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Sample records for metabolically stable bradykinin

  1. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Directory of Open Access Journals (Sweden)

    Glen Daniel

    2009-05-01

    Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin

  2. D-Arg0-Bradykinin-Arg-Arg, a Latent Vasoactive Bradykinin B2 Receptor Agonist Metabolically Activated by Carboxypeptidases

    Directory of Open Access Journals (Sweden)

    Hélène Bachelard

    2018-03-01

    Full Text Available We previously reported hypotensive and vasodilator effects from C-terminally extended bradykinin (BK sequences that behave as B2 receptor (B2R agonists activated by vascular or plasma peptidases. D-Arg0-BK-Arg-Arg (r-BK-RR is a novel prodrug peptide hypothetically activated by two catalytic cycles of Arg-carboxypeptidases (CPs to release the direct agonist D-Arg0-BK. N-terminally extending the BK sequence with D-Arg0 in the latter peptide was meant to block the second kinin inactivation pathway in importance, aminopeptidase P. The affinity of r-BK and r-BK-RR for recombinant B2R was assessed using a [3H]BK binding displacement assay. Their pharmacology was evaluated in human isolated umbilical vein, a contractile bioassay for the B2R, in a morphological assay involving the endocytosis of B2R-green fusion protein (GFP and in anesthetized rats instrumented to record hemodynamic responses to bolus intravenous injection of both peptides. r-BK exhibited an affinity equal to that of BK for the rat B2R, while r-BK-RR was 61-fold less potent. In the vein and the B2R-GFP internalization assay, r-BK was a direct agonist unaffected by the blockade of angiotensin converting enzyme (ACE with enalaprilat, or Arg-CPs with Plummer’s inhibitor. However, the in vitro effects of r-BK-RR were reduced by these inhibitors, more so by enalaprilat. In anesthetized rats, r-BK and r-BK-RR were equipotent hypotensive agents and their effects were inhibited by icatibant (a B2R antagonist. The hypotensive effects of r-BK were potentiated by enalaprilat, but not influenced by the Arg-CPs inhibitor, which is consistent with a minor role of Arg-CPs in the metabolism of r-BK. However, in rats pretreated with both enalaprilat and Plummer’s inhibitor, the hypotensive responses and the duration of the hypotensive episode to r-BK were significantly potentiated. The hypotensive responses to r-BK-RR were not affected by enalaprilat, but were reduced by pre-treatment with the Arg

  3. Bradykinin, ch. 26

    International Nuclear Information System (INIS)

    Talamo, R.C.; Haber, E.; Austen, K.F.

    1976-01-01

    A radioimmunoassay for bradykinin is described. Methods of obtaining and processing blood and synovial fluid and subsequent isolation of bradykinin are given. To prepare the bradykinin immunogen, bradykinin is coupled to ovalbumin, using toluene diisocyanate. In order to determine the extent of coupling , ) 714C{-2,3 pro-bradykinin is used. Tyr 8 -bradykinin is iodinated with 125 I by a modification of the Hunter-greenwood method. The iodination mixture is purified by an anion exchanger. Bound and free hormones are separated by dextran-coated charcoal. The sensitivity of the method is about 0.1 ng/ml. )

  4. Metabolic studies in man using stable isotopes

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Krumbiegel, P.

    1993-01-01

    In this project, stable isotope compounds and stable isotope pharmaceuticals were used (with emphasis on the application of 15 N) to study several aspects of nitrogen metabolism in man. Of the many methods available, the 15 N stable isotope tracer technique holds a special position because the methodology for application and nitrogen isotope analysis is proven and reliable. Valid routine methods using 15 N analysis by emission spectrometry have been demonstrated. Several methods for the preparation of biological material were developed during our participation in the Coordinated Research Programme. In these studies, direct procedures (i.e. use of diluted urine as a samples without chemical preparation) or rapid isolation methods were favoured. Within the scope of the Analytical Quality Control Service (AQCS) enriched stable isotope reference materials for medical and biological studies were prepared and are now available through the International Atomic Energy Agency. The materials are of special importance as the increasing application of stable isotopes as tracers in medical, biological and agricultural studies has focused interest on reliable measurements of biological material of different origin. 24 refs

  5. Metabolic alkalosis in adults with stable cystic fibrosis.

    Science.gov (United States)

    Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

    2012-01-01

    The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Retrospective chart review. Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

  6. Metabolic Alkalosis in Adults with Stable Cystic Fibrosis

    OpenAIRE

    Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

    2012-01-01

    Background: The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Methods: Retrospective chart review. Results: Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6...

  7. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs

    OpenAIRE

    Hewitt, Matthew M.; Adams, Gregory; Mazzone, Stuart B.; Mori, Nanako; Yu, Li; Canning, Brendan J.

    2016-01-01

    Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonis...

  8. Combination cancer chemotherapy with one compound: pluripotent bradykinin antagonists.

    Science.gov (United States)

    Stewart, John M; Gera, Lajos; Chan, Daniel C; York, Eunice J; Simkeviciene, Vitalija; Bunn, Paul A; Taraseviciene-Stewart, Laimute

    2005-08-01

    Lung and prostate cancers are major health problems worldwide. Treatments with standard chemotherapy agents are relatively ineffective. Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the cancer in different pathways, but new therapeutic agents are needed for the treatment of both tumor types. Bradykinin (BK) antagonists offer advantages of combination therapy in one compound. These promising multitargeted anti-cancer compounds selectively stimulate apoptosis in cancers and also inhibit both angiogenesis and matrix metalloprotease (MMP) action in treated lung and prostate tumors in nude mice. The highly potent, metabolism-resistant bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=4-hydroxyproline; Igl=alpha-(2-indanyl)glycine; Oic=octahydroindole-2-carboxylic acid) and its non-peptide mimetic, BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)amide] are superior to the widely used but toxic chemotherapeutic drugs cisplatin and taxotere. In certain combinations, they act synergistically with standard anti-cancer drugs. Due to its structure and biological activity, BKM-570 is an attractive lead compound for derivatization and evaluation for lung and prostate cancer drugs.

  9. Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin.

    Science.gov (United States)

    Bunn, S J; Marley, P D; Livett, B G

    1990-04-01

    The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.

  10. Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism

    Science.gov (United States)

    2016-01-01

    Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13C), nitrogen (15N), oxygen (18O), and hydrogen (2H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to “trace” the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC‐MS to LC‐MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level

  11. A stable-isotope mass spectrometry-based metabolic footprinting approach to analyze exudates from phytoplankton

    DEFF Research Database (Denmark)

    Weber, Ralf J. M.; Selander, Erik; Sommer, Ulf

    2013-01-01

    Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological...... interactions. Despite this importance, little is known about the bioactive compounds present in phytoplankton exudates. We report a stable-isotope metabolic footprinting method to characterise exudates from aquatic autotrophs. Exudates from 13C-enriched alga were concentrated by solid phase extraction...

  12. Application of Stable Isotope-Assisted Metabolomics for Cell Metabolism Studies

    Science.gov (United States)

    You, Le; Zhang, Baichen; Tang, Yinjie J.

    2014-01-01

    The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1) properly designed tracer experiments; (2) stringent sampling and quenching protocols to minimize isotopic alternations; (3) efficient metabolite separations; (4) high resolution mass spectrometry to resolve overlapping peaks and background noises; and (5) data analysis methods and databases to decipher isotopic clusters over a broad m/z range (mass-to-charge ratio). This paper overviews mass spectrometry based techniques for precise determination of metabolites and their isotopologues. It also discusses applications of isotopic approaches to track substrate utilization, identify unknown metabolites and their chemical formulas, measure metabolite concentrations, determine putative metabolic pathways, and investigate microbial community populations and their carbon assimilation patterns. In addition, 13C-metabolite fingerprinting and metabolic models can be integrated to quantify carbon fluxes (enzyme reaction rates). The fluxome, in combination with other “omics” analyses, may give systems-level insights into regulatory mechanisms underlying gene functions. More importantly, 13C-tracer experiments significantly improve the potential of low-resolution gas chromatography-mass spectrometry (GC-MS) for broad-scope metabolism studies. We foresee the isotope-assisted metabolomics to be an indispensable tool in industrial biotechnology, environmental microbiology, and medical research. PMID:24957020

  13. Metabolism and pharmacokinetic of cyclo-peptides and peptides. Use of radioelement and stable isotopes

    International Nuclear Information System (INIS)

    Aninat, C.

    2003-10-01

    More and more peptides and proteins are used in therapeutic. Three mainly techniques are used for pharmacokinetic and metabolism studies: immunoassay, radioactively labeled molecules and mass spectrometry. In the first part of this work, we have used uniformly labelled peptides (C-peptide and insulin) with stables ( 13 C, 15 N, and 13 C/ 15 N) or radioactive ( 14 C) isotopes to investigated these kind of studies. These works are based on isotope dilution mass spectrometry assay. In a second time we have investigated the metabolism of a particular cyclo-peptides families composed of two amino acids: the diketo-piperazine. These compounds are found in mammals and in microorganisms. There are not recognized by proteolytic enzymes. We have estimated if the main enzymes implicated in the metabolism of xenobiotics, the P450 cytochrome mono-oxygenases, were able to recognized them

  14. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.

    Science.gov (United States)

    Hewitt, Matthew M; Adams, Gregory; Mazzone, Stuart B; Mori, Nanako; Yu, Li; Canning, Brendan J

    2016-06-01

    Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N(G)-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Enhancement of bradykinin and resensitization of its B2 receptor.

    Science.gov (United States)

    Marcic, B; Deddish, P A; Jackman, H L; Erdös, E G

    1999-03-01

    We studied the enhancement of the effects of bradykinin B2 receptor agonists by agents that react with active centers of angiotensin-converting enzyme (ACE) independent of enzymatic inactivation. The potentiation and the desensitization and resensitization of B2 receptor were assessed by measuring [3H]arachidonic acid release and [Ca2+]i mobilization in Chinese hamster ovary cells transfected to express human ACE and B2 receptor, or in endothelial cells with constitutively expressed ACE and receptor. Administration of bradykinin or its ACE-resistant analogue desensitized the receptor, but it was resensitized (arachidonic acid release or [Ca2+]i mobilization) by agents such as enalaprilat (1 micromol/L). Enalaprilat was inactive in the absence of ACE expression. La3+ (100 micromol/L) inhibited the apparent resensitization, probably by blocking the entry of extracellular calcium. Enalaprilat resensitized the receptor via ACE to release arachidonic acid by bradykinin at a lower concentration (5 nmol/L) than required to mobilize [Ca2+]i (1 micromol/L). Monoclonal antibodies inhibiting the ACE N-domain active center and polyclonal antiserum potentiated bradykinin. The snake venom peptide BPP5a and metabolites of angiotensin and bradykinin (angiotensin-[1-9], angiotensin-[1-7], bradykinin-[1-8]; 1 micromol/L) enhanced arachidonic acid release by bradykinin. Angiotensin-(1-9) and -(1-7) also resensitized the receptor. Enalaprilat potentiated the bradykinin effect in cells expressing a mutant ACE with a single N-domain active site. Agents that reacted with a single active site, on the N-domain or on the C-domain, potentiated bradykinin not by blocking its inactivation but by inducing crosstalk between ACE and the receptor. Enalaprilat enhanced signaling via ACE by Galphai in lower concentration than by Galphaq-coupled receptor.

  16. Quantitative imaging of subcellular metabolism with stable isotopes and multi-isotope imaging mass spectrometry

    Science.gov (United States)

    Steinhauser, Matthew L.; Lechene, Claude P.

    2014-01-01

    Multi-isotope imaging mass spectrometry (MIMS) is the quantitative imaging of stable isotope labels in cells with a new type of secondary ion mass spectrometer (NanoSIMS). The power of the methodology is attributable to (i) the immense advantage of using non-toxic stable isotope labels, (ii) high resolution imaging that approaches the resolution of usual transmission electron microscopy and (iii) the precise quantification of label down to 1 part-per-million and spanning several orders of magnitude. Here we review the basic elements of MIMS and describe new applications of MIMS to the quantitative study of metabolic processes including protein and nucleic acid synthesis in model organisms ranging from microbes to humans. PMID:23660233

  17. Potentiation by aminopeptidase P of blood pressure response to bradykinin.

    OpenAIRE

    Kitamura, S; Carbini, L A; Carretero, O A; Simmons, W H; Scicli, A G

    1995-01-01

    We examined whether a specific aminopeptidase P (APP) inhibitor, apstatin, increases vasodepressor responses to bradykinin in anaesthetized rats, and whether it would augment blood pressure responses further after treatment with the angiotensin-converting enzyme inhibitor (ACEi), lisinopril. Apstatin doubled the maximum blood pressure response to bradykinin. The area under the curve (AUC), which incorporates both peak blood pressure changes and duration of response, was doubled in apstatin-tr...

  18. Multiple stable isotope tracer technique for studying the metabolic kinetics of amino acids in hepatic failure

    Energy Technology Data Exchange (ETDEWEB)

    Zongqin, Xia; Tengchang, Dai; Jianhua, Zhang; Yaer, Hu; Bingyao, Yu; Xingrong, Xu; Guanlu, Huang; Gengrong, Shen; Yaqiu, Zhou; Hong, Yu

    1987-08-01

    In order to study the mechanism of the imbalance of amino acid metabolism during hepatic failure, a stable isotope tracer method for observing simultaneously the metabolic kinetics of several amino acids has been established. /sup 15/N-L-Ala, (2,3-D/sub 3/)-Leu and (2,3-D/sub 3/)-Phe were chosen as nonessential, branched chain and aromatic amino acids. A single iv injection of 40 mg N-Ala, 20 mg deuterated Leu and 20 mg deuterated Phe was given to each human subject. Blood samples were taken just before and at different times (up to 60 min) after the injection. Total free amino acids were isolated from the plasma with a small dowex 50 x 8 column and converted to trifluoroacetyl derivatives. Their abundances were then analyzed with a GC-MS system and typical double exponential time course curves were found for all the three labelled amino acids. A two-pool model was designed and applied for compartmental analysis. Significant changes were found in the kinetic parameters of Phe and Leu in patients with fulminant hepatitis or heptic cirrhosis. The half-lives of both Phe pools were longer and the pool sizes were larger than normal subjects, while the half-lives and pool sizes of Leu changes in the opposite direction. No marked change was found in Ala. The significance of intracellular imbalance of Phe and Leu metabolism was discussed. It is evident that the combination of GCMS technique and multiple-tracers labelled with stable isotopes is of great potential for similar purposes.

  19. Stable Breathing in Patients With Obstructive Sleep Apnea Is Associated With Increased Effort but Not Lowered Metabolic Rate.

    Science.gov (United States)

    de Melo, Camila M; Taranto-Montemurro, Luigi; Butler, James P; White, David P; Loring, Stephen H; Azarbarzin, Ali; Marques, Melania; Berger, Philip J; Wellman, Andrew; Sands, Scott A

    2017-10-01

    In principle, if metabolic rate were to fall during sleep in a patient with obstructive sleep apnea (OSA), ventilatory requirements could be met without increased respiratory effort thereby favoring stable breathing. Indeed, most patients achieve periods of stable flow-limited breathing without respiratory events for periods during the night for reasons that are unclear. Thus, we tested the hypothesis that in patients with OSA, periods of stable breathing occur when metabolic rate (VO2) declines. Twelve OSA patients (apnea-hypopnea index >15 events/h) completed overnight polysomnography including measurements of VO2 (using ventilation and intranasal PO2) and respiratory effort (esophageal pressure). Contrary to our hypothesis, VO2 did not differ between stable and unstable breathing periods in non-REM stage 2 (208 ± 20 vs. 213 ± 18 mL/min), despite elevated respiratory effort during stable breathing (26 ± 2 versus 23 ± 2 cmH2O, p = .03). However, VO2 was lowered during deeper sleep (244 to 179 mL/min from non-REM stages 1 to 3, p = .04) in conjunction with more stable breathing. Further analysis revealed that airflow obstruction curtailed metabolism in both stable and unstable periods, since CPAP increased VO2 by 14% in both cases (p = .02, .03, respectively). Patients whose VO2 fell most during sleep avoided an increase in PCO2 and respiratory effort. OSA patients typically convert from unstable to stable breathing without lowering metabolic rate. During sleep, OSA patients labor with increased respiratory effort but fail to satisfy metabolic demand even in the absence of overt respiratory events. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  20. A Stable-Isotope Mass Spectrometry-Based Metabolic Footprinting Approach to Analyze Exudates from Phytoplankton

    Directory of Open Access Journals (Sweden)

    Mark R. Viant

    2013-10-01

    Full Text Available Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological interactions. Despite this importance, little is known about the bioactive compounds present in phytoplankton exudates. We report a stable-isotope metabolic footprinting method to characterise exudates from aquatic autotrophs. Exudates from 13C-enriched alga were concentrated by solid phase extraction and analysed by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. We used the harmful algal bloom forming dinoflagellate Alexandrium tamarense to prove the method. An algorithm was developed to automatically pinpoint just those metabolites with highly 13C-enriched isotope signatures, allowing us to discover algal exudates from the complex seawater background. The stable-isotope pattern (SIP of the detected metabolites then allowed for more accurate assignment to an empirical formula, a critical first step in their identification. This automated workflow provides an effective way to explore the chemical nature of the solutes exuded from phytoplankton cells and will facilitate the discovery of novel dissolved bioactive compounds.

  1. Angiotensin and bradykinin interactions with phospholipids

    International Nuclear Information System (INIS)

    Elliott, M.E.; Goodfriend, T.L.

    1979-01-01

    Reversible interactions were demonstrated between some phospholipids and some polypeptides related to angiotensin and bradykinin. The extent of the interaction was dependent on the structures of the lipid and peptide. The naturally occurring compounds that interacted most avidly were cardiolipin and (des-Asp 1 )-angiotensins. The apparent dissociation constant of this complex in chloroform was 10 -5 M. The complex contained more than one cardiolipin molecule/molecule of peptide. Kinins interacted most strongly with lecithin. The phospholipids altered the chromatographic behaviour of radioiodinated derivatives of the polypeptides, and solubilized radioactive and unlabeled polypeptides in chloroform. In aqueous media, cardiolipin suspensions preferentially bound (des-Asp 1 )-angiotensin II, and inhibited its binding by antibody. The interactions were sensitive to pH and cations in the aqueous phase, and were reversed by some reagents added to the organic phase. These interactions have direct implications for binding reactions of peptides in vitro, and may bear upon the actions of the hormones in vivo. (Auth.)

  2. Growth versus metabolic tissue replacement in mouse tissues determined by stable carbon and nitrogen isotope analysis

    Science.gov (United States)

    Macavoy, S. E.; Jamil, T.; Macko, S. A.; Arneson, L. S.

    2003-12-01

    Stable isotope analysis is becoming an extensively used tool in animal ecology. The isotopes most commonly used for analysis in terrestrial systems are those of carbon and nitrogen, due to differential carbon fractionation in C3 and C4 plants, and the approximately 3‰ enrichment in 15N per trophic level. Although isotope signatures in animal tissues presumably reflect the local food web, analysis is often complicated by differential nutrient routing and fractionation by tissues, and by the possibility that large organisms are not in isotopic equilibrium with the foods available in their immediate environment. Additionally, the rate at which organisms incorporate the isotope signature of a food through both growth and metabolic tissue replacement is largely unknown. In this study we have assessed the rate of carbon and nitrogen isotopic turnover in liver, muscle and blood in mice following a diet change. By determining growth rates, we were able to determine the proportion of tissue turnover caused by growth versus that caused by metabolic tissue replacement. Growth was found to account for approximately 10% of observed tissue turnover in sexually mature mice (Mus musculus). Blood carbon was found to have the shortest half-life (16.9 days), followed by muscle (24.7 days). Liver carbon turnover was not as well described by the exponential decay equations as other tissues. However, substantial liver carbon turnover was observed by the 28th day after diet switch. Surprisingly, these tissues primarily reflect the carbon signature of the protein, rather than carbohydrate, source in their diet. The nitrogen signature in all tissues was enriched by 3 - 5‰ over their dietary protein source, depending on tissue type, and the isotopic turnover rates were comparable to those observed in carbon.

  3. Metabolic syndrome and mortality in stable coronary heart disease: relation to gender

    DEFF Research Database (Denmark)

    Kragelund, Charlotte; Køber, Lars; Faber, Jens

    2007-01-01

    BACKGROUND: Metabolic syndrome (MS) is associated with subsequent development of type 2 diabetes and cardiovascular disease in the general population. The impact of MS on mortality in patients with stable coronary heart disease is less well defined, and the association of prognosis to gender...... follow-up of 9.2 years. RESULTS: At follow-up 296 (28%) patients had died. 315 (30%) patients had MS based on the definition by the World Health Organization. Patients with MS more frequently had diabetes and three-vessel disease of the coronary arteries. Men had a more severe risk profile than women....... In a multivariable Cox regression analysis, MS was not associated with excess mortality risk in the overall population [adjusted HR=1.3 (95% CI: 0.7-2.3), p=0.43]. In gender specific analyses MS increased risk of all-cause mortality in women [adjusted HR=2.2 (95% CI: 1.1-4.3), p=0.02], but not in men [adjusted HR=1...

  4. Effect of added dietary cobalt on metabolism and distribution of radioactive selenium and stable minerals

    International Nuclear Information System (INIS)

    Van Ryssen, J.B.J.; Miller, W.J.; Gentry, R.P.; Neathery, M.W.

    1987-01-01

    Retention of 75 Se following a single oral dose and stable Co, Cu, Zn, and Mg were determined in tissues of calves fed a diet containing 0, 10, or 40 ppm supplemental Co for 21 d. Concentrations of 75 Se in tissue were numerically higher with 10 ppm Co than with the other two diets, but the effect was significant only in small intestine tissues of calves fed 40 ppm Co. Dietary Co did not affect fecal 75 Se. Average total fecal 75 Se excretion was 53, 48, and 51% of the dose over 6 d in calves fed 0, 10, and 40 ppm added Co. Concentrations of Co in tissues increased with increased supplementation. Dietary Co did not significantly affect growth, feed intake, tissue Zn, tissue Cu, blood hemoglobin, packed cell volume, plasma alkaline phosphatase, or plasma glutamic oxaloacetic transaminase. Magnesium in heart and skeletal muscle was increased in calves fed 40 ppm Co. Although high amounts of added dietary Co had some influence on metabolism of Se, the magnitude and extent of the effects appeared to be too small to be of practical concern

  5. New bradykinin analogues modified with 1-aminocyclopentane-1-carboxylic acid

    Czech Academy of Sciences Publication Activity Database

    Labudda-Dawidowska, O.; Sobolewski, D.; Sleszyňska, M.; Derdowska, I.; Slaninová, Jiřina; Wierzba, T.; Prahl, A.

    2006-01-01

    Roč. 12, Supplement (2006), s. 180 ISSN 1075-2617. [European Peptide Symposium /29./. 03.09.2006-08.09.2006, Gdansk] Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin * Apc Subject RIV: CC - Organic Chemistry

  6. Realistic Fasting Does Not Affect Stable Isotope Levels of a Metabolically Efficient Salamander

    Science.gov (United States)

    Stable isotopes are commonly used to examine various aspects of animal ecology. The use of stable isotopes generally proceeds under the implicit assumption that resource use is the only factor driving variation in stable isotope levels; however, a wealth of studies demonstrate a...

  7. Utilization of stable isotopes for the study of in vivo compartmental metabolism of poly-insaturate fatty acids

    International Nuclear Information System (INIS)

    Brossard, N.; Croset, M.; Lecerf, J.; Lagarde, M.; Pachiaudi, C.; Normand, S.; Riou, J.P.; Chirouze, V.; Tayot, J.L.

    1994-01-01

    In order to study the compartmental metabolism of the 22:6n-3 fatty acid, and particularly the role of the transport plasmatic forms for the tissue uptake (especially brain), a technique is developed using carbon 13 stable isotope and an isotopic mass spectrometry coupled to gaseous chromatography technique. This method has been validated in rat with docosahexaenoic acid enriched in 13 C and esterified in triglycerides. The compartmental metabolism is monitored by measuring the variation of 22:6n-3 isotopic enrichment in the various lipoprotein lipidic fractions, in blood globules and in the brain. 1 fig., 1 tab., 12 refs

  8. Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.

    Directory of Open Access Journals (Sweden)

    Federica Defendi

    Full Text Available BACKGROUND: The kinins (primarily bradykinin, BK represent the mediators responsible for local increase of vascular permeability in hereditary angioedema (HAE, HAE I-II associated with alterations of the SERPING1 gene and HAE with normal C1-Inhibitor function (HAE-nC1INH. Besides C1-Inhibitor function and concentration, no biological assay of kinin metabolism is actually available to help physicians for the diagnosis of angioedema (AE. We describe enzymatic tests on the plasma for diagnosis of BK-dependent AE. METHODS: The plasma amidase assays are performed using the Pro-Phe-Arg-p-nitroanilide peptide substrate to evaluate the spontaneous amidase activity and the proenzyme activation. We analyzed data of 872 patients presenting with BK-dependent AE or BK-unrelated diseases, compared to 303 controls. Anti-high MW kininogen (HK immunoblot was achieved to confirm HK cleavage in exemplary samples. Reproducibility, repeatability, limit of blank, limit of detection, precision, linearity and receiver operating characteristics (ROC were used to calculate the diagnostic performance of the assays. RESULTS: Spontaneous amidase activity was significantly increased in all BK-dependent AE, associated with the acute phase of disease in HAE-nC1INH, but preserved in BK-unrelated disorders. The increase of the amidase activity was associated to HK proteolysis, indicating its relevance to identify kininogenase activity. The oestrogens, known for precipitating AE episodes, were found as triggers of enzymatic activity. Calculations from ROC curves gave the optimum diagnostic cut-off for women (9.3 nmol⋅min(-1⋅mL(-1, area under curve [AUC] 92.1%, sensitivity 80.0%, and specificity 90.1% and for men (6.6 nmol·min(-1⋅mL(-1, AUC 91.0%, sensitivity 87.0% and specificity 81.2%. CONCLUSION: The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.

  9. Combining metagenomics with metaproteomics and stable isotope probing reveals metabolic pathways used by a naturally occurring marine methylotroph

    DEFF Research Database (Denmark)

    Grob, Carolina; Taubert, Martin; Howat, Alexandra M.

    2015-01-01

    A variety of culture-independent techniques have been developed that can be used in conjunction with culture-dependent physiological and metabolic studies of key microbial organisms in order to better understand how the activity of natural populations influences and regulates all major......, we retrieved virtually the whole genome of this bacterium and determined its metabolic potential. Through protein-stable isotope probing, the RuMP cycle was established as the main carbon assimilation pathway, and the classical methanol dehydrogenase-encoding gene mxaF, as well as three out of four...... identified xoxF homologues were found to be expressed. This proof-of-concept study is the first in which the culture-independent techniques of DNA-SIP and protein-SIP have been used to characterize the metabolism of a naturally occurring Methylophaga-like bacterium in the marine environment (i...

  10. 24-Hour protein, arginine and citrulline metabolism in fed critically ill children – a stable isotope tracer study

    Science.gov (United States)

    de Betue, Carlijn T.I.; Garcia Casal, Xiomara C.; van Waardenburg, Dick A.; Schexnayder, Stephen M.; Joosten, Koen F.M.; Deutz, Nicolaas E.P.; Engelen, Marielle P.K.J.

    2017-01-01

    Background & aims The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4–8h) time period and extrapolate results to 24-hour. However, 24-hour measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-hour appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children. Methods In eight critically ill children, admitted to the pediatric (n=4) or cardiovascular (n=4) intensive care unit, aged 0–10 years, receiving continuous (par)enteral nutrition with protein intake 1.0–3.7 g/kg/day, a 24-hour stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour. Results Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14–19% for intravenous tracers and 23–26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-hour level of whole body protein balance differed per individual. Conclusions In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm. PMID:28089618

  11. Influence of bradykinin on diacylglycerol and phosphatidic acid accumulation in cultured bovine adrenal chromaffin cells.

    Science.gov (United States)

    Owen, P J; Boarder, M R

    1991-09-01

    Earlier studies have shown that bradykinin stimulated release of catecholamines from chromaffin cells by an influx of calcium through dihydropyridine-insensitive channels, and also that bradykinin stimulated (poly)phosphoinositide hydrolysis. To investigate membrane-bound second messengers in chromaffin cells, and to elucidate any role these may play in stimulus-secretion coupling, we have studied the influence of bradykinin on diacylglycerol and phosphatidic acid (PA). Using equilibrium labelling of primary cultures of chromaffin cells with [3H]arachidonic acid or [3H]glycerol, we found no influence of bradykinin (10 nM) on labelled diacylglycerol formation, either in the presence or absence of inhibitors of diacylglycerol lipase or kinase. However, when we used cells prelabelled with 32Pi for 2.5 h, we found that bradykinin produced a substantial stimulation of label found in PA, with an EC50 value of about 1 nM. This bradykinin stimulation of [32P]PA formation was only partially dependent on extracellular calcium, in contrast to the smaller response to nicotine, which was completely dependent on extracellular calcium. Short (10 min) pretreatment with tetradecanoylphorbol acetate (TPA) almost completely eliminated the bradykinin-stimulated formation of inositol phosphates, but failed to affect bradykinin stimulation of label in PA, suggesting that PA production in response to bradykinin is not downstream of phospholipase C activation. TPA alone failed to stimulate [32P]PA substantially, whereas long-term (24 or 48 h) treatment with TPA failed to attenuate the response to bradykinin. Diacylglycerol kinase inhibitors were also without effect on the bradykinin stimulation of [32P]PA. These results suggest that bradykinin stimulates PA production by a mechanism independent of the activation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Investigation of the microbial metabolism of carbon dioxide and hydrogen in the kangaroo foregut by stable isotope probing.

    Science.gov (United States)

    Godwin, Scott; Kang, Alicia; Gulino, Lisa-Maree; Manefield, Mike; Gutierrez-Zamora, Maria-Luisa; Kienzle, Marco; Ouwerkerk, Diane; Dawson, Kerri; Klieve, Athol V

    2014-09-01

    Kangaroos ferment forage material in an enlarged forestomach analogous to the rumen, but in contrast to ruminants, they produce little or no methane. The objective of this study was to identify the dominant organisms and pathways involved in hydrogenotrophy in the kangaroo forestomach, with the broader aim of understanding how these processes are able to predominate over methanogenesis. Stable isotope analysis of fermentation end products and RNA stable isotope probing (RNA-SIP) were used to investigate the organisms and biochemical pathways involved in the metabolism of hydrogen and carbon dioxide in the kangaroo forestomach. Our results clearly demonstrate that the activity of bacterial reductive acetogens is a key factor in the reduced methane output of kangaroos. In in vitro fermentations, the microbial community of the kangaroo foregut produced very little methane, but produced a significantly greater proportion of acetate derived from carbon dioxide than the microbial community of the bovine rumen. A bacterial operational taxonomic unit closely related to the known reductive acetogen Blautia coccoides was found to be associated with carbon dioxide and hydrogen metabolism in the kangaroo foregut. Other bacterial taxa including members of the genera Prevotella, Oscillibacter and Streptococcus that have not previously been reported as containing hydrogenotrophic organisms were also significantly associated with metabolism of hydrogen and carbon dioxide in the kangaroo forestomach.

  13. Systematic NMR Analysis of Stable Isotope Labeled Metabolite Mixtures in Plant and Animal Systems: Coarse Grained Views of Metabolic Pathways

    Science.gov (United States)

    Chikayama, Eisuke; Suto, Michitaka; Nishihara, Takashi; Shinozaki, Kazuo; Hirayama, Takashi; Kikuchi, Jun

    2008-01-01

    Background Metabolic phenotyping has become an important ‘bird's-eye-view’ technology which can be applied to higher organisms, such as model plant and animal systems in the post-genomics and proteomics era. Although genotyping technology has expanded greatly over the past decade, metabolic phenotyping has languished due to the difficulty of ‘top-down’ chemical analyses. Here, we describe a systematic NMR methodology for stable isotope-labeling and analysis of metabolite mixtures in plant and animal systems. Methodology/Principal Findings The analysis method includes a stable isotope labeling technique for use in living organisms; a systematic method for simultaneously identifying a large number of metabolites by using a newly developed HSQC-based metabolite chemical shift database combined with heteronuclear multidimensional NMR spectroscopy; Principal Components Analysis; and a visualization method using a coarse-grained overview of the metabolic system. The database contains more than 1000 1H and 13C chemical shifts corresponding to 142 metabolites measured under identical physicochemical conditions. Using the stable isotope labeling technique in Arabidopsis T87 cultured cells and Bombyx mori, we systematically detected >450 HSQC peaks in each 13C-HSQC spectrum derived from model plant, Arabidopsis T87 cultured cells and the invertebrate animal model Bombyx mori. Furthermore, for the first time, efficient 13C labeling has allowed reliable signal assignment using analytical separation techniques such as 3D HCCH-COSY spectra in higher organism extracts. Conclusions/Significance Overall physiological changes could be detected and categorized in relation to a critical developmental phase change in B. mori by coarse-grained representations in which the organization of metabolic pathways related to a specific developmental phase was visualized on the basis of constituent changes of 56 identified metabolites. Based on the observed intensities of 13C atoms of

  14. Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit.

    Science.gov (United States)

    Griesbacher, T.; Lembeck, F.

    1987-01-01

    1 The inhibition of the bradykinin-induced plasma extravasation by six bradykinin (Bk) antagonists was tested on rabbit skin. All of them showed inhibitory effects without an agonistic action in the does used. B4310 (Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk) was the most active antagonist and was therefore used in the subsequent experiments. 2 B4310 (5-500 nM) antagonized the bradykinin-induced reduction of the venous outflow from the rabbit isolated ear in dose-dependent manner without affecting the arterial vasoconstriction induced by angiotensin II. 3 The bradykinin-induced release of prostaglandin E2 (PGE2) from the perfused rabbit ear was reduced by 63% when B4310 (800 nM) was infused before, during and after the bradykinin injection. 4 Bradykinin was injected into the ear artery of anaesthetized rabbits and the reflex hypotensive response was used as indicator of the nociception. The response was antagonized by a local infusion of B4310 (50 and 500 nM). The antagonism was dose-dependent and reversible. The parallel shift of the dose-response curve to bradykinin suggests a competitive inhibition. However, B4310 did not antagonize acetylcholine-induced nociceptor stimulation. 5 B4310 inhibited bradykinin-induced stimulation of the trigeminal nerve which results in a substance P-mediated contraction of the iris sphincter muscle. A pA2 of 7.59 was calculated. B4310 did not inhibit capsaicin-induced contractions. 6 It is concluded that B4310 inhibits specifically five different actions of bradykinin which are related to its possible pathophysiological role. PMID:3479223

  15. Use of stable isotopes for the in vivo study of metabolic disorders

    International Nuclear Information System (INIS)

    Faull, K.F.; Gan, I.; Halpern, B.; Danke, D.M.

