular enzyme activities were determined spectrophotometrically. Trichoderma enzymes important for the degradation of fungal cell walls (N-acetyl-beta-glucosaminidase and laminarinase) were shown to be induced by inactive L. edodes mycelia in liquid culture. The changes that occurred in the extracellular enzyme activities of L. edodes and mycoparasitic Trichoderma spp. (T. aureoviride, T. harzianum and T. viride) were examined during antagonistic interactions on solid medium. The extracellular enzyme patterns of both partners proved to be altered. Trichoderma spp. were induced to produce N-acetyl-beta-glucosaminidase and laminarinase in the presence of active L. edodes mycelia, similarly as observed in liquid culture. The activities of both laccase and manganese peroxidase of L. edodes decreased after physical contact with active Trichoderma mycelia, possibly in consequence of the beginning of degradation of L. edodes by the Trichoderma enzymes. However, besides a decrease in manganese peroxidase activity, an enhancement of L. edodes laccase activity was observed on solid media containing crude culture fluids from Trichoderma liquid cultures. The metabolites responsible for these effects proved to be heat stable. Induction and inhibition of several extracellular enzymes of both partners were shown in dual cultures of L. edodes and Trichoderma strains, indicating the important role of these enzymes in the antagonistic interaction between the two species. As the main problem during the large-scale cultivation of L. edodes is the contamination of the growth substrate by Trichoderma mycelia, the

  12. Entamoeba histolytica: induction of cyclooxygenase-2 expression during amoebic liver abscess formation in hamsters (Mesocricetus auratus).

    Science.gov (United States)

    Sánchez-Ramírez, B; Ramírez-Gil, M; Vázquez-Moctezuma, I; Ramos-Martínez, E; Talamás-Rohana, P

    2004-01-01

    Experimental amoebic liver abscess in hamsters curses with an increase in both, systemic levels of prostaglandin E2 (PGE(2)) and local cyclooxygenase activity in liver microsomes. The cellular source of PGE(2) and the isoform of cyclooxygenase responsible are not completely evidenced. Cyclooxygenase-2 (COX-2) protein and gene expression were demonstrated on macrophages and polymorphonuclear cells as a result of Entamoeba histolytica infection in hamsters at 2, 4, and 7 days postinfection by immunohistochemistry and RT-PCR. E. histolytica trophozoites located in the lesion showed a strong positive signal for COX-2, however the enzyme was not detected in cultured trophozoites by Western blot. Our results indicate that the increment in PGE(2) is the result of COX-2 activity from cells of the reticuloendothelial system and reinforce the possibility that PGE(2) production by enzyme induction in macrophages may be a mechanism by which E. histolytica modulates the host immune response in this parasitic infection.

  13. A model of annular linear induction pumps

    Energy Technology Data Exchange (ETDEWEB)

    Momozaki, Yoichi [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-10-27

    The present work explains how the magnetic field and the induced current are obtained when the distributed coils are powered by a 3 phase power supply.  From the magnetic field and the induced current, the thrust and the induction losses in the pump can be calculated to estimate the pump performance.

  14. atriplex halimus (amarantacees) callogenesis induction from ...

    African Journals Online (AJOL)

    Y. Halfaoui

    1 janv. 2018 ... callogenesis from adult walnut leaves (Juglans Regia L.). Chilean J. Agric. Res., 2009, 69 (3),. 460-466. [32] Haouala F., Farhat N. & Chabchoub L. Effets du type et de la position de l'explant sur l'induction de cals chez le gerbera (Gerbera jamesonii Bolus). Tropicultura, 2010, 28 (1),. 57-60. [33] Naz S.

  15. The differential induction machine: Theory and performance

    Indian Academy of Sciences (India)

    Differential drive; electric vehicle drive; induction machine. 1. Introduction. The concept of a differential motor was presented (Crelerot et al 1993), but was never anal- ysed in detail nor verified experimentally. This paper presents the theory, construction and performance of the machine, based on experimental results from a ...

  16. Adventitious shoots induction and plant regeneration from ...

    African Journals Online (AJOL)

    A highly efficient regeneration system is a prerequisite step for successful genetic transformation of watermelon cultivars (Citrullus lanatus L.). The objective of this study was to establish efficient in vitro plant regeneration for three watermelon cultivars. To achieve optimal conditions for adventitious shoot induction, the ...

  17. Harmonic analysis of Doubly Fed Induction Generators

    DEFF Research Database (Denmark)

    Lindholm, Morten; Rasmussen, Tonny Wederberg

    2003-01-01

    This paper gives an overview of the frequency spectrum of the stator and rotor currents in a doubly fed induction generator (DFIG) used in wind power applications. The paper also presents a method to eliminate higher harmonics and interharmonics in the DFIG stator current. The method is implemented...

  18. Sputum induction as a simple diagnostic tool?

    African Journals Online (AJOL)

    Objectives. To assess the value of sputum induction (SI) as a diagnostic tool for patients with suspected pulmonary tuberculosis (PTB) who are unable to expectorate or who have a negative sputum smear, Design, Study of an inpatient cohort undergoing SL Setting, Mseleni Hospital, a rural district hospital in northern ...

  19. Four quadrant control of induction motors

    Science.gov (United States)

    Hansen, Irving G.

    1991-03-01

    Induction motors are the nation's workhorse, being the motor of choice in most applications due to their simple rugged construction. It has been estimated that 14 to 27 percent of the country's total electricity use could be saved with adjustable speed drives. Until now, induction motors have not been suited well for variable speed or servo-drives, due to the inherent complexity, size, and inefficiency of their variable speed controls. Work at NASA Lewis Research Center on field oriented control of induction motors using pulse population modulation method holds the promise for the desired drive electronics. The system allows for a variable voltage to frequency ratio which enables the user to operate the motor at maximum efficiency, while having independent control of both the speed and torque of an induction motor in all four quadrants of the speed torque map. Multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of machine. The pulse population technique, results to date, and projections for implementation of this existing new motor control technology are discussed.

  20. Thyristor stack for pulsed inductive plasma generation.

    Science.gov (United States)

    Teske, C; Jacoby, J; Schweizer, W; Wiechula, J

    2009-03-01

    A thyristor stack for pulsed inductive plasma generation has been developed and tested. The stack design includes a free wheeling diode assembly for current reversal. Triggering of the device is achieved by a high side biased, self supplied gate driver unit using gating energy derived from a local snubber network. The structure guarantees a hard firing gate pulse for the required high dI/dt application. A single fiber optic command is needed to achieve a simultaneous turn on of the thyristors. The stack assembly is used for switching a series resonant circuit with a ringing frequency of 30 kHz. In the prototype pulsed power system described here an inductive discharge has been generated with a pulse duration of 120 micros and a pulse energy of 50 J. A maximum power transfer efficiency of 84% and a peak power of 480 kW inside the discharge were achieved. System tests were performed with a purely inductive load and an inductively generated plasma acting as a load through transformer action at a voltage level of 4.1 kV, a peak current of 5 kA, and a current switching rate of 1 kA/micros.

  1. (Saccharum officinarum L) genotypes to callus induction ...

    African Journals Online (AJOL)

    Jane

    2010-12-20

    Dec 20, 2010 ... Cultivar CSSG-668 was found to be the best genotype yielding maximum embryogenic callus and regeneration whereas cultivar CPF-. 245 exhibited lowest callus induction frequency. Five different concentrations (0 ..... Planta, 89: 299-302. Bower R, Birch RG (1992). Transgenic sugarcane plants via micro-.

  2. Impedance Calculations of Induction Machine Rotor Conductors ...

    African Journals Online (AJOL)

    The exact calculation of the impedance of induction machine rotor conductors at several operating frequencies are necessary if the dynamic behaviour of the machine is to give a good correlation between the simulated starting torque and current and the experimental results. This paper describes a method of' calculating ...

  3. Combined Approach for Solving the Electromagnetic Induction ...

    African Journals Online (AJOL)

    Nafiisah

    approaches to the reconstruction problem: the pixel-based approach and the parameter-based approach. This paper describes how both approaches may be combined for a more systematic reconstruction. Keywords: Electromagnetic induction, inverse problem, image reconstruction. *For correspondences and reprints ...

  4. Combined Approach for Solving the Electromagnetic Induction ...

    African Journals Online (AJOL)

    Inverse electromagnetic induction is an imaging technique for reconstructing the conductivity and permeability distributions in a region of interest from measurements of impedance made at its boundary. In general, there are two approaches to the reconstruction problem: the pixel-based approach and the parameter-based ...

  5. Free positioning for inductive wireless power system

    NARCIS (Netherlands)

    Waffenschmidt, E.

    2012-01-01

    In inductive wireless power transmission system a lateral displacement of the receiver coil to the transmitter coil leads to a change ofthe coupling factor and thus an unwanted variation of the power transfer. Here, an algorithm to determine the turn distribution to achieve homogeneous coupling

  6. impedance calculations of induction machine rotor conductors.

    African Journals Online (AJOL)

    Dr Obe

    4. Krause.P.C: Lipo, T.A.: Analysis and. Simplified Representations of a Rectifier- inverter indution motor drive. IEEE. Transactions on power Apparatus and systems. Vol. PAS-88. No.5. May 1969. PP. 588-596. 5. Jordan. H.E: Analysis of induction machines in Dynamic systems. I EEE. Transactions on power Apparatus and.

  7. Teaching Inductive Reasoning in Primary Education.

    Science.gov (United States)

    de Koning, Els; Hamers, Jo H. M.; Sijtsma, Klaas; Vermeer, Adri

    2002-01-01

    Used a three-phase teaching procedure based on the development of metacognition to extend emphasis on inductive reasoning in primary education to Grades 3 and 4. Found that teachers could apply the programs as intended, but needed support to shift attention from reasoning product to reasoning process. Program learning effects indicated that better…

  8. Hitting Is Contagious: Experience and Action Induction

    Science.gov (United States)

    Gray, Rob; Beilock, Sian L.