    1975-01-01

    Deuterated tyrosine has been used to study tyrosine metabolism in one normal and two tyrosinemic patients. The labeled tyrosine was ingested orally, after which urine and serum samples were examined at regular intervals for residual labeled tyrosine and tyrosine metabolites. Deuteration measurements were made with a combined GC-MS instrument operating under computer control using time averaging and mass fragmentometry. Initial experiments were done with a loading of 829 μmoles of deuterated tyrosine/kg body wt., but we have been able to reduce this by one-third without any loss of precision. The rate of deuterated tyrosine metabolism has allowed us to distinguish between individuals having different clinical manifestations but similar biochemical abnormalities. The sensitivity of the method suggests the procedure has value in the study of metabolic defects

  16. Mass spectrometric methods for studying nutrient mineral and trace element absorption and metabolism in humans using stable isotopes: a review

    International Nuclear Information System (INIS)

    Crews, H.M.; Eagles, J.; Mellon, F.A.; Luten, J.B.; McGaw, B.A.

    1994-01-01

    Mass spectrometric methods for determining stable isotopes of nutrient minerals and trace elements in human metabolic studies are described and discussed. The advantages and disadvantages of the techniques of electron ionization, fast atom bombardment, thermal ionization, and inductively coupled plasma and gas chromatography mass spectrometry are evaluated with reference to their accuracy, precision, sensitivity, and convenience, and the demands of human nutrition research. Examples of specific applications are described and the significance of current developments in mass spectrometry are discussed with reference to present and probable future research needs. (Author)

  17. Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy

    NARCIS (Netherlands)

    van Manen, H.J.; Lenferink, Aufrid T.M.; Otto, Cornelis

    2008-01-01

    We have combined nonresonant Raman microspectroscopy and spectral imaging with stable isotope labeling by amino acids in cell culture (SILAC) to selectively detect the incorporation of deuterium-labeled phenylalanine, tyrosine, and methionine into proteins in intact, single HeLa cells. The C−D

  18. Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

    Science.gov (United States)

    Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

    2004-02-12

    A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

  19. Utilization of carbon 13-labelled stable isotopes for studying drug toxicity on cellular metabolism

    International Nuclear Information System (INIS)

    Herve, M.; Wietzerbin, J.; Tran-Dinh, S.

    1994-01-01

    A new approach for studying the effects of two drugs, amphotericine B (AMB), an anti-fungal antibiotic, and 2-deoxy-D-glucose (DG), on the glucose metabolism in brewer yeast cells (Saccharomyces cerevisiae), is presented; AMB interacts with the membrane sterols, inducing formation of pores through which ions and small molecules can pass. DG may enter in the cytosol, where it is phosphoryled by hexokinase into deoxy-D-glucose 6-phosphate (DG6P) which disappears very slowly. DG slows down the glycolysis process and induces the formation of new substances. This paper shows the advantages of utilizing carbon 13-labelled substrates combined to the NMR-13C and NMR-1H techniques. 6 figs., 5 refs

  20. Use of stable isotopes in the study of human cholesterol metabolism

    International Nuclear Information System (INIS)

    Virelizier, H.; Hagemann, R.

    1979-01-01

    An experimental procedure based on the use of stable isotopes spiked molecules of cholesterol, allows the measurement in faecal cholesterol of the relative parts coming from the plasma by transfer (deuterium spiked molecules), from the non absorbed alimentary cholesterol ( 13 C spiked molecules) and from the external intestinal secretion (not labelled way). The patient receive a dose of D 8 (2, 2', 3, 4, 4', 6, 7, 7') cholesterol intravenously and an oral dose of 3,4 13 C cholesterol. The plasmatic cholesterol transfer is calculated from the ratio of the measured dilutions of the faecal and plasmatic D 8 cholesterol. The non absorbed cholesterol is estimated from the percentage of 13 C cholesterol measured in the faecal sterols within the six days following the oral dose ingestion. The D 8 cholesterol dilutions are measured using the GC-MS technique on the trimethylsilyl derivatives of cholesterol. Dilutions up to 1/4000 can be measured. The 13 C enriched faecal cholesterol is converted into CO 2 and the 13 C/ 12 C ratios are measured on a dual collector mass spectrometer. Dilutions up to 1/5000 of the 3,4 13 C cholesterol can be detected. The details of the analytical procedure are given

  1. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study

    Science.gov (United States)

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Mayo, Juan C.

    2017-01-01

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type. PMID:28933733

  2. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study.

    Science.gov (United States)

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Rodriguez-Gonzalez, Pablo; Garcia-Alonso, Jose I; Mayo, Juan C; Sainz, Rosa M

    2017-07-26

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/ SLC2A ) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13 C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13 C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13 C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13 C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.

  3. Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

    Science.gov (United States)

    Torres, Armando; Torregrosa, Vicens; Marcen, Roberto; Campistol, Josep María; Arias, Manuel; Hernández, Domingo; Fernández, Constantino; Esforzado, Nuria; Paschoalin, Raphael; Pérez, Nuria; García, Ana Isabel; Del Amo, Montserrat; Pomés, Jaume; González Rinne, Ana; Marrero, Domingo; Pérez, Estefanía; Henríquez, Fernando; Díaz, Juan Manuel; Silva, Irene; López, Verónica; Perello, Manuel; Ramos, David; Beneyto, Isabel; Cruzado, José María; Martínez Castelao, Alberto; Bravo, Juan; Rodríguez, Minerva; Díaz, Carmen; Crespo, Josep; Anaya, Fernando; Rodríguez, María Luisa; Cubero, Juan José; Pascual, Pilar; Romero, Rafael; Andrés Belmonte, Amado; Checa, María Dolores; Jiménez, Carlos; Escuin, Fernando; Crespo, Marta; Mir, Marisa; Gómez, Gonzalo; Bayes, Beatriz; González, María José; Gutiérrez, Alex; Cuberes, Marta; Rodríguez Benoit, Alberto; García, Teresa; Llamas, Francisco; Ortega, Agustín; Conde, José Luis; Gómez Alamillo, Carlos

    2016-01-01

    The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  4. [{sup 11}C]NNC 22-0215, a metabolically stable dopamine D{sub 1} radioligand for PET

    Energy Technology Data Exchange (ETDEWEB)

    Foged, Christian; Halldin, Christer; Swahn, Carl-Gunnar; Ginovart, Nathalie; Karlsson, Per; Lundkvist, Camilla; Farde, Lars

    1998-07-01

    NNC 22-0215 has been found to be a metabolically stable dopamine D{sub 1} antagonist with high affinity and selectivity for D{sub 1} receptors in vitro. We prepared [{sup 11}C]NNC 22-0215 with a specific radioactivity of about 50 GBq/{mu}mol at time of administration. In PET experiments with [{sup 11}C]NNC 22-0215 there was a rapid uptake of radioactivity in the cynomolgus monkey brain (1.8% of total radioactivity injected). Radioactivity accumulated most markedly in the striatum and the neocortex. The striatum to cerebellum ratio was about 4, with specific binding that remained at a plateau level from 50 min to 100 min after injection. Binding in the striatum and neocortex was markedly displaced by SCH 23390, whereas binding in the cerebellum was not reduced. Metabolite studies showed that about 80% of the radioactivity in the monkey plasma represented unchanged radioligand 30 min after injection. The rate of metabolism in monkey plasma in vivo was also determined for a series of structurally related {sup 11}C-labelled benzazepines, previously used as dopamine D{sub 1} receptor ligands for PET. Results indicate a significantly slower rate of metabolism for [{sup 11}C]NNC 22-0215 than for any of the previously labelled benzazepines. Thus [{sup 11}C]NNC 22-0215 has potential for imaging of selective binding to the dopamine D{sub 1} receptors in the human brain with high count rates at time of equilibrium.

  5. Synthesis of a metabolically stable modified long-chain fatty acid salt and its photolabile derivative

    Energy Technology Data Exchange (ETDEWEB)

    Stoll, G.H.; Voges, R.; Gerok, W.; Kurz, G. (Institut fuer Organische Chemie and Biochemie, Universitaet Freiburg (Germany))

    1991-05-01

    An analogue of the long-chain fatty acid salt, sodium stearate, was synthesized in which the hydrogen atoms at carbons 2, 3, and 18 were replaced by fluorine. The key step in the synthesis was the addition of 3-iodo-2,2,3,3-tetrafluoropropanoic acid amide to 15,15,15-trifluoro-1-pentadecene. Radioactivity was introduced by catalytic reduction of 2,2,3,3,18,18,18-heptafluoro-4-octadecenoic acid amide with carrier-free tritium gas yielding a product with the specific radioactivity of 2.63 TBq/mmol. The resulting 2,2,3,3,18,18,18-heptafluoro-4-octadecenoic acid has a pKa of about 0.5 and is completely dissociated under normal physiological conditions. The fluorinated fatty acid salt analogue is readily taken up into hepatocytes and proved to be metabolically inert. In an approach to the identification of proteins involved in long-chain fatty acid salt transport across membranes and intracellular compartments, the photolabile derivative 11,11-azo-2,2,3,3,18,18,18-heptafluoro(G-3H)octadecanoic acid sodium salt was synthesized with a specific radioactivity of 2.63 TBq/mmol. Photolysis of the photolabile derivative, using a light source with a maximum emission at 350 nm, occurred with a half-life of 1.5 min. The generated carbene reacted with 14C-labeled methanol and acetonitrile with covalent bond formation of 6-13%. Its efficacy for photoaffinity labeling was demonstrated by incorporation into serum albumin, the extracellular fatty acid salt-binding protein, as well as into the intracellular fatty acid salt-binding protein (FABP) of rat liver with the molecular weight of 14,000.

  6. Bradykinin B2 receptor-mediated phosphoinositide hydrolysis in bovine cultured tracheal smooth muscle cells.

    OpenAIRE

    Marsh, K. A.; Hill, S. J.

    1992-01-01

    1. Bovine tracheal smooth muscle cells were established in culture to study agonist-induced phosphoinositide (PI) hydrolysis in this tissue. 2. Bradykinin (0.1 nM-10 microM) evoked a concentration-dependent increase (log EC50 (M) = -9.4 +/- 0.2; n = 8) in the accumulation of total [3H]-inositol phosphates in cultured tracheal smooth muscle cells whereas the selective B1 receptor agonist des-Arg9-bradykinin (10 microM) was significantly less effective (16% of bradykinin maximal response; relat...

  7. Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics.

    Science.gov (United States)

    Pietzke, Matthias; Zasada, Christin; Mudrich, Susann; Kempa, Stefan

    2014-01-01

    Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. Here, we describe pulsed stable isotope-resolved metabolomics (pSIRM) as a tool for the dynamic metabolic characterization of cellular metabolism. We have adapted gas chromatography-coupled mass spectrometric methods for metabolomic profiling and stable isotope-resolved metabolomics. In addition, we have improved robustness and reproducibility and implemented a strategy for the absolute quantification of metabolites. By way of examples, we have applied this methodology to characterize central carbon metabolism of a panel of cancer cell lines and to determine the mode of metabolic inhibition of glycolytic inhibitors in times ranging from minutes to hours. Using pSIRM, we observed that 2-deoxyglucose is a metabolic inhibitor, but does not directly act on the glycolytic cascade.

  8. Hereditary angioedema: a bradykinin-mediated swelling disorder.

    Science.gov (United States)

    Björkqvist, Jenny; Sala-Cunill, Anna; Renné, Thomas

    2013-03-01

    Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

  9. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

    Science.gov (United States)

    Cicardi, Marco; Banerji, Aleena; Bracho, Francisco; Malbrán, Alejandro; Rosenkranz, Bernd; Riedl, Marc; Bork, Konrad; Lumry, William; Aberer, Werner; Bier, Henning; Bas, Murat; Greve, Jens; Hoffmann, Thomas K; Farkas, Henriette; Reshef, Avner; Ritchie, Bruce; Yang, William; Grabbe, Jürgen; Kivity, Shmuel; Kreuz, Wolfhart; Levy, Robyn J; Luger, Thomas; Obtulowicz, Krystyna; Schmid-Grendelmeier, Peter; Bull, Christian; Sitkauskiene, Brigita; Smith, William B; Toubi, Elias; Werner, Sonja; Anné, Suresh; Björkander, Janne; Bouillet, Laurence; Cillari, Enrico; Hurewitz, David; Jacobson, Kraig W; Katelaris, Constance H; Maurer, Marcus; Merk, Hans; Bernstein, Jonathan A; Feighery, Conleth; Floccard, Bernard; Gleich, Gerald; Hébert, Jacques; Kaatz, Martin; Keith, Paul; Kirkpatrick, Charles H; Langton, David; Martin, Ludovic; Pichler, Christiane; Resnick, David; Wombolt, Duane; Fernández Romero, Diego S; Zanichelli, Andrea; Arcoleo, Francesco; Knolle, Jochen; Kravec, Irina; Dong, Liying; Zimmermann, Jens; Rosen, Kimberly; Fan, Wing-Tze

    2010-08-05

    Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

  10. Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant.

    Science.gov (United States)

    Krause, Karoline; Metz, Martin; Zuberbier, Torsten; Maurer, Marcus; Magerl, Markus

    2010-04-01

    The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.

  11. Characterization of urinary metabolites from four synthetic bradykinin potentiating peptides (BPPs) in mice.

    Science.gov (United States)

    Silva, Carlos A; Ianzer, Danielle A; Portaro, Fernanda C V; Konno, Katsuhiro; Faria, Marcella; Fernandes, Beatriz L; Camargo, Antonio C M

    2008-09-01

    BPPs have been identified in the venom of the Bothrops jararaca snake, or deduced from precursor proteins expressed either in the venom gland or in the brain of the snake. Their potentiating activity on bradykinin (Bk) is assumed to occur through a somatic angiotensin-converting enzyme (sACE) inhibitory mechanism. We have demonstrated that synthetic BPPs show remarkable functional differences, despite their high amino acid sequence similarities. Recently, we demonstrated that BPP-10c, after i.p. administration, was found in its intact form and in the form of a unique metabolite (des-Pro(10) BPP-10c) in mouse urine. Given this finding, we selected a number of BPPs with different structure-activities - BPP-5a (BPP-7a (BPP-9a (BPP-12b (BPP metabolites in mouse urine by MALDI-TOF mass spectrometry. Biotransformation results indicated the following: BPP-7a showed a higher resistance to proteolytic cleavage; BPP-5a is metabolized in tripeptides (BPP-9a was identified in the intact form and in the form of two metabolites (BPP-12a proved to be very susceptible to hydrolysis by proteolytic enzymes. Thus, the results obtained support the hypothesis that diverse biological functions for each BPP could be mediated by different interactions with alternative targets, and not only by sACE inhibition.

  12. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

    DEFF Research Database (Denmark)

    Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas

    2000-01-01

    -infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer....... In addition, PPTs were significantly decreased (Peffect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle...

  13. Critically ill neonates displayed stable vital parameters and reduced metabolic acidosis during neonatal emergency airborne transport in Sweden.

    Science.gov (United States)

    Frid, Ingrid; Ågren, Johan; Kjellberg, Mattias; Normann, Erik; Sindelar, Richard

    2018-02-26

    This study evaluated the medical quality of acute airborne transports carried out by a neonatal emergency transport service in a Swedish healthcare region from 2012 to 2015. The transport charts and patient records of all infants transported to the regional centre were reviewed for transport indications and vital parameters and outcomes. We identified 187 acute airborne transports and the main indications for referral were therapeutic hypothermia after perinatal asphyxia, extremely preterm birth and respiratory failure. There were 37 deaths, but none of these occurred during transport and none of the deaths that occurred within 24 hours after transport were found to be related to the transport per se. No differences were found in vital parameters or ventilator settings before and after transport, except for an improvement in blood pH (7.22 ± 0.13 versus 7.27 ± 0.13, mean ± SD, p < 0.01), due to a decrease in base deficit (-8.0 ± 6.8 versus -5.4 ± 6.3 mmol, p < 0.001), while the partial pressure of carbon dioxide remained unchanged. During air transport, critically ill neonates displayed stable vital parameters and reduced metabolic acidosis. No transport-related mortality was found, but the high number of extremely preterm infants transported indicates the potential for improving in-utero transport. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  14. The use of radioisotopes and low abundance stable isotopes for the study of bioavailability and the metabolism of iron, zinc and copper

    International Nuclear Information System (INIS)

    Aggett, P.J.; Fairweather Tait, S.

    1994-01-01

    The use of whole body counting and imaging with ''area of interest'' counting to monitor the metabolism of zinc in healthy volunteers and patients with coeliac diseases and cirrhosis is described as are studies of interaction between iron and copper. Stable isotopes of iron, copper and zinc have been used to investigate the metabolism of these elements in young infants and have proved useful in assessing the validity of current estimated requirements particularly of iron. Stable isotopes have also been used to improve the classic metabolic balance approach to the study of the homeostasis of zinc in zinc deprived volunteers, and have progressed to studies using plasma kinetic curves of the systemic compartmentation of zinc

  15. Bradykinin stimulation of nitric oxide production is not sufficient for gamma-globin induction

    Directory of Open Access Journals (Sweden)

    Čokić Vladan P.

    2014-01-01

    Full Text Available Introduction. Hydroxycarbamide, used in therapy of hemoglobinopathies, enhances nitric oxide (NO production both in primary human umbilical vein endothelial cells (HUVECs and human bone marrow endothelial cell line (TrHBMEC. Moreover, NO increases γ-globin and fetal hemoglobin levels in human erythroid progenitors. Objective. In order to find out whether simple physiologic stimulation of NO production by components of hematopoietic microenvironment can increase γ-globin gene expression, the effects of NO-inducer bradykinin were examined in endothelial cells. Methods. The study was performed in co-cultures of human erythroid progenitors, TrHBMEC and HUVECs by ozone-based chemiluminescent determination of NO and real-time quantitative RT-PCR. Results. In accordance with previous reports, the endogenous factor bradykinin increased endothelial cell production of NO in a dose- and time-dependent manner (0.1-0.6 μM up to 30 minutes. This induction of NO in HUVECs and TrHBMEC by bradykinin was blocked by competitive inhibitors of NO synthase (NOS, demonstrating NOS-dependence. It has been shown that bradykinin significantly reduced endothelial NOS (eNOS mRNA level and eNOS/Я-actin ratio in HUVEC (by twofold. In addition, bradykinin failed to increase γ-globin mRNA expression in erythroid progenitors only, as well as in co-culture studies of erythroid progenitors with TrHBMEC and HUVEC after 24 hours of treatment. Furthermore, bradykinin did not induce γ/β globin ratio in erythroid progenitors in co-cultures with HUVEC. Conclusion. Bradykinin mediated eNOS activation leads to short time and low NO production in endothelial cells, insufficient to induce γ-globin gene expression. These results emphasized the significance of elevated and extended NO production in augmentation of γ-globin gene expression. [Projekat Ministarstva nauke Republike Srbije, br. 175053

  16. Bowman-Birk Protease Inhibitor from Vigna unguiculata Seeds Enhances the Action of Bradykinin-Related Peptides

    Directory of Open Access Journals (Sweden)

    Alice da Cunha M. Álvares

    2014-10-01

    Full Text Available The hydrolysis of bradykinin (Bk by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin inhibitor (BTCI and also under the effect of trypsin and chymotrypsin were evaluated. Two synthetic Bk-related peptides, Bk1 and Bk2, were used to investigate the importance of additional C-terminal amino acid residues on serine protease activity. BTCI forms complexes with Bk and analogues at pH 5.0, 7.4 and 9.0, presenting binding constants ranging from 103 to 104 M−1. Formation of BTCI-Bk complexes is probably driven by hydrophobic forces, coupled with slight conformational changes in BTCI. In vitro assays using guinea pig (Cavia porcellus ileum showed that Bk retains the ability to induce smooth muscle contraction in the presence of BTCI. Moreover, no alteration in the inhibitory activity of BTCI in complex with Bk and analogous was observed. When the BTCI and BTCI-Bk complexes were tested in vivo, a decrease of vascular resistance and consequent hypotension and potentiating renal and aortic vasodilatation induced by Bk and Bk2 infusions was observed. These results indicate that BTCI-Bk complexes may be a reliable strategy to act as a carrier and protective approach for Bk-related peptides against plasma serine proteases cleavage, leading to an increase in their half-life. These findings also indicate that BTCI could remain stable in some tissues to inhibit chymotrypsin or trypsin-like enzymes that cleave and inactivate bradykinin in situ.

  17. Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS.

    Science.gov (United States)

    Krieg, Thomas; Qin, Qining; Philipp, Sebastian; Alexeyev, Mikhail F; Cohen, Michael V; Downey, James M

    2004-12-01

    In the rabbit heart, bradykinin and ACh trigger preconditioning by a mechanism involving ATP-sensitive potassium channel-dependent production of reactive oxygen species (ROS). Recent evidence indicates that the pathway by which bradykinin causes ROS generation includes nitric oxide synthase (NOS) and protein kinase G (PKG). On the other hand, Akt was shown to be essential for ACh to generate ROS. This study determines whether these two G-coupled receptor agonists indeed have similar signaling targets, i.e., whether Akt is involved in bradykinin's pathway and whether NOS is involved in ACh's pathway. Isolated adult rabbit cardiomyocytes were incubated for 15 min in reduced MitoTracker red, which becomes fluorescent only after exposure to ROS. Bradykinin (400 nM) and ACh (250 microM) caused a 51.4 +/- 14.8% and 39.8 +/- 11.7% increase, respectively, in ROS production (P hydrochloride (L-NIO, 5 microM). L-NIO also blocked the anti-infarct effect of ACh (550 microM) in isolated rabbit hearts exposed to 30 min of regional ischemia. We conclude that both bradykinin and ACh trigger ROS generation by sequentially activating Akt and NOS.

  18. Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2

    International Nuclear Information System (INIS)

    Burch, R.M.; Axelrod, J.

    1987-01-01

    In Swiss 3T3 fibroblasts bradykinin stimulated inositol phosphate (InsP) formation and prostaglandin E 2 (PGE 2 ) synthesis. The EC 50 values for stimulation of PGE 2 synthesis and InsP formation by bradykinin were similar, 200 pM and 275 pM, respectively. Guanosine-5'-[γ-thio]triphosphate stimulated PGE 2 synthesis and InsP formation, and guanosine-5'-[β-thio]diphosphate inhibited both PGE 2 synthesis and InsP formation stimulated by bradykinin. Neither bradykinin-stimulated PGE 2 synthesis nor InsP formation was sensitive to pertussis toxin. Phorbol ester, dexamethasone, and cycloheximide distinguished between bradykinin-stimulated PGE 2 synthesis and InsP formation. Phorbol 12-myristate 13-acetate enhanced bradykinin-stimulated PGE 2 synthesis but inhibited bradykinin-stimulated InsP formation. Pretreatment of cells with dexamethasone for 24 hr inhibited bradykinin-stimulated PGE 2 synthesis but was without effect on bradykinin-stimulated InsP formation. Cycloheximide inhibited on bradykinin-stimulated InsP formation. When bradykinin was added to cells prelabeled with [ 3 H] choline, the phospholipase A 2 products lysophosphatidylcholine and glycerophosphocholine were generated. The data suggest that bradykinin receptors are coupled by GTP-binding proteins to both phospholipase C and phospholipase A 2 and that phospholipase A 2 is the enzyme that catalyzes release of arachidonate for prostaglandin synthesis

  19. DMPD: Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17669557 Multifunctional effects of bradykinin on glial cells in relation to potent... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells i...n relation to potentialanti-inflammatory effects. PubmedID 17669557 Title Multifunction

  20. Angiotensin I-converting enzyme inhibitors potentiate bradykinin's inotropic effects independently of blocking its inactivation.

    Science.gov (United States)

    Minshall, R D; Erdös, E G; Vogel, S M

    1997-08-04

    The positive inotropic effects of bradykinin (BK) and 2 analogs resistant to angiotensin I-converting enzyme (ACE) were potentiated on isolated guinea pig atrial preparations by enalaprilat. The stable BK analogs, dextran-BK and [Hyp3-Tyr(Me)8]-BK, were as active as BK. Pretreatment for 5 min with enalaprilat augmented the maximal positive inotropic effect of [Hyp3-Tyr(Me)8]-BK 2.8-fold, from 19% to 53% and that of BK from 28% to 42% over baseline; inotropic responses to dextran-BK (1 microM) were similarly increased. The activity of atrial ACE, a zinc-requiring enzyme, was completely inhibited by 8-hydroxyquinoline-5-sulfonic acid (QSA, 10 mM), which raised the maximal inotropic effect of BK to 39% above baseline. This value rose to 67% when in addition to QSA, 1 microM enalaprilat was added; enalaprilat thus, potentiated the effects of BK independently of enzyme inhibition. The positive inotropic effects to BK and its analogs decline with time in the presence of these agonists. After 10 min of exposure, the response to 1 microM [Hyp3-Tyr(Me)8]-BK decreased to about half, and after 20 min, to 0. Enalaprilat, when present in the tissue bath, prevented the decline in inotropy; even after tachyphylaxis occurred, it reversed this decrease in activity when added. The effects of 1 microM [Hyp3-Tyr(Me)8]-BK, in the absence or presence of enalaprilat, were abolished by the BK B2 receptor antagonist icatibant (0.75 microM). The results indicate that ACE inhibitors, by potentiating the BK effects and blocking BK B2-receptor desensitization, may contribute to the beneficial cardiac effects of BK independently of blocking its inactivation.

  1. The research of radioimmunoassay using double abs for bradykinin

    International Nuclear Information System (INIS)

    Cheng Jinxuan; Wang Li; Duan Jinhong; Han Fengyun; Liu Jinsheng; Wang Zhengang; Ren Minfeng

    1996-01-01

    Bradykinin (BK) is a potent vasodilative substance, and plays great physiological and pathological roles in animals and human beings. To measure the quantity of BK, the radioimmunoassay (RIA) has been devised, but the traditional RIA method has certain defects, such as presence of numerous interfering factors and errors and time consuming. Now, we produce anti-BK serum in rabbits by using BK-ovalbumin conjugate as an immunogen, and the 125 I labeled Tyr 8 -BK by using a modified chloramine-T method. High specific activity has been obtained after purification with DEAE-Sephadex A-25 column chromatography. We use the donkey anti-rabbit Ab and PEG 6000 to separate the bound from the free 125 I-tyr 8 -BK. The limitation range of standard curve is from 25 to 1600 pg, NSB is 3.1%, affinity constant (K) is 0.8 x 10 10 L/mol, and there is no significant interference with other biological BK analogues. The blood samples are treated by adding Polybrene (inhibitor) and PEG 6000 to deposit the big serum proteins in order to reduce the disturbing substances. This method has been shown to be a sensitive, specific, reliable, simple and convenient measure of the serum BK level. By this method, the serum BK quantities in men, women and rats are respectively 1584 +- 347 pg/ml, 1642 +- 302 pg/ml and 1805 +- 225 pg/ml, and recycling rate is 95%, the inter-group CV is 5.0% and outer-group CV = 9.2%

  2. Bradykinin-induced lung inflammation and bronchoconstriction: role in parainfluenze-3 virus-induced inflammation and airway hyperreactivity.

    Science.gov (United States)

    Broadley, Kenneth J; Blair, Alan E; Kidd, Emma J; Bugert, Joachim J; Ford, William R

    2010-12-01

    Inhaled bradykinin causes bronchoconstriction in asthmatic subjects but not nonasthmatics. To date, animal studies with inhaled bradykinin have been performed only in anesthetized guinea pigs and rats, where it causes bronchoconstriction through sensory nerve pathways. In the present study, airway function was recorded in conscious guinea pigs by whole-body plethysmography. Inhaled bradykinin (1 mM, 20 s) caused bronchoconstriction and influx of inflammatory cells to the lungs, but only when the enzymatic breakdown of bradykinin by angiotensin-converting enzyme and neutral endopeptidase was inhibited by captopril (1 mg/kg i.p.) and phosphoramidon (10 mM, 20-min inhalation), respectively. The bronchoconstriction and cell influx were antagonized by the B(2) kinin receptor antagonist 4-(S)-amino-5-(4-{4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl}piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132) when given by inhalation (1 and 10 μM, 20 min) and are therefore mediated via B(2) kinin receptors. However, neither intraperitioneal MEN16132 nor the peptide B(2) antagonist icatibant, by inhalation, antagonized these bradykinin responses. Sensitization of guinea pigs with ovalbumin was not sufficient to induce airway hyperreactivity (AHR) to the bronchoconstriction by inhaled bradykinin. However, ovalbumin challenge of sensitized guinea pigs caused AHR to bradykinin and histamine. Infection of guinea pigs by nasal instillation of parainfluenza-3 virus produced AHR to inhaled histamine and lung influx of inflammatory cells. These responses were attenuated by the bradykinin B(2) receptor antagonist MEN16132 and H-(4-chloro)DPhe-2'(1-naphthylalanine)-(3-aminopropyl)guanidine (VA999024), an inhibitor of tissue kallikrein, the enzyme responsible for lung synthesis of bradykinin. These results suggest that bradykinin is involved in virus-induced inflammatory cell influx and AHR.

  3. Ketamine alleviates bradykinin-induced disruption of the mouse cerebrovascular endothelial cell-constructed tight junction barrier via a calcium-mediated redistribution of occludin polymerization

    International Nuclear Information System (INIS)

    Chen, Jui-Tai; Lin, Yi-Ling; Chen, Ta-Liang; Tai, Yu-Ting; Chen, Cheng-Yu; Chen, Ruei-Ming

    2016-01-01

    Highlights: • Ketamine could suppress bradykinin-induced intracellular calcium mobilization. • Ketamine induced B1R protein and mRNA expressions but did not change B2R protein levels. • Ketamine attenuated bradykinin-induced redistribution of occludin tight junctions. • Ketamine prevented bradykinin-induced breakage of the MCEC-constructed tight junction barrier. - Abstract: Following brain injury, a sequence of mechanisms leads to disruption of the blood-brain barrier (BBB) and subsequent cerebral edema, which is thought to begin with activation of bradykinin. Our previous studies showed that ketamine, a widely used intravenous anesthetic agent, can suppress bradykinin-induced cell dysfunction. This study further aimed to evaluate the protective effects of ketamine against bradykinin-induced disruption of the mouse cerebrovascular endothelial cell (MCEC)-constructed tight junction barrier and the possible mechanisms. Exposure of MCECs to bradykinin increased intracellular calcium (Ca 2+ ) concentrations in a time-dependent manner. However, pretreatment of MCECs with ketamine time- and concentration-dependently lowered the bradykinin-induced calcium influx. As to the mechanisms, although exposure of MCECs to ketamine induced bradykinin R1 receptor protein and mRNA expression, this anesthetic did not change levels of the bradykinin R2 receptor, a major receptor that responds to bradykinin stimulation. Bradykinin increased amounts of soluble occludin in MCECs, but pretreatment with ketamine alleviated this disturbance in occludin polymerization. Consequently, exposure to bradykinin decreased the transendothelial electronic resistance in the MCEC-constructed tight junction barrier. However, pretreatment with ketamine attenuated the bradykinin-induced disruption of the tight junction barrier. Taken together, this study shows that ketamine at a therapeutic concentration can protect against bradykinin-induced breakage of the BBB via suppressing calcium

  4. Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Kevin M Wheelock

    Full Text Available To examine the association of bradykinin and related peptides with the development of diabetic nephropathy lesions in 243 participants with type 1 diabetes (T1D from the Renin-Angiotensin System Study who, at baseline, were normoalbuminuric, normotensive and had normal or increased glomerular filtration rate (GFR.Plasma concentrations of bradykinin and related peptides were measured at baseline by quantitative mass spectrometry. All participants were randomly assigned at baseline to receive placebo, enalapril or losartan during the 5 years between kidney biopsies. Kidney morphometric data were available from kidney biopsies at baseline and after 5 years. Relationships of peptides with changes in morphometric variables were assessed using multiple linear regression after adjustment for age, sex, diabetes duration, HbA1c, mean arterial pressure, treatment assignment and, for longitudinal analyses, baseline structure.Baseline median albumin excretion rate of study participants was 5.0 μg/min, and mean GFR was 128 mL/min/1.73 m2. After multivariable adjustment, higher plasma concentration of bradykinin (1-8 was associated with greater glomerular volume (partial r = 0.191, P = 0.019 and total filtration surface area (partial r = 0.211, P = 0.010, and higher bradykinin (1-7 and hyp3-bradykinin (1-7 were associated with lower cortical interstitial fractional volume (partial r = -0.189, P = 0.011; partial r = -0.164, P = 0.027 respectively. In longitudinal analyses, higher bradykinin was associated with preservation of surface density of the peripheral glomerular basement membrane (partial r = 0.162, P = 0.013, and for participants randomized to losartan, higher hyp3-bradykinin (1-8 was associated with more limited increase in cortical interstitial fractional volume (partial r = -0.291, P = 0.033.Higher plasma bradykinin and related peptide concentrations measured before clinical onset of diabetic nephropathy in persons with T1D were associated with

  5. Investigation of the microbial metabolism of carbon dioxide and hydrogen in the kangaroo foregut by stable isotope probing

    OpenAIRE

    Godwin, Scott; Kang, Alicia; Gulino, Lisa-Maree; Manefield, Mike; Gutierrez-Zamora, Maria-Luisa; Kienzle, Marco; Ouwerkerk, Diane; Dawson, Kerri; Klieve, Athol V

    2014-01-01

    Kangaroos ferment forage material in an enlarged forestomach analogous to the rumen, but in contrast to ruminants, they produce little or no methane. The objective of this study was to identify the dominant organisms and pathways involved in hydrogenotrophy in the kangaroo forestomach, with the broader aim of understanding how these processes are able to predominate over methanogenesis. Stable isotope analysis of fermentation end products and RNA stable isotope probing (RNA-SIP) were used to ...

  6. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  7. New acylated bradykinin analogues: effect on rat blood pressure and rat uterus

    Czech Academy of Sciences Publication Activity Database

    Dawidowska, O.; Prahl, A.; Wierzba, T.; Nowakowski, L.; Kowalczyk, W.; Slaninová, Jiřina; Lammek, B.

    2005-01-01

    Roč. 11, - (2005), s. 436-439 ISSN 1075-2617 Grant - others:SCSR(PL) 0160/T09/2004/26; SCSR(PL) DS8000-5-0023-4 Institutional research plan: CEZ:AV0Z4055905 Keywords : bradykinin * B2 antagonists * rat blood pressure assay Subject RIV: CE - Biochemistry Impact factor: 1.803, year: 2005

  8. New bradykinin analogues acylated on the N-terminus: effect on rat uterus and blood pressure

    Czech Academy of Sciences Publication Activity Database

    Labudda, O.; Wierzba, T.; Sobolewski, D.; Sleszyňska, M.; Gawiňski, L.; Plačková, Malgorzata; Slaninová, Jiřina; Prahl, A.