    2011-01-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing…

  9. early versus delayed induction of labour

    African Journals Online (AJOL)

    preference. A recent meta-analysis has indicated that early administration of intravenous oxytocin for induction of contractions after PROM at term is associated with an increase in the likelihood of caesarean section (CS) without convincing evidence that the mother and fetus will be more effectively protected against the risks ...

  10. Single phase induction motor with starting performance

    Energy Technology Data Exchange (ETDEWEB)

    Popescu, M.; Demeter, E. [Research Institute for Electrical Machines, ICPE-ME, Bucharest (Romania); Navrapescu, V. [University `Politehnica` Bucharest, Electrical Engineering Faculty Splaiul Independentei, Bucharest (Romania)

    1997-12-31

    The paper presents problems related to a special type of single phase induction motor. The main novelty consists in the use of a conducting (aluminium casted) shell distributed on the periferic region of the rotor. As a result the starting performance, as well as the rated ones, is much improved in comparison with the conventional construction. (orig.) 4 refs.

  11. Titrated Misoprostol Versus Dinoprostone for Labor Induction

    African Journals Online (AJOL)

    uncontrolled diabetes, severe preeclampsia or eclampsia, and women who have contraindications to receive the induction medications (allergy, history of severe asthma) excluded from this study. Studied women were randomized into; Group I: 104 women included and received oral 200 µg misoprostol in 200 ml water ...

  12. Concentration on Callus Induction in Sugarcane

    African Journals Online (AJOL)

    ABSTRACT: Experiment was designed and conducted to determine the most appropriate concentration of 2, 4-Dichlorophenoxy Acetic Acid suitable for callus induction in sugarcane. Explants were obtained from apical meristems of two sugarcane cultivars (SP726180 and CO-. 001) and cultured in a modified MS medium ...

  13. Inductive Generalization of Analytically Learned Goal Hierarchies

    Science.gov (United States)

    Könik, Tolga; Nejati, Negin; Kuter, Ugur

    We describe a new approach for learning procedural knowledge represented as teleoreactive logic programs using relational behavior traces as input. This representation organizes task decomposition skills hierarchically and associate explicitly defined goals with them. Our approach integrates analytical learning with inductive generalization in order to learn these skills. The analytical component predicts the goal dependencies in a successful solution and generates a teleoreactive logic program that can solve similar problems by determining the structure of the skill hierarchy and skill applicability conditions (preconditions), which may be overgeneral. The inductive component experiments with these skills on new problems and uses the data collected in this process to refine the preconditions. Our system achieves this by converting the data collected during the problem solving experiments into the positive and negative examples of preconditions that can be learned with a standard Inductive Logic Programming system. We show that this conversion uses one of the main commitments of teleoreactive logic programs: associating all skills with explicitly defined goals. We claim that our approach uses less expert effort compared to a purely inductive approach and performs better compared to a purely analytical approach.

  14. Between autobiography and reality : Popper's inductive years

    NARCIS (Netherlands)

    ter Hark, M.R.M.

    On the basis of his unpublished thesis 'Gewohnheit und Gesetzerlebnis in der Erziehung' (1926-7) a historical reconstruction is given of the genesis of Popper's ideas on induction and demarcation which differs radically from his own account in Unended quest. It is shown not only that he

  15. Concentration on Callus Induction in Sugarcane

    African Journals Online (AJOL)

    SP726180 and CO-. 001) and cultured in a modified MS medium supplemented with varying concentrations of. 2,4-D. After sterilization, the explants were incubated in the growth chamber at 270C and monitored for callus induction for four Weeks.

  16. Inductive ionospheric solver for magnetospheric MHD simulations

    Directory of Open Access Journals (Sweden)

    H. Vanhamäki

    2011-01-01

    Full Text Available We present a new scheme for solving the ionospheric boundary conditions required in magnetospheric MHD simulations. In contrast to the electrostatic ionospheric solvers currently in use, the new solver takes ionospheric induction into account by solving Faraday's law simultaneously with Ohm's law and current continuity. From the viewpoint of an MHD simulation, the new inductive solver is similar to the electrostatic solvers, as the same input data is used (field-aligned current [FAC] and ionospheric conductances and similar output is produced (ionospheric electric field. The inductive solver is tested using realistic, databased models of an omega-band and westward traveling surge. Although the tests were performed with local models and MHD simulations require a global ionospheric solution, we may nevertheless conclude that the new solution scheme is feasible also in practice. In the test cases the difference between static and electrodynamic solutions is up to ~10 V km−1 in certain locations, or up to 20-40% of the total electric field. This is in agreement with previous estimates. It should also be noted that if FAC is replaced by the ground magnetic field (or ionospheric equivalent current in the input data set, exactly the same formalism can be used to construct an inductive version of the KRM method originally developed by Kamide et al. (1981.