    2007-01-01

    Roč. 54, č. 1 (2007), s. 193-198 ISSN 0001-527X Grant - others:State Comittee for Scientific Research(PL) PB1108/T09/2005/28 Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin * antagonists * acylation Subject RIV: CE - Biochemistry Impact factor: 1.261, year: 2007 www.actabp.pl

  9. Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide

    NARCIS (Netherlands)

    Ricciardolo, F. L.; Rado, V.; Fabbri, L. M.; Sterk, P. J.; Di Maria, G. U.; Geppetti, P.

    1999-01-01

    Gastroesophageal acid reflux into the airways can trigger asthma attacks. Indeed, citric acid inhalation causes bronchoconstriction in guinea pigs, but the mechanism of this effect has not been fully clarified. We investigated the role of tachykinins, bradykinin, and nitric oxide (NO) on the citric

  10. Solute concentration affects bradykinin-mediated increases in renal prostaglandin E2

    International Nuclear Information System (INIS)

    Zenser, T.V.; Davis, E.S.; Rapp, N.S.; Davis, B.B.

    1981-01-01

    The effects of solute concentration on the bradykinin-mediated increase in inner medullary slice prostaglandin E2 (PGE2) synthesis were investigated. PG content was determined by specific RIA. Bradykinin stimulation was prevented by the addition of the following solutes to Krebs buffer: 1.0 M urea, 0.5 or 1.0 M NaCl, 0.5 or 1.0 M mannitol, 1.0 M urea plus 0.5 M NaCl, or 1.0 M mannitol plus 0.5 M NaCl. By contrast, basal PGE2 synthesis was increased by 1.0 M mannitol or by 1.0 M mannitol plus 0.5 M NaCl, but decreased by 1.0 M urea. Urea elicited a concentration-dependent, reversible inhibition of bradykinin stimulation, with 0.01 M urea being the lowest effective concentration. By contrast, basal PGE2 synthesis was only reduced at a urea concentration greater than 0.6 M. Arachidonic acid-mediated increases in both PGE2 and PGF2 alpha synthesis were not prevented by 1.0 M urea. The latter suggests that neither PG endoperoxide synthetase nor PG endoperoxide E isomerase are inhibited by urea. The data indicate that different hypertonic solutions have different effects on basal PG production, but all inhibit bradykinin stimulation

  11. Pain, wheal and flare in human forearm skin induced by bradykinin and 5-hydroxytryptamine

    DEFF Research Database (Denmark)

    Jensen, Kai; Tuxen, C; Pedersen-Bjergaard, U

    1990-01-01

    Pain was induced in 19 healthy individuals by double-blind injections into the forearm skin of 0.05 ml of physiological saline with or without active substances added. Bradykinin (0.5 nmol), 5-hydroxytryptamine (0.5 nmol) and a mixture of the two substances in half dosage (0.25 nmol + 0.25 nmol...

  12. Novel analogues of bradykinin conformationally restricted in the C-terminal part of the molecule

    Czech Academy of Sciences Publication Activity Database

    Sleszynska, M.; Wierzba, T. H.; Malinowski, K.; Borovičková, Lenka; Maluch, I.; Sobolewski, D.; Lammek, B.; Slaninová, Jiřina; Prahl, A.

    2011-01-01

    Roč. 17, č. 5 (2011), s. 366-372 ISSN 1075-2617 Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin analogues * B2 receptor antagonists * sterically restricted residue * in vivo rat blood pressure test * in vitro rat uterus Subject RIV: CC - Organic Chemistry Impact factor: 1.799, year: 2011

  13. Synthesis of bradykinin labelled with tritium on the phenylalanine residue in position 5

    International Nuclear Information System (INIS)

    Seproedi, J.; Teplan, I.; Medzihradszky, K.

    1976-01-01

    The polypeptide hormone bradykinine, labelled with tritium in the phenylalanine chain in position 5, has been prepared. The preparation method is described; the tritium atom is incorporated in the last step of the synthesis. The hormone can therefore be labelled immediately before use, which avoids autoradiolysis during storage

  14. Bradykinin or acetylcholine as vasodilators to test endothelial venous function in healthy subjects

    Directory of Open Access Journals (Sweden)

    Eneida R. Rabelo

    2008-01-01

    Full Text Available INTRODUCTION: The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES: The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS: Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique. We studied 23 healthy volunteers; 31% were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m². The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13, as well as the mean responses for each dose of both drugs (r = 0.96. The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION: There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation.

  15. Cyclooxygenase inhibitors attenuate bradykinin-induced vasoconstriction in septic isolated rat lungs

    NARCIS (Netherlands)

    Fischer, L. G.; Hollmann, M. W.; Horstman, D. J.; Rich, G. F.

    2000-01-01

    Cyclooxygenase (COX) products play an important role in modulating sepsis and subsequent endothelial injury. We hypothesized that COX inhibitors may attenuate endothelial dysfunction during sepsis, as measured by receptor-mediated bradykinin (BK)-induced vasoconstriction and/or receptor-independent

  16. Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation.

    Science.gov (United States)

    Griesbacher, T.; Lembeck, F.; Saria, A.

    1989-01-01

    1. Six competitive bradykinin (Bk) antagonists were tested for their agonistic properties on the rat uterus. Five of these peptides showed agonistic effects only at concentrations at least two orders of magnitude higher than those of bradykinin. 2. The antagonistic potency of Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk (B4310) in the rat uterus (pA2 = 7.24) and in the rat duodenum (pA2 = 7.31) was very similar to that determined in an earlier study for the antagonism of the bradykinin-induced stimulation of the trigeminal nerve in the rabbit iris sphincter muscle preparation (pA2 = 7.59). 3. The fall in mean arterial blood pressure induced by i.a. injections of bradykinin was greatly reduced during an i.a. infusion of B4310, but not 10 min thereafter, which indicates a rapid inactivation of B4310 in vivo. Bacitracin possibly interferes with the enzymatic cleavage of B4310 but seems to have no effect on the degradation of bradykinin. 4. An i.a. infusion of captopril greatly enhanced the potency of bradykinin in inducing a fall in arterial blood pressure, confirming the important role of angiotensin converting enzyme in the cleavage of bradykinin. However, the design of this experiment did not allow conclusions about the effect of captopril on the degradation of B4310. 5. B4310 incubated with rat lung tissue disappeared from the incubation medium within a few minutes, i.e. as fast as bradykinin, which explains its short duration of action in vivo. Captopril partially inhibited the cleavage of both bradykinin and B4310.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2655805

  17. Stable Overexpression of the Constitutive Androstane Receptor Reduces the Requirement for Culture with Dimethyl Sulfoxide for High Drug Metabolism in HepaRG Cells.

    Science.gov (United States)

    van der Mark, Vincent A; Rudi de Waart, D; Shevchenko, Valery; Elferink, Ronald P J Oude; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

    2017-01-01

    Dimethylsulfoxide (DMSO) induces cellular differentiation and expression of drug metabolic enzymes in the human liver cell line HepaRG; however, DMSO also induces cell death and interferes with cellular activities. The aim of this study was to examine whether overexpression of the constitutive androstane receptor (CAR, NR1I3), the nuclear receptor controlling various drug metabolism genes, would sufficiently promote differentiation and drug metabolism in HepaRG cells, optionally without using DMSO. By stable lentiviral overexpression of CAR, HepaRG cultures were less affected by DMSO in total protein content and obtained increased resistance to acetaminophen- and amiodarone-induced cell death. Transcript levels of CAR target genes were significantly increased in HepaRG-CAR cultures without DMSO, resulting in increased activities of cytochrome P450 (P450) enzymes and bilirubin conjugation to levels equal or surpassing those of HepaRG cells cultured with DMSO. Unexpectedly, CAR overexpression also increased the activities of non-CAR target P450s, as well as albumin production. In combination with DMSO treatment, CAR overexpression further increased transcript levels and activities of CAR targets. Induction of CYP1A2 and CYP2B6 remained unchanged, whereas CYP3A4 was reduced. Moreover, the metabolism of low-clearance compounds warfarin and prednisolone was increased. In conclusion, CAR overexpression creates a more physiologically relevant environment for studies on hepatic (drug) metabolism and differentiation in HepaRG cells without the utilization of DMSO. DMSO still may be applied to accomplish higher drug metabolism, required for sensitive assays, such as low-clearance studies and identification of (rare) metabolites, whereas reduced total protein content after DMSO culture is diminished by CAR overexpression. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  18. iMS2Flux – a high–throughput processing tool for stable isotope labeled mass spectrometric data used for metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    Poskar C Hart

    2012-11-01

    Full Text Available Abstract Background Metabolic flux analysis has become an established method in systems biology and functional genomics. The most common approach for determining intracellular metabolic fluxes is to utilize mass spectrometry in combination with stable isotope labeling experiments. However, before the mass spectrometric data can be used it has to be corrected for biases caused by naturally occurring stable isotopes, by the analytical technique(s employed, or by the biological sample itself. Finally the MS data and the labeling information it contains have to be assembled into a data format usable by flux analysis software (of which several dedicated packages exist. Currently the processing of mass spectrometric data is time-consuming and error-prone requiring peak by peak cut-and-paste analysis and manual curation. In order to facilitate high-throughput metabolic flux analysis, the automation of multiple steps in the analytical workflow is necessary. Results Here we describe iMS2Flux, software developed to automate, standardize and connect the data flow between mass spectrometric measurements and flux analysis programs. This tool streamlines the transfer of data from extraction via correction tools to 13C-Flux software by processing MS data from stable isotope labeling experiments. It allows the correction of large and heterogeneous MS datasets for the presence of naturally occurring stable isotopes, initial biomass and several mass spectrometry effects. Before and after data correction, several checks can be performed to ensure accurate data. The corrected data may be returned in a variety of formats including those used by metabolic flux analysis software such as 13CFLUX, OpenFLUX and 13CFLUX2. Conclusion iMS2Flux is a versatile, easy to use tool for the automated processing of mass spectrometric data containing isotope labeling information. It represents the core framework for a standardized workflow and data processing. Due to its flexibility

  19. Bradykinin and vasopressin activate phospholipase D in rat Leydig cells by a protein kinase C-dependent mechanism

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Hansen, Harald S.

    1993-01-01

    of PMA and vasopressin (AVP), PMA and bradykinin, or AVP and bradykinin produced no additive phosphatidylethanol or choline response, suggesting that AVP, bradykinin and PMA stimulated phospholipase D catalysed phosphatidylcholine hydrolysis by a similar protein kinase C-dependent mechanism. Furthermore......, LH (10 ng/ml), insulin (500 nmol/l), GH (100 ng/ml), interleukin-1ß (5 U/ml) and platelet-activating factor (200 nmol/l) were found not to activate phospholipase D, whereas the Ca ionophore A23187 (10 µmol/l) stimulated phosphatidylethanol formation, suggesting that Ca might be a regulator...

  20. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Directory of Open Access Journals (Sweden)

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  1. Identification of metabolically active bacteria in the gut of the generalist Spodoptera littoralis via DNA stable isotope probing using 13C-glucose.

    Science.gov (United States)

    Shao, Yongqi; Arias-Cordero, Erika M; Boland, Wilhelm

    2013-11-13

    Guts of most insects are inhabited by complex communities of symbiotic nonpathogenic bacteria. Within such microbial communities it is possible to identify commensal or mutualistic bacteria species. The latter ones, have been observed to serve multiple functions to the insect, i.e. helping in insect reproduction(1), boosting the immune response(2), pheromone production(3), as well as nutrition, including the synthesis of essential amino acids(4,) among others.     Due to the importance of these associations, many efforts have been made to characterize the communities down to the individual members. However, most of these efforts were either based on cultivation methods or relied on the generation of 16S rRNA gene fragments which were sequenced for final identification. Unfortunately, these approaches only identified the bacterial species present in the gut and provided no information on the metabolic activity of the microorganisms. To characterize the metabolically active bacterial species in the gut of an insect, we used stable isotope probing (SIP) in vivo employing (13)C-glucose as a universal substrate. This is a promising culture-free technique that allows the linkage of microbial phylogenies to their particular metabolic activity. This is possible by tracking stable, isotope labeled atoms from substrates into microbial biomarkers, such as DNA and RNA(5). The incorporation of (13)C isotopes into DNA increases the density of the labeled DNA compared to the unlabeled ((12)C) one. In the end, the (13)C-labeled DNA or RNA is separated by density-gradient ultracentrifugation from the (12)C-unlabeled similar one(6). Subsequent molecular analysis of the separated nucleic acid isotopomers provides the connection between metabolic activity and identity of the species. Here, we present the protocol used to characterize the metabolically active bacteria in the gut of a generalist insect (our model system), Spodoptera littoralis (Lepidoptera, Noctuidae). The

  2. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  3. Metabolic routing of dietary nutrients in birds: effects of diet quality and macronutrient composition revealed using stable isotopes.

    Science.gov (United States)

    Podlesak, David W; McWilliams, Scott R

    2006-01-01

    During fall migration many songbirds switch from consuming primarily insects to consuming mostly fruit. Fruits with more carbohydrates and less protein may be sufficient to rebuild expended fat stores, but such fruits may be inadequate to replace catabolized protein. We manipulated the concentrations and isotopic signatures of macronutrients in diets fed to birds to study the effects of diet quality on metabolic routing of dietary nutrients. We estimated that approximately 45% and 75%, respectively, of the carbon in proteinaceous tissue of birds switched to high- or low-protein diets came from nonprotein dietary sources. In contrast, we estimated that approximately 100% and 20%-80%, respectively, of the nitrogen in proteinaceous tissues of birds switched to high- or low-protein diets was attributable to dietary protein. Thus, the routing and assimilation of dietary carbon and nitrogen differed depending on diet composition. As a result, delta (15)N of tissues collected from wild animals that consume high-quality diets may reliably indicate the dietary protein source, whereas delta (13)C of these same tissues is likely the product of metabolic routing of carbon from several macronutrients. These results have implications for how isotopic discrimination is best estimated and how we can study macronutrient routing in wild animals.

  4. Noninvasive imaging of intracellular lipid metabolism in macrophages by Raman microscopy in combination with stable isotopic labeling.

    Science.gov (United States)

    Matthäus, Christian; Krafft, Christoph; Dietzek, Benjamin; Brehm, Bernhard R; Lorkowski, Stefan; Popp, Jürgen

    2012-10-16

    Monocyte-derived macrophages play a key role in atherogenesis because their transformation into foam cells is responsible for deposition of lipids in plaques within arterial walls. The appearance of cytosolic lipid droplets is a hallmark of macrophage foam cell formation, and the molecular basics involved in this process are not well understood. Of particular interest is the intracellular fate of different individual lipid species, such as fatty acids or cholesterol. Here, we utilize Raman microscopy to image the metabolism of such lipids and to trace their subsequent storage patterns. The combination of microscopic information with Raman spectroscopy provides a powerful molecular imaging method, which allows visualization at the diffraction limit of the employed laser light and biochemical characterization through associated spectral information. In order to distinguish the molecules of interest from other naturally occurring lipids spectroscopically, deuterium labels were introduced. Intracellular distribution and metabolic changes were observed for serum albumin-complexed palmitic and oleic acid and cholesterol and quantitatively evaluated by monitoring the increase in CD scattering intensities at 0.5, 1, 3, 6, 24, 30, and 36 h. This approach may also allow for investigating the cellular trafficking of other molecules, such as nutrients, metabolites, and drugs.

  5. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans.

    Science.gov (United States)

    Humphrey, M J; Jevons, S; Tarbit, M H

    1985-11-01

    The pharmacokinetic profile of UK-49,858 (fluconazole), a novel triazole antifungal agent which is being developed for oral and intravenous use, was determined in mice, rats, dogs, and humans. Comparative data following oral and intravenous administration showed that bioavailability was essentially complete in all four species. Peak concentrations in plasma of drug normalized to a 1-mg/kg dose level following oral administration, were relatively high: 0.7, 0.6, 1.1, and 1.4 micrograms/ml in mice, rats, dogs, and humans, respectively. The volumes of distribution ranged between 1.1 liter/kg in mice and 0.7 liter/kg in humans, which are approximate to the values for total body water. Whole body autoradiography studies in mice following intravenous administration of [14C]UK-49,858 demonstrated that the drug was evenly distributed throughout the tissues, including the central nervous system and the gastrointestinal tract. Plasma protein binding was low (11 to 12%) in all species. Marked species differences were observed in elimination half-lives, with mean values of 4.8, 4.0, 14, and 22 h in mice, rats, dogs, and humans, respectively. The major route of elimination of the drug was renal clearance, with about 70% of the dose being excreted unchanged in the urine in each species. Studies with [14C]UK-49,858 on metabolism and excretion (intravenous and oral) in mice and dogs showed that about 90% of the dose was recovered as unchanged drug in urine and feces, confirming the metabolic stability of the drug. This pharmacokinetic profile is markedly different from that of imidazole antifungal drugs and undoubtedly contributes to the excellent efficacy of UK-49,858 in vivo.

  6. Binding modes of dihydroquinoxalinones in a homology model of bradykinin receptor 1.

    Science.gov (United States)

    Ha, Sookhee N; Hey, Pat J; Ransom, Rick W; Harrell, C Meacham; Murphy, Kathryn L; Chang, Ray; Chen, Tsing-Bau; Su, Dai-Shi; Markowitz, M Kristine; Bock, Mark G; Freidinger, Roger M; Hess, Fred J

    2005-05-27

    We report the first homology model of human bradykinin receptor B1 generated from the crystal structure of bovine rhodopsin as a template. Using an automated docking procedure, two B1 receptor antagonists of the dihydroquinoxalinone structural class were docked into the receptor model. Site-directed mutagenesis data of the amino acid residues in TM1, TM3, TM6, and TM7 were incorporated to place the compounds in the binding site of the homology model of the human B1 bradykinin receptor. The best pose in agreement with the mutation data was selected for detailed study of the receptor-antagonist interaction. To test the model, the calculated antagonist-receptor binding energy was correlated with the experimentally measured binding affinity (K(i)) for nine dihydroquinoxalinone analogs. The model was used to gain insight into the molecular mechanism for receptor function and to optimize the dihydroquinoxalinone analogs.

  7. MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.

    Science.gov (United States)

    Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi

    2010-04-01

    Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

  8. Two new bradykinin-related peptides from the venom of the social wasp Protopolybia exigua (Saussure).

    Science.gov (United States)

    Mendes, Maria Anita; Palma, Mario Sergio

    2006-11-01

    Two bradykinin-related peptides (Protopolybiakinin-I and Protopolybiakinin-II) were isolated from the venom of the social wasp Protopolybia exigua by RP-HPLC, and sequenced by Edman degradation method. Peptide sequences of Protopolybiakinin-I and Protopolybiakinin-II were DKNKKPIRVGGRRPPGFTR-OH and DKNKKPIWMAGFPGFTPIR-OH, respectively. Synthetic peptides with identical sequences to the bradykinin-related peptides and their biological functions were characterized. Protopolybiakinin-I caused less potent constriction of the isolated rat ileum muscles than bradykinin (BK). In addition, it caused degranulation of mast cells which was seven times more potent than BK. This peptide causes algesic effects due to the direct activation of B(2)-receptors. Protopolybiakinin-II is not an agonist of rat ileum muscle and had no algesic effects. However, Protopolybiakinin-II was found to be 10 times more potent as a mast cell degranulator than BK. The amino acid sequence of Protopolybiakinin-I is the longest among the known wasp kinins.

  9. Identification of metabolically active methanogens in anaerobic digester by DNA Stable-Isotope Probing using 13C-acetate

    Directory of Open Access Journals (Sweden)

    V. Gowdaman

    2015-04-01

    Full Text Available Anaerobic digestion is gaining enormous attention due to the ability to covert organic wastes into biogas, an alternative sustainable energy. Methanogenic community plays a significant role in biogas production and also for proficient functioning of the anaerobic digester. Therefore, this study was carried out to investigate the methanogen diversity of a food waste anaerobic digester. After endogenous respiration, the digester samples were supplemented with isotopes of acetate to enrich methanogen population, and were analyzed using DNA-SIP (Stable-Isotope Probing. Following separation and fractionation of heavy (13C and light (12C DNA, PCR amplification was carried out using archaeal 16S rRNA gene followed by DGGE analysis. Sequencing of the prominent DGGE bands revealed the dominance of Methanocorpusculum labreanum species belonging to hydrogenotrophic Methanomicrobiales, which can produce methane in the presence of H2/CO2 and requires acetate for its growth. This is the first instance where Methanocorpusculum labreanum is being reported as a dominant species in an anaerobic digester operative on food waste.

  10. Metabolic flux analysis of the phenylpropanoid pathway in wound-healing potato tuber tissue using stable isotope-labeled tracer and LC-MS spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Fumio; Morino, Keiko; Miyashita, Masahiro; Miyagawa, Hisashi [Kyoto Univ. (Japan). Department of Agriculture

    2003-05-01

    The metabolic flux of two phenylpropanoid metabolites, N-p-coumaroyloctopamine (p-CO) and chlorogenic acid (CGA), in the wound-healing potato tuber tissue was quantitatively analyzed by a newly developed method based upon the tracer experiment using stable isotope-labeled compounds and LC-MS. Tuber disks were treated with aqueous solution of L-phenyl-d{sub 5}-alanine, and the change in the ratio of stable isotope-labeled compound to non-labeled (isotope abundance) was monitored for p-CO and CGA in the tissue extract by LC-MS. The time-dependent change in the isotope abundance of each metabolite was fitted to an equation that was derived from the formation and conversion kinetics of each compound. Good correlations were obtained between the observed and calculated isotope abundances for both p-CO and CGA. The rates of p-CO formation and conversion (i.e. fluxes) were 1.15 and 0.96 nmol (g FW){sup -1}h{sup -1}, respectively, and for CGA, the rates 4.63 and 0.42 nmol (g FW){sup -1}h{sup -1}, respectively. This analysis enabled a direct comparison of the biosynthetic activity between these two compounds. (author)

  11. Study on the metabolism of physiological amounts of Cr(III) intragastrical administration in normal rats using activable enriched stable isotope Cr-50 compound as a tracer

    International Nuclear Information System (INIS)

    Feng, W.Y.; Ding, W.J.; Qian, Q.F.; Chai, Z.F.

    1998-01-01

    In order to study the metabolism of physiological amounts of 51 Cr (10μg/100 g of body wt.) intragastrically administered in rats, the activable enriched stable isotope Cr-50 compound Cr 2 O 3 was used as a tracer. The absorption and distribution of 51 Cr(III) in rats with time were studied. Significant 51 Cr contents were found in all the organs and tissues of interest. The kidney, liver and bone contain higher amounts of 51 Cr than others. The fact that specific activities of 51 Cr are notably high in kidney, bone, spleen and pancreas and decrease gradually with time suggests that there are tighter binding of chromium in these organs. The excretion of 51 Cr at various time intervals was also studied. Almost totally intragastrically administered dose was excreted in the feces. The increased urinary excretion of 51 Cr with time indicates that the urine-chromium is the metabolic derivative of organism. In view of the tissues distribution and excretion, it can be concluded that no more than 1% of the dose was absorbed from the gastrointestinal tract. (author)

  12. Biphenyl-metabolizing bacteria in the rhizosphere of horseradish and bulk soil contaminated by polychlorinated biphenyls as revealed by stable isotope probing.

    Science.gov (United States)

    Uhlik, Ondrej; Jecna, Katerina; Mackova, Martina; Vlcek, Cestmir; Hroudova, Miluse; Demnerova, Katerina; Paces, Vaclav; Macek, Tomas

    2009-10-01

    DNA-based stable isotope probing in combination with terminal restriction fragment length polymorphism was used in order to identify members of the microbial community that metabolize biphenyl in the rhizosphere of horseradish (Armoracia rusticana) cultivated in soil contaminated with polychlorinated biphenyls (PCBs) compared to members of the microbial community in initial, uncultivated bulk soil. On the basis of early and recurrent detection of their 16S rRNA genes in clone libraries constructed from [(13)C]DNA, Hydrogenophaga spp. appeared to dominate biphenyl catabolism in the horseradish rhizosphere soil, whereas Paenibacillus spp. were the predominant biphenyl-utilizing bacteria in the initial bulk soil. Other bacteria found to derive carbon from biphenyl in this nutrient-amended microcosm-based study belonged mostly to the class Betaproteobacteria and were identified as Achromobacter spp., Variovorax spp., Methylovorus spp., or Methylophilus spp. Some bacteria that were unclassified at the genus level were also detected, and these bacteria may be members of undescribed genera. The deduced amino acid sequences of the biphenyl dioxygenase alpha subunits (BphA) from bacteria that incorporated [(13)C]into DNA in 3-day incubations of the soils with [(13)C]biphenyl are almost identical to that of Pseudomonas alcaligenes B-357. This suggests that the spectrum of the PCB congeners that can be degraded by these enzymes may be similar to that of strain B-357. These results demonstrate that altering the soil environment can result in the participation of different bacteria in the metabolism of biphenyl.

  13. Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

    Science.gov (United States)

    Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

    2017-02-01

    Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Biphenyl-Metabolizing Bacteria in the Rhizosphere of Horseradish and Bulk Soil Contaminated by Polychlorinated Biphenyls as Revealed by Stable Isotope Probing▿ †

    Science.gov (United States)

    Uhlik, Ondrej; Jecna, Katerina; Mackova, Martina; Vlcek, Cestmir; Hroudova, Miluse; Demnerova, Katerina; Paces, Vaclav; Macek, Tomas

    2009-01-01

    DNA-based stable isotope probing in combination with terminal restriction fragment length polymorphism was used in order to identify members of the microbial community that metabolize biphenyl in the rhizosphere of horseradish (Armoracia rusticana) cultivated in soil contaminated with polychlorinated biphenyls (PCBs) compared to members of the microbial community in initial, uncultivated bulk soil. On the basis of early and recurrent detection of their 16S rRNA genes in clone libraries constructed from [13C]DNA, Hydrogenophaga spp. appeared to dominate biphenyl catabolism in the horseradish rhizosphere soil, whereas Paenibacillus spp. were the predominant biphenyl-utilizing bacteria in the initial bulk soil. Other bacteria found to derive carbon from biphenyl in this nutrient-amended microcosm-based study belonged mostly to the class Betaproteobacteria and were identified as Achromobacter spp., Variovorax spp., Methylovorus spp., or Methylophilus spp. Some bacteria that were unclassified at the genus level were also detected, and these bacteria may be members of undescribed genera. The deduced amino acid sequences of the biphenyl dioxygenase α subunits (BphA) from bacteria that incorporated [13C]into DNA in 3-day incubations of the soils with [13C]biphenyl are almost identical to that of Pseudomonas alcaligenes B-357. This suggests that the spectrum of the PCB congeners that can be degraded by these enzymes may be similar to that of strain B-357. These results demonstrate that altering the soil environment can result in the participation of different bacteria in the metabolism of biphenyl. PMID:19700551

  15. Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ruolan Dong

    2015-11-01

    Full Text Available Background/Aims: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF. However, whether bradykinin can regulate TF expression remains to be investigated. Methods: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. Results: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-κB level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. Conclusion: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.

  16. Cardiovascular effects of intrathecally administered bradykinin in the rat: characterization of receptors with antagonists.

    OpenAIRE

    Lopes, P.; Regoli, D.; Couture, R.

    1993-01-01

    1. The effects of intrathecal (i.t.) pretreatment with selective B1 or B2 kinin receptor antagonists were studied on the cardiovascular response to i.t. injection of bradykinin (BK) in conscious freely moving rats. 2. BK (81 pmol) produced an increase in mean arterial pressure (MAP: 9-13 mmHg) and decrease in heart rate (HR: 20-30 beats min-1) that reached a maximum 2 min after injection. 3. The BK-induced cardiovascular responses were dose-dependently and reversibly reduced by four antagonis...

  17. Factor XII-independent activation of the bradykinin-forming cascade

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

    2013-01-01

    and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...

  18. A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

    Directory of Open Access Journals (Sweden)

    Carvalho K.M.

    1999-01-01

    Full Text Available A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11 and angiotensin-converting enzyme (EC 3.4.15.1, respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM and for atrial natriuretic peptide (Km = 5 µM suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.

  19. Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke

    2009-01-01

    PURPOSE: Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK...

  20. New bradykinin analogues acetylated on their N-terminus: Effect on rat blood pressure and rat uterus

    Czech Academy of Sciences Publication Activity Database

    Labudda-Dawidowska, O.; Sobolewski, D.; Sleszyňska, M.; Derdowska, I.; Slaninová, Jiřina; Wierzba, T.; Prahl, A.

    2006-01-01

    Roč. 12, Supplement (2006), s. 190 ISSN 1075-2617. [European Peptide Symposium /29./. 03.09.2006-08.09.2006, Gdansk] Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin * N-terminus * rat uterus Subject RIV: CC - Organic Chemistry

  1. Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a Variety of Acyl Substituents

    Czech Academy of Sciences Publication Activity Database

    Sleszynska, M.; Wierzba, T. H.; Malinowski, K.; Tůmová, Tereza; Lammek, B.; Slaninová, Jiřina; Prahl, A.

    2012-01-01

    Roč. 18, č. 2 (2012), s. 117-124 ISSN 1573-3149 Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin analogues * B-2 receptor antagonists * bulky acyl groups * in vivo rat blood pressure test * in vitro rat uterus test Subject RIV: CE - Biochemistry Impact factor: 1.280, year: 2012

  2. Direct protein-protein interaction between PLCγ1 and the bradykinin B2 receptor-Importance of growth conditions

    International Nuclear Information System (INIS)

    Duchene, Johan; Chauhan, Sharmila D.; Lopez, Frederic; Pecher, Christiane; Esteve, Jean-Pierre; Girolami, Jean-Pierre; Bascands, Jean-Loup; Schanstra, Joost P.

    2005-01-01

    Recently, we have described a novel protein-protein interaction between the G-protein coupled bradykinin B2 receptor and tyrosine phosphatase SHP-2 via an immunoreceptor tyrosine-based inhibition motif (ITIM) sequence located in the C-terminal part of the B2 receptor and the Src homology (SH2) domains of SHP-2. Here we show that phospholipase C (PLC)γ1, another SH2 domain containing protein, can also interact with this ITIM sequence. Using surface plasmon resonance analysis, we observed that PLCγ1 interacted with a peptide containing the phosphorylated form of the bradykinin B2 receptor ITIM sequence. In CHO cells expressing the wild-type B2 receptor, bradykinin-induced transient recruitment and activation of PLCγ1. Interestingly, this interaction was only observed in quiescent and not in proliferating cells. Mutation of the key ITIM residue abolished this interaction with and activation of PLCγ1. Finally we also identified bradykinin-induced PLCγ1 recruitment and activation in primary culture renal mesangial cells

  3. Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB

    NARCIS (Netherlands)

    Ricciardolo, F. L. M.; Petecchia, L.; Sorbello, V.; Di Stefano, A.; Usai, C.; Massaglia, G. M.; Gnemmi, I.; Mognetti, B.; Hiemstra, P. S.; Sterk, P. J.; Sabatini, F.

    2016-01-01

    Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor-kappa B (NF-kB) is potentially involved in BK B2 receptor (B2R) regulation. In this observational cross-sectional study, B2R and NF-kB expression was evaluated in bronchial biopsies from mild asthmatics (after

  4. Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

    Science.gov (United States)

    Abdulla, M H; Duff, M; Swanton, H; Johns, E J

    2016-11-01

    This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  5. Application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report of an IAEA consultants' meeting held in Vienna, Austria, 14-16 December 1992

    International Nuclear Information System (INIS)

    1993-01-01

    A Consultants' Meeting convened by the IAEA in December 1992, made recommendations on the organization of a Co-ordinated Research Programme (CRP) using stable isotopic techniques for international comparative studies of amino acid, protein, and energy metabolism in chronically undernourished people. The CRP will use recent developments in stable isotope tracer techniques ( 13 C and 15 N) to assess the impact of infection in undernourished people on the kinetics of protein breakdown, protein synthesis, amino acid metabolism, and on the synthetic rates of selected plasma proteins. Studies will be conducted in developing countries, particularly in young children. The programme goals are to (i) elaborate methods and model protocols which can be implemented in developing countries to investigate the impact on protein metabolism of infection superimposed on chronic undernutrition; (ii) test they hypothesis that dietary requirements for protein and amino acids are related to the place of nutrition and are altered substantially when infection is superimposed on chronic undernutrition. When feasible, the primary focus on protein/amino acid metabolism will be extended to assessments of protein/energy interactions when H 2 18 O becomes more readily available and/or at research sites with indirect calorimetry equipment. The data generated should be appropriate as a basis for reevaluating amino acid/protein requirements in these populations. Refs

  6. Bradykinin-potentiating PEPTIDE-10C, an argininosuccinate synthetase activator, protects against H2O2-induced oxidative stress in SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    Querobino, Samyr Machado; Ribeiro, César Augusto João; Alberto-Silva, Carlos

    2018-05-01

    Bradykinin-potentiating peptides (BPPs - 5a, 7a, 9a, 10c, 11e, and 12b) of Bothrops jararaca (Bj) were described as argininosuccinate synthase (AsS) activators, improving l-arginine availability. Agmatine and polyamines, which are l-arginine metabolism products, have neuroprotective properties. Here, we investigated the neuroprotective effects of low molecular mass fraction from Bj venom (LMMF) and two synthetic BPPs (BPP-10c, BPP-12b, BPP-10c showed higher protective capacity than BPP-12b. LMMF pretreatment was unable to prevent the reduction of cell viability caused by H 2 O 2 . The neuroprotective mechanism of BPP-10c against oxidative stress was investigated. BPP-10c reduced ROS generation and lipid peroxidation in relation to cells treated only with H 2 O 2 . BBP-10c increased AsS expression and was not neuroprotective in the presence of MDLA, a specific inhibitor of AsS. BPP-10c reduced iNOS expression and nitrate levels but decreased NF-kB expression. Furthermore, BPP-10c protected the mitochondrial membrane against oxidation. Overall, we demonstrated for the first time neuroprotective mechanisms of BPPs against oxidative stress, opening new perspectives to the study and application of these peptides for the treatment of neurodegenerative diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher

    2002-01-01

    been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years...... increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P increases the interstitial concentrations......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...

  8. Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs

    OpenAIRE

    Ma, Jie; Luo, Yu; Ge, Lilin; Wang, Lei; Zhou, Mei; Zhang, Yingqi; Duan, Jinao; Chen, Tianbao; Shaw, Chris

    2014-01-01

    The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin ge...

  9. Stable isotopes

    International Nuclear Information System (INIS)

    Evans, D.K.