  17. Open Problems in Universal Induction & Intelligence

    Directory of Open Access Journals (Sweden)

    Marcus Hutter

    2009-07-01

    Full Text Available Specialized intelligent systems can be found everywhere: finger print, handwriting, speech, and face recognition, spam filtering, chess and other game programs, robots, et al. This decade the first presumably complete mathematical theory of artificial intelligence based on universal induction-prediction-decision-action has been proposed. This informationtheoretic approach solidifies the foundations of inductive inference and artificial intelligence. Getting the foundations right usually marks a significant progress and maturing of a field. The theory provides a gold standard and guidance for researchers working on intelligent algorithms. The roots of universal induction have been laid exactly half-a-century ago and the roots of universal intelligence exactly one decade ago. So it is timely to take stock of what has been achieved and what remains to be done. Since there are already good recent surveys, I describe the state-of-the-art only in passing and refer the reader to the literature. This article concentrates on the open problems in universal induction and its extension to universal intelligence.

  18. Transporter-Enzyme Interplay: Deconvoluting Effects of Hepatic Transporters and Enzymes on Drug Disposition Using Static and Dynamic Mechanistic Models.

    Science.gov (United States)

    Varma, Manthena V; El-Kattan, Ayman F

    2016-07-01

    A large body of evidence suggests hepatic uptake transporters, organic anion-transporting polypeptides (OATPs), are of high clinical relevance in determining the pharmacokinetics of substrate drugs, based on which recent regulatory guidances to industry recommend appropriate assessment of investigational drugs for the potential drug interactions. We recently proposed an extended clearance classification system (ECCS) framework in which the systemic clearance of class 1B and 3B drugs is likely determined by hepatic uptake. The ECCS framework therefore predicts the possibility of drug-drug interactions (DDIs) involving OATPs and the effects of genetic variants of SLCO1B1 early in the discovery and facilitates decision making in the candidate selection and progression. Although OATP-mediated uptake is often the rate-determining process in the hepatic clearance of substrate drugs, metabolic and/or biliary components also contribute to the overall hepatic disposition and, more importantly, to liver exposure. Clinical evidence suggests that alteration in biliary efflux transport or metabolic enzymes associated with genetic polymorphism leads to change in the pharmacodynamic response of statins, for which the pharmacological target resides in the liver. Perpetrator drugs may show inhibitory and/or induction effects on transporters and enzymes simultaneously. It is therefore important to adopt models that frame these multiple processes in a mechanistic sense for quantitative DDI predictions and to deconvolute the effects of individual processes on the plasma and hepatic exposure. In vitro data-informed mechanistic static and physiologically based pharmacokinetic models are proven useful in rationalizing and predicting transporter-mediated DDIs and the complex DDIs involving transporter-enzyme interplay. © 2016, The American College of Clinical Pharmacology.

  19. Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity

    Science.gov (United States)

    Fendt, Sarah-Maria; Buescher, Joerg Martin; Rudroff, Florian; Picotti, Paola; Zamboni, Nicola; Sauer, Uwe

    2010-01-01

    What is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite concentrations, or both could limit the metabolic reaction rates. These relationships imply different correlations between changes in enzyme capacity and metabolite concentration, which we tested by quantifying metabolite, transcript, and enzyme abundances upon local (single-enzyme modulation) and global (GCR2 transcription factor mutant) perturbations in Saccharomyces cerevisiae. Our results reveal an inverse relationship between fold-changes in substrate metabolites and their catalyzing enzymes. These data provide evidence for the hypothesis that reaction rates are jointly limited by enzyme capacity and metabolite concentration. Hence, alteration in one network constituent can be efficiently buffered by converse alterations in the other constituent, implying a passive mechanism to maintain metabolic homeostasis upon perturbations in enzyme capacity. PMID:20393576

  20. Mutation of the Inducible ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE2 Alters Lignin Composition and Improves Saccharification1[W][OPEN

    Science.gov (United States)

    Sundin, Lisa; Vanholme, Ruben; Geerinck, Jan; Goeminne, Geert; Höfer, René; Kim, Hoon; Ralph, John; Boerjan, Wout

    2014-01-01

    ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE1 (ATR1) and ATR2 provide electrons from NADPH to a large number of CYTOCHROME P450 (CYP450) enzymes in Arabidopsis (Arabidopsis thaliana). Whereas ATR1 is constitutively expressed, the expression of ATR2 appears to be induced during lignin biosynthesis and upon stresses. Therefore, ATR2 was hypothesized to be preferentially involved in providing electrons to the three CYP450s involved in lignin biosynthesis: CINNAMATE 4-HYDROXYLASE (C4H), p-COUMARATE 3-HYDROXYLASE1 (C3H1), and FERULATE 5-HYDROXYLASE1 (F5H1). Here, we show that the atr2 mutation resulted in a 6% reduction in total lignin amount in the main inflorescence stem and a compositional shift of the remaining lignin to a 10-fold higher fraction of p-hydroxyphenyl units at the expense of syringyl units. Phenolic profiling revealed shifts in lignin-related phenolic metabolites, in particular with the substrates of C4H, C3H1 and F5H1 accumulating in atr2 mutants. Glucosinolate and flavonol glycoside biosynthesis, both of which also rely on CYP450 activities, appeared less affected. The cellulose in the atr2 inflorescence stems was more susceptible to enzymatic hydrolysis after alkaline pretreatment, making ATR2 a potential target for engineering plant cell walls for biofuel production. PMID:25315601