    1986-01-01

    Seventy-five percent of the world's stable isotope supply comes from one producer, Oak Ridge Nuclear Laboratory (ORNL) in the US. Canadian concern is that foreign needs will be met only after domestic needs, thus creating a shortage of stable isotopes in Canada. This article describes the present situation in Canada (availability and cost) of stable isotopes, the isotope enrichment techniques, and related research programs at Chalk River Nuclear Laboratories (CRNL)

  10. Identification and functional analysis of a novel bradykinin inhibitory peptide in the venoms of New World Crotalinae pit vipers

    International Nuclear Information System (INIS)

    James Graham, Robert Leslie; Graham, Ciaren; McClean, Stephen; Chen, Tianbao; O'Rourke, Martin; Hirst, David; Theakston, David; Shaw, Chris

    2005-01-01

    A novel undecapeptide has been isolated and structurally characterized from the venoms of three species of New World pit vipers from the subfamily, Crotalinae. These include the Mexican moccasin (Agkistrodon bilineatus), the prairie rattlesnake (Crotalus viridis viridis), and the South American bushmaster (Lachesis muta). The peptide was purified from all three venoms using a combination of gel permeation chromatography and reverse-phase HPLC. Automated Edman degradation sequencing and MALDI-TOF mass spectrometry established its peptide primary structure as: Thr-Pro-Pro-Ala-Gly-Pro-Asp-Val-Gly-Pro-Arg-OH, with a non-protonated molecular mass of 1063.18 Da. A synthetic replicate of the peptide was found to be an antagonist of bradykinin action at the rat vascular B2 receptor. This is the first bradykinin inhibitory peptide isolated from snake venom. Database searching revealed the peptide to be highly structurally related (10/11 residues) with a domain residing between the bradykinin-potentiating peptide and C-type natriuretic peptide domains of a recently cloned precursor from tropical rattlesnake (Crotalus durissus terrificus) venom gland. BIP thus represents a novel biological entity from snake venom

  11. Analgesic and anti-inflammatory actions on bradykinin route of a polysulfated fraction from alga Ulva lactuca.

    Science.gov (United States)

    de Araújo, Ianna Wivianne Fernandes; Rodrigues, José Ariévilo Gurgel; Quinderé, Ana Luíza Gomes; Silva, Jane de Fátima Teixeira; Maciel, Gabrielle de Freitas; Ribeiro, Natássia Albuquerque; de Sousa Oliveira Vanderlei, Edfranck; Ribeiro, Kátia Alves; Chaves, Hellíada Vasconcelos; Pereira, Karuza Maria Alves; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2016-11-01

    We investigated structural features of polysaccharides from Ulva lactuca and their effects on the classical models of nociception and inflammation. Crude extract was obtained by enzymatic digestion and isolated by ion exchange chromatography on DEAE-cellulose. The fraction with higher yield was used in the tests (SP-Ul). Swiss mice received SP-Ul (1, 3 or 9mg/kg; i.v.), 30min prior to injection of 0.8%-acetic acid or 1%-formalin or prior to a thermal stimulus. At same doses, SP-Ul was tested on Wistar rats on paw edema elicited by different irritants (carrageenan, dextran, bradykinin, histamine or serotonin). The results of infrared characterization indicated the presence of hydroxyl groups, sulfate, uronic acid and glycosidic linkages in all SP fractions spectrums. SP-Ul decreased significantly the antinociception in response to acetic acid or formalin (second phase), but not in the hot-plate test, suggesting that its analgesia occurs through a peripheral mechanism. SP-Ul did not reduce carrageenan-induced paw edema as supported by both histological and myeloperoxidase activity assessments. However, SP-Ul (1mg/kg; s.c.) reduced dextran-elicited edema, showing vascular anti-inflammatory effect, with bradykinin as major target because it did not reduce histamine- and serotonin-induced paw edemas. Therefore, SP-Ul acts on bradykinin pathway in its antinociceptive and anti-inflammatory responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Activation of bradykinin B2 receptor induced the inflammatory responses of cytosolic phospholipase A2 after the early traumatic brain injury.

    Science.gov (United States)

    Chao, Honglu; Liu, Yinlong; Lin, Chao; Xu, Xiupeng; Li, Zheng; Bao, Zhongyuan; Fan, Liang; Tao, Chao; Zhao, Lin; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

    2018-06-09

    Phospholipase A 2 is a known aggravator of inflammation and deteriorates neurological outcomes after traumatic brain injury (TBI), however the exact inflammatory mechanisms remain unknown. This study investigated the role of bradykinin and its receptor, which are known initial mediators within inflammation activation, as well as the mechanisms of the cytosolic phospholipase A 2 (cPLA 2 )-related inflammatory responses after TBI. We found that cPLA 2 and bradykinin B2 receptor were upregulated after a TBI. Rats treated with the bradykinin B2 receptor inhibitor LF 16-0687 exhibited significantly less cPLA 2 expression and related inflammatory responses in the brain cortex after sustaining a controlled cortical impact (CCI) injury. Both the cPLA 2 inhibitor and the LF16-0687 improved CCI rat outcomes by decreasing neuron death and reducing brain edema. The following TBI model utilized both primary astrocytes and primary neurons in order to gain further understanding of the inflammation mechanisms of the B2 bradykinin receptor and the cPLA 2 in the central nervous system. There was a stronger reaction from the astrocytes as well as a protective effect of LF16-0687 after the stretch injury and bradykinin treatment. The protein kinase C pathway was thought to be involved in the B2 bradykinin receptor as well as the cPLA 2 -related inflammatory responses. Rottlerin, a Protein Kinase C (PKC) δ inhibitor, decreased the activity of the cPLA 2 activity post-injury, and LF16-0687 suppressed both the PKC pathway and the cPLA 2 activity within the astrocytes. These results indicated that the bradykinin B2 receptor-mediated pathway is involved in the cPLA 2 -related inflammatory response from the PKC pathway. Copyright © 2018. Published by Elsevier B.V.

  13. An experimental study of zinc 65 transfer to a fresh water fish, with special consideration of the two routes of absorption and the stable element metabolism

    International Nuclear Information System (INIS)

    Berg, A.; Brazzelli, A.

    1975-01-01

    The use of 65 Zn as a tracer allows the determination of important parameters of zinc metabolism (rates of direct and intestinal retention, turnover coefficient). Because of the very low value of the latter parameter (around 0.3% day), the equilibrium state cannot be estimated from a short term experiment. In the fish species studied (Carassius auratus L.) direct absorption contributes more than intestinal absorption in the total retention rate and can probably alone fulfill the total zinc requirements of the fish. The total retention rate, together with the total Zn content are subject to homeostatic regulation, thus indicating the metabolic role of the element zinc. It follows that direct accumulation of radiozinc is inversely proportional to zinc concentration in water (as the ion Zn ++ ). Similarly the intestinal accumulation of radiozinc inversely proportional to the dose of ingested zinc. The low turnover coefficient is responsible for the very slow rate of excretion of previously absorbed radiozinc. The radioecological implications of this study of zinc metabolism are underlined. The danger of cumulative concentration of radioactivity through ingestion of highly radioactive food is neutralized by the processes of metabolic regulation. One must be particularly careful in drawing conclusions about the equilibrium level of radioaccumulation because of the low turnover of the element [fr

  14. Outcome of Venom Bradykinin Potentiating Factor on Renin Angiotensin System in Irradiated Rats

    International Nuclear Information System (INIS)

    Ashry, O.; Farouk, H.; Moustafa, M.; Abu Sinn, G.; Abd ElBaset, A.

    2011-01-01

    Scorpion Venom contains a strong bradykinin potentiating factor (BPF) exhibiting angiotensin converting enzyme inhibition (ACEI). Irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Interruption of the RAS by an ACEI or angiotensin II receptor blocker (ARB) losartan (LOS) and/or gamma-rays (4 Gy) were evaluated. Rats received 6 doses of BPF (1μg/g body wt) or of LOS (5 μg/g body wt). Treatment with BPF induced significant elevation in the level of potassium (K) and significant drop in the level of sodium (Na) and uric acid. Treatment with LOS significantly depressed the level of Na and uric acid compared to control. Irradiation discerned a significant elevation in malondialdehyde (MDA), advanced oxidative protein product (AOPP), aldosterone, Na, urea and creatinine, and a significant drop in the haematological values, glutathione (GSH), calcium (Ca) and uric acid. A significant decrease in MDA, aldosterone, urea, creatinine and uric acid compared to irradiated group was observed in irradiated treated groups. Irradiated animals treated with LOS showed a significant decrease in Na and chloride (Cl) compared to the irradiated group. Considerable amelioration of radiation-induced depression in haematopoiesis, improvement of oxidative stress and kidney function by BPF as ACEI or LOS as ARB are detected. Results add further identification to the properties of BPF

  15. Angiotensin-(1-7) augments endothelium-dependent relaxations of porcine coronary arteries to bradykinin by inhibiting angiotensin-converting enzyme 1.

    Science.gov (United States)

    Raffai, Gábor; Khang, Gilson; Vanhoutte, Paul M

    2014-05-01

    Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II to angiotensin-(1-7) that activates Mas receptors, inhibits ACE1, and modulates bradykinin receptor sensitivity. This in vitro study compared the direct and indirect effects of angiotensin-(1-7), the ACE1 inhibitor captopril, and diminazene aceturate (DIZE) an alleged ACE2 activator in rings of porcine coronary arteries, by measuring changes of isometric tension. Angiotensin-(1-7), captopril, and DIZE did not cause significant changes in tension before or after desensitization of bradykinin receptors in preparations contracted with U46619. Bradykinin caused concentration-dependent and endothelium-dependent relaxations that were not affected by DIZE but were potentiated to a similar extent by angiotensin-(1-7) and captopril, given alone or in combination. Bradykinin responses potentiated by angiotensin-(1-7) and captopril were not affected by the BK1 antagonist SSR240612 and remained augmented in the presence of either N-nitro-L-arginine methyl ester hydrochloride plus indomethacin or TRAM-34 plus UCL-1684. ACE2 was identified in the coronary endothelium by immunofluorescence, but its basal activity was not influenced by DIZE. These results suggest that in coronary arteries, angiotensin-(1-7) and captopril both improves NO bioavailability and enhances endothelium-dependent hyperpolarization to bradykinin solely by ACE1 inhibition. Endothelial ACE2 activity cannot be increased by DIZE to produce local adequate amounts of angiotensin-(1-7) to influence vascular tone.

  16. Ranakinestatin-PPF from the skin secretion of the Fukien gold-striped pond frog, Pelophylax plancyi fukienensis: a prototype of a novel class of bradykinin B2 receptor antagonist peptide from ranid frogs.

    Science.gov (United States)

    Ma, Jie; Luo, Yu; Ge, Lilin; Wang, Lei; Zhou, Mei; Zhang, Yingqi; Duan, Jinao; Chen, Tianbao; Shaw, Chris

    2014-01-01

    The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin-a specific bradykinin B2-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B2-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10(-6)M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10(-11)M and 10(-5)M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B1- (desArg-HOE140) and B2-receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-receptors. Ranakinestatin-PPF-thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B2-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.

  17. Strong cytotoxic effect of the bradykinin antagonist BKM-570 in ovarian cancer cells--analysis of the molecular mechanisms of its antiproliferative action.

    Science.gov (United States)

    Jutras, Stephanie; Bachvarova, Magdalena; Keita, Mamadou; Bascands, Jean-Loup; Mes-Masson, Anne-Marie; Stewart, John M; Gera, Lajos; Bachvarov, Dimcho

    2010-12-01

    The standard chemotherapy for epithelial ovarian cancer (EOC) patients is currently a combination of taxane and platinum. However, most EOC patients still suffer relapses, and there is an immediate need for the development of novel and more effective therapeutic modalities against this deadly disease. Recently, the nonpeptide bradykinin (BK) antagonist 2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-l-tyrosine-N-(4-amino-2,2,6,6-tetramethyl-piperidyl) amide (BKM-570) was shown to cause impressive growth inhibition of lung and prostate tumors, displaying superior in vivo inhibitory effects than convential chemotherapeutic drugs. Here, we investigated BKM-570 cytotoxic effects in two EOC cell lines, derived from different EOC histopathologies: a clear cell carcinoma (TOV-21), and an endometrioid carcinoma (TOV-112). We showed that BKM-570 effectively inhibited the growth of ovarian cancer cells, as its cytotoxic effects were comparable to those of cisplatin, and were independent of the functional status of BK receptors. Moreover, BKM-570 synergized with cisplatin in inhibiting EOC cell growth. To better understand the molecular mechanisms of the antiproliferative action of this BK antagonist in EOC cells, we performed gene expression profiling in TOV-21 and TOV-112 cells following treatment with 10 μM BKM-570 for 24 h. BKM-570 displayed similar cytotoxic effects in the two cell lines analyzed, as genes with previously shown involvement in apoptosis/antiapoptosis and cell adhesion were proportionally upregulated and downregulated in both cell lines, whereas genes involved in basic cellular mechanisms, including cell growth and maintenance, metabolism, cell cycle control, inflammatory and immune response, signal transduction, protein biosynthesis, transcription regulation, and transport, were predominantly downregulated upon treatment. Our data are indicative of the therapeutic potential of BKM-570 and related compounds in EOC management. © 2010 The Authors

  18. An enhanced in vivo stable isotope labeling by amino acids in cell culture (SILAC) model for quantification of drug metabolism enzymes.

    Science.gov (United States)

    MacLeod, A Kenneth; Fallon, Padraic G; Sharp, Sheila; Henderson, Colin J; Wolf, C Roland; Huang, Jeffrey T-J

    2015-03-01

    Many of the enzymes involved in xenobiotic metabolism are maintained at a low basal level and are only synthesized in response to activation of upstream sensor/effector proteins. This induction can have implications in a variety of contexts, particularly during the study of the pharmacokinetics, pharmacodynamics, and drug-drug interaction profile of a candidate therapeutic compound. Previously, we combined in vivo SILAC material with a targeted high resolution single ion monitoring (tHR/SIM) LC-MS/MS approach for quantification of 197 peptide pairs, representing 51 drug metabolism enzymes (DME), in mouse liver. However, as important enzymes (for example, cytochromes P450 (Cyp) of the 1a and 2b subfamilies) are maintained at low or undetectable levels in the liver of unstimulated metabolically labeled mice, quantification of these proteins was unreliable. In the present study, we induced DME expression in labeled mice through synchronous ligand-mediated activation of multiple upstream nuclear receptors, thereby enhancing signals for proteins including Cyps 1a, 2a, 2b, 2c, and 3a. With this enhancement, 115 unique, lysine-containing, Cyp-derived peptides were detected in the liver of a single animal, as opposed to 56 in a pooled sample from three uninduced animals. A total of 386 peptide pairs were quantified by tHR/SIM, representing 68 Phase I, 30 Phase II, and eight control proteins. This method was employed to quantify changes in DME expression in the hepatic cytochrome P450 reductase null (HRN) mouse. We observed compensatory induction of several enzymes, including Cyps 2b10, 2c29, 2c37, 2c54, 2c55, 2e1, 3a11, and 3a13, carboxylesterase (Ces) 2a, and glutathione S-transferases (Gst) m2 and m3, along with down-regulation of hydroxysteroid dehydrogenases (Hsd) 11b1 and 17b6. Using DME-enhanced in vivo SILAC material with tHR/SIM, therefore, permits the robust analysis of multiple DME of importance to xenobiotic metabolism, with improved utility for the study of

  19. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  20. Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B1 receptor-sensitized responses.

    Science.gov (United States)

    Errasti, A E; Rey-Ares, V; Daray, F M; Rogines-Velo, M P; Sardi, S P; Paz, C; Podestá, E J; Rothlin, R P

    2001-08-01

    In isolated human umbilical vein (HUV), the contractile response to des-Arg9-bradykinin (des-Arg9-BK), selective BK B1 receptor agonist, increases as a function of the incubation time. Here, we evaluated whether cyclooxygenase (COX) pathway is involved in BK B1-sensitized response obtained in 5-h incubated HUV rings. The effect of different concentrations of indomethacin, sodium salicylate, ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before concentration-response curves (CRC) was studied. All treatments produced a significant rightward shift of the CRC to des-Arg9-BK in a concentration-dependent manner, which provides pharmacological evidence that COX pathway is involved in the BK B1 responses. Moreover, in this tissue, the NS-398 pKb (5.2) observed suggests that COX-2 pathway is the most relevant. The strong correlation between published pIC50 for COX-2 and the NSAIDs' pKbs estimated further supports the hypothesis that COX-2 metabolites are involved in BK B1 receptor-mediated responses. In other rings, indomethacin (30, 100 micromol/l) or NS-398 (10, 30 micromol/l) produced a significant rightward shift of the CRC to BK, selective BK B2 agonist, and its pKbs were similar to the values to inhibit BK B1 receptor responses, suggesting that COX-2 pathway also is involved in BK B2 receptor responses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are present before and after 5-h in vitro incubation and apparently COX-2 does not suffer additional induction.

  1. Cardiovascular and vasoconstrictive actions of skate bradykinin in the little skate, Leucoraja erinacea (Elasmobranchii).

    Science.gov (United States)

    Dasiewicz, Patricia J; Conlon, J Michael; Anderson, W Gary

    2011-11-01

    The vasoconstrictive and cardiovascular actions of a recently identified bradykinin (BK)-related peptide (Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe) from the little skate, Leucoraja erinacea were examined in the unanesthetised little skate. Intra-arterial administration of a skate BK (0.1-1 nmolkg(-1)) produced a hypertensive response with a rise in blood pressure reaching a maximum elevation of 28.7±4.8% over baseline (Pskate BK. Further, in vivo administration of 1 nmolkg(-1) skate BK induced a significant delayed increase in stroke volume (reaching a maximum of 54.4±14.7% above baseline) without significant effect on either cardiac output or heart rate. In vitro, skate BK constricted the 1st branchial, mesenteric (EC(50) 2.7×10(-9)M) and coeliac (EC(50) 3.1×10(-9)M) arterial preparations of the skate. In contrast, skate [Arg(9)]BK, the mammalian B(1) receptor agonist des-[Arg(9)]BK, and the mammalian B(2) receptor antagonist HOE-140 failed to induce vasoconstriction in these isolated arterial preparations. The vasoconstrictor actions of skate BK in the isolated mesenteric, coeliac and branchial arterial preparations were significantly inhibited when co-administrated with esculetin and phentolamine. Indomethacin also inhibited the vasoconstrictor actions of skate BK in the isolated branchial artery. We conclude that, as in mammals and teleost fish, multiple pathways involving at least the alpha adrenergic and leukotriene synthesis pathway are involved in mediating the vasoconstrictive actions of BK in vascular smooth muscle of the little skate. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

    Science.gov (United States)

    Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

    2016-02-15

    To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

  4. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    2014-01-01

    Is entrepreneurship a more stable career choice for high employment turnover individuals? We find that a transition to entrepreneurship induces a shift towards stayer behavior and identify job matching, job satisfaction and lock-in effects as main drivers. These findings have major implications...

  5. Uses of stable isotopes

    International Nuclear Information System (INIS)

    Axente, Damian

    1998-01-01

    The most important fields of stable isotope use with examples are presented. These are: 1. Isotope dilution analysis: trace analysis, measurements of volumes and masses; 2. Stable isotopes as tracers: transport phenomena, environmental studies, agricultural research, authentication of products and objects, archaeometry, studies of reaction mechanisms, structure and function determination of complex biological entities, studies of metabolism, breath test for diagnostic; 3. Isotope equilibrium effects: measurement of equilibrium effects, investigation of equilibrium conditions, mechanism of drug action, study of natural processes, water cycle, temperature measurements; 4. Stable isotope for advanced nuclear reactors: uranium nitride with 15 N as nuclear fuel, 157 Gd for reactor control. In spite of some difficulties of stable isotope use, particularly related to the analytical techniques, which are slow and expensive, the number of papers reporting on this subject is steadily growing as well as the number of scientific meetings organized by International Isotope Section and IAEA, Gordon Conferences, and regional meeting in Germany, France, etc. Stable isotope application development on large scale is determined by improving their production technologies as well as those of labeled compound and the analytical techniques. (author)

  6. Internal correction of spectral interferences and mass bias for selenium metabolism studies using enriched stable isotopes in combination with multiple linear regression.

    Science.gov (United States)

    Lunøe, Kristoffer; Martínez-Sierra, Justo Giner; Gammelgaard, Bente; Alonso, J Ignacio García

    2012-03-01

    The analytical methodology for the in vivo study of selenium metabolism using two enriched selenium isotopes has been modified, allowing for the internal correction of spectral interferences and mass bias both for total selenium and speciation analysis. The method is based on the combination of an already described dual-isotope procedure with a new data treatment strategy based on multiple linear regression. A metabolic enriched isotope ((77)Se) is given orally to the test subject and a second isotope ((74)Se) is employed for quantification. In our approach, all possible polyatomic interferences occurring in the measurement of the isotope composition of selenium by collision cell quadrupole ICP-MS are taken into account and their relative contribution calculated by multiple linear regression after minimisation of the residuals. As a result, all spectral interferences and mass bias are corrected internally allowing the fast and independent quantification of natural abundance selenium ((nat)Se) and enriched (77)Se. In this sense, the calculation of the tracer/tracee ratio in each sample is straightforward. The method has been applied to study the time-related tissue incorporation of (77)Se in male Wistar rats while maintaining the (nat)Se steady-state conditions. Additionally, metabolically relevant information such as selenoprotein synthesis and selenium elimination in urine could be studied using the proposed methodology. In this case, serum proteins were separated by affinity chromatography while reverse phase was employed for urine metabolites. In both cases, (74)Se was used as a post-column isotope dilution spike. The application of multiple linear regression to the whole chromatogram allowed us to calculate the contribution of bromine hydride, selenium hydride, argon polyatomics and mass bias on the observed selenium isotope patterns. By minimising the square sum of residuals for the whole chromatogram, internal correction of spectral interferences and mass

  7. The Prestudy for Studying Inorganic Nutrient Metabolism in Humans : the Aplication of ICP-MS for Determination of Stable Isotope Ratio of Fe and Zn

    International Nuclear Information System (INIS)

    Rukihati; Sumadjo

    2001-01-01

    A method is described for the determination of isotope ratio of Fe and Zn by means of inductively coupled plasma-mass spectrometry (ICP-MS). The mass spectrometer was operated in low resolution mode to provide maximal sensitivity. Typical conditions for operations were: plasma power 0.85 k W, reflected power 56 Fe/ 54 Fe, 57 Fe/ 54 Fe, 58 Fe/ 54 Fe, dan 64 Zn/ 67 Zn, 66 Zn/ 67 Zn, 68 Zn/ 67 Zn, 70 Zn/ 67 Zn measured by ICP-MS showed a good level of agreement with TIMS (thermal ionization mass spectrometry). This method was prepared for studying the absorption and/or metabolism of inorganic nutrients in humans. (author)

  8. Metabolism of Seriola lalandi during Starvation as Revealed by Fatty Acid Analysis and Compound-Specific Analysis of Stable Isotopes within Amino Acids.

    Directory of Open Access Journals (Sweden)

    Fernando Barreto-Curiel

    Full Text Available Fish starvation is defined as food deprivation for a long period of time, such that physiological processes become confined to basal metabolism. Starvation provides insights in physiological processes without interference from unknown factors in digestion and nutrient absorption occurring in fed state. Juveniles of amberjack Seriola lalandi were isotopically equilibrated to a formulated diet for 60 days. One treatment consisted of fish that continued to be fed and fish in the other treatment were not fed for 35 days. The isotopic signatures prior to the beginning of and after the starvation period, for fish in the starvation and control treatments, were analysed for lipid content, fatty acid composition and isotopic analysis of bulk (EA-IRMS and of amino acids (compound specific isotope analysis, CSIA. There were three replicates for the starvation group. Fatty acid content in muscle and liver tissue before and after starvation was determined to calculate percent change. Results showed that crude lipid was the most used source of energy in most cases; the PUFAs and LC-PUFAs were highly conserved. According to the protein signature in bulk (δ15N and per amino acid (δ13C and δ15N, in muscle tissue, protein synthesis did not appear to occur substantially during starvation, whereas in liver, increases in δ13C and δ15N indicate that protein turnover occurred, probably for metabolic routing to energy-yielding processes. As a result, isotopic values of δ15N in muscle tissue do not change, whereas CSIA net change occurred in the liver tissue. During the study period of 35 days, muscle protein was largely conserved, being neither replenished from amino acid pools in the plasma and liver nor catabolized.

  9. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

  10. Pharmaceuticals labelled with stable isotopes

    International Nuclear Information System (INIS)

    Krumbiegel, P.

    1986-11-01

    The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13 C, 15 N, and 2 H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2 H, 13 C, and 15 N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

  11. Effects of a novel bradykinin B1 receptor antagonist and angiotensin II receptor blockade on experimental myocardial infarction in rats.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available The aim of the present study was to evaluate the cardiovascular effects of the novel bradykinin B1 receptor antagonist BI-113823 following myocardial infarction (MI and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin II type 1 (AT1 receptor antagonist after MI in rats.Sprague Dawley rats were subjected to permanent occlusion of the left descending coronary artery. Cardiovascular function was determined at 7 days post MI. Treatment with either B1 receptor antagonist (BI-113823 or AT1 receptor antagonist (irbesartan alone or in combination improved post-MI cardiac function as evidenced by attenuation of elevated left ventricular end diastolic pressure (LVEDP; greater first derivative of left ventricular pressure (± dp/dt max, left ventricle ejection fraction, fractional shorting, and better wall motion; as we as reductions in post-MI up-regulation of matrix metalloproteinases 2 (MMP-2 and collagen III. In addition, the cardiac up-regulation of B1 receptor and AT1 receptor mRNA were markedly reduced in animals treated with BI 113823, although bradykinin B2 receptor and angiotensin 1 converting enzyme (ACE1 mRNA expression were not significantly affected by B1 receptor blockade.The present study demonstrates that treatment with the novel B1 receptor antagonist, BI-113823 improves post-MI cardiac function and does not influence the cardiovascular effects of AT1 receptor antagonist following MI.

  12. Isolation and characterization of a novel bradykinin potentiating peptide (BPP) from the skin secretion of Phyllomedusa hypochondrialis.

    Science.gov (United States)

    Conceição, Katia; Konno, Katsuhiro; de Melo, Robson Lopes; Antoniazzi, Marta M; Jared, Carlos; Sciani, Juliana M; Conceição, Isaltino M; Prezoto, Benedito C; de Camargo, Antônio Carlos Martins; Pimenta, Daniel C

    2007-03-01

    Bradykinin potentiating peptides (BPPs) from Bothrops jararaca venom were first described in the middle of 1960s and were the first natural inhibitors of the angiotensin-converting enzyme (ACE). BPPs present a classical motif and can be recognized by their typical pyroglutamyl (Pyr)/proline rich sequences presenting, invariably, a proline residue at the C-terminus. In the present study, we describe the isolation and biological characterization of a novel BPP isolated from the skin secretion of the Brazilian tree-frog Phyllomedusa hypochondrialis. This new BPP, named Phypo Xa presents the sequence Pyr-Phe-Arg-Pro-Ser-Tyr-Gln-Ile-Pro-Pro and is able to potentiate bradykinin activities in vivo and in vitro, as well as efficiently and competitively inhibit ACE. This is the first canonical BPP (i.e. Pyr-Aaa(n)-Gln-Ile-Pro-Pro) to be found not only in the frog skin but also in any other natural source other than the snake venoms.

  13. Importance of the terminal α-amino group of bradykinin and some kynins on capillary permeability increase

    International Nuclear Information System (INIS)

    Sugavara, S.

    1979-01-01

    A simple and reliable method is described for the quantitative evaluation of vascular permeability increase induced by vasoactive drugs with Evans blue labelled with iodine-125 or 131. By using this method the importance of α-amino group of bradykinin (Bk), kallidin (Kd) and methionyl-kallidin (Met-Kd) on the biological activity were studied after reacting the kinins with pyridoxal 5'-phosphate followed by reduction with sodium borohydride. Phosphopyridoxyl-kinins were formed leaving free the guanidino groups. Aminoacid analysis of phosphopyridoxyl-kinin showed that the efficiency of the reaction was extremely good in the blockage of α-amino groups [phosphopyridoxyl-bradikinin (PP-Bk) = 98,8%, phosphopyridoxyl-kallidin (PP-Kd) = 95,2%, phosphopyridoxyl-methionyl-kallidin (PP-Met-Kd) = 98,0%. Log dose-response curves were obtained for Bk, Kd, Met-Kd, acetyl-bradykinin (Ac-Bk), PP-Bk, PP-Kd and PP-Met-Kd and the relative potencies calculated through the Lineweaver-Burk plots. The relative potencies were: PP-Bk about 16% the activity of Bk, Ac-Bk about 31% the activity of Bk, PP-Kd about 17% the activity of Kd, PP-Met-Kd about 12% the activity of Met-Kd. The results show that the terminal α-amino group of kinins is important in the mechanisms of biological activity. (Author) [pt

  14. Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine.

    Science.gov (United States)

    Westrop, Gareth D; Wang, Lijie; Blackburn, Gavin J; Zhang, Tong; Zheng, Liang; Watson, David G; Coombs, Graham H

    2017-01-01

    Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus.

  15. Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T

  16. New insights into the stereochemical requirements of the bradykinin B2 receptor antagonists binding

    Science.gov (United States)

    Lupala, Cecylia S.; Gomez-Gutierrez, Patricia; Perez, Juan J.

    2016-01-01

    Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a receptor up-regulated during inflammation episodes or tissue trauma and B2 that is constitutively expressed in a variety of cell types. The goal of the present work is to carry out a structure-activity study of BK B2 antagonism, taking into account the stereochemical features of diverse non-peptide antagonists and the way these features translate into ligand anchoring points to complementary regions of the receptor, through the analysis of the respective ligand-receptor complex. For this purpose an atomistic model of the BK B2 receptor was built by homology modeling and subsequently refined embedded in a lipid bilayer by means of a 600 ns molecular dynamics trajectory. The average structure from the last hundred nanoseconds of the molecular dynamics trajectory was energy minimized and used as model of the receptor for docking studies. For this purpose, a set of compounds with antagonistic profile, covering maximal diversity were selected from the literature. Specifically, the set of compounds include Fasitibant, FR173657, Anatibant, WIN64338, Bradyzide, CHEMBL442294, and JSM10292. Molecules were docked into the BK B2 receptor model and the corresponding complexes analyzed to understand ligand-receptor interactions. The outcome of this study is summarized in a 3D pharmacophore that explains the observed structure-activity results and provides insight into the design of novel molecules with antagonistic profile. To prove the validity of the pharmacophore hypothesized a virtual screening process was also carried out. The pharmacophore was used as query to identify new hits using diverse databases of molecules. The results of this study revealed a set of new

  17. A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules.

    Science.gov (United States)

    Gilio, Joyce M; Portaro, Fernanda Cv; Borella, Maria I; Lameu, Claudiana; Camargo, Antonio Cm; Alberto-Silva, Carlos

    2013-11-06

    The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure-activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs - including BPP-10c - are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability

  18. A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules

    Science.gov (United States)

    2013-01-01

    Background The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Results The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without

  19. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  20. Bradykinin-related compounds as new drugs for cancer and inflammation.

    Science.gov (United States)

    Stewart, John M; Gera, Lajos; Chan, Daniel C; Bunn, Paul A; York, Eunice J; Simkeviciene, Vitalija; Helfrich, Barbara

    2002-04-01

    Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-lgl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Ig1, alpha-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg x kg(-1) day(-1) beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg x kg(-1), M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.

  1. Stable isotopes

    International Nuclear Information System (INIS)

    Brazier, J.L.; Guinamant, J.L.

    1995-01-01

    According to the progress which has been realised in the technology of separating and measuring isotopes, the stable isotopes are used as preferable 'labelling elements' for big number of applications. The isotopic composition of natural products shows significant variations as a result of different reasons like the climate, the seasons, or their geographic origins. So, it was proved that the same product has a different isotopic composition of alimentary and agriculture products. It is also important in detecting the pharmacological and medical chemicals. This review article deals with the technology, like chromatography and spectrophotometry, adapted to this aim, and some important applications. 17 refs. 6 figs

  2. Stable Tetraquarks

    Energy Technology Data Exchange (ETDEWEB)

    Quigg, Chris [Fermilab

    2018-04-13

    For very heavy quarks, relations derived from heavy-quark symmetry imply novel narrow doubly heavy tetraquark states containing two heavy quarks and two light antiquarks. We predict that double-beauty states will be stable against strong decays, whereas the double-charm states and mixed beauty+charm states will dissociate into pairs of heavy-light mesons. Observing a new double-beauty state through its weak decays would establish the existence of tetraquarks and illuminate the role of heavy color-antitriplet diquarks as hadron constituents.

  3. Stable beams

    CERN Multimedia

    2015-01-01

    Stable beams: two simple words that carry so much meaning at CERN. When LHC page one switched from "squeeze" to "stable beams" at 10.40 a.m. on Wednesday, 3 June, it triggered scenes of jubilation in control rooms around the CERN sites, as the LHC experiments started to record physics data for the first time in 27 months. This is what CERN is here for, and it’s great to be back in business after such a long period of preparation for the next stage in the LHC adventure.   I’ve said it before, but I’ll say it again. This was a great achievement, and testimony to the hard and dedicated work of so many people in the global CERN community. I could start to list the teams that have contributed, but that would be a mistake. Instead, I’d simply like to say that an achievement as impressive as running the LHC – a machine of superlatives in every respect – takes the combined effort and enthusiasm of everyone ...

  4. Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    P. A. Virych

    2017-01-01

    Full Text Available Damage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM and gadolinium (300 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction.

  5. Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Mu Yang

    2011-01-01

    Full Text Available Objectives: The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata, in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues. Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

  6. Perinatal development influences mechanisms of bradykinin-induced relaxations in pulmonary resistance and conduit arteries differently.

    Science.gov (United States)

    Boels, P J; Deutsch, J; Gao, B; Haworth, S G

    2001-07-01

    As bradykinin (BYK) relaxes conduit (EPA) and resistance (RPA) pulmonary arteries from both perinatal and adult lungs, we investigated whether this vasodilator's relaxation-mechanisms were altered during perinatal development, differed between EPA and RPA and differed with other endothelium-dependent vasodilators, acetyicholine (ACH) and substance P (SP). Arteries from mature foetal (5 days), neonatal (approximately 5 min), newborn (60-84 h) and adult pigs (> or =6 months) were isolated, mounted for in vitro isometric force recording, activated with PGF(2alpha) (30 micromol/l) and relaxed with BYK (10 pmol/l-1 micromol/l), SP (10 pmol/l-0.1 micromol/l) or ACH (1 nmol/l-1 mmol/l). (i) BYK: L-NAME (100 micromol/l) attenuated relaxations in foetal EPA ( approximately 55%) but nearly abolished them in the adult ( approximately 80%). In RPA, L-NAME nearly abolished ( approximately 90%) relaxations in the foetus and this effect diminished progressively with age to approximately 20% in the adult. Indomethacin (IND, micromol/l) attenuated relaxations in neonatal (approximately 25%), new-born and adult EPA (both approximately 45%). Together, L-NAME and IND abolished relaxations in all EPA and in neonatal RPA but not in older RPA. SKF525a (100 micromol/l) attenuated relaxations in foetal RPA ( approximately 4%), diminishing in the adult RPA to approximately 10%. Together, SKF52Sa and L-NAME largely abolished relaxations in postnatal RPA (approximately 80%). Activation with K(+)=125 mmol/l attenuated relaxations in adult EPA (approximately 80%), foetal RPA ( approximately 45%) and neonatal RPA (approximately 75%) and abolished relaxations in RPA from older ages. (ii) ACH: L-NAME abolished relaxations in new-born EPA and RPA. In adult EPA, combined L-NAME and IND moderately attenuated relaxations. (iii) SP: Combined application of L-NAME and IND attenuated relaxations to a similar degree in new-born and adult EPA and RPA. In postnatal EPA, BYK-relaxations depend completely on

  7. Neutral endopeptidase up-regulation in isolated human umbilical artery: involvement in desensitization of bradykinin-induced vasoconstrictor effects.

    Science.gov (United States)

    Pelorosso, Facundo Germán; Halperin, Ana Verónica; Palma, Alejandro Martín; Nowak, Wanda; Errasti, Andrea Emilse; Rothlin, Rodolfo Pedro

    2007-02-01

    Previous reports show that bradykinin B(2) receptors mediate contractile responses induced by bradykinin (BK) in human umbilical artery (HUA). However, although it has been reported that BK-induced responses can desensitize in several inflammatory models, the effects of prolonged in vitro incubation on BK-induced vasoconstriction in HUA have not been studied. In isolated HUA rings, BK-induced responses after a 5-h in vitro incubation showed a marked desensitization compared with responses at 2 h. Inhibition of either angiotensin-converting enzyme (ACE) or neutral endopeptidase (NEP), both BK-inactivating enzymes, failed to modify responses to BK at 2 h. After 5 h, ACE inhibition produced only a slight potentiation of BK-induced responses. In contrast, BK-induced vasoconstriction at 5 h was markedly potentiated by NEP inhibition. Moreover, NEP activity, measured by hydrolysis of its synthetic substrate (Z-Ala-Ala-Leu-p-nitroanilide), showed a 2.4-fold increase in 5-h incubated versus 2-h incubated tissues, which was completely reversed by cycloheximide (CHX) treatment. Furthermore, CHX significantly potentiated BK-induced responses, suggesting that NEP-mediated kininase activity increase at 5 h depends on de novo protein synthesis. In addition, under NEP inhibition, CHX treatment failed to produce an additional potentiation of BK-induced vasoconstriction. Still, NEP up-regulation was confirmed by Western blot, showing a 2.1-fold increase in immunoreactive NEP in 5-h incubated versus 2-h incubated HUA. In summary, the present study provides strong pharmacological evidence that NEP is up-regulated and plays a key role in desensitization of BK-induced vasoconstriction after prolonged in vitro incubation in HUA. Our results provide new insights into the possible mechanisms involved in BK-induced response desensitization during sustained inflammatory conditions.

  8. Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells.

    Science.gov (United States)

    El-Bizri, Nesrine; Bkaily, Ghassan; Wang, Shimin; Jacques, Danielle; Regoli, Domenico; D'Orléans-Juste, Pedro; Sukarieh, Rami

    2003-03-01

    Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10(-10) M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10(-6) M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10(-10)-10(-7) M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10(-7) M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10(-7) M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.

  9. Further Identification of the Effect of Bradykinin Potentiating Factor Isolated From Scorpion Venom on Irradiated White Rat

    International Nuclear Information System (INIS)

    Hasan, H.F.

    2011-01-01

    Scorpion venom of Androctonus amoreuxi contains a strong bradykinin potentiating factor (BPF) that augments bradykinin effect through enhancing its release and acts as an angiotensin converting enzyme inhibitor (ACEI). Both irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Possible interruption of the RAS with an ACEI induced by BPF isolated from the scorpion, Androctonus amoreuxi venom or the presence of angiotensin II receptor blocker (ARB) losartan and/or γ- radiation were evaluated. The examined parameters included blood erythrocytes count (RBC), total leucocytic count (WBC), haemoglobin content (Hb) and hematocrit value (Hct) as well as, glutathione content (GSH), malondialdehyde (MDA) and advanced oxidative protein product (AOPP) of kidney homogenate besides aldosterone, sodium, potassium, chloride, calcium, urea, creatinine and uric acid levels of serum. A group of rats (70 - 80 gm each) were received i.p. injection of BPIF (1μg / g body wt) twice per week for three weeks, while the other group received i.p. injection of losartan (5μg / g body wt) twice per week for three weeks. γ-Irradiation was performed at a dose level of 4Gy. All animals were examined after an investigation period of 21 days from γ- irradiation. Either BPF or losartan was performed together with irradiation. The results pointed out that irradiation discerned a significant elevation in the level of MDA, AOPP, aldosterone, sodium, urea and creatinine, and a significant drop in the haematological values (RBCs, WBCs, Hb and Hct), GSH, calcium and uric acid. Repeated injections of BPF or losartan had a beneficial result against the deleterious effect of γ- irradiation. The present investigation clarifies comparable effects for treatment of radiation damage to the kidney through RAS by BPF as (ACEI) and losartan as (ARB). The present work adds further identification to the properties of BPF in controlling of radiation damage. Therapeutic agents from

  10. Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes

    International Nuclear Information System (INIS)

    Shaw, J.H.; Wolfe, R.R.

    1988-01-01

    We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC

  11. Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs

    Directory of Open Access Journals (Sweden)

    Jie Ma

    2014-01-01

    Full Text Available The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs. Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific bradykinin B2-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV, named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B2-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10−6 M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10−11 M and 10−5 M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B1- (desArg-HOE140 and B2-receptor (HOE140 antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B2-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.

  12. Analysis of Human Bradykinin Receptor Gene and Endothelial Nitric Oxide Synthase Gene Polymorphisms in End-Stage Renal Disease Among Malaysians

    Directory of Open Access Journals (Sweden)

    R. Vasudevan

    2014-06-01

    Full Text Available The aim of this study was to determine the association of the c.894G>T; p.Glu298Asp polymorphism and the variable number tandem repeat (VNTR polymorphism of the endothelial nitric oxide synthase (eNOS gene and c.181C>T polymorphism of the bradykinin type 2 receptor gene (B2R in Malaysian end-stage renal disease (ESRD subjects.

  13. Gap junctions and hydrogen peroxide are involved in endothelium-derived hyperpolarising responses to bradykinin in omental arteries and veins isolated from pregnant women.

    Science.gov (United States)

    Hammond, Stephanie; Mathewson, Alastair M; Baker, Philip N; Mayhew, Terry M; Dunn, William R

    2011-10-01

    Altered endothelial function may underlie human cardiovascular diseases, including hypertension, diabetes and pre-eclampsia. While much is known about endothelial function in small arteries, very little is known about endothelial responses in small veins isolated from humans. Therefore, we assessed endothelium-dependent responses in omental arteries and veins isolated from healthy pregnant women, focussing on endothelium-dependent hyperpolarising (EDH) mechanisms. Human omental arteries and veins were obtained from women undergoing elective caesarean sections and examined using pressure myography. In pressurised vessels, the effects of proposed inhibitors of EDH production/function were examined on responses to bradykinin. The expression of connexins Cx37, 40 and 43 was assessed using immunohistochemistry. Bradykinin caused vasodilatation in human pressurised omental arteries and veins. In both vessels, responses to bradykinin were partially blocked in the presence of the gap junction uncoupler, carbenoxolone, and reduced further with the addition of catalase, which acts to degrade H(2)O(2). The effect of catalase alone was more pronounced in venous preparations. All three connexins were expressed in both arteries and veins, with a similar distribution pattern, where Cx37 and Cx40 were located mainly in the endothelium and Cx43 located mostly in the media. These data show that, in human omental vessels, an EDH mechanism is produced in response to bradykinin that involves gap junction communication and the production of H(2)O(2). These mechanisms may be involved in the haemodynamic alterations that take place during pregnancy, and any aberration in their function could contribute to raised blood pressure in hypertensive disorders of pregnancy, such as pre-eclampsia. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).

    Science.gov (United States)

    Lopes, Denise M; Junior, Norberto E G; Costa, Paula P C; Martins, Patrícia L; Santos, Cláudia F; Carvalho, Ellaine D F; Carvalho, Maria D F; Pimenta, Daniel C; Cardi, Bruno A; Fonteles, Manassés C; Nascimento, Nilberto R F; Carvalho, Krishnamurti M

    2014-11-01

    Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells

    International Nuclear Information System (INIS)

    Higashida, H.; Streaty, R.A.; Klee, W.; Nirenberg, M.

    1986-01-01

    The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or Ca 2+ into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored 45 Ca-labelled Ca 2+ into the cytoplasm, which activates Ca 2+ -dependent K + channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K + efflux from cells and, to a lesser extent, to activation of Ca 2+ -dependent ion channels and Ca 2+ channels. In contrast, injection of inositol 1,4,5-trisphosphate or Ca 2+ into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that [bradykinin-receptor] complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase

  16. Potentiation of the actions of bradykinin by angiotensin I-converting enzyme inhibitors. The role of expressed human bradykinin B2 receptors and angiotensin I-converting enzyme in CHO cells.

    Science.gov (United States)

    Minshall, R D; Tan, F; Nakamura, F; Rabito, S F; Becker, R P; Marcic, B; Erdös, E G

    1997-11-01

    Part of the beneficial effects of angiotensin I-converting enzyme (ACE) inhibitors are due to augmenting the actions of bradykinin (BK). We studied this effect of enalaprilat on the binding of [3H]BK to Chinese hamster ovary (CHO) cells stably transfected to express the human BK B2 receptor alone (CHO-3B) or in combination with ACE (CHO-15AB). In CHO-15AB cells, enalaprilat (1 mumol/L) increased the total number of low-affinity [3H]BK binding sites on the cells at 37 degrees C, but not at 4 degrees C, from 18.4 +/- 4.3 to 40.3 +/- 11.9 fmol/10(6) cells (P potentiated the release of [3H]arachidonic acid and the liberation of inositol 1,4,5-trisphosphate (IP3) induced by BK and [Hyp3-Tyr(Me)8]BK. Moreover, enalaprilat (1 mumol/L) completely and immediately restored the response of the B2 receptor, desensitized by the agonist (1 mumol/L [Hyp3-Tyr(Me)8]BK); this effect was blocked by the antagonist, HOE 140. Finally, enalaprilat, but not the prodrug enalapril, decreased internalization of the receptor from 70 +/- 9% to 45 +/- 9% (P desensitization, and decrease internalization, thereby potentiating BK beyond blocking its hydrolysis.

  17. Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

    Science.gov (United States)

    Sena, C M; Rosário, L M; Parker, P J; Patel, V; Boarder, M R

    1996-03-01

    In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin

  18. Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

    Science.gov (United States)

    Omar, Ali Zainal; Maulood, Ismail M.

    2017-09-01

    The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

  19. Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

    Science.gov (United States)

    Matrai, Mate; Hetthéssy, Judit R; Nadasy, Gyorgy L; Szekacs, Bela; Mericli, Metin; Acs, Nandor; Monos, Emil; Arbib, Nissim; Varbiro, Szabolcs

    2016-07-01

    Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

  20. Interaction between bradykinin potentiating nonapeptide (BPP9a) and {beta}-cyclodextrin: A structural and thermodynamic study

    Energy Technology Data Exchange (ETDEWEB)

    Lula, Ivana; De Sousa, Frederico B. [Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG (Brazil); Denadai, Angelo M.L. [Centro Federal de Educacao Tecnologica de Minas Gerais, CEFET-MG, Campus VII, 35.183-006, Timoteo, MG (Brazil); Ferreira de Lima, Guilherme; Duarte, Helio Anderson [Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG (Brazil); Mares Guia, Thiago R. dos [Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); Faljoni-Alario, Adelaide [Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, 05508-900, Sao Paulo, SP (Brazil); Santoro, Marcelo M. [Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); Camargo, Antonio C.M. de [Center for Applied Toxinology CAT-CEPID, Laboratorio Especial de Toxicologia Aplicada, Instituto Butantan, 05503-900, Sao Paulo, SP (Brazil); Santos, Robson A.S. dos [Departamento de Fisiologia e Biofisica, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); and others

    2012-02-01

    Herein, we demonstrate the physical and chemical characterizations of the supramolecular complex formed between {beta}-cyclodextrin ({beta}CD) and bradykinin potentiating nonapeptide (BPP9a), an endogenous toxin found in Bothrops jararaca. Circular dichroism results indicate a conformational change in the BPP9a secondary structure upon its complexation with {beta}CD. Nuclear magnetic resonance results, mainly from NOESY experiments, and theoretical calculations showed a favorable interaction between the tryptophan residue of BPP9a and the {beta}CD cavity. Thermodynamic inclusion parameters were investigated by isothermal titration calorimetry, demonstrating that {beta}CD/BPP9a complex formation is an exothermic process that results in a reduction in entropy. Additionally, in vitro degradation study of BPP9a against trypsin (37 Degree-Sign C, pH 7.2) showed higher stability of peptide in presence of {beta}CD. This {beta}CD/BPP9a complex, which presents new chemical properties arising from the peptide inclusion process, may be useful as an antihypertensive drug in oral pharmaceutical formulations. Highlights: Black-Right-Pointing-Pointer Cd and NMR showed evidences for the existence of more than one structure in solution. Black-Right-Pointing-Pointer Complexation with {beta}CD reduces the conformational rigidity of the peptide. Black-Right-Pointing-Pointer {beta}CD cavity recognize Trp and/or Pro segments of BPP9a. Black-Right-Pointing-Pointer Interactions involving disaggregation of BPP9a assemblies and binding with {beta}CD.

  1. Stable Isotope Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tissue samples (skin, bone, blood, muscle) are analyzed for stable carbon, stable nitrogen, and stable sulfur analysis. Many samples are used in their entirety for...

  2. Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C.

    Science.gov (United States)

    Tang, Y; Li, G D

    2004-12-01

    Overwhelming evidence indicates that endothelial cell dysfunction in diabetes is characterised by diminished endothelium-dependent relaxation, but the matter of the underlying molecular mechanism remains unclear. As nitric oxide (NO) production from the endothelium is the major player in endothelium-mediated vascular relaxation, we investigated the effects of high glucose on NO production, and the possible alterations of signalling pathways implicated in this scenario. NO production and intracellular Ca(2+) levels ([Ca(2+)](i)) were assessed using the fluorescent probes 4,5-diaminofluorescein diacetate and fura-2 respectively. Exposure of cultured bovine aortic endothelial cells to high glucose for 5 or 10 days significantly reduced NO production induced by bradykinin (but not by Ca(2+) ionophore) in a time- and dose-dependent manner. This was probably due to an attenuation in bradykinin-induced elevations of [Ca(2+)](i) under these conditions, since a close correlation between [Ca(2+)](i) increases and NO generation was observed in intact bovine aortic endothelial cells. Both bradykinin-promoted intracellular Ca(2+) mobilisation and extracellular Ca(2+) entry were affected. Moreover, bradykinin-induced formation of Ins(1,4,5)P(3), a phospholipase C product leading to increases in [Ca(2+)](i), was also inhibited following high glucose culture. This abnormality was not attributable to a decrease in inositol phospholipids, but possibly to a reduction in the number of bradykinin receptors. The alterations in NO production, the increases in [Ca(2+)](i), and the bradykinin receptor number due to high glucose could be largely reversed by protein kinase C inhibitors and D: -alpha-tocopherol (antioxidant). Chronic exposure to high glucose reduces NO generation in endothelial cells, probably by impairing phospholipase-C-mediated Ca(2+) signalling due to excess protein kinase C activation. This defect in NO release may contribute to the diminished endothelium

  3. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

    Directory of Open Access Journals (Sweden)

    Jihong Xing

    2016-11-01

    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

  4. [Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors].

    Science.gov (United States)

    Beauchêne, C; Martins-Héricher, J; Denis, D; Martin, L; Maillard, H

    2018-05-04

    Episodes of acquired bradykinin-mediated angioedema due to angiotensin-converting enzyme (ACE) inhibitors may result in fatal outcomes. There is no consensus regarding emergency pharmacological management of these episodes. Treatment options include icatibant and C1INH concentrate. Tranexamic acid is administered for moderate episodes. Its efficacy in the treatment of ACE inhibitor-induced episodes of angioedema is not established. The aim of this retrospective study is to assess the benefits of emergency tranexamic acid administration in the management of ACE inhibitor-induced episodes of angioedema. Retrospective analysis of the medical files of patients who consulted between 2010 and 2016 in two French tertiary care hospitals for a bradykinic angioedema attributed to an ACE treatment. All of them had received tranexamic acid as a first line treatment. Thirty three patients who had experienced severe episode of angioedema were included. Twenty seven patients showed significant improvement when treated with tranexamic acid alone. The six remaining patients were treated with icatibant (5/33) or C1INH concentrate (1/33), due to partial improvement after tranexamic acid therapy. None of the patients were intubated, no fatalities were recorded and no side effects were reported. Tranexamic acid is an easily accessible and affordable therapy that may provide effective treatment for ACE inhibitor-induced episodes of angioedema. It may help while waiting for a more specific treatment (icatibant and C1INH concentrate) that is at times unavailable in emergency departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study.

    Science.gov (United States)

    Campos, Regis Albuquerque; Valle, Solange Oliveira Rodrigues; França, Alfeu Tavares; Cordeiro, Elisabete; Serpa, Faradiba Sarquis; Mello, Yara Ferreira; Malheiros, Teresinha; Toledo, Eliana; Mansour, Elie; Fusaro, Gustavo; Grumach, Anete Sevciovic

    2014-01-01

    Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

  6. Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study

    Directory of Open Access Journals (Sweden)

    Regis Albuquerque Campos

    Full Text Available CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil.DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients.METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored.RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age. The symptoms were: subcutaneous edema (22/24; abdominal pain (15/24 and upper airway obstruction (10/24. The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%; 10-20 (5/24; 20.8%; 20-30 (8/24; 33.4%; 30-60 (5/24; 20.8%; and 2 hours (1/24; 4.3%. The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6.CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

  7. Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB.

    Science.gov (United States)

    Ricciardolo, F L M; Petecchia, L; Sorbello, V; Di Stefano, A; Usai, C; Massaglia, G M; Gnemmi, I; Mognetti, B; Hiemstra, P S; Sterk, P J; Sabatini, F

    2016-03-01

    Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor-kappa B (NF-kB) is potentially involved in BK B2 receptor (B2R) regulation. In this observational cross-sectional study, B2R and NF-kB expression was evaluated in bronchial biopsies from mild asthmatics (after diluent/allergen challenge) and healthy controls, examining the role of NF-kB in B2R expression in primary human fibroblasts from normal and asthmatic subjects (HNBFb and HABFb). B2R and NF-kB (total and nuclear) expression was analysed by immunohistochemistry in biopsies from 10 mild intermittent asthmatics (48 h after diluent/allergen challenge) and 10 controls undergoing bronchoscopy. B2R co-localization in 5B5(+) and αSMA(+) mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABFb/HNBFb incubated with interleukin (IL)-4/IL-13 with/without BK, and after NF-kB inhibitor, by Western blotting. Bronchial mucosa B2R and nuclear NF-kB expression was higher in asthmatics after diluent (B2R only) and allergen challenge than in controls (P kB (total and nuclear) increased after allergen compared with after diluent (P kB inhibitor (P kB expression. NF-kB inhibitor blocked IL-4/IL-13-induced increase in B2R expression in cultured fibroblasts, suggesting a role as potential anti-asthma drug. © 2015 John Wiley & Sons Ltd.

  8. Stable convergence and stable limit theorems

    CERN Document Server

    Häusler, Erich

    2015-01-01

    The authors present a concise but complete exposition of the mathematical theory of stable convergence and give various applications in different areas of probability theory and mathematical statistics to illustrate the usefulness of this concept. Stable convergence holds in many limit theorems of probability theory and statistics – such as the classical central limit theorem – which are usually formulated in terms of convergence in distribution. Originated by Alfred Rényi, the notion of stable convergence is stronger than the classical weak convergence of probability measures. A variety of methods is described which can be used to establish this stronger stable convergence in many limit theorems which were originally formulated only in terms of weak convergence. Naturally, these stronger limit theorems have new and stronger consequences which should not be missed by neglecting the notion of stable convergence. The presentation will be accessible to researchers and advanced students at the master's level...

  9. Effect of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of calcium channel blockers

    Directory of Open Access Journals (Sweden)

    P. A. Virych

    2017-05-01

    Full Text Available The development of modern organic chemistry and molecular modeling technologies simplify the search for potential inhibitors of various receptor systems and biological processes. The one of the directions is the development of analgesics of broad spectrum and low toxicity. It is important to search for inhibitors of the kinin-kallikrein system that regulates many functions: inflammation, pain, carcinogenesis, vascular tone, smooth muscle contraction and other. Derivatives of 3-substituted 1,4-benzodiazepine-2-ones have a unique spatial conformation that allows one to simulate β-structures of bioactive peptides. The functional activity of compounds is determined by properties of their peripheral chemical radicals. We analyzed the effect of 3-substituted 1,4-benzodiazepin-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction and relaxation of the stomach in the presence of calcium channel blockers: verapamil (1 μM, gadolinium (300 μM and 2-aminoethyl diphenylborinate (0.1 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in incubation solution were 10–6 M. Data processing on dynamics of contraction was performed according to the method of Burdyha and Kosterin. Compounds MX-1775 and MX-1925 reduced maximal normalized rate (Vn of bradykinin-induced smooth muscle contraction in the presence of Gd3+ by 21.2% and 31.0% respectively. Compound MX-1925 increased Vn of relaxation by 11.6%. A similar effect is typical for MX-2011, where there is an increase by 34.6%. In the presence of verapamil this compound additionally decreased Vn contraction by 20.5%. Substances MX-1775, MX-2004 and MX-1925 restored maximal normalized rate of relaxation to original values of bradykinin-induced contraction. In the presence of 2-aminoethyldiphenylborinate MX-1775 additionally reduced Vn of contractions by 7.5%. 3-substituted 1,4-benzo­diazepine-2-ones did not change the maximal

  10. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  11. Angina Pectoris (Stable Angina)

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Angina Pectoris (Stable Angina) Updated:Aug 21,2017 You may have heard the term “angina pectoris” or “stable angina” in your doctor’s office, ...

  12. Isolation: analysis and properties of three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom.

    Science.gov (United States)

    Ferreira, L A; Galle, A; Raida, M; Schrader, M; Lebrun, I; Habermehl, G

    1998-04-01

    In the course of systematic investigations on low-molecular-weight compounds from the venom of Crotalidae and Viperidae, we have isolated and characterized at least three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom by gel filtration on Sephadex G-25 M, Sephadex G-10 followed by HPLC. The peptides showed bradykinin-potentiating action on isolated guinea-pig ileum, for which the BPP-V was more active than of BPP-II, and BPP-III, rat arterial blood pressure, and a relevant angiotensin-converting enzyme (ACE) competitive inhibiting activity. The kinetic studies showed a Ki of the order of 9.7 x 10(-3) microM to BPP-II, 7 x 10(-3) microM to BPP-III, and 3.3 x 10(-3) microM to BPP-V. The amino acid sequence of the BPP-III has been determined to be pGlu-Gly-Gly-Trp-Pro-Arg-Pro-Gly-Pro-Glu-Ile-Pro-Pro, and the amino acid compositions of the BPP-II and BPP-V by amino acid analysis were 2Glu-2Gly-1Arg-4Pro-1Ile and 2Glu-2Gly-1Ser-3Pro-2Val-1Ile, with molecular weight of 1372, 1046, and 1078, respectively.

  13. Identification of bradykinin: related peptides from Phyllomedusa nordestina skin secretion using electrospray ionization tandem mass spectrometry after a single-step liquid chromatography

    Directory of Open Access Journals (Sweden)

    K Conceição

    2009-01-01

    Full Text Available Amphibian skin secretions are a source of potential new drugs with medical and biotechnological applications. Rich in peptides produced by holocrine-type serous glands in the integument, these secretions play different roles, either in the regulation of physiological skin functions or in the defense against predators or microorganisms. The aim of the present work was to identify novel peptides with bradykinin-like structure and/or activity present in the skin of Phyllomedusa nordestina. In order to achieve this goal, the crude skin secretion of this frog was pre-fractionated by solid phase extraction and separated by reversed-phase chromatography. The fractions were screened for low-molecular-mass peptides and sequenced by mass spectrometry. It was possible to identify three novel bradykinin-related peptides, namely: KPLWRL-NH2 (Pnor 3, RPLSWLPK (Pnor 5 and VPPKGVSM (Pnor 7 presenting vascular activities as assessed by intravital microscopy. Pnor 3 and Pnor 7 were able to induce vasodilation. On the other hand, Pnor 5 was a potent vasoconstrictor. These effects were reproduced by their synthetic analogues.

  14. Administration of angiotensin II and a bradykinin B2 receptor blocker in midpregnancy impairs gestational outcome in guinea pigs.

    Science.gov (United States)

    Valdés, Gloria; Schneider, Daniela; Corthorn, Jenny; Ortíz, Rita; Acuña, Stephanie; Padilla, Oslando

    2014-06-04

    The opposing renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) are upregulated in pregnancy and localize in the utero-placental unit. To test their participation as counter-regulators, circulating angiotensin II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS balance during the period of maximal trophoblast invasion and placental development would provoke increased blood pressure, defective trophoblast invasion and a preeclampsia-like syndrome. Pregnant guinea-pigs received subcutaneous infusions of AII (200 μg/kg/day), the B2R antagonist Bradyzide (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non-pregnant cycling animals were included in a control group (C NP) or received AII + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined during cycle in C NP, and on the last day of infusion, and 6 and 26 days thereafter in the remaining groups. Twenty six days after the infusions blood and urine were extracted, fetuses, placentas and kidneys were weighed, and trophoblast invasion of spiral arteries was defined in the utero-placental units by immunocytochemistry. Systolic blood pressure transiently rose in a subgroup of the pregnant females while receiving AII + BDZ infusion, but not in AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ-treated pregnant and non-pregnant females. Aborted and dead fetuses were increased in dams that received AII and AII + BDZ. The fetal/placental weight ratio was reduced in litters of AII + BDZ-treated mothers. All groups that received interventions during pregnancy showed reduced replacement of endothelial cells by extravillous trophoblasts in lateral and myometrial spiral arteries. The acute effects on fetal viability, and the persistently impaired renal

  15. Effect of LF 16-0687MS, a new nonpeptide bradykinin B2 receptor antagonist, in a rat model of closed head trauma.

    Science.gov (United States)

    Pruneau, D; Chorny, I; Benkovitz, V; Artru, A; Roitblat, L; Shapira, Y

    1999-11-01

    Bradykinin is an endogenous nonapeptide which potently dilates the cerebral vasculature and markedly increases vascular permeability. These effects are mediated by B2 receptors located on the vascular endothelium. Previous experimental studies have shown that blockade of the kallikreinkinin system, which mediates the formation of bradykinin, afforded a reduction of the brain edema that developed following a cryogenic cortical lesion. In the present study, we investigated the effect of LF 16-0687MS, a novel nonpeptide B2 receptor antagonist, on cerebral edema and neurological severity score (NSS) after closed head injury to rats. LF 16-0687MS or its vehicle (NaCl 0.9%) was continuously infused at 10, 30, and 100 microg/kg/min over 23 h starting 1 h after a focal trauma to the left hemisphere was induced using a weight-drop device. The extent of edema formation was evaluated 24 h after trauma from left and right hemispheres samples by measurement of specific gravity and water content. In a separate study, a neurological severity score based on scoring of behavioural and motor functions was evaluated 1 h and over 1 week after trauma. LF 16-0687MS at 100 microg/kg/min markedly reduced the development of brain edema as indicated by a 68% increase in specific gravity (p<0.05) and a 64% decrease of water content (p<0.05) in the left hemisphere. In addition the recovery of neurological function was significantly improved by 100 microg/kg/min LF 16-0687MS from day 3 to day 7 after CHT. In a separate experiment, we also showed that LF 16-0687MS at 100 microg/kg/min given either 1 h before or 30 min after CHT did not affect mean arterial blood pressure. These results show that blockade of bradykinin B2 receptors is an effective approach to reduce cerebral edema and to improve neurological outcome after a focal contusion to the cranium.

  16. Stable Boundary Layer Issues

    OpenAIRE

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The development of robust stable boundary layer parameterizations for use in NWP and climate models is hampered by the multiplicity of processes and their unknown interactions. As a result, these models suffer ...

  17. ESI-MS/MS Identification of a Bradykinin-Potentiating Peptide from Amazon Bothrops atrox Snake Venom Using a Hybrid Qq-oaTOF Mass Spectrometer

    Science.gov (United States)

    Coutinho-Neto, Antonio; Caldeira, Cleópatra A. S.; Souza, Gustavo H. M. F.; Zaqueo, Kayena D.; Kayano, Anderson M.; Silva, Rodrigo S.; Zuliani, Juliana P.; Soares, Andreimar M.; Stábeli, Rodrigo G.; Calderon, Leonardo A.

    2013-01-01

    A bradykinin-potentiating peptide (BPP) from Amazon Bothrops atrox venom with m/z 1384.7386 was identified and characterized by collision induced dissociation (CID) using an ESI-MS/MS spectra obtained in positive ion mode on a hybrid Qq-oaTOF mass spectrometer, Xevo G2 QTof MS (Waters, Manchester, UK). De novo peptide sequence analysis of the CID fragmentation spectra showed the amino acid sequence ZKWPRPGPEIPP, with a pyroglutamic acid and theoretical monoisotopic m/z 1384.7378, which is similar to experimental data, showing a mass accuracy of 0.6 ppm. The peptide is homologous to other BPP from Bothrops moojeni and was named as BPP-BAX12. PMID:23430539

  18. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  19. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General Article Volume 21 Issue 9 September 2016 pp 803- ... Keywords. Evolutionary game theory, evolutionary stable state, conflict, cooperation, biological games.

  20. Stable Boundary Layer Issues

    NARCIS (Netherlands)

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The

  1. Synergistic Effect of Bone Marrow Transplantation and Bradykinin Potential Factor Isolated from Venom on Thymus and Spleen of Sublethally Irradiated Guinea Pigs

    International Nuclear Information System (INIS)

    Abu-Sinna, G.; Kafafy, Y.; Nassar, A.Y.; Salman, A.

    2005-01-01

    The buthus occitanus, scorpion venom contains a strong bradykinin potentiating factor (BPF) that augments bradykinin effects through enhancing its release. Based on the cytoprotective ability of BPF, the present work investigates it as a radioprotectant. Sublethal whole-body y-irradiation at 1.5 Gy was used. Bone marrow cells suspension (BM cells) alone or in combination with BPF was utilized. Three to four weeks-aged male Guinea pigs were grouped into two major groups. The first was non-irradiated control that was divided into subgroups treated i.p. with BM cells (2.5xl06 cells), one dose of BPF (lug/g b wt), BM cells+ BPF, one week spaced two doses of BPF, BM cells+ 2 doses of BPF, one week spaced three doses of BPF or BM cells+ 3 doses of BPF. Second major group (irradiated group) at 1.5 Gy that, subdivided and treated similarly. 5 animals from each group were killed at 7, 14 and 21 days from the initiation of treatment (3 h after irradiation). The subgroups of non-irradiated animals showed an increase in spleen wt and colony formation, thymus population, and globulins content particularly in those subgroups that stayed for the later time periods (14 and 21 days) and that treated with combined BM cells+ BPF or that groups that were treated with two or three BPF doses. Irradiation caused dramatic destruction in thymus and the spleen reflected on reduction of the lower globulins content. Treatment with BM cells, BM cells+ double doses of BPF or triple doses of BPF caused complete recovery in all measured indices, the best result was observed in those of subgroups treated with BM cells+ double doses of BPF or treated with triple doses of BPF. They completely normalized the investigated parameters after 14 and 21 days respectively

  2. [Study on the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse].

    Science.gov (United States)

    Wang, Hui; Zhang, Jiaxiang; Li, Shulong; Zha, Wansheng; Wang, Feng; Zhu, Qixing

    2015-07-01

    To study the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (ODMLT). On the first days, intradermal injection by 50% TCE and the amount of FCA mixture 100 µl for initial sensitization; on 4, 7, 10 days, painted abdominal skin by 100 µl 50% TCE for three sensitization, on 17, 19 days, painted on the back skin by 100 µl 30% TCE for initial excitation and the last challenge; 24 h before each challenge, PKSI-527+TCE group received intraperitoneal injection by inhibitor PKSI-527 (50 mg/kg); solvent control group treat without TCE and sensitization and excitation reagent the same proportion of olive oil and acetone mixture, blank control group without any treatment. Before killing the mouse, renal weight and body weight were recorded. The renals and plasma were separated at 24 h, 48 h, 72 h and 7 d after the last challenge and observed pathological of the renals. Expression of B1R and B2R in renal were examined by immunofluorescence technique. Plasma were examined by ELISA for BK. The renal pathological examination revealed the apparent damage of TCE sensitized mice which compared to solvent control group showed obvious cellular infiltration, vacuolar degeneration of renal tubular epithelial cells. The renal damage of PKSI-527+TCE-sensitized groups which compared to the corresponding point of TCE-sensitized groups showed significantly reduced. The expression of BK in 24 h, 48 h and 72 h TCE-sensitized groups were significant higher than solvent control group and related TCE non-sensitized groups (P trichloroethylene-sensitized mouse and the expression change of bradykinin and its receptors B1R and B2R which may play an important role in the process.

  3. Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect

    Directory of Open Access Journals (Sweden)

    Takuto Nakamura

    2017-01-01

    Full Text Available Aminopeptidase A (APA cleaves angiotensin (Ang II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv APA in a conscious, unrestrained state after pretreatment with (i vehicle, (ii 80 μg of telmisartan, an Ang II type-1 (AT1 receptor blocker, (iii 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg. Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg. In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response.

  4. The acute impact of polyphenols from Hibiscus sabdariffa in metabolic homeostasis: an approach combining metabolomics and gene-expression analyses.