  1. Effects of pharmaceuticals present in aquatic environment on Phase I metabolism in fish.

    Science.gov (United States)

    Burkina, Viktoriia; Zlabek, Vladimir; Zamaratskaia, Galia

    2015-09-01

    The fate of pharmaceuticals in aquatic environments is an issue of concern. Current evidence indicates that the risks to fish greatly depend on the nature and concentrations of the pharmaceuticals and might be species-specific. Assessment of risks associated with the presence of pharmaceuticals in water is hindered by an incomplete understanding of the metabolism of these pharmaceuticals in aquatic species. In mammals and fish, pharmaceuticals are primarily metabolized by cytochrome P450 enzymes (CYP450). Thus, CYP450 activity is a crucial factor determining the detoxification abilities of organisms. Massive numbers of toxicological studies have investigated the interactions of human pharmaceuticals with detoxification systems in various fish species. In this paper, we review the effects of pharmaceuticals found in aquatic environments on fish hepatic CYP450. Moreover, we discuss the roles of nuclear receptors in cellular regulation and the effects of various groups of chemicals on fish, presented in the recent literature. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. How Do Enzymes 'Meet' Nanoparticles and Nanomaterials?

    Science.gov (United States)

    Chen, Ming; Zeng, Guangming; Xu, Piao; Lai, Cui; Tang, Lin

    2017-11-01

    Enzymes are fundamental biological catalysts responsible for biological regulation and metabolism. The opportunity for enzymes to 'meet' nanoparticles and nanomaterials is rapidly increasing due to growing demands for applications in nanomaterial design, environmental monitoring, biochemical engineering, and biomedicine. Therefore, understanding the nature of nanomaterial-enzyme interactions is becoming important. Since 2014, enzymes have been used to modify, degrade, or make nanoparticles/nanomaterials, while numerous nanoparticles/nanomaterials have been used as materials for enzymatic immobilization and biosensors and as enzyme mimicry. Among the various nanoparticles and nanomaterials, metal nanoparticles and carbon nanomaterials have received extensive attention due to their fascinating properties. This review provides an overview about how enzymes meet nanoparticles and nanomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Prediction of Wild-type Enzyme Characteristics

    DEFF Research Database (Denmark)

    Geertz-Hansen, Henrik Marcus

    a sequence-based approach to discovery of proteolytic enzymes in metagenomes obtained from the Polar oceans. We show that microorganisms living in these extreme environments of constant low temperature harbour genes encoding novel proteolytic enzymes with potential industrial relevance. The second article...... of biotechnology, including enzyme discovery and characterization. This work presents two articles on sequence-based discovery and functional annotation of enzymes in environmental samples, and two articles on analysis and prediction of enzyme thermostability and cofactor requirements. The first article presents...... substitutions in Rossmann fold sequences. In summary, this work presents novel methods for prediction of enzyme characteristics, and exemplify the largely untapped potential for discovery of new biocatalysts in environmental samples....

  4. Production of Enzymes from Marine Actinobacteria.

    Science.gov (United States)

    Zhao, X Q; Xu, X N; Chen, L Y

    Marine actinobacteria are well recognized for their capabilities to produce valuable natural products, which have great potential for applications in medical, agricultural, and fine chemical industries. In addition to producing unique enzymes responsible for biosynthesis of natural products, many marine actinobacteria also produce hydrolytic enzymes which are able to degrade various biopolymers, such as cellulose, xylan, and chitin. These enzymes are important to produce biofuels and biochemicals of interest from renewable biomass. In this chapter, the recent reports of novel enzymes produced by marine actinobacteria are reviewed, and advanced technologies that can be applied to search for novel marine enzymes as well as for improved enzyme production by marine actinobacteria are summarized, which include ribosome engineering, genome mining, as well as synthetic biology studies. © 2016 Elsevier Inc. All rights reserved.

  5. Evaluation of pressure tuning of enzymes

    DEFF Research Database (Denmark)

    Naghshineh, Mahsa

    and high energy consumption. Therefore, searching for an environmentally friendly method of pectin extraction is a task for science and industry. Employment of hydrolytic enzymes may represent a green approach to obtain intact pectin polymer. However, the low stability/activity of enzymes, and low polymer...... yield of enzymatic extraction limits the application of enzyme in pectin production. There is evidence that emerging technology of high hydrostatic pressure processing can result in stabilization and activation of some enzymes. Therefore, the use of high hydrostatic pressure in combination with enzyme...... (cellulase/xylanase: 50/0, 50/25, 50/50, 25/50, and 0/50 U/g lime peel) at ambient pressure, 100 and 200 MPa were used to extract pectin from dried lime peel waste. It was found that pressure level, type and concentration of enzyme significantly influenced pectin yield and degree of esterification (DE...