    Science.gov (United States)

    Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Fernández-Arroyo, Salvador; Senan-Campos, Oriol; Massucci, Francesco A; Hernández-Aguilera, Anna; Sales-Pardo, Marta; Guimerà, Roger; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-09-01

    We explored the acute multifunctional effects of polyphenols from Hibiscus sabdariffa in humans to assess possible consequences on the host's health. The expected dynamic response was studied using a combination of transcriptomics and metabolomics to integrate specific functional pathways through network-based methods and to generate hypotheses established by acute metabolic effects and/or modifications in the expression of relevant genes. Data were obtained from healthy male volunteers after 3 hours of ingestion of an aqueous Hibiscus sabdariffa extract. The data were compared with data obtained prior to the ingestion, and the overall findings suggest that these particular polyphenols had a simultaneous role in mitochondrial function, energy homeostasis and protection of the cardiovascular system. These findings suggest beneficial actions in inflammation, endothelial dysfunction, and oxidation, which are interrelated mechanisms. Among other effects, the activation of the heme oxygenase-biliverdin reductase axis, the systemic inhibition of the renin-angiotensin system, the inhibition of the angiotensin-converting enzyme, and several actions mirroring those of the peroxisome proliferator-activated receptor agonists further support this notion. We also found concordant findings in the serum of the participants, which include a decrease in cortisol levels and a significant increase in the active vasodilator metabolite of bradykinin (des-Arg(9)-bradykinin). Therefore, our data support the view that polyphenols from Hibiscus sabdariffa play a regulatory role in metabolic health and in the maintenance of blood pressure, thus implying a multi-faceted impact in metabolic and cardiovascular diseases.

  5. Co-ordinated research programme on application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report on the second research co-ordination meeting

    International Nuclear Information System (INIS)

    1996-01-01

    The use of isotopes has revolutionized the field of human nutrition research, but has been of greatest benefit to industrialized countries. The International Atomic Energy Agency is sponsoring programmes using isotopic and related technologies in human nutrition research to address issues that are of priority to developing countries. Scientists participating in the Coordinated Research Programme (CRP) on ''Amino Acid and Protein Metabolism in Malnourished Populations of Developing Countries'' are conducting research on the interaction between infection and amino acid metabolism, particularly the potential diversion of substrates from anabolic pathways to fight infection in marginally nourished children during periods of infections. This topic is of great importance to the nutritional status of children in developing countries, who frequently or chronically have infections and who, as a consequence, may have alterations in nutrient requirements. The CRP has developed and implemented a standardized protocol for measuring leucine oxidation during infection in 8 different countries. The CRP is expected to contribute important new knowledge about interactions between protein utilization, the stresses of unhygienic environments, and infections in marginally nourished people. This information is expected to be applicable to efforts to increase efficient utilization of limited food resources in developing countries. Another highlight of the CRP is that it represents an international team of nutrition scientists who together are building nutritional biology research capabilities in developing countries. Refs, figs, tabs

  6. The antibiotic tiamulin is a potent inducer and inhibitor of cytochrome P4503A via the formation of a stable metabolic intermediate complex. Studies in primary hepatocyte cultures and liver microsomes of the pig.

    Science.gov (United States)

    Witkamp, R F; Nijmeijer, S M; Monshouwer, M; Van Miert, A S

    1995-05-01

    Tiamulin is a semisynthetic antibiotic frequently used in agricultural animals. The drug has been shown to produce clinically important--often lethal--interactions with other compounds that are simultaneously administered. To explain this, it has been suggested that tiamulin selectively inhibits oxidative drug metabolism via the formation of a cytochrome P450 metabolic intermediate complex. The aim of the present study was to provide further support for this hypothesis. When hepatic microsomes and cultured primary pig hepatocytes were incubated with tiamulin, a maximum in the absorbance spectrum at 455 nm was observed, which disappeared after adding KFe(CN)6. When hepatocytes were incubated with tiamulin for 72 hr, cytochrome P450 content and cytochrome P4503A apoprotein levels were increased. Tiamulin strongly inhibited and concentration dependently inhibited the hydroxylation rate of testosterone at the 6 beta-position in both microsomes and hepatocytes, and the microsomal N-demethylation rate of ethylmorphine. Other testosterone hydroxylations were inhibited to a lesser extent or not affected. The relative inhibition of the hydroxylation of testosterone at the 6 beta-position was more pronounced in microsomes from rifampicin- and triacetyloleandomycin-treated pigs. The results indicate that cytochrome P450 complex formation can at least partly explain the interactions observed with tiamulin. Tiamulin seems to be a strong, probably selective, inhibitor of the cytochrome P4503A subfamily and an interesting tool for further research.

  7. Co-ordinated research programme on application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report on the second research co-ordination meeting

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The use of isotopes has revolutionized the field of human nutrition research, but has been of greatest benefit to industrialized countries. The International Atomic Energy Agency is sponsoring programmes using isotopic and related technologies in human nutrition research to address issues that are of priority to developing countries. Scientists participating in the Coordinated Research Programme (CRP) on ``Amino Acid and Protein Metabolism in Malnourished Populations of Developing Countries`` are conducting research on the interaction between infection and amino acid metabolism, particularly the potential diversion of substrates from anabolic pathways to fight infection in marginally nourished children during periods of infections. This topic is of great importance to the nutritional status of children in developing countries, who frequently or chronically have infections and who, as a consequence, may have alterations in nutrient requirements. The CRP has developed and implemented a standardized protocol for measuring leucine oxidation during infection in 8 different countries. The CRP is expected to contribute important new knowledge about interactions between protein utilization, the stresses of unhygienic environments, and infections in marginally nourished people. This information is expected to be applicable to efforts to increase efficient utilization of limited food resources in developing countries. Another highlight of the CRP is that it represents an international team of nutrition scientists who together are building nutritional biology research capabilities in developing countries. Refs, figs, tabs.

  8. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process......This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...

  9. Applications of stable isotopes

    International Nuclear Information System (INIS)

    Letolle, R.; Mariotti, A.; Bariac, T.

    1991-06-01

    This report reviews the historical background and the properties of stable isotopes, the methods used for their measurement (mass spectrometry and others), the present technics for isotope enrichment and separation, and at last the various present and foreseeable application (in nuclear energy, physical and chemical research, materials industry and research; tracing in industrial, medical and agronomical tests; the use of natural isotope variations for environmental studies, agronomy, natural resources appraising: water, minerals, energy). Some new possibilities in the use of stable isotope are offered. A last chapter gives the present state and forecast development of stable isotope uses in France and Europe

  10. Analysing Stable Time Series

    National Research Council Canada - National Science Library

    Adler, Robert

    1997-01-01

    We describe how to take a stable, ARMA, time series through the various stages of model identification, parameter estimation, and diagnostic checking, and accompany the discussion with a goodly number...

  11. Ocena częstości występowania składowych zespołu metabolicznego w grupie pacjentów ze stabilną dusznicą bolesną kwalifikowanych do planowej koronarografii = Assessment of frequency of components of metabolic syndrome in patients with stable angina qualified for planning angiography

    Directory of Open Access Journals (Sweden)

    Katarzyna Sawicka

    2016-09-01

    łu metabolicznego wśród badanej populacji. 6. Osoby mieszkające w mieście częściej narażone są na występowanie zespołu metabolicznego niż mieszkańcy wsi. 7. Nie istnieje istotna statystycznie zależność pomiędzy paleniem papierosów i spożywaniem alkoholu, a występowaniem zespołu metabolicznego. 8. Występowanie zespołu metabolicznego stwierdzono równie często w grupie osób, które twierdziły, że odżywiają się zdrowo, jak i u tych, które nie prowadzą zdrowego stylu odżywiania. Słowa kluczowe: zespół metaboliczny, dusznica bolesna stabilna, koronarografia Summary Admission. With stable angina pectoris involves the metabolic syndrome. The metabolic syndrome is a collection of interrelated metabolic factors such as impaired glucose tolerance, insulin resistance, hyperinsulinemia, obesity, lipid disorders, hypertension. This team is the main cause of the development of cardiovascular disease atherosclerosis and type 2 diabetes for the development of the metabolic syndrome are responsible genetic predisposition and associated environmental factors, including a lack of physical activity and calorie diet [1]. Materials and methods of research. In this paper method was used diagnostic survey. To collect information used proprietary questionnaire. The survey consisted of 37 questions, including 33 closed questions and 4 semi-open questions in which it was possible to enter their own answers by the respondents. Questions allowed to collect data on the demographic characteristics of the study population and resource evaluation of respondents' knowledge about the individual components of the metabolic syndrome. Findings. 1. Results of the study indicate that 70% of patients with stable angina pectoris referred for elective coronary angiography are components of metabolic syndrome. 2. There is a relationship between the place of residence of the patient, and the presence of components of the metabolic syndrome: in people living in the city is more common

  12. Calcium stable isotope geochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gausonne, Nikolaus [Muenster Univ. (Germany). Inst. fuer Mineralogie; Schmitt, Anne-Desiree [Strasbourg Univ. (France). LHyGeS/EOST; Heuser, Alexander [Bonn Univ. (Germany). Steinmann-Inst. fuer Geologie, Mineralogie und Palaeontologie; Wombacher, Frank [Koeln Univ. (Germany). Inst. fuer Geologie und Mineralogie; Dietzel, Martin [Technische Univ. Graz (Austria). Inst. fuer Angewandte Geowissenschaften; Tipper, Edward [Cambridge Univ. (United Kingdom). Dept. of Earth Sciences; Schiller, Martin [Copenhagen Univ. (Denmark). Natural History Museum of Denmark

    2016-08-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  13. Calcium stable isotope geochemistry

    International Nuclear Information System (INIS)

    Gausonne, Nikolaus; Schmitt, Anne-Desiree; Heuser, Alexander; Wombacher, Frank; Dietzel, Martin; Tipper, Edward; Schiller, Martin

    2016-01-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  14. Tracing metabolic routes of dietary carbohydrate and protein in rainbow trout (Oncorhynchus mykiss) using stable isotopes ([¹³C]starch and [¹⁵N]protein): effects of gelatinisation of starches and sustained swimming.

    Science.gov (United States)

    Felip, Olga; Ibarz, Antoni; Fernández-Borràs, Jaume; Beltrán, Marta; Martín-Pérez, Miguel; Planas, Josep V; Blasco, Josefina

    2012-03-01

    Here we examined the use of stable isotopes, [¹³C]starch and [¹⁵N]protein, as dietary tracers to study carbohydrate assimilation and distribution and protein utilisation, respectively, by rainbow trout (Oncorhynchus mykiss). The capacity of glucose uptake and use by tissues was studied, first, by varying the digestibility of carbohydrate-rich diets (30 % carbohydrate), using raw starch and gelatinised starch (GS) and, second, by observing the effects of two regimens of activity (voluntary swimming, control; sustained swimming at 1·3 body lengths/s, exercise) on the GS diet. Isotopic ratio enrichment (¹³C and ¹⁵N) of the various tissue components (protein, lipid and glycogen) was measured in the liver, muscles, viscera and the rest of the fish at 11 and 24 h after a forced meal. A level of 30 % of digestible carbohydrates in the food exceeded the capacity of rainbow trout to use this nutrient, causing long-lasting hyperglycaemia that raises glucose uptake by tissues, and the synthesis of glycogen and lipid in liver. Total 13C recovered 24 h post-feeding in the GS group was lower than at 11 h, indicating a proportional increase in glucose oxidation, although the deposition of lipids in white muscle (WM) increased. Prolonged hyperglycaemia was prevented by exercise, since sustained swimming enhances the use of dietary carbohydrates, mainly through conversion to lipids in liver and oxidation in muscles, especially in red muscle (RM). Higher recoveries of total 15N for exercised fish at 24 h, mainly into the protein fraction of both RM and WM, provide evidence that sustained swimming improves protein deposition, resulting in an enhancement of the protein-sparing effect.

  15. [[Length polymorphism of minisatellite repeat B2-VNTR of the bradykinin B2 receptor gene in healthy Russians and in patients with coronary heart disease].

    Science.gov (United States)

    Suchkova, I O; Pavlinova, L I; Larionova, E E; Alenina, N V; Solov'ev, K V; Baranova, T V; Belotserkovskaia, E V; Sasina, L K; Bader, M; Denisenko, A D; Mustafina, O E; Khusnutdinova, E K; Patkin, E L

    2014-01-01

    Bradykinin B2 receptor is involved in many processes, including the regulation of blood pressure and smooth muscle contraction, vasodilation, inflammation, edema, cell proliferation, pain. It is suggested that this receptor may be one of the factors that have cardioprotective and infarct-limiting effects. It is assumed that certain genetic variants in both coding and non-coding regions ofBDKRB2 gene may influence its expression. In the 3'-untranslated region of BDKRB2 exon 3 the minisatellite repeat B2-VNTR is located. B2-VNTR has previously been shown to affect the BDKRB2 mRNA stability. Therefore, it is important to perform the molecular genetic analysis of this minisatellite in patients with different forms of coronary heart disease in order to reveal possible associations between specific B2-VNTR alleles and certain clinical forms of coronary heart disease. In the present study, a comparative analysis of the allele and genotype frequencies of B2-VNTR was carried out in groups of healthy individuals and patients with two clinical forms of coronary heart disease (angina pectoris and myocardial infarction), ethnically Russian. The results of the B2-VNTR length polymorphism analysis indicate that this tandem repeat may be attributed to a class of low polymorphic and non-hypervariable minisatellite. In all analyzed groups we revealed three B2-VNTR alleles, consisting of 43, 38 and 33 repeat units. Alleles of 43 and 33 repeats were major in all investigated groups. No statistically significant differences were found in the B2-VNTR allele and genotype frequencies between men and women in control group, and also between healthy men and men with angina pectoris and myocardial infarction. Thus, B2-VNTR length polymorphism was not associated with these clinical forms of coronary heart disease in Russian men. However, we do not exclude the possibility of association between the B2-VNTR short alleles (38 and 33 repeats) and cardioprotective effects of bradykinin B2 receptor

  16. The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant in patients with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Rätsep Indrek

    2009-12-01

    Full Text Available Abstract Background Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Methods Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE, mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS, the Disability Rating Scale (DRS and a modified version of the Oxford Handicap Scale (HIREOS. Results 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163 in the combined Anatibant treated group, compared to 19.3% (11/57 in the placebo group (relative risk = 1.37; 95% CI 0·76 to 2·46. All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36. The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. Conclusion This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in

  17. The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

    Science.gov (United States)

    Shakur, Haleema; Andrews, Peter; Asser, Toomas; Balica, Laura; Boeriu, Cristian; Quintero, Juan Diego Ciro; Dewan, Yashbir; Druwé, Patrick; Fletcher, Olivia; Frost, Chris; Hartzenberg, Bennie; Mantilla, Jorge Mejia; Murillo-Cabezas, Francisco; Pachl, Jan; Ravi, Ramalingam R; Rätsep, Indrek; Sampaio, Cristina; Singh, Manmohan; Svoboda, Petr; Roberts, Ian

    2009-12-03

    Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial

  18. Bradykinin type 2 receptor -9/-9 genotype is associated with triceps brachii muscle hypertrophy following strength training in young healthy men

    Directory of Open Access Journals (Sweden)

    Popadic Gacesa Jelena Z

    2012-11-01

    Full Text Available Abstract Background Bradykinin type 2 receptor (B2BRK genotype was reported to be associated with changes in the left-ventricular mass as a response to aerobic training, as well as in the regulation of the skeletal muscle performance in both athletes and non-athletes. However, there are no reports on the effect of B2BRK 9-bp polymorphism on the response of the skeletal muscle to strength training, and our aim was to determine the relationship between the B2BRK SNP and triceps brachii functional and morphological adaptation to programmed physical activity in young adults. Methods In this 6-week pretest-posttest exercise intervention study, twenty nine healthy young men (21.5 ± 2.7 y, BMI 24.2 ± 3.5 kg/m2 were put on a 6-week exercise protocol using an isoacceleration dynamometer (5 times a week, 5 daily sets with 10 maximal elbow extensions, 1 minute rest between sets. Triceps brachii muscle volumes were assessed by using magnetic resonance imaging before and after the strength training. Bradykinin type 2 receptor 9 base pair polymorphism was determined for all participants. Results Following the elbow extensors training, an average increase in the volume of both triceps brachii was 5.4 ± 3.4% (from 929.5 ± 146.8 cm3 pre-training to 977.6 ± 140.9 cm3 after training, p9 allele compared to individuals with one or two +9 alleles (−9/-9, 8.5 ± 3.8%; vs. -9/+9 and +9/+9 combined, 4.7 ± 4.5%, p B2BRK genotype (−9/-9, 50.2 ± 19.2%; vs. -9/+9 and +9/+9 combined, 46.8 ± 20.7%, p > 0.05. Conclusions We found that muscle morphological response to targeted training – hypertrophy – is related to polymorphisms of B2BRK. However, no significant influence of different B2BRK genotypes on functional muscle properties after strength training in young healthy non athletes was found. This finding could be relevant, not only in predicting individual muscle adaptation capacity to training or sarcopenia related to aging and inactivity, but also in

  19. Stable isotope studies

    International Nuclear Information System (INIS)

    Ishida, T.

    1992-01-01

    The research has been in four general areas: (1) correlation of isotope effects with molecular forces and molecular structures, (2) correlation of zero-point energy and its isotope effects with molecular structure and molecular forces, (3) vapor pressure isotope effects, and (4) fractionation of stable isotopes. 73 refs, 38 figs, 29 tabs

  20. Interactive Stable Ray Tracing

    DEFF Research Database (Denmark)

    Dal Corso, Alessandro; Salvi, Marco; Kolb, Craig

    2017-01-01

    Interactive ray tracing applications running on commodity hardware can suffer from objectionable temporal artifacts due to a low sample count. We introduce stable ray tracing, a technique that improves temporal stability without the over-blurring and ghosting artifacts typical of temporal post-pr...

  1. The Stable Concordance Genus

    OpenAIRE

    Kearney, M. Kate

    2013-01-01

    The concordance genus of a knot is the least genus of any knot in its concordance class. Although difficult to compute, it is a useful invariant that highlights the distinction between the three-genus and four-genus. In this paper we define and discuss the stable concordance genus of a knot, which describes the behavior of the concordance genus under connected sum.

  2. Stable radiographic scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    Stable compositions which are useful in the preparation of Technetium-99m-based scintigraphic agents are discussed. They are comprised of ascorbic acid or a pharmaceutically acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in oxidized pertechnetate-99m (sup(99m)TcO 4 - ) solution

  3. Some stable hydromagnetic equilibria

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J L; Oberman, C R; Kulsrud, R M; Frieman, E A [Project Matterhorn, Princeton University, Princeton, NJ (United States)

    1958-07-01

    We have been able to find and investigate the properties of equilibria which are hydromagnetically stable. These equilibria can be obtained, for example, by wrapping conductors helically around the stellarator tube. Systems with I = 3 or 4 are indicated to be optimum for stability purposes. In some cases an admixture of I = 2 fields can be advantageous for achieving equilibrium. (author)

  4. High-precision mass spectrometric analysis using stable isotopes in studies of children

    NARCIS (Netherlands)

    Schierbeek, Henk; van den Akker, Chris H. P.; Fay, Laurent B.; van Goudoever, Johannes B.

    2012-01-01

    The use of stable isotopes combined with mass spectrometry (MS) provides insight into metabolic processes within the body. Herein, an overview on the relevance of stable isotope methodology in pediatric research is presented. Applications for the use of stable isotopes with MS cover carbohydrate,

  5. Nitric oxide inhibits the bradykinin B2 receptor-mediated adrenomedullary catecholamine release but has no effect on adrenal blood flow response in vivo.

    Science.gov (United States)

    Bouallegue, Ali; Yamaguchi, Nobuharu

    2005-06-01

    The role of nitric oxide (NO) in bradykinin (BK)-induced adrenal catecholamine secretion still remains obscure. The present study was to investigate whether an inhibition of NO synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) would modulate BK-induced adrenal catecholamine secretion (ACS) and adrenal vasodilating response (AVR) in anesthetized dogs. Plasma catecholamine concentrations were determined with an HPLC coupled with an electrochemical detector. All drugs were locally administered to the left adrenal gland via intra-arterial infusion. BK dose-dependently increased both ACS and AVR. Hoe-140, a selective B(2) antagonist, significantly blocked the BK-induced increases in both ACS and AVR. In the presence of L-NAME, the BK-induced ACS was significantly enhanced, while the simultaneous AVR remained unaffected. These results suggest that the both BK-induced ACS and AVR are primarily mediated by B(2) receptors in the canine adrenal gland. Our results also suggest that the enhanced ACS in response to BK in the presence of L-NAME may have resulted from a specific inhibition of NO formation in the adrenal gland. It is concluded that the BK-induced NO may play an inhibitory role in the B(2)-receptor-mediated mechanisms regulating ACS, while it may not be implicated in the B(2)-receptor-mediated AVR under in vivo conditions.

  6. Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. 2. Synthesis and structure-activity relationships of alpha,alpha-cycloalkylglycine sulfonamides.

    Science.gov (United States)

    Fattori, Daniela; Rossi, Cristina; Fincham, Christopher I; Caciagli, Valerio; Catrambone, Fernando; D'Andrea, Piero; Felicetti, Patrizia; Gensini, Martina; Marastoni, Elena; Nannicini, Rossano; Paris, Marielle; Terracciano, Rosa; Bressan, Alessandro; Giuliani, Sandro; Maggi, Carlo A; Meini, Stefania; Valenti, Claudio; Quartara, Laura

    2007-02-08

    Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.

  7. Stable isotope analysis

    International Nuclear Information System (INIS)

    Tibari, Elghali; Taous, Fouad; Marah, Hamid

    2014-01-01

    This report presents results related to stable isotopes analysis carried out at the CNESTEN DASTE in Rabat (Morocco), on behalf of Senegal. These analyzes cover 127 samples. These results demonstrate that Oxygen-18 and Deuterium in water analysis were performed by infrared Laser spectroscopy using a LGR / DLT-100 with Autosampler. Also, the results are expressed in δ values (‰) relative to V-SMOW to ± 0.3 ‰ for oxygen-18 and ± 1 ‰ for deuterium.

  8. Forensic Stable Isotope Biogeochemistry

    Science.gov (United States)

    Cerling, Thure E.; Barnette, Janet E.; Bowen, Gabriel J.; Chesson, Lesley A.; Ehleringer, James R.; Remien, Christopher H.; Shea, Patrick; Tipple, Brett J.; West, Jason B.

    2016-06-01

    Stable isotopes are being used for forensic science studies, with applications to both natural and manufactured products. In this review we discuss how scientific evidence can be used in the legal context and where the scientific progress of hypothesis revisions can be in tension with the legal expectations of widely used methods for measurements. Although this review is written in the context of US law, many of the considerations of scientific reproducibility and acceptance of relevant scientific data span other legal systems that might apply different legal principles and therefore reach different conclusions. Stable isotopes are used in legal situations for comparing samples for authenticity or evidentiary considerations, in understanding trade patterns of illegal materials, and in understanding the origins of unknown decedents. Isotope evidence is particularly useful when considered in the broad framework of physiochemical processes and in recognizing regional to global patterns found in many materials, including foods and food products, drugs, and humans. Stable isotopes considered in the larger spatial context add an important dimension to forensic science.

  9. Ca-48 metabolism studies

    International Nuclear Information System (INIS)

    Van der Merwe, D.G.

    1987-03-01

    Calcium metabolism has been studied in depth physiologically and is a relatively well-understood element in biochemistry and medicine. There is still only restricted knowledge of the metabolic fate of calcium in normal and abnormal paediatric subjects. The latter is partially owing to inadequate techniques for tracing and modelling calcium pathways in children. The advent of radioactive tracers has unquestionably enhanced medical research and improved the quality of many metabolic studies. The present study was aimed at the development, promotion and justification of a new tracer technique using the stable isotope, calcium-48. The obvious advantages of such a technique are its harmlessness tothe subject, its applicability to both short- and long-term studies as well as its usefulness to the study for which it was originally motivated, viz research defining the actual relationship between a calcium-deficient diet and the occurrence of rickets in rural Black children in South Africa. Exploratory instrumental analyses were performed specifically with serum samples. This proved successful enough to develop a less specific pre-concentration technique which improved the sensitivity and reduces the cost of doing calcium-48 metabolism studies. The results of a simple metabolic study are presented whereby the scope of the technique is demonstrated in a real situation. The possibilities and limitations of double-isotope metabolic studies are discussed, particularly with regard to strontium as the second tracer

  10. Stable isotope utilization for research on human nutrition

    International Nuclear Information System (INIS)

    Desjeux, J.F.

    1994-01-01

    In the framework of nutritional molecule metabolism research, this paper presents the various stable isotopes used as labels for biological molecules, the reasons for their application in human nutritional study (mainly because of their non toxicity) and the various analysis methods (isotope ratio mass spectrometry, coupled gaseous chromatography and mass spectrometry, nuclear magnetic resonance). Several application examples in nutrition research are then discussed: metabolic conversion measurement for a molecule into its different metabolites, energetic losses. 23 refs

  11. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  12. Stable plastid transformation in Scoparia dulcis L.

    Science.gov (United States)

    Muralikrishna, Narra; Srinivas, Kota; Kumar, Kalva Bharath; Sadanandam, Abbagani

    2016-10-01

    In the present investigation we report stable plastid transformation in Scoparia dulcis L., a versatile medicinal herb via particle gun method. The vector KNTc, harbouring aadA as a selectable marker and egfp as a reporter gene which were under the control of synthetic promoter pNG1014a, targets inverted repeats, trnR / t rnN of the plastid genome. By use of this heterologous vector, recovery of transplastomic lines with suitable selection protocol have been successfully established with overall efficiency of two transgenic lines for 25 bombarded leaf explants. PCR and Southern blot analysis demonstrated stable integration of foreign gene into the target sequences. The results represent a significant advancement of the plastid transformation technology in medicinal plants, which relevantly implements a change over in enhancing and regulating of certain metabolic pathways.

  13. Integrative Metabolic Signatures for Hepatic Radiation Injury.

    Directory of Open Access Journals (Sweden)

    Irwin Jack Kurland

    Full Text Available Radiation-induced liver disease (RILD is a dose-limiting factor in curative radiation therapy (RT for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice.Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI and were contrasted to mice, which received 10 Gy whole body irradiation (WBI. Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry.Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate, fatty acids (lineolate, n-hexadecanoic acid and DNA damage markers (uridine.We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney.

  14. Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

    Directory of Open Access Journals (Sweden)

    Aghdas Dehghani

    2015-01-01

    Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

  15. Antagonism of bradykinin B2 receptor prevents inflammatory responses in human endothelial cells by quenching the NF-kB pathway activation.

    Directory of Open Access Journals (Sweden)

    Erika Terzuoli

    Full Text Available Bradykinin (BK induces angiogenesis by promoting vessel permeability, growth and remodeling. This study aimed to demonstrate that the B2R antagonist, fasitibant, inhibits the BK pro-angiogenic effects.We assesed the ability of fasibitant to antagonize the BK stimulation of cultured human cells (HUVEC and circulating pro-angiogenic cells (PACs, in producing cell permeability (paracellular flux, migration and pseocapillary formation. The latter parameter was studied in vitro (matrigel assay and in vivo in mice (matrigel plug and in rat model of experimental osteoarthritis (OA. We also evaluated NF-κB activation in cultured cells by measuring its nuclear translocation and its downstream effectors such as the proangiogenic ciclooxygenase-2 (COX-2, prostaglandin E-2 and vascular endothelial growth factor (VEGF.HUVEC, exposed to BK (1-10 µM, showed increased permeability, disassembly of adherens and tight-junction, increased cell migration, and pseudocapillaries formation. We observed a significant increase of vessel density in the matrigel assay in mice and in rats OA model. Importantly, B2R stimulation elicited, both in HUVEC and PACs, NF-κB activation, leading to COX-2 overexpression, enhanced prostaglandin E-2 production. and VEGF output. The BK/NF-κB axis, and the ensuing amplification of inflammatory/angiogenic responses were fully prevented by fasitibant as well as by IKK VII, an NF-κB. Inhibitor.This work illustrates the role of the endothelium in the inflammation provoked by the BK/NF-κB axis. It also demonstates that B2R blockade by the antaogonist fasibitant, abolishes both the initial stimulus and its amplification, strongly attenuating the propagation of inflammation.

  16. Identification of snake bradykinin-potentiating peptides (BPPs)-simile sequences in rat brain--Potential BPP-like precursor protein?

    Science.gov (United States)

    Campeiro, Joana D'Arc; Neshich, Izabella P; Sant'Anna, Osvaldo A; Lopes, Robson; Ianzer, Danielle; Assakura, Marina T; Neshich, Goran; Hayashi, Mirian A F

    2015-08-01

    Bradykinin-potentiating peptides (BPPs) from the South American pit viper snake venom were the first natural inhibitors of the human angiotensin I-converting enzyme (ACE) described. The pioneer characterization of the BPPs precursor from the snake venom glands by our group showed for the first time the presence of the C-type natriuretic peptide (CNP) in this same viper precursor protein. The confirmation of the BPP/CNP expression in snake brain regions correlated with neuroendocrine functions stimulated us to pursue the physiological correlates of these vasoactive peptides in mammals. Notably, several snake toxins were shown to have endogenous physiological correlates in mammals. In the present work, we expressed in bacteria the BPPs domain of the snake venom gland precursor protein, and this purified recombinant protein was used to raise specific polyclonal anti-BPPs antibodies. The correspondent single protein band immune-recognized in adult rat brain cytosol was isolated by 2D-SDS/PAGE and/or HPLC, before characterization by MS fingerprint analysis, which identified this protein as superoxide dismutase (SOD, EC 1.15.1.1), a classically known enzyme with antioxidant activity and important roles in the blood pressure modulation. In silico analysis showed the exposition of the BPP-like peptide sequences on the surface of the 3D structure of rat SOD. These peptides were chemically synthesized to show the BPP-like biological activities in ex vivo and in vivo pharmacological bioassays. Taken together, our data suggest that SOD protein have the potential to be a source for putative BPP-like bioactive peptides, which once released may contribute to the blood pressure control in mammals. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea.

    Science.gov (United States)

    Anderson, W Gary; Leprince, Jérôme; Conlon, J Michael

    2008-08-01

    A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.

  18. Substances labelled in metabolically stable positions. Pt. 3

    International Nuclear Information System (INIS)

    Maeding, P.; Steinbach, J.; Kasper, H.

    1994-01-01

    The synthesis of 11 C-ring-labelled substances such as phenylalanine is the reduction of [1- 11 C]-nitrobenzene to 11 C-ring-labelled aniline. The appropriate diazonium salt is chosen to be the labelled synthone for further reactions. (orig./EF)

  19. Theory of stable allocations

    Directory of Open Access Journals (Sweden)

    Pantelić Svetlana

    2014-01-01

    Full Text Available The Swedish Royal Academy awarded the 2012 Nobel Prize in Economics to Lloyd Shapley and Alvin Roth, for the theory of stable allocations and the practice of market design. These two American researchers worked independently from each other, combining basic theory and empirical investigations. Through their experiments and practical design they generated a flourishing field of research and improved the performance of many markets. Born in 1923 in Cambridge, Massachusetts, Shapley defended his doctoral thesis at Princeton University in 1953. For many years he worked at RAND, and for more than thirty years he was a professor at UCLA University. He published numerous scientific papers, either by himself or in cooperation with other economists.

  20. Applications of stable isotopes

    International Nuclear Information System (INIS)

    Gregg, C.T.

    1977-01-01

    Clinical applications include the galactose breath test which consists of oral administration of 13 C-labeled galactose and measurement of the 13 C content of respired CO 2 as a function of time in patients with cirrhotic livers for diagnosis of liver dysfunction. Another application was the breath test to study glucose metabolism in children. Respired 13 CO 2 from ingested glucose- 13 C was measured for normal and diabetic children. Studies on mice in which 60 percent of the body carbon was replaced with 13 C failed to show significant effects of the isotope. Studies on biochemical applications include nuclear magnetic resonance studies of 13 C-labeled amino acids from Chlorella pyrenoidosa; studies on 15 N nmr spectra of arginine-guanidino- 13 C-2,3-- 15 N 2 as a function of pH; and isolation of fatty acids from algae

  1. Bi-stable optical actuator

    Science.gov (United States)

    Holdener, Fred R.; Boyd, Robert D.

    2000-01-01

    The present invention is a bi-stable optical actuator device that is depowered in both stable positions. A bearing is used to transfer motion and smoothly transition from one state to another. The optical actuator device may be maintained in a stable position either by gravity or a restraining device.

  2. Stable isotopes in plant nutrition, soil fertility and environmental studies

    International Nuclear Information System (INIS)

    1991-01-01

    The individual contributions in these proceedings are indexed separately. Main topics covered include the measurement of biological nitrogen fixation, studies of soil organic matter, investigations of nutrient uptake and use by plants, studies of plant metabolism and new methodologies in the analysis of stable isotopes. Refs, figs and tabs

  3. Protein-based stable isotope probing.

    Science.gov (United States)

    Jehmlich, Nico; Schmidt, Frank; Taubert, Martin; Seifert, Jana; Bastida, Felipe; von Bergen, Martin; Richnow, Hans-Hermann; Vogt, Carsten

    2010-12-01

    We describe a stable isotope probing (SIP) technique that was developed to link microbe-specific metabolic function to phylogenetic information. Carbon ((13)C)- or nitrogen ((15)N)-labeled substrates (typically with >98% heavy label) were used in cultivation experiments and the heavy isotope incorporation into proteins (protein-SIP) on growth was determined. The amount of incorporation provides a measure for assimilation of a substrate, and the sequence information from peptide analysis obtained by mass spectrometry delivers phylogenetic information about the microorganisms responsible for the metabolism of the particular substrate. In this article, we provide guidelines for incubating microbial cultures with labeled substrates and a protocol for protein-SIP. The protocol guides readers through the proteomics pipeline, including protein extraction, gel-free and gel-based protein separation, the subsequent mass spectrometric analysis of peptides and the calculation of the incorporation of stable isotopes into peptides. Extraction of proteins and the mass fingerprint measurements of unlabeled and labeled fractions can be performed in 2-3 d.

  4. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  5. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Quitterer, Ursula, E-mail: ursula.quitterer@pharma.ethz.ch [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland); Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland)

    2011-06-10

    Highlights: {yields} A new FRET-based method detects AT1/B2 receptor heterodimerization. {yields} First time application of AT1-Cerulean as a FRET donor. {yields} Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. {yields} A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. {yields} AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R

  6. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    International Nuclear Information System (INIS)

    Quitterer, Ursula; Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said

    2011-01-01

    Highlights: → A new FRET-based method detects AT1/B2 receptor heterodimerization. → First time application of AT1-Cerulean as a FRET donor. → Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. → A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. → AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R heterodimerization, confocal FRET imaging of

  7. One-dimensional stable distributions

    CERN Document Server

    Zolotarev, V M

    1986-01-01

    This is the first book specifically devoted to a systematic exposition of the essential facts known about the properties of stable distributions. In addition to its main focus on the analytic properties of stable laws, the book also includes examples of the occurrence of stable distributions in applied problems and a chapter on the problem of statistical estimation of the parameters determining stable laws. A valuable feature of the book is the author's use of several formally different ways of expressing characteristic functions corresponding to these laws.

  8. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  9. Stable isotope research pool inventory

    International Nuclear Information System (INIS)

    1980-12-01

    This report contains a listing of electromagnetically separated stable isotopes which are available for distribution within the United States for non-destructive research use from the Oak Ridge National Laboratory on a loan basis. This inventory includes all samples of stable isotopes in the Materials Research Collection and does not designate whether a sample is out on loan or in reprocessing

  10. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  11. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  12. Stable isotope-resolved metabolomics and applications for drug development

    Science.gov (United States)

    Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

    2012-01-01

    Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

  13. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  14. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  15. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat

    DEFF Research Database (Denmark)

    Teperino, Raffaele; Amann, Sabine; Bayer, Martina

    2012-01-01

    Diabetes, obesity, and cancer affect upward of 15% of the world's population. Interestingly, all three diseases juxtapose dysregulated intracellular signaling with altered metabolic state. Exactly which genetic factors define stable metabolic set points in vivo remains poorly understood. Here, we...

  16. Stable configurations in social networks

    Science.gov (United States)

    Bronski, Jared C.; DeVille, Lee; Ferguson, Timothy; Livesay, Michael

    2018-06-01

    We present and analyze a model of opinion formation on an arbitrary network whose dynamics comes from a global energy function. We study the global and local minimizers of this energy, which we call stable opinion configurations, and describe the global minimizers under certain assumptions on the friendship graph. We show a surprising result that the number of stable configurations is not necessarily monotone in the strength of connection in the social network, i.e. the model sometimes supports more stable configurations when the interpersonal connections are made stronger.

  17. Development of Stable Isotope Technology

    International Nuclear Information System (INIS)

    Jeong, Do Young; Kim, Cheol Jung; Han, Jae Min

    2009-03-01

    KAERI has obtained an advanced technology with singular originality for laser stable isotope separation. Objectives for this project are to get production technology of Tl-203 stable isotope used for medical application and are to establish the foundation of the pilot system, while we are taking aim at 'Laser Isotope Separation Technology to make resistance to the nuclear proliferation'. And we will contribute to ensuring a nuclear transparency in the world society by taking part in a practical group of NSG and being collaboration with various international groups related to stable isotope separation technology

  18. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  19. Stable isotope research pool inventory

    International Nuclear Information System (INIS)

    1984-03-01

    This report contains a listing of electromagnetically separated stable isotopes which are available at the Oak Ridge National Laboratory for distribution for nondestructive research use on a loan basis. This inventory includes all samples of stable isotopes in the Research Materials Collection and does not designate whether a sample is out on loan or is in reprocessing. For some of the high abundance naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56

  20. French days on stable isotopes

    International Nuclear Information System (INIS)

    2000-01-01

    These first French days on stable isotopes took place in parallel with the 1. French days of environmental chemistry. Both conferences had common plenary sessions. The conference covers all aspects of the use of stable isotopes in the following domains: medicine, biology, environment, tracer techniques, agronomy, food industry, geology, petroleum geochemistry, cosmo-geochemistry, archaeology, bio-geochemistry, hydrology, climatology, nuclear and particle physics, astrophysics, isotope separations etc.. Abstracts available on CD-Rom only. (J.S.)

  1. Stable isotope research pool inventory

    International Nuclear Information System (INIS)

    1982-01-01

    This report contains a listing of electromagnetically separated stable isotopes which are available for distribution within the United States for nondestructive research use from the Oak Ridge National Laboratory on a loan basis. This inventory includes all samples of stable isotopes in the Material Research Collection and does not designate whether a sample is out on loan or in reprocessing. For some of the high abundance naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56

  2. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  3. Stable isotope tracers and exercise physiology: past, present and future.

    Science.gov (United States)

    Wilkinson, Daniel J; Brook, Matthew S; Smith, Kenneth; Atherton, Philip J

    2017-05-01

    Stable isotope tracers have been invaluable assets in physiological research for over 80 years. The application of substrate-specific stable isotope tracers has permitted exquisite insight into amino acid, fatty-acid and carbohydrate metabolic regulation (i.e. incorporation, flux, and oxidation, in a tissue-specific and whole-body fashion) in health, disease and response to acute and chronic exercise. Yet, despite many breakthroughs, there are limitations to 'substrate-specific' stable isotope tracers, which limit physiological insight, e.g. the need for intravenous infusions and restriction to short-term studies (hours) in controlled laboratory settings. In recent years significant interest has developed in alternative stable isotope tracer techniques that overcome these limitations, in particular deuterium oxide (D 2 O or heavy water). The unique properties of this tracer mean that through oral administration, the turnover and flux through a number of different substrates (muscle proteins, lipids, glucose, DNA (satellite cells)) can be monitored simultaneously and flexibly (hours/weeks/months) without the need for restrictive experimental control. This makes it uniquely suited for the study of 'real world' human exercise physiology (amongst many other applications). Moreover, using D 2 O permits evaluation of turnover of plasma and muscle proteins (e.g. dynamic proteomics) in addition to metabolomics (e.g. fluxomics) to seek molecular underpinnings, e.g. of exercise adaptation. Here, we provide insight into the role of stable isotope tracers, from substrate-specific to novel D 2 O approaches, in facilitating our understanding of metabolism. Further novel potential applications of stable isotope tracers are also discussed in the context of integration with the snowballing field of 'omic' technologies. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  4. Avaliação do Metabolismo Nutricional em Poedeiras pela Técnica dos Isótopos Estáveis do Ccarbono (13C/12C Nutritional Metabolism Evaluation of Laying Hens Using Stable-Carbon Isotopes (13C/12C

    Directory of Open Access Journals (Sweden)

    AS Carrijo

    2000-09-01

    Full Text Available Os isótopos estáveis do carbono que eram utilizados em estudos ecológicos e paleoecológicos apresentaram um incremento nos últimos trinta anos, na utilização em estudos dietéticos em animais. Entretanto, existem poucas informações sobre o padrão metabólico e sobre as taxas de turnover do 13C em aves. O presente experimento estabeleceu curvas de substituição e taxas de movimentação do 13C no ovo e no fígado de aves de postura adultas, pela substituição da ração comercial por dietas compostas de grãos dos ciclos fotossintéticos C3 e C4, durante 50 dias. A diferença no conteúdo isotópico do delta per mil do carbono-13 (delta‰ 13C entre as duas dietas foi de 16,13‰. A taxa de substituição do 13C das dietas, nos tecidos, adequou-se num modelo exponencial, descrevendo o turnover do carbono nos tecidos analisados. As taxas de movimentação do 13C, nas aves alimentadas com dieta baseada em grãos C3, foi maior no fígado em relação ao ovo, com valores para a meia-vida de 2,9 e 3,7 dias, respectivamente. As aves que receberam ração com grãos C4 apresentaram uma taxa de turnover no ovo superior àquela obtida para o fígado, com meia-vida de 4,0 e 5,3 dias, respectivamente. Os valores do delta‰13C observados para ovo e fígado diferiram em aproximadamente 2‰ daqueles referentes às dietas.The stable carbon isotopes used in ecology and paleoecology during the last 30 years has now been used in dietary studies of animals. However, there are not enough studies on the metabolism patterns and turnover rates of the 13C in avian. This experiment established the turnover rates of the 13C in egg and liver tissues of adult laying hens through the substitution of commercial diets by diets containing C3 and C4 photosynthetic cycle grains for 50 days. The delta‰13C difference in two diets contents was 16.13‰. The diets 13C turnover rates in tissues were adapted in an exponential model that describes the isotopic carbon

  5. [Current Treatment of Stable Angina].

    Science.gov (United States)

    Toggweiler, Stefan; Jamshidi, Peiman; Cuculi, Florim

    2015-06-17

    Current therapy for stable angina includes surgical and percutaneous revascularization, which has been improved tremendously over the last decades. Smoking cessation and regular exercise are the cornerstone for prevention of further cerebrovascular events. Medical treatment includes treatment of cardiovascular risk factors and antithrombotic management, which can be a challenge in some patients. Owing to the fact the coronary revascularization is readily accessible these days in many industrialized countries, the importance of antianginal therapy has decreased over the past years. This article presents a contemporary overview of the management of patients with stable angina in the year 2015.

  6. Metabolic Surgery

    DEFF Research Database (Denmark)

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

  7. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  8. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  9. Advances in ammonia metabolism and hepatic encephalopathy

    International Nuclear Information System (INIS)

    Soeters, P.B.; Wilson, J.H.P.; Meijer, A.J.; Holm, E.

    1988-01-01

    There are four main 'parts' within the book: the first is devoted to peripheral and hepatic ammonia metabolism, the urea cycle, acid base status and its regulation; part two addresses animal models in liver failure, GABA-ergic neurotransmission and its relevance in hepatic failure; a third part concerns neurochemistry including brain ammonia metabolism, serotonin metabolism and energy status, in vivo evaluated with modern techniques like infusion of compounds labeled with stable or radioactive isotopes and with NMR, while the last section provides a description of the determination of ammonia and the treatment of encephalopathy with established but also with experimental techniques. refs.; figs.; tabs

  10. Possibility of stable quark stars

    International Nuclear Information System (INIS)

    Bowers, R.L.; Gleeson, A.M.; Pedigo, R.D.

    1976-08-01

    A recent zero temperature equation of state which contains quark-partons separated from conventional baryons by a phase transition is used to investigate the stability of quark stars. The sensitivity to the input physics is also considered. The conclusions, which are found to be relatively model independent, indicate that a separately identifiable class of stable objects called quark stars does not exist

  11. Radiation-stable polyolefin compositions

    International Nuclear Information System (INIS)

    Rekers, J.W.

    1986-01-01

    This invention relates to compositions of olefinic polymers suitable for high energy radiation treatment. In particular, the invention relates to olefinic polymer compositions that are stable to sterilizing dosages of high energy radiation such as a gamma radiation. Stabilizers are described that include benzhydrol and benzhydrol derivatives; these stabilizers may be used alone or in combination with secondary antioxidants or synergists

  12. NMR-based stable isotope resolved metabolomics in systems biochemistry

    International Nuclear Information System (INIS)

    Fan, Teresa W-M.; Lane, Andrew N.

    2011-01-01

    An important goal of metabolomics is to characterize the changes in metabolic networks in cells or various tissues of an organism in response to external perturbations or pathologies. The profiling of metabolites and their steady state concentrations does not directly provide information regarding the architecture and fluxes through metabolic networks. This requires tracer approaches. NMR is especially powerful as it can be used not only to identify and quantify metabolites in an unfractionated mixture such as biofluids or crude cell/tissue extracts, but also determine the positional isotopomer distributions of metabolites derived from a precursor enriched in stable isotopes such as 13 C and 15 N via metabolic transformations. In this article we demonstrate the application of a variety of 2-D NMR editing experiments to define the positional isotopomers of compounds present in polar and non-polar extracts of human lung cancer cells grown in either [U– 13 C]-glucose or [U– 13 C, 15 N]-glutamine as source tracers. The information provided by such experiments enabled unambiguous reconstruction of metabolic pathways, which is the foundation for further metabolic flux modeling.

  13. Uses and limits of radiotracers in the study of drugs and xenobiotics metabolism

    International Nuclear Information System (INIS)

    Cohen, Y.

    1980-01-01

    This review deals with scientific papers issued in 1977-1978, on labelling of drugs and xenobiotics and their metabolism. It is divided in five parts: site of label; in vivo metabolism in animals and human beings; in vitro metabolism on tissue slices, cells culture, microsomes, membrane receptors; metabolism of xenobiotics: nutrients, food additives, detergents, plastics and fabrics; discussion. Metabolic studies, nowadays, associate radiotracers, stable isotopes with high performing procedures for analytical separation [fr

  14. [Studies on the relation between glucose metabolism and c-AMP formation in dental pulps in the presence of inflammatory chemical mediators in vitro].

    Science.gov (United States)

    Kiyohara, H

    1989-01-01

    The relationship between glucose metabolism and cyclic-AMP production in dental pulp in the presence of chemical mediators was investigated in vitro. It is generally accepted that oxidation of glucose-6-14C is indicative of metabolism by the glycolytic pathway whereas that of glucose-1-14C occurs by the hexose monophosphate shunt. The 14CO2 productions from both routes were compared in dental pulp from cattle and rats in the presence of each of several chemical mediators: bradykinin (1.7-3.3 micrograms/ml), prostaglandin E1 (0.3 micrograms/ml), prostaglandin E2 (0.3 micrograms/ml), histamine (33 micrograms/ml), and 5-hydroxytryptamine (33 micrograms/ml). The effects of dental filling materials on glucose oxidation, and cyclic-AMP production by chemical mediators in pulp tissues were also investigated. The results obtained were as follows: 1) Glucose oxidation in dental pulp was stimulated by chemical mediators generally by way of the Embden-Meyerhof Parnas pathway, and was further stimulated by the medium containing bradykinin. However, it was depressed in the presence of higher concentrations of chemical mediators, especially depressed in the HMS pathway. 2) The oxidation ratio of glucose-1-14C to glucose-6-14C (G1/G6) in dental pulp was 4 to 8 in the cattle and 0.6 in the rat, showing clear differences in glucose oxidation between the two animals. 3) Moreover, glucose oxidation in rat dental pulp was 60 to 80 times higher in the EMP pathway and 5 to 10 times higher in the HMS pathway than those in the cattle. 4) Dental filling materials such as silicate cement, zinc phosphate cement, calcium hydroxide, and eugenol cement severely depressed glucose-6-14C oxidation in bovine dental pulp when used at high concentrations, but not at low concentrations. 5) The chemical mediators tested in this experiment (PGE1, PGE2, histamine, 5-HT, bradykinin, and substance P) stimulated cyclic AMP production in rat dental pulp. The production was highest with PGE1 and PGE2. The

  15. In vivo iron metabolism by IRMS

    Science.gov (United States)

    Iron isotopes are used in both biological and geological investigations. Three low-abundance stable isotopes are available for human studies. They have been widely used to study iron metabolism. They have provided valuable insights into iron deficiency, one of the most common micronutrient deficienc...

  16. Toward Practical Secure Stable Matching

    Directory of Open Access Journals (Sweden)

    Riazi M. Sadegh

    2017-01-01

    Full Text Available The Stable Matching (SM algorithm has been deployed in many real-world scenarios including the National Residency Matching Program (NRMP and financial applications such as matching of suppliers and consumers in capital markets. Since these applications typically involve highly sensitive information such as the underlying preference lists, their current implementations rely on trusted third parties. This paper introduces the first provably secure and scalable implementation of SM based on Yao’s garbled circuit protocol and Oblivious RAM (ORAM. Our scheme can securely compute a stable match for 8k pairs four orders of magnitude faster than the previously best known method. We achieve this by introducing a compact and efficient sub-linear size circuit. We even further decrease the computation cost by three orders of magnitude by proposing a novel technique to avoid unnecessary iterations in the SM algorithm. We evaluate our implementation for several problem sizes and plan to publish it as open-source.

  17. Stable isotope research pool inventory

    International Nuclear Information System (INIS)

    1986-08-01

    This report contains a listing of electromagnetically separated stable isotopes which are available at the Oak Ridge National Laboratory for distribution for nondestructive research use on a loan basis. This inventory includes all samples of stable isotopes in the Research Materials Collection and does not designate whether a sample is out on loan or is in reprocessing. For some of the high-abundance, naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56. All requests for the loan of samples should be submitted with a summary of the purpose of the loan to: Iotope Distribution Office, Oak Ridge National Laboratory, P.O. Box X, Oak Ridge, Tennessee 37831. Requests from non-DOE contractors and from foreign institutions require DOE approval

  18. Stable isotopes and the environment

    International Nuclear Information System (INIS)

    Krouse, H.R.

    1990-01-01

    Whereas traditionally, stable isotope research has been directed towards resource exploration and development, it is finding more frequent applications in helping to assess the impacts of resource utilization upon ecosystems. Among the many pursuits, two themes are evident: tracing the transport and conversions of pollutants in the environment and better understanding of the interplay among environmental receptors, e.g. food web studies. Stable isotope data are used primarily to identify the presence of pollutants in the environment and with a few exceptions, the consequence of their presence must be assessed by other techniques. Increasing attention has been given to the isotopic composition of humans with many potential applications in areas such as paleodiets, medicine, and criminology. In this brief overview examples are used from the Pacific Rim to illustrate the above concepts. 26 refs., 1 tab., 3 figs

  19. Towards stable acceleration in LINACS

    CERN Document Server

    Dubrovskiy, A D

    2014-01-01

    Ultra-stable and -reproducible high-energy particle beams with short bunches are needed in novel linear accelerators and, in particular, in the Compact Linear Collider CLIC. A passive beam phase stabilization system based on a bunch compression with a negative transfer matrix element R56 and acceleration at a positive off-crest phase is proposed. The motivation and expected advantages of the proposed scheme are outlined.

  20. Stable Structures for Distributed Applications

    OpenAIRE

    Eugen DUMITRASCU; Ion IVAN

    2008-01-01

    For distributed applications, we define the linear, tree and graph structure types with different variants and modalities to aggregate them. The distributed applications have assigned structures that through their characteristics influence the costs of stages for developing cycle and the costs for exploitation, transferred to each user. We also present the quality characteristics of a structure for a stable application, which is focused on stability characteristic. For that characteristic we ...

  1. Progress in stable isotope analysis and new possibilities of clinical investigations

    International Nuclear Information System (INIS)

    Roth, E.

    1989-01-01

    The use of stable isotopes in medicine rests on three possibilities offered by labelling: identification of an element, a molecule, or a fragment of a molecule along its biological pathway; quantification of biological pools by isotopic dilution; measurement of metabolization rates, and more generally of clearances. Whenever a corporal function experiences a disregulation reflected either by changes in metabolic activity or modifications of the importance of pools of certain molecules, the possibility exists of making use of isotopes in diagnosis. Examples of practical applications of stable isotopes are given and analytical problems that had to be solved are underlined

  2. Use of stable isotopes in developing countries: safe markers for nutrition regime study

    International Nuclear Information System (INIS)

    Klein, P.D.; Klein, E.R.

    1987-01-01

    Possible use of stable radioisotopes in studies on nutrition and medicine problems that may be used in investigations of babies, children, pregnant women is shown. Attention is paid to behaviour of limited number of elements: hydrogen, carbon, nitrogen, oxygen. The IAEA plans implementation of a new coordinated research program on use of stable isotopes for studying nutrition problems and related diseases. The program emphasis will be placed on protein metabolism measurements and estimation of energy consumption in control population groups in developing countries

  3. DNA stable-isotope probing (DNA-SIP).

    Science.gov (United States)

    Dunford, Eric A; Neufeld, Josh D

    2010-08-02

    DNA stable-isotope probing (DNA-SIP) is a powerful technique for identifying active microorganisms that assimilate particular carbon substrates and nutrients into cellular biomass. As such, this cultivation-independent technique has been an important methodology for assigning metabolic function to the diverse communities inhabiting a wide range of terrestrial and aquatic environments. Following the incubation of an environmental sample with stable-isotope labelled compounds, extracted nucleic acid is subjected to density gradient ultracentrifugation and subsequent gradient fractionation to separate nucleic acids of differing densities. Purification of DNA from cesium chloride retrieves labelled and unlabelled DNA for subsequent molecular characterization (e.g. fingerprinting, microarrays, clone libraries, metagenomics). This JoVE video protocol provides visual step-by-step explanations of the protocol for density gradient ultracentrifugation, gradient fractionation and recovery of labelled DNA. The protocol also includes sample SIP data and highlights important tips and cautions that must be considered to ensure a successful DNA-SIP analysis.

  4. Organic synthesis with stable isotopes

    International Nuclear Information System (INIS)

    Daub, G.H.; Kerr, V.N.; Williams, D.L.; Whaley, T.W.

    1978-01-01

    Some general considerations concerning organic synthesis with stable isotopes are presented. Illustrative examples are described and discussed. The examples include DL-2-amino-3-methyl- 13 C-butanoic-3,4- 13 C 2 acid (DL-valine- 13 C 3 ); methyl oleate-1- 13 C; thymine-2,6- 13 C 2 ; 2-aminoethanesulfonic- 13 C acid (taurine- 13 C); D-glucose-6- 13 C; DL-2-amino-3-methylpentanoic-3,4- 13 C 2 acid (DL-isoleucine- 13 C 2 ); benzidine- 15 N 2 ; and 4-ethylsulfonyl-1-naphthalene-sulfonamide- 15 N

  5. Stable isotopes - separation and application

    International Nuclear Information System (INIS)

    Lockhart, I.M.

    1980-01-01

    In this review, methods used for the separation of stable isotopes ( 12 C, 13 C, 14 N, 15 N, 16 O, 17 O, 18 O, 34 S) will be described. The synthesis of labelled compounds, techniques for detection and assay, and areas of application will also be discussed. Particular attention will be paid to the isotopes of carbon, nitrogen, and oxygen; to date, sulphur isotopes have only assumed a minor role. The field of deuterium chemistry is too extensive for adequate treatment; it will therefore be essentially excluded. (author)

  6. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  7. Stable cosmology in chameleon bigravity

    Science.gov (United States)

    De Felice, Antonio; Mukohyama, Shinji; Oliosi, Michele; Watanabe, Yota

    2018-02-01

    The recently proposed chameleonic extension of bigravity theory, by including a scalar field dependence in the graviton potential, avoids several fine-tunings found to be necessary in usual massive bigravity. In particular it ensures that the Higuchi bound is satisfied at all scales, that no Vainshtein mechanism is needed to satisfy Solar System experiments, and that the strong coupling scale is always above the scale of cosmological interest all the way up to the early Universe. This paper extends the previous work by presenting a stable example of cosmology in the chameleon bigravity model. We find a set of initial conditions and parameters such that the derived stability conditions on general flat Friedmann background are satisfied at all times. The evolution goes through radiation-dominated, matter-dominated, and de Sitter eras. We argue that the parameter space allowing for such a stable evolution may be large enough to encompass an observationally viable evolution. We also argue that our model satisfies all known constraints due to gravitational wave observations so far and thus can be considered as a unique testing ground of gravitational wave phenomenologies in bimetric theories of gravity.

  8. Stable Heavy Hadrons in ATLAS

    CERN Document Server

    Mackeprang, Rasmus

    2007-01-01

    Several extensions to the SM feature heavy long-lived particles with masses of O(10^2-10^3 GeV) and mean lifetimes fulfilling $CT \\geq 10m$. Among such theories are supersymmetric scenarios as well as extra-dimensional models in which the heavy new particles are seen as Kaluza-Klein excitations of the well-known SM particles. Such particles will, from the point of view of a collider experiment be seen as stable. This thesis is concerned with the case where the exotic heavy particles emph{can} be considered stable while traversing the detector. Specifically the case is considered where the particles in question carry the charge of the strong nuclear force, commonly referred to as emph{colour charge}. A simulation kit has been developed using GEANT4. This framework is the current standard in experimental particle physics for the simulation of interactions of particles with matter, and it is used extensively for detector simulation. The simulation describes the interactions of these particles with matter which i...

  9. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  10. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  11. Stable isotope mass spectrometry in petroleum exploration

    International Nuclear Information System (INIS)

    Mathur, Manju

    1997-01-01

    The stable isotope mass spectrometry plays an important role to evaluate the stable isotopic composition of hydrocarbons. The isotopic ratios of certain elements in petroleum samples reflect certain characteristics which are useful for petroleum exploration

  12. Stable rotating dipole solitons in nonlocal media

    DEFF Research Database (Denmark)

    Lopez-Aguayo, Servando; Skupin, Stefan; Desyatnikov, Anton S.

    2006-01-01

    We present the first example of stable rotating two-soliton bound states in nonlinear optical media with nonlocal response. We show that, in contrast to media with local response, nonlocality opens possibilities to generate stable azimuthons.......We present the first example of stable rotating two-soliton bound states in nonlinear optical media with nonlocal response. We show that, in contrast to media with local response, nonlocality opens possibilities to generate stable azimuthons....

  13. Tempered stable laws as random walk limits

    OpenAIRE

    Chakrabarty, Arijit; Meerschaert, Mark M.

    2010-01-01

    Stable laws can be tempered by modifying the L\\'evy measure to cool the probability of large jumps. Tempered stable laws retain their signature power law behavior at infinity, and infinite divisibility. This paper develops random walk models that converge to a tempered stable law under a triangular array scheme. Since tempered stable laws and processes are useful in statistical physics, these random walk models can provide a basic physical model for the underlying physical phenomena.

  14. Stable States of Biological Organisms

    Science.gov (United States)

    Yukalov, V. I.; Sornette, D.; Yukalova, E. P.; Henry, J.-Y.; Cobb, J. P.

    2009-04-01

    A novel model of biological organisms is advanced, treating an organism as a self-consistent system subject to a pathogen flux. The principal novelty of the model is that it describes not some parts, but a biological organism as a whole. The organism is modeled by a five-dimensional dynamical system. The organism homeostasis is described by the evolution equations for five interacting components: healthy cells, ill cells, innate immune cells, specific immune cells, and pathogens. The stability analysis demonstrates that, in a wide domain of the parameter space, the system exhibits robust structural stability. There always exist four stable stationary solutions characterizing four qualitatively differing states of the organism: alive state, boundary state, critical state, and dead state.

  15. Super-stable Poissonian structures

    International Nuclear Information System (INIS)

    Eliazar, Iddo

    2012-01-01

    In this paper we characterize classes of Poisson processes whose statistical structures are super-stable. We consider a flow generated by a one-dimensional ordinary differential equation, and an ensemble of particles ‘surfing’ the flow. The particles start from random initial positions, and are propagated along the flow by stochastic ‘wave processes’ with general statistics and general cross correlations. Setting the initial positions to be Poisson processes, we characterize the classes of Poisson processes that render the particles’ positions—at all times, and invariantly with respect to the wave processes—statistically identical to their initial positions. These Poisson processes are termed ‘super-stable’ and facilitate the generalization of the notion of stationary distributions far beyond the realm of Markov dynamics. (paper)

  16. Super-stable Poissonian structures

    Science.gov (United States)

    Eliazar, Iddo

    2012-10-01

    In this paper we characterize classes of Poisson processes whose statistical structures are super-stable. We consider a flow generated by a one-dimensional ordinary differential equation, and an ensemble of particles ‘surfing’ the flow. The particles start from random initial positions, and are propagated along the flow by stochastic ‘wave processes’ with general statistics and general cross correlations. Setting the initial positions to be Poisson processes, we characterize the classes of Poisson processes that render the particles’ positions—at all times, and invariantly with respect to the wave processes—statistically identical to their initial positions. These Poisson processes are termed ‘super-stable’ and facilitate the generalization of the notion of stationary distributions far beyond the realm of Markov dynamics.

  17. Periodicity of the stable isotopes

    CERN Document Server

    Boeyens, J C A

    2003-01-01

    It is demonstrated that all stable (non-radioactive) isotopes are formally interrelated as the products of systematically adding alpha particles to four elementary units. The region of stability against radioactive decay is shown to obey a general trend based on number theory and contains the periodic law of the elements as a special case. This general law restricts the number of what may be considered as natural elements to 100 and is based on a proton:neutron ratio that matches the golden ratio, characteristic of biological and crystal growth structures. Different forms of the periodic table inferred at other proton:neutron ratios indicate that the electronic configuration of atoms is variable and may be a function of environmental pressure. Cosmic consequences of this postulate are examined. (author)

  18. Stable massive particles at colliders

    Energy Technology Data Exchange (ETDEWEB)

    Fairbairn, M.; /Stockholm U.; Kraan, A.C.; /Pennsylvania U.; Milstead, D.A.; /Stockholm U.; Sjostrand, T.; /Lund U.; Skands, P.; /Fermilab; Sloan, T.; /Lancaster U.

    2006-11-01

    We review the theoretical motivations and experimental status of searches for stable massive particles (SMPs) which could be sufficiently long-lived as to be directly detected at collider experiments. The discovery of such particles would address a number of important questions in modern physics including the origin and composition of dark matter in the universe and the unification of the fundamental forces. This review describes the techniques used in SMP-searches at collider experiments and the limits so far obtained on the production of SMPs which possess various colour, electric and magnetic charge quantum numbers. We also describe theoretical scenarios which predict SMPs, the phenomenology needed to model their production at colliders and interactions with matter. In addition, the interplay between collider searches and open questions in cosmology such as dark matter composition are addressed.

  19. The Myopic Stable Set for Social Environments

    NARCIS (Netherlands)

    Demuynck, Thomas; Herings, P. Jean-Jacques; Saulle, Riccardo; Seel, Christian

    2017-01-01

    We introduce a new solution concept for models of coalition formation, called the myopic stable set. The myopic stable set is defined for a very general class of social environments and allows for an infinite state space. We show that the myopic stable set exists and is non-empty. Under minor

  20. Effectiveness and risks of stable iodine prophylaxis

    International Nuclear Information System (INIS)

    Waight, P.J.

    1995-01-01

    The factors upon which the efficacy of stable iodine prophylaxis depends are reviewed, with particular reference to the dose of stable iodine, the timing of the dose, the influence of dietary iodine and the impact of the other prospective actions. The risks of stable iodine ingestion are estimated, and their application to the principle of Justification in outlined. (Author)

  1. Temperature and Humidity Control in Livestock Stables

    DEFF Research Database (Denmark)

    Hansen, Michael; Andersen, Palle; Nielsen, Kirsten M.

    2010-01-01

    The paper describes temperature and humidity control of a livestock stable. It is important to have a correct air flow pattern in the livestock stable in order to achieve proper temperature and humidity control as well as to avoid draught. In the investigated livestock stable the air flow...

  2. Reducing the transfer of radioiodine to milk in cows by adding stable iodine to the forage

    International Nuclear Information System (INIS)

    Kiefer, P.; Voigt, G.

    1999-05-01

    The publication reports the activities for the study and explains the measured results achieved. The usefulness of stable iodine administration to cows for reducing radioiodine transfer to the milk is explained. It was found that enhanced stable radioiodine doses have an effect on the iodine metabolism of dairy cows that has to be taken into account. Initially, a literature study was carried out, which then served as a basis for defining subsequent study objectives and experiments. The evaluation of the results yields information about the effects of stable iodine on the radioiodine transfer, as well as the metabolic pathways of iodine in dairy cows. In order to achieve a clear transfer reducing effect (by a factor of 2), doses of 1g/d have to be fed to a cow. This dose will lead to a stable iodine concentration in the milk of about 10 mg/kg. The WHO recommends a daily maximum dose of 0.5 mg of stable iodine in order to safely prevent adverse health effects in man. Ingestion of more than 2 mg/d may induce in man thyroid disorders and other metabolic disorders. In some countries, the reference level for dairy milk accepted is 0.5 mg of iodine/kg of milk. (orig./CB) [de

  3. Basal metabolism in tropical birds: Latitude, altitude, and the 'pace of life'

    OpenAIRE

    Londoño, GA; Chappell, MA; Castañeda, MDR; Jankowski, JE; Robinson, SK

    2015-01-01

    © 2014 The Authors. Life history varies across latitudes, with the 'pace of life' being 'slower' in tropical regions. Because life history is coupled to energy metabolism via allocation tradeoffs and links between performance capacity and energy use, low metabolic intensity is expected in tropical animals. Low metabolism has been reported for lowland tropical birds, but it is unclear if this is due to 'slow' life history or to a warm, stable environment. We measured basal metabolic rates (BMR...

  4. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  5. Moltex Energy's stable salt reactors

    International Nuclear Information System (INIS)

    O'Sullivan, R.; Laurie, J.

    2016-01-01

    A stable salt reactor is a molten salt reactor in which the molten fuel salt is contained in fuel rods. This concept was invented in 1951 and re-discovered and improved recently by Moltex Energy Company. The main advantage of using molten salt fuel is that the 2 problematic fission products cesium and iodine do not exist in gaseous form but rather in a form of a salt that present no danger in case of accident. Another advantage is the strongly negative temperature coefficient for reactivity which means the reactor self-regulates. The feasibility studies have been performed on a molten salt fuel composed of sodium chloride and plutonium/uranium/lanthanide/actinide trichloride. The coolant fluid is a mix of sodium and zirconium fluoride salts that will need low flow rates. The addition of 1 mol% of metal zirconium to the coolant fluid reduces the risk of corrosion with standard steels and the addition of 2% of hafnium reduces the neutron dose. The temperature of the coolant is expected to reach 650 Celsius degrees at the exit of the core. This reactor is designed to be modular and it will be able to burn actinides. (A.C.)

  6. Rare stable isotopes in meteorites

    International Nuclear Information System (INIS)

    Wilson, G.C.

    1981-01-01

    Secondary Ion Mass Spectrometry (SIMS) using accelerators has been applied with success to cosmic ray exposure ages and terrestrial residence times of meteorites by measuring cosmogenic nuclides of Be, Cl, and I. It is proposed to complement this work with experiments on rare stable isotopes, in the hope of setting constraints on the processes of solar nebula/meteoritic formation. The relevant species can be classified as: a) daughter products of extinct nuclides (halflife less than or equal to 2 x 10 8 y) -chronology of the early solar system; b) products of high temperature astrophysical processes - different components incorporated into the solar nebula; and c) products of relatively low temperature processes, stellar winds and cosmic ray reactions - early solar system radiation history. The use of micron-scale primary ion beams will allow detailed sampling of phases within meteorites. Strategies of charge-state selection, molecular disintegration and detection should bring a new set of targets within analytical range. The developing accelerator field is compared to existing (keV energy) ion microprobes

  7. Stable piecewise polynomial vector fields

    Directory of Open Access Journals (Sweden)

    Claudio Pessoa

    2012-09-01

    Full Text Available Let $N={y>0}$ and $S={y<0}$ be the semi-planes of $mathbb{R}^2$ having as common boundary the line $D={y=0}$. Let $X$ and $Y$ be polynomial vector fields defined in $N$ and $S$, respectively, leading to a discontinuous piecewise polynomial vector field $Z=(X,Y$. This work pursues the stability and the transition analysis of solutions of $Z$ between $N$ and $S$, started by Filippov (1988 and Kozlova (1984 and reformulated by Sotomayor-Teixeira (1995 in terms of the regularization method. This method consists in analyzing a one parameter family of continuous vector fields $Z_{epsilon}$, defined by averaging $X$ and $Y$. This family approaches $Z$ when the parameter goes to zero. The results of Sotomayor-Teixeira and Sotomayor-Machado (2002 providing conditions on $(X,Y$ for the regularized vector fields to be structurally stable on planar compact connected regions are extended to discontinuous piecewise polynomial vector fields on $mathbb{R}^2$. Pertinent genericity results for vector fields satisfying the above stability conditions are also extended to the present case. A procedure for the study of discontinuous piecewise vector fields at infinity through a compactification is proposed here.