  6. Industrial fungal enzymes: an occupational allergen perspective.

    Science.gov (United States)

    Green, Brett J; Beezhold, Donald H

    2011-01-01

    Occupational exposure to high-molecular-weight allergens is a risk factor for the development and pathogenesis of IgE-mediated respiratory disease. In some occupational environments, workers are at an increased risk of exposure to fungal enzymes used in industrial production. Fungal enzymes have been associated with adverse health effects in the work place, in particular in baking occupations. Exposure-response relationships have been demonstrated, and atopic workers directly handling fungal enzymes are at an increased risk for IgE-mediated disease and occupational asthma. The utilization of new and emerging fungal enzymes in industrial production will present new occupational exposures. The production of antibody-based immunoassays is necessary for the assessment of occupational exposure and the development of threshold limit values. Allergen avoidance strategies including personal protective equipment, engineering controls, protein encapsulation, and reduction of airborne enzyme concentrations are required to mitigate occupational exposure to fungal enzymes.

  7. Industrial Fungal Enzymes: An Occupational Allergen Perspective

    Directory of Open Access Journals (Sweden)

    Brett J. Green

    2011-01-01

    Full Text Available Occupational exposure to high-molecular-weight allergens is a risk factor for the development and pathogenesis of IgE-mediated respiratory disease. In some occupational environments, workers are at an increased risk of exposure to fungal enzymes used in industrial production. Fungal enzymes have been associated with adverse health effects in the work place, in particular in baking occupations. Exposure-response relationships have been demonstrated, and atopic workers directly handling fungal enzymes are at an increased risk for IgE-mediated disease and occupational asthma. The utilization of new and emerging fungal enzymes in industrial production will present new occupational exposures. The production of antibody-based immunoassays is necessary for the assessment of occupational exposure and the development of threshold limit values. Allergen avoidance strategies including personal protective equipment, engineering controls, protein encapsulation, and reduction of airborne enzyme concentrations are required to mitigate occupational exposure to fungal enzymes.

  8. Cooperation of Aspergillus nidulans enzymes increases plant polysaccharide saccharification

    NARCIS (Netherlands)

    Tramontina, Robson; Robl, Diogo; Maitan-Alfenas, Gabriela Piccolo; de Vries, Ronald P

    2016-01-01

    Efficient polysaccharide degradation depends on interaction between enzymes acting on the main chain and the side chains. Previous studies demonstrated cooperation between several enzymes, but not all enzyme combinations have been explored. A better understanding of enzyme cooperation would enable

  9. Nitric oxide is not a negative regulator of metamorphic induction in the abalone Haliotis asinina

    Directory of Open Access Journals (Sweden)

    Nobuo eUeda

    2014-07-01

    Full Text Available Nitric oxide (NO is a second messenger molecule synthesized by the enzyme nitric oxide synthase (NOS that requires the molecular chaperone heat shock protein 90 (HSP90 for normal enzymatic activity. Past studies have revealed that both NO and HSP90 act as negative regulators (repressors of metamorphosis in a diverse range of marine invertebrates, including several molluscan species. Here, we test the role of NO in the metamorphic induction of a vetigastropod mollusc, the tropical abalone Haliotis asinina. Specifically, we 1 test the effects of NO-manipulating pharmacological agents, 2 measure the temporal expression of NOS and HSP90 genes through metamorphosis, and 3 assess the spatial expression of NOS and HSP90 in larvae. We find that inhibition of NOS reduces rates of metamorphosis, indicating that NO facilitates, rather than represses, induction of metamorphosis in H. asinina. The marked increase in NOS expression in putative sensory cells localized to the anterior foot of competent larvae is consistent with NO as an inductive molecule for metamorphosis. In contrast to NOS, HSP90 transcript abundance decreases at competence and there is no evidence of NOS and HSP90 transcript co-localization. This study provides the first evidence of NO as an inductive facilitator of molluscan metamorphosis. Our experimental data suggest that NO modulates signals derived from live inductive substrates via the larval foot to regulate metamorphosis. Inter-specific comparisons of spatial NOS expression in molluscs suggest that the localized pattern of NOS or its protein product is related to the regulatory action of NO in metamorphosis.

  10. Functional characterization of neuroendocrine regulation of branchial carbonic anhydrase induction in the euryhaline crab Callinectes sapidus.

    Science.gov (United States)

    Mitchell, Reed T; Henry, Raymond P

    2014-12-01

    Carbonic anhydrase (CA) plays an essential role as a provider of counterions for Na(+)/H(+) and Cl(-)/HCO3 (-) exchange in branchial ionic uptake processes in euryhaline crustaceans. CA activity and gene expression are low in crabs acclimated to full-strength seawater, with transfer to low salinity resulting in large-scale inductions of mRNA and subsequent enzyme activity in the posterior ion-regulating gills (e.g., G7). In the green crab Carcinus maenas, CA has been shown to be under inhibitory neuroendocrine control by a putative hormone in the x-organ-sinus gland complex (XOSG), located in the eyestalk. This study characterizes the neuroendocrine regulation of CA induction in the blue crab Callinectes sapidus, a commonly used experimental organism for crustacean osmoregulation. In crabs acclimated to full-strength seawater, eyestalk ligation (ESL) triggered a 1.8- and 100-fold increase in CA activity and mRNA, respectively. Re-injection with eyestalk homogenates abolished increases in CA activity and fractionally reduced CA gene expression. ESL also enhanced CA induction by 33% after 96 h in crabs transferred to 15 ppt salinity. Injection of eyestalk homogenates into intact crabs transferred from 35 to 15 ppt diminished by 43% the CA induction stimulated by low salinity. These results point to the presence of a repressor hormone in the eyestalk. Separate injections of medullary tissue (MT) and sinus gland (SG), two components of the eyestalk, reduced salinity-stimulated CA activity by 22% and 49%, suggesting that the putative repressor is localized to the SG. Crabs injected with SG extract harvested from crabs acclimated to 5 ppt showed no decrease in CA activity, demonstrating that the hormone is down-regulated at low salinity. Our results show the presence in the XOSG of an inhibitory compound that regulates salinity-stimulated CA induction. © 2014 Marine Biological Laboratory.

  11. ENZYME RESISTANCE OF GENETICALLY MODIFIED STARCH POTATOES

    Directory of Open Access Journals (Sweden)

    A. Sh. Mannapova

    2015-01-01

    Full Text Available Here in this article the justification of expediency of enzyme resistant starch use in therapeutic food products is presented . Enzyme resistant starch is capable to resist to enzymatic hydrolysis in a small intestine of a person, has a low glycemic index, leads to decrease of postprandial concentration of glucose, cholesterol, triglycerides in blood and insulin reaction, to improvement of sensitivity of all organism to insulin, to increase in sense of fulness and to reduction of adjournment of fats. Resistant starch makes bifidogenшс impact on microflora of a intestine of the person, leads to increase of a quantity of lactobacillus and bifidobacterium and to increased production of butyric acid in a large intestine. In this regard the enzyme resistant starch is an important component in food for prevention and curing of human diseases such as diabetes, obesity, colitis, a cancer of large and direct intestine. One method is specified by authors for imitation of starch digestion in a human body. This method is based on the definition of an enzyme resistance of starch in vitro by its hydrolysis to glucose with application of a glucoamylase and digestive enzyme preparation Pancreatin. This method is used in researches of an enzyme resistance of starch, of genetically modified potato, high amylose corn starch Hi-Maize 1043 and HYLON VII (National Starch Food Innovation, USA, amylopectin and amylose. It is shown that the enzyme resistance of the starch emitted from genetically modified potatoes conforms to the enzyme resistance of the high amylose corn starch “Hi-Maize 1043 and HYLON VII starch”, (National Starch Food Innovation, the USA relating to the II type of enzyme resistant starch. It is established that amylopectin doesn't have the enzyme resistant properties. The results of researches are presented. They allow us to make the following conclusion: amylose in comparison with amylopectin possesses higher enzyme resistance and gives to

  12. Digestive Enzyme Supplementation in Gastrointestinal Diseases

    OpenAIRE

    Ianiro, Gianluca; Pecere, Silvia; Giorgio, Valentina; Gasbarrini, Antonio; Cammarota, Giovanni

    2016-01-01

    Background: Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. Methods: This review, performed through a non-systematic search of the available literature, will provide an over...

  13. Ethylene-forming enzyme of plants

    Energy Technology Data Exchange (ETDEWEB)

    Serebryanyi, A.M.; Krasheninnikova, G.A.; Vakhnina, L.V. [Semenov Inst. of Chemical Physics, Moscow (Russian Federation)

    1995-07-01

    The properties of ethylene-forming enzyme (EFE) (or 1-amino-cyclopropane-1-carboxylic acid oxidase; ACC-oxidase), the terminal enzyme in the synthesis of one of the main plant phytohormones, are reviewed. The properties of the isolated enzyme differ from those in the cell. There are apparently two forms of EFE in cells, one localized in vacuoles and the other in the cytosol. In cells EFE appears to be associated with membranes. 73 refs.

  14. The use of enzymes for beer brewing

    OpenAIRE

    Donkelaar, van, Laura H.G.; Mostert, Joost; Zisopoulos, Filippos K.; Boom, Remko M.; Goot, van der, Atze Jan

    2016-01-01

    The exergetic performance of beer produced by the conventional malting and brewing process is compared with that of beer produced using an enzyme-assisted process. The aim is to estimate if the use of an exogenous enzyme formulation reduces the environmental impact of the overall brewing process. The exergy efficiency of malting was 77%. The main exergy losses stem from the use of natural gas for kilning and from starch loss during germination. The exergy efficiency of the enzyme production p...

  15. Induction of rat cytochrome P-450 3 and its mRNA by 3,4,5,3',4',5'-hexachlorobiphenyl (HCB): comparison to the induction of P-450c in liver and extrahepatic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Yeowell, H.N.; Waxman, D.J.; Linko, P.; Goldstein, J.A.

    1987-05-01

    The present study assesses the effects of HCB on P-450 3 (P-450a/P-450 UT-F) and its translatable mRNA in adult male rats. Although a 50% increase in hepatic polysomal P-450 3 mRNA could be detected within 24 hours following a single dose of HCB, maximal induction was not observed until 5 days. In contrast, P-450c mRNA peaked 2-3 days after a single dose of HCB. The increase in P-450 3 and its associated steroid hormone 7..cap alpha..-hydroxylase activity also occurred later than the increase in P-450c. Neither P-450 3 nor 7..cap alpha..-OHase activity was detected in lung, kidney or prostate microsomes isolated from control or HCB-treated rats, whereas P-450c was induced in all three extrahepatic tissues (prostate > lung = kidney). These findings establish that P-450 3, which is relatively resistant to induction by many xenobiotics, can be induced several-fold by HCB. P-450 3 induction proceeds more slowly and to a significantly lower extent than P-450c induction, and in contrast to P-450c, does not occur in extrahepatic tissues. Finally, increased enzyme synthesis appears to be the major mechanism for the induction of P-450 3 by HCB.

  16. Convergence of the identification algorithm applied to the mutual inductance of the induction motor

    National Research Council Canada - National Science Library

    Jąderko, Andrzej; Pietryka, Jędrzej

    2012-01-01

    A new observer of induction motor state variables is proposed in the paper. A nonlinearity of the main magnetic path is expressed as a function of a properly chosen parameter versus the position vector length...

  17. [Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

    Science.gov (United States)

    Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

    2010-06-01

    With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

  18. Peptide-modified surfaces for enzyme immobilization.

    Directory of Open Access Journals (Sweden)

    Jinglin Fu

    Full Text Available BACKGROUND: Chemistry and particularly enzymology at surfaces is a topic of rapidly growing interest, both in terms of its role in biological systems and its application in biocatalysis. Existing protein immobilization approaches, including noncovalent or covalent attachments to solid supports, have difficulties in controlling protein orientation, reducing nonspecific absorption and preventing protein denaturation. New strategies for enzyme immobilization are needed that allow the precise control over orientation and position and thereby provide optimized activity. METHODOLOGY/PRINCIPAL FINDINGS: A method is presented for utilizing peptide ligands to immobilize enzymes on surfaces with improved enzyme activity and stability. The appropriate peptide ligands have been rapidly selected from high-density arrays and when desirable, the peptide sequences were further optimized by single-point variant screening to enhance both the affinity and activity of the bound enzyme. For proof of concept, the peptides that bound to β-galactosidase and optimized its activity were covalently attached to surfaces for the purpose of capturing target enzymes. Compared to conventional methods, enzymes immobilized on peptide-modified surfaces exhibited higher specific activity and stability, as well as controlled protein orientation. CONCLUSIONS/SIGNIFICANCE: A simple method for immobilizing enzymes through specific interactions with peptides anchored on surfaces has been developed. This approach will be applicable to the immobilization of a wide variety of enzymes on surfaces with optimized orientation, location and performance, and provides a potential mechanism for the patterned self-assembly of multiple enzymes on surfaces.

  19. Modified kinetics of enzymes interacting with nanoparticles

    Science.gov (United States)

    Díaz, Sebastián. A.; Breger, Joyce C.; Malanoski, Anthony; Claussen, Jonathan C.; Walper, Scott A.; Ancona, Mario G.; Brown, Carl W.; Stewart, Michael H.; Oh, Eunkeu; Susumu, Kimihiro; Medintz, Igor L.

    2015-08-01

    Enzymes are important players in multiple applications, be it bioremediation, biosynthesis, or as reporters. The business of catalysis and inhibition of enzymes is a multibillion dollar industry and understanding the kinetics of commercial enzymes can have a large impact on how these systems are optimized. Recent advances in nanotechnology have opened up the field of nanoparticle (NP) and enzyme conjugates and two principal architectures for NP conjugate systems have been developed. In the first example the enzyme is bound to the NP in a persistent manner, here we find that key factors such as directed enzyme conjugation allow for enhanced kinetics. Through controlled comparative experiments we begin to tease out specific mechanisms that may account for the enhancement. The second system is based on dynamic interactions of the enzymes with the NP. The enzyme substrate is bound to the NP and the enzyme is free in solution. Here again we find that there are many variables , such as substrate positioning and NP selection, that modify the kinetics.

  20. Potential of enzymes for wood debarking

    Energy Technology Data Exchange (ETDEWEB)

    Raettoe, M.; Kantelinen, A.; Bailey, M.; Viikari, L. (VTT Biotechnical Lab., Espoo (Finland))

    1993-02-01

    The effect of enzymatic pretreatment on the energy consumption of wood debarking was studied on the laboratory scale using enzymes to degrade the cambial layer. The energy consumed in debarking spruce was decreased as much as 80% after pretreatment with pectinolytic enzymes. In addition to polygalacturonase activity, pectin lyase and xylanase activities were also present in the most efficient enzyme preparation. Due to the complex composition of the cambium and inner phloem, these and other enzymes that hydrolyze the various inner bark components are probably needed for efficient debarking.