  8. Stable Structures for Distributed Applications

    Directory of Open Access Journals (Sweden)

    Eugen DUMITRASCU

    2008-01-01

    Full Text Available For distributed applications, we define the linear, tree and graph structure types with different variants and modalities to aggregate them. The distributed applications have assigned structures that through their characteristics influence the costs of stages for developing cycle and the costs for exploitation, transferred to each user. We also present the quality characteristics of a structure for a stable application, which is focused on stability characteristic. For that characteristic we define the estimated measure indicators for a level. The influence of the factors of stability and the ways for increasing it are thus identified, and at the same time the costs of development stages, the costs of usage and the costs of maintenance to be keep on between limits that assure the global efficiency of application. It is presented the base aspects for distributed applications: definition, peculiarities and importance. The aspects for the development cycle of distributed application are detailed. In this article, we alongside give the mechanisms for building the defined structures and analyze the complexity of the defined structures for a distributed application of a virtual store.

  9. The use of stable isotopes as minerals tracers in human nutrition research

    International Nuclear Information System (INIS)

    Sajet, A. S.

    2007-01-01

    The idea of using stable isotopes as tracers in metabolic studies of vital systems started when it was noted that stable isotopes have the ability to unite with biomolecules.The article aims to review the methods used to measure quantities of tracer in doses given to donors orally or via intravenous injection, determinants of detection and their estimation as well as the use of mass spectrometer and other devices to measure different stable isotopes. In fact, the use of stable isotopes in nutrition research is an essential technique in order to understand many of the processes related to minerals absorption and the human body composition of water, fat and bones, transportation of food components within the body and estimation of the ages of red blood cells. It is possible to use the secretion of stable isotopes taken by injection to determine the paths of excretion or estimate self-retaining material by the intestine. The stable isotope technology helps to know the mechanics of minerals absorption and excretion in the body. It was possible to find out metabolic reactions of metals using mathematical models based on the measurement of tracers amount in biological fluids in order to know the absorbance situation of metals in the body.

  10. Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179

    Directory of Open Access Journals (Sweden)

    Carmen Clapp

    2011-07-01

    Full Text Available Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK. Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS, as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activation of phospholipase C and the formation of inositol 1,4,5-triphosphate leading to a reduced release of Ca2+ from intracellular stores. The [Ca2+]i rise evoked by BK also involves the influx of extracellular Ca2+ via canonical transient receptor potential (TRPC channels. Vasoinhibins likely interfere with TRPC-mediated Ca2+ entry since La3+, which is an enhancer of TRPC4 and TRPC5 channel activity, prevented vasoinhibins from blocking the stimulation by BK of endothelial cell NO production and proliferation, and vasoinhibins reduced the BK-induced increase of TRPC5 mRNA expression. Finally, vasoinhibins prevented the BK-induced phosphorylation of eNOS at Ser1179, a post-translational modification that facilitates Ca2+-calmodulin activation of eNOS. Together, our data show that vasoinhibins, by lowering NO production through the inhibition of both [Ca2+]i mobilization and eNOS phosphorylation, prevent the BK-induced stimulation of endothelial cell proliferation. Thus, vasoinhibins help to regulate BK effects on angiogenesis and vascular homeostasis.

  11. Clinical and Biochemical Uses of Stable Iodine Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Koutras, D. A. [Thyroid Section, Alexandra Hospital, Athens (Greece)

    1970-07-01

    Iodine and thyroid function are closely linked, since the only known role of iodine is its participation in the synthesis of thyroid hormones. Iodine metabolism may be represented as a metabolic cycle consisting of three main pools: the Plasma Inorganic Iodine (PIl) pool into which dietary iodine goes and from where it is either taken up by the thyroid or excreted by the kidneys, the intrathyroidal iodine pool, where. thyroid hormone synthesis occurs, and finally the peripheral pool of thyroid hormones, of which about 80% are deiodinated and 20% excreted with the faeces. Endemic goitre is usually due to iodine deficiency. There is no renal homeostatic mechanism to keep the PII level constant, and so adaptation to iodine deficiency occurs by increasing the thyroidal iodide clearance rate. Stable iodine measurements are necessary for a complete study of iodine metabolism. Estimates of the serum Protein-Bound Iodine (PBl) are the best index of thyroid function, estimates of the PII and of the urinary iodine are the best indices of iodine nutrition. (author)

  12. Uptake, incorporation and metabolism of (3H)triolein in the isolated perfused rabbit heart

    International Nuclear Information System (INIS)

    Weis, M.T.; Palazzo, A.J.; Williams, J.L. Jr.; Malik, K.U.

    1990-01-01

    The purpose of these experiments was to study the uptake and metabolism of exogenous triglyceride in the isolated perfused rabbit heart. When infused into the rabbit heart, [9,10-3H(N)]triolein was retained and incorporated into a lipid fraction that had the chromatographic mobility of authentic triolein. Incorporation of labeled triolein was not likely to be the result of a lipoprotein lipase-mediated lipolysis/resynthesis cycle, since: (i) The distribution of radioactivity following administration of [3H]oleic acid was markedly different from the distribution of radioactivity following the administration of [3H]triolein; (ii) heparin was administered to the rabbits at the time of sacrifice; and (iii) the hearts were perfused with a protein-free buffer for 20 min prior to the labelling period. When isoproterenol was administered to hearts labelled with [3H]triolein, there was an increased output of total radioactivity, composed of labelled free fatty acids, diacylglycerol and monoacylglycerol. In these same hearts, there was an increased output of glycerol in response to isoproterenol. However, following the administration of bradykinin or angiotensin II, neither the radioactivity nor the glycerol content of the perfusate was changed. These data suggest that [3H]triolein is selectively incorporated into the triglyceride pool of the isolated perfused rabbit heart. Furthermore, this [3H]triolein is available to hormonally-activated lipolytic enzymes

  13. Advanced thermally stable jet fuels

    Energy Technology Data Exchange (ETDEWEB)

    Schobert, H.H.

    1999-01-31

    The Pennsylvania State University program in advanced thermally stable coal-based jet fuels has five broad objectives: (1) Development of mechanisms of degradation and solids formation; (2) Quantitative measurement of growth of sub-micrometer and micrometer-sized particles suspended in fuels during thermal stressing; (3) Characterization of carbonaceous deposits by various instrumental and microscopic methods; (4) Elucidation of the role of additives in retarding the formation of carbonaceous solids; (5) Assessment of the potential of production of high yields of cycloalkanes by direct liquefaction of coal. Future high-Mach aircraft will place severe thermal demands on jet fuels, requiring the development of novel, hybrid fuel mixtures capable of withstanding temperatures in the range of 400--500 C. In the new aircraft, jet fuel will serve as both an energy source and a heat sink for cooling the airframe, engine, and system components. The ultimate development of such advanced fuels requires a thorough understanding of the thermal decomposition behavior of jet fuels under supercritical conditions. Considering that jet fuels consist of hundreds of compounds, this task must begin with a study of the thermal degradation behavior of select model compounds under supercritical conditions. The research performed by The Pennsylvania State University was focused on five major tasks that reflect the objectives stated above: Task 1: Investigation of the Quantitative Degradation of Fuels; Task 2: Investigation of Incipient Deposition; Task 3: Characterization of Solid Gums, Sediments, and Carbonaceous Deposits; Task 4: Coal-Based Fuel Stabilization Studies; and Task 5: Exploratory Studies on the Direct Conversion of Coal to High Quality Jet Fuels. The major findings of each of these tasks are presented in this executive summary. A description of the sub-tasks performed under each of these tasks and the findings of those studies are provided in the remainder of this volume

  14. Protein Stable Isotope Fingerprinting (P-SIF): Multidimensional Protein Chromatography Coupled to Stable Isotope-Ratio Mass Spectrometry

    Science.gov (United States)

    Pearson, A.; Bovee, R. J.; Mohr, W.; Tang, T.

    2012-12-01

    As metagenomics increases our insight into microbial community diversity and metabolic potential, new approaches are required to determine the biogeochemical expression of this potential within ecosystems. Because stable isotopic analysis of the major bioactive elements (C, N) has been used historically to map flows of substrates and energy among macroscopic food webs, similar principles may apply to microbes. To address this challenge, we have developed a new analytical approach called Protein Stable Isotope Fingerprinting (P-SIF). P-SIF generates natural stable isotopic fingerprints of microbial individual or community proteomes. The main advantage of P-SIF is the potential to bridge the gap between diversity and function, thereby providing a window into the "black box" of environmental microbiology and helping to decipher the roles of uncultivated species. Our method implements a three-way, orthogonal scheme to separate mixtures of whole proteins into subfractions dominated by single or closely-related proteins. Protein extracts first are isoelectrically focused in a gel-free technique that yields 12 fractions separated over a gradient of pH 3-10. Each fraction then is separated by size-exclusion chromatography into 20 pools, ranging from >100kD to ~10kD. Finally, each of these pools is subjected to HPLC and collected in 40 time-slices based on protein hydrophobicity. Theoretical calculation reveals that the true chromatographic resolution of the total scheme is 5000, somewhat less than the 9600 resulting fractions. High-yielding fractions are subjected to δ13C analysis by spooling-wire microcombustion irMS (SWiM-irMS) optimized for samples containing 1-5 nmol carbon. Here we will present the method, results for a variety of pure cultures, and preliminary data for a sample of mixed environmental proteins. The data show the promise of this method for unraveling the metabolic complexity hidden within microbial communities.

  15. Population Games, Stable Games, and Passivity

    Directory of Open Access Journals (Sweden)

    Michael J. Fox

    2013-10-01

    Full Text Available The class of “stable games”, introduced by Hofbauer and Sandholm in 2009, has the attractive property of admitting global convergence to equilibria under many evolutionary dynamics. We show that stable games can be identified as a special case of the feedback-system-theoretic notion of a “passive” dynamical system. Motivated by this observation, we develop a notion of passivity for evolutionary dynamics that complements the definition of the class of stable games. Since interconnections of passive dynamical systems exhibit stable behavior, we can make conclusions about passive evolutionary dynamics coupled with stable games. We show how established evolutionary dynamics qualify as passive dynamical systems. Moreover, we exploit the flexibility of the definition of passive dynamical systems to analyze generalizations of stable games and evolutionary dynamics that include forecasting heuristics as well as certain games with memory.

  16. Stable-label intravenous glucose tolerance test minimal model

    International Nuclear Information System (INIS)

    Avogaro, A.; Bristow, J.D.; Bier, D.M.; Cobelli, C.; Toffolo, G.

    1989-01-01

    The minimal model approach to estimating insulin sensitivity (Sl) and glucose effectiveness in promoting its own disposition at basal insulin (SG) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with [6,6- 2 H 2 ]glucose, [2- 2 H]glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated S*l derived from the stable-label IVGTT was greater than Sl in each case except one, and the tracer-estimated SG* was less than SG in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of +/- 5% (range 3-9%) compared to average precisions of +/- 74% (range 7-309%) for SG and +/- 22% (range 3-72%) for Sl. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women

  17. Insights from quantitative metaproteomics and protein-stable isotope probing into microbial ecology.

    Science.gov (United States)

    von Bergen, Martin; Jehmlich, Nico; Taubert, Martin; Vogt, Carsten; Bastida, Felipe; Herbst, Florian-Alexander; Schmidt, Frank; Richnow, Hans-Hermann; Seifert, Jana

    2013-10-01

    The recent development of metaproteomics has enabled the direct identification and quantification of expressed proteins from microbial communities in situ, without the need for microbial enrichment. This became possible by (1) significant increases in quality and quantity of metagenome data and by improvements of (2) accuracy and (3) sensitivity of modern mass spectrometers (MS). The identification of physiologically relevant enzymes can help to understand the role of specific species within a community or an ecological niche. Beside identification, relative and absolute quantitation is also crucial. We will review label-free and label-based methods of quantitation in MS-based proteome analysis and the contribution of quantitative proteome data to microbial ecology. Additionally, approaches of protein-based stable isotope probing (protein-SIP) for deciphering community structures are reviewed. Information on the species-specific metabolic activity can be obtained when substrates or nutrients are labeled with stable isotopes in a protein-SIP approach. The stable isotopes ((13)C, (15)N, (36)S) are incorporated into proteins and the rate of incorporation can be used for assessing the metabolic activity of the corresponding species. We will focus on the relevance of the metabolic and phylogenetic information retrieved with protein-SIP studies and for detecting and quantifying the carbon flux within microbial consortia. Furthermore, the combination of protein-SIP with established tools in microbial ecology such as other stable isotope probing techniques are discussed.

  18. Adaptation of a Commonly Used, Chemically Defined Medium for Human Embryonic Stem Cells to Stable Isotope Labeling with Amino Acids in Cell Culture

    DEFF Research Database (Denmark)

    Liberski, A. R.; Al-Noubi, M. N.; Rahman, Z. H.

    2013-01-01

    Metabolic labeling with stable isotopes is a prominent technique for comparative quantitative proteomics, and stable isotope labeling with amino acids in cell culture (SILAC) is the most commonly used approach. SILAC is, however, traditionally limited to simple tissue culture regimens and only ra...

  19. Metabolism and disease

    National Research Council Canada - National Science Library

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  20. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  1. Stable isotopes and biomarkers in microbial ecology

    NARCIS (Netherlands)

    Boschker, H.T.S.; Middelburg, J.J.

    2002-01-01

    The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

  2. Modelling stable atmospheric boundary layers over snow

    NARCIS (Netherlands)

    Sterk, H.A.M.

    2015-01-01

    Thesis entitled:

    Modelling Stable Atmospheric Boundary Layers over Snow

    H.A.M. Sterk

    Wageningen, 29th of April, 2015

    Summary

    The emphasis of this thesis is on the understanding and forecasting of the Stable Boundary Layer (SBL) over snow-covered surfaces. SBLs

  3. Gas phase thermal diffusion of stable isotopes

    International Nuclear Information System (INIS)

    Eck, C.F.

    1979-01-01

    The separation of stable isotopes at Mound Facility is reviewed from a historical perspective. The historical development of thermal diffusion from a laboratory process to a separation facility that handles all the noble gases is described. In addition, elementary thermal diffusion theory and elementary cascade theory are presented along with a brief review of the uses of stable isotopes

  4. Development of new technology for the use of stable isotopic tracers in the study of human health and disease

    International Nuclear Information System (INIS)

    Hacyey, D.L.; Klein, P.D.; Szczepanik, P.A.; Niu, W.; Stellaard, F.; Tserng, K.Y.

    1977-01-01

    This program has five major aspects: first, the development of analytical instrumentation of requisite sensitivity, stability, and simplicity to conduct stable isotope measurements in a routine manner; second, the development of appropriately labeled compounds for metabolic investigations, initially through custom syntheses but eventually through commercial sources; third, development of analytical methodology to isolate, purify, and determine the isotopic content of specific organic compounds reflecting metabolic processes or disease states; fourth, collaborative development of clinical applications and testing on a routine basis, through a network of clinical centers around the country; and finally, the collection and dissemination of stable isotope information on an international scale through survey publications and conferences

  5. Structure of acid-stable carmine.

    Science.gov (United States)

    Sugimoto, Naoki; Kawasaki, Yoko; Sato, Kyoko; Aoki, Hiromitsu; Ichi, Takahito; Koda, Takatoshi; Yamazaki, Takeshi; Maitani, Tamio

    2002-02-01

    Acid-stable carmine has recently been distributed in the U.S. market because of its good acid stability, but it is not permitted in Japan. We analyzed and determined the structure of the major pigment in acid-stable carmine, in order to establish an analytical method for it. Carminic acid was transformed into a different type of pigment, named acid-stable carmine, through amination when heated in ammonia solution. The features of the structure were clarified using a model compound, purpurin, in which the orientation of hydroxyl groups on the A ring of the anthraquinone skeleton is the same as that of carminic acid. By spectroscopic means and the synthesis of acid-stable carmine and purpurin derivatives, the structure of the major pigment in acid-stable carmine was established as 4-aminocarminic acid, a novel compound.

  6. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  7. Co-ordinated research programme on applications of stable isotope tracers in human nutrition research

    International Nuclear Information System (INIS)

    1992-01-01

    This document provides a very brief report on the final Research Co-ordination Meeting of this Co-ordinated Research Project (CRP): the final report on the CRP will be published by the IAEA in the IAEA-TECDOC series. The present document contains a detailed proposal for a new Co-ordinated Research Programme on ''Stable Isotope Tracer Techniques for Studies on Protein-Energy Interactions'', and a brief series of notes on stable isotopic methods for investigating protein and amino-acid metabolism in man. Refs

  8. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  9. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  10. Application of stable isotopes and isotope pattern deconvolution-ICPMS to speciation of endogenous and exogenous Fe and Se in rats

    International Nuclear Information System (INIS)

    Gonzalez Iglesias, H.; Fernandez-Sanchez, M.L.; Garcia Alonso, J.I.; Lopez Sastre, J.B.; Sanz-Medel, A.

    2009-01-01

    Full text: Enriched stable isotopes are crucial to study essential trace element metabolism (e.g. Se, Fe) in biological systems. Measuring isotope ratios by ICPMS and using appropriate mathematical calculations, based on isotope pattern deconvolution (IPD) may provide quantitative data about endogenous and exogenous essential or toxic elements and their metabolism. In this work, IPD was applied to explore the feasibility of using two Se (or Fe) enriched stable isotopes, one as metabolic tracer and the other as quantitation tracer, to discriminate between the endogenous and supplemented Se (or Fe) species in rat fluids by collision cell ICPMS coupled to HPLC separation. (author)

  11. Ballooning stable high beta tokamak equilibria

    International Nuclear Information System (INIS)

    Tuda, Takashi; Azumi, Masafumi; Kurita, Gen-ichi; Takizuka, Tomonori; Takeda, Tatsuoki

    1981-04-01

    The second stable regime of ballooning modes is numerically studied by using the two-dimensional tokamak transport code with the ballooning stability code. Using the simple FCT heating scheme, we find that the plasma can locally enter this second stable regime. And we obtained equilibria with fairly high beta (β -- 23%) stable against ballooning modes in a whole plasma region, by taking into account of finite thermal diffusion due to unstable ballooning modes. These results show that a tokamak fusion reactor can operate in a high beta state, which is economically favourable. (author)

  12. Development of stable isotope manufacturing in Russia

    International Nuclear Information System (INIS)

    Pokidychev, A.; Pokidycheva, M.

    1999-01-01

    For the past 25 years, Russia has relied heavily on the electromagnetic separation process for the production of middle and heavy mass stable isotopes. The separation of most light isotopes had been centered in Georgia which, after the collapse of the USSR, left Russia without this capability. In the mid-1970s, development of centrifuge technology for the separation of stable isotopes was begun. Alternative techniques such as laser separation, physical-chemical methods, and ion cyclotron resonance have also been investigated. Economic considerations have played a major role in the development and current status of the stable isotope enrichment capabilities of Russia

  13. Metabolic Compensation and Circadian Resilience in Prokaryotic Cyanobacteria

    Science.gov (United States)

    Johnson, Carl Hirschie; Egli, Martin

    2014-01-01

    For a biological oscillator to function as a circadian pacemaker that confers a fitness advantage, its timing functions must be stable in response to environmental and metabolic fluctuations. One such stability enhancer, temperature compensation, has long been a defining characteristic of these timekeepers. However, an accurate biological timekeeper must also resist changes in metabolism, and this review suggests that temperature compensation is actually a subset of a larger phenomenon, namely metabolic compensation, which maintains the frequency of circadian oscillators in response to a host of factors that impinge on metabolism and would otherwise destabilize these clocks. The circadian system of prokaryotic cyanobacteria is an illustrative model because it is composed of transcriptional and nontranscriptional oscillators that are coupled to promote resilience. Moreover, the cyanobacterial circadian program regulates gene activity and metabolic pathways, and it can be manipulated to improve the expression of bioproducts that have practical value. PMID:24905782

  14. The use of metabolic balance studies in the objective discrimination between intestinal insufficiency and intestinal failure

    DEFF Research Database (Denmark)

    Prahm, August P; Brandt, Christopher F; Askov-Hansen, Carsten

    2017-01-01

    Background: In research settings that use metabolic balance studies (MBSs) of stable adult patients with short bowel syndrome, intestinal failure (IF) and dependence on parenteral support (PS) have been defined objectively as energy absorption metabolic rate (BMR), wet......, to objectivize the cause of nutritional dyshomeostasis (oral failure, malabsorption, or both), and to quantify the effects of treatment....

  15. Whole-body CO2 production as an index of the metabolic response to sepsis

    Science.gov (United States)

    Whole-body carbon dioxide (CO2) production (RaCO2) is an index of substrate oxidation and energy expenditure; therefore, it may provide information about the metabolic response to sepsis. Using stable isotope techniques, we determined RaCO2 and its relationship to protein and glucose metabolism in m...

  16. Stable Isotope Group 1982 progress report

    International Nuclear Information System (INIS)

    Stewart, M.K.

    1983-06-01

    The work of the Stable Isotope Group of the Institute of Nuclear Sciences during 1982, in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and mass spectrometer instrumentation, is described

  17. Bartolome Island, Galapagos Stable Oxygen Calibration Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Galapagos Coral Stable Oxygen Calibration Data. Sites: Bartolome Island: 0 deg, 17'S, 90 deg 33' W. Champion Island: 1 deg, 15'S, 90 deg, 05' W. Urvina Bay (Isabela...

  18. Stable Isotope Group 1983 progress report

    International Nuclear Information System (INIS)

    Stewart, M.K.

    1984-06-01

    The work of the Stable Isotope Group of the Institute of Nuclear Sciences in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and related fields, and mass spectrometer instrumentation, during 1983, is described

  19. Stable atomic hydrogen: Polarized atomic beam source

    International Nuclear Information System (INIS)

    Niinikoski, T.O.; Penttilae, S.; Rieubland, J.M.; Rijllart, A.

    1984-01-01

    We have carried out experiments with stable atomic hydrogen with a view to possible applications in polarized targets or polarized atomic beam sources. Recent results from the stabilization apparatus are described. The first stable atomic hydrogen beam source based on the microwave extraction method (which is being tested ) is presented. The effect of the stabilized hydrogen gas density on the properties of the source is discussed. (orig.)

  20. The use of stable isotope compositions of selected elements in food origin control

    International Nuclear Information System (INIS)

    Wierzchnicki, R.

    2002-01-01

    Stable isotope ratios have been used widely for authentication of foodstuffs especially for detection of added water and sugar in fruit juices and wines. Hydrogen and oxygen composition are particularly interesting probes for geographical origin and authenticity identification. Carbon and nitrogen composition of fruits contains the finger-print of their metabolism and growing condition. Exemplary data are presented which demonstrated the usefulness of the Isotope Ratio Mass Spectrometry (IRMS) methods for authenticating wines and fruits (juice and pulp). (author)

  1. Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat.

    Science.gov (United States)

    Zhang, Lei; Zhao, Haiyu; Liu, Yang; Dong, Honghuan; Lv, Beiran; Fang, Min; Zhao, Huihui

    2016-06-01

    This study was conducted to establish the multicomponent sequential metabolism (MSM) method based on comparative analysis along the digestive system following oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a traditional Chinese medicine widely used for harmonizing other ingredients in a formulae. The licorice water extract (LWE) dissolved in Krebs-Ringer buffer solution (1 g/mL) was used to carry out the experiments and the comparative analysis was performed using HPLC and LC-MS/MS methods. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to measure the LWE metabolic profile along the digestive system. The incubation experiment showed that the LWE was basically stable in digestive juice. A comparative analysis presented the metabolic profile of each prototype and its corresponding metabolites then. Liver was the major metabolic organ for LWE, and the metabolism by the intestinal flora and gut wall was also an important part of the process. The MSM method was practical and could be a potential method to describe the metabolic routes of multiple components before absorption into the systemic blood stream. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Accumulation and metabolism of radioactive nuclides

    International Nuclear Information System (INIS)

    Morita, Shigeki

    1981-01-01

    The distribution of 90 Sr and 137 Cs with a long effective half life showing relatively simple behaviors, into the fish was examined from the data of field work. 137 Cs tended to show higher coefficients of concentration in the order of shellfish, crustaceans and fishes in accordance with the food chain. If the concentration caused by the food chain was neglected, the biological half life was influenced by the body weight even among the same species of fish, and the coefficient of concentration showed differences due to growth and metabolic function. In comparison with stable Cs, the 137 Cs showed a coefficient of concentration 1.5 times that of 133 Cs in the fish muscle. With the exception of seaweeds, the distribution rate of 90 Sr was not so high, but its coefficient of concentration was higher than that of stable Sr in the fish muscle. However, the coefficient of concentration of stable Sr was higher in bones because of its slower metabolism. (Chiba, N.)

  3. Essences in Metabolic Engineering of Lignan Biosynthesis

    Directory of Open Access Journals (Sweden)

    Honoo Satake

    2015-05-01

    Full Text Available Lignans are structurally and functionally diverse phytochemicals biosynthesized in diverse plant species and have received wide attentions as leading compounds of novel drugs for tumor treatment and healthy diets to reduce of the risks of lifestyle-related non-communicable diseases. However, the lineage-specific distribution and the low-amount of production in natural plants, some of which are endangered species, hinder the efficient and stable production of beneficial lignans. Accordingly, the development of new procedures for lignan production is of keen interest. Recent marked advances in the molecular and functional characterization of lignan biosynthetic enzymes and endogenous and exogenous factors for lignan biosynthesis have suggested new methods for the metabolic engineering of lignan biosynthesis cascades leading to the efficient, sustainable, and stable lignan production in plants, including plant cell/organ cultures. Optimization of light conditions, utilization of a wide range of elicitor treatments, and construction of transiently gene-transfected or transgenic lignan-biosynthesizing plants are mainly being attempted. This review will present the basic and latest knowledge regarding metabolic engineering of lignans based on their biosynthetic pathways and biological activities, and the perspectives in lignan production via metabolic engineering.

  4. Monitoring in situ biodegradation of hydrocarbons by using stable carbon isotopes

    International Nuclear Information System (INIS)

    Aggarwal, P.K.; Hinchee, R.E.

    1991-01-01

    Spilled or leaked nonhalogenated petroleum hydrocarbons in the soil can generally be metabolized by indigenous, aerobic bacteria. In situ biological degradation of hydrocarbons may be accelerated by supplying inorganic nutrients and/or oxygen. Approaches to monitoring and verifying enhanced in situ biodegradation have included measurements of changes over time in the (a) concentration of hydrocarbons, (b) temperature, (c) number of hydrocarbon-degrading microorganisms, (d) ratio of fast-degrading hydrocarbons (e.g., pristanes or phytanes), and (e) metabolic intermediates. Measurements of oxygen consumption over time and elevated carbon dioxide concentrations in soil gas also have been used as indicators of hydrocarbon degradation. An alternative approach that may help substantiate biodegradation is to measure stable carbon isotope ratios in soil gas CO 2 . Stable carbon isotope ratio analysis is inexpensive and commercially available at many laboratories. Carbon dioxide produced by hydrocarbon degradation may be distinguished from that produced by other processes based on the carbon isotopic compositions characteristic of the source material and/or fractionation accompanying microbial metabolism. Here the authors demonstrate the applicability of the stable isotope technique for monitoring enhanced. aerobic biodegradation of hydrocarbons using data from three locations in the United States

  5. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  6. Local Search Approaches in Stable Matching Problems

    Directory of Open Access Journals (Sweden)

    Toby Walsh

    2013-10-01

    Full Text Available The stable marriage (SM problem has a wide variety of practical applications, ranging from matching resident doctors to hospitals, to matching students to schools or, more generally, to any two-sided market. In the classical formulation, n men and n women express their preferences (via a strict total order over the members of the other sex. Solving an SM problem means finding a stable marriage where stability is an envy-free notion: no man and woman who are not married to each other would both prefer each other to their partners or to being single. We consider both the classical stable marriage problem and one of its useful variations (denoted SMTI (Stable Marriage with Ties and Incomplete lists where the men and women express their preferences in the form of an incomplete preference list with ties over a subset of the members of the other sex. Matchings are permitted only with people who appear in these preference lists, and we try to find a stable matching that marries as many people as possible. Whilst the SM problem is polynomial to solve, the SMTI problem is NP-hard. We propose to tackle both problems via a local search approach, which exploits properties of the problems to reduce the size of the neighborhood and to make local moves efficiently. We empirically evaluate our algorithm for SM problems by measuring its runtime behavior and its ability to sample the lattice of all possible stable marriages. We evaluate our algorithm for SMTI problems in terms of both its runtime behavior and its ability to find a maximum cardinality stable marriage. Experimental results suggest that for SM problems, the number of steps of our algorithm grows only as O(n log(n, and that it samples very well the set of all stable marriages. It is thus a fair and efficient approach to generate stable marriages. Furthermore, our approach for SMTI problems is able to solve large problems, quickly returning stable matchings of large and often optimal size, despite the

  7. Metabolic syndrome and menopause

    OpenAIRE

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  8. Study into the effects of stable iodine diets for reducing the transfer of radioiodine to cow milk

    International Nuclear Information System (INIS)

    Kiefer, P.; Voigt, G.

    1999-01-01

    The results of a literature study were taken as a basis for the experimental planning approach. The experimental results and their evaluation yielded new insight into the usefulness of stable iodine diets with respect to the iodine metabolism and the radioiodine transfer in dairy cows. (orig./CB) [de

  9. [Metabolic functions and sport].

    Science.gov (United States)

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  10. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  11. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J; Davis, E J

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  12. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  13. Perspective: Highly stable vapor-deposited glasses

    Science.gov (United States)

    Ediger, M. D.

    2017-12-01

    This article describes recent progress in understanding highly stable glasses prepared by physical vapor deposition and provides perspective on further research directions for the field. For a given molecule, vapor-deposited glasses can have higher density and lower enthalpy than any glass that can be prepared by the more traditional route of cooling a liquid, and such glasses also exhibit greatly enhanced kinetic stability. Because vapor-deposited glasses can approach the bottom of the amorphous part of the potential energy landscape, they provide insights into the properties expected for the "ideal glass." Connections between vapor-deposited glasses, liquid-cooled glasses, and deeply supercooled liquids are explored. The generality of stable glass formation for organic molecules is discussed along with the prospects for stable glasses of other types of materials.

  14. Concentration of stable elements in food products

    International Nuclear Information System (INIS)

    Montford, M.A.; Shank, K.E.; Hendricks, C.; Oakes, T.W.

    1980-01-01

    Food samples were taken from commercial markets and analyzed for stable element content. The concentrations of most stable elements (Ag, Al, As, Au, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Cu, Fe, Hf, I, K, La, Mg, Mn, Mo, Na, Rb, Sb, Sc, Se, Sr, Ta, Th, Ti, V, Zn, Zr) were determined using multiple-element neutron activation analysis, while the concentrations of other elements (Cd, Hg, Ni, Pb) were determined using atomic absorption. The relevance of the concentrations found are noted in relation to other literature values. An earlier study was extended to include the determination of the concentration of stable elements in home-grown products in the vicinity of the Oak Ridge National Laboratory. Comparisons between the commercial and local food-stuff values are discussed

  15. Stable Chimeras and Independently Synchronizable Clusters

    Science.gov (United States)

    Cho, Young Sul; Nishikawa, Takashi; Motter, Adilson E.

    2017-08-01

    Cluster synchronization is a phenomenon in which a network self-organizes into a pattern of synchronized sets. It has been shown that diverse patterns of stable cluster synchronization can be captured by symmetries of the network. Here, we establish a theoretical basis to divide an arbitrary pattern of symmetry clusters into independently synchronizable cluster sets, in which the synchronization stability of the individual clusters in each set is decoupled from that in all the other sets. Using this framework, we suggest a new approach to find permanently stable chimera states by capturing two or more symmetry clusters—at least one stable and one unstable—that compose the entire fully symmetric network.

  16. On some topological properties of stable measures

    DEFF Research Database (Denmark)

    Nielsen, Carsten Krabbe

    1996-01-01

    Summary The paper shows that the set of stable probability measures and the set of Rational Beliefs relative to a given stationary measure are closed in the strong topology, but not closed in the topology of weak convergence. However, subsets of the set of stable probability measures which...... are characterized by uniformity of convergence of the empirical distribution are closed in the topology of weak convergence. It is demonstrated that such subsets exist. In particular, there is an increasing sequence of sets of SIDS measures who's union is the set of all SIDS measures generated by a particular...... system and such that each subset consists of stable measures. The uniformity requirement has a natural interpretation in terms of plausibility of Rational Beliefs...

  17. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

  18. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  19. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  20. Faster and Simpler Approximation of Stable Matchings

    Directory of Open Access Journals (Sweden)

    Katarzyna Paluch

    2014-04-01

    Full Text Available We give a 3 2 -approximation algorithm for finding stable matchings that runs in O(m time. The previous most well-known algorithm, by McDermid, has the same approximation ratio but runs in O(n3/2m time, where n denotes the number of people andm is the total length of the preference lists in a given instance. In addition, the algorithm and the analysis are much simpler. We also give the extension of the algorithm for computing stable many-to-many matchings.

  1. Moving stable solitons in Galileon theory

    International Nuclear Information System (INIS)

    Masoumi, Ali; Xiao Xiao

    2012-01-01

    Despite the no-go theorem Endlich et al. (2011) which rules out static stable solitons in Galileon theory, we propose a family of solitons that evade the theorem by traveling at the speed of light. These domain-wall-like solitons are stable under small fluctuations-analysis of perturbation shows neither ghost-like nor tachyon-like instabilities, and perturbative collision of these solitons suggests that they pass through each other asymptotically, which maybe an indication of the integrability of the theory itself.

  2. Bordism, stable homotopy and adams spectral sequences

    CERN Document Server

    Kochman, Stanley O

    1996-01-01

    This book is a compilation of lecture notes that were prepared for the graduate course "Adams Spectral Sequences and Stable Homotopy Theory" given at The Fields Institute during the fall of 1995. The aim of this volume is to prepare students with a knowledge of elementary algebraic topology to study recent developments in stable homotopy theory, such as the nilpotence and periodicity theorems. Suitable as a text for an intermediate course in algebraic topology, this book provides a direct exposition of the basic concepts of bordism, characteristic classes, Adams spectral sequences, Brown-Peter

  3. Stable isotopes in Lithuanian bioarcheological material

    Science.gov (United States)

    Skipityte, Raminta; Jankauskas, Rimantas; Remeikis, Vidmantas

    2015-04-01

    Investigation of bioarcheological material of ancient human populations allows us to understand the subsistence behavior associated with various adaptations to the environment. Feeding habits are essential to the survival and growth of ancient populations. Stable isotope analysis is accepted tool in paleodiet (Schutkowski et al, 1999) and paleoenvironmental (Zernitskaya et al, 2014) studies. However, stable isotopes can be useful not only in investigating human feeding habits but also in describing social and cultural structure of the past populations (Le Huray and Schutkowski, 2005). Only few stable isotope investigations have been performed before in Lithuanian region suggesting a quite uniform diet between males and females and protein intake from freshwater fish and animal protein. Previously, stable isotope analysis has only been used to study a Stone Age population however, more recently studies have been conducted on Iron Age and Late medieval samples (Jacobs et al, 2009). Anyway, there was a need for more precise examination. Stable isotope analysis were performed on human bone collagen and apatite samples in this study. Data represented various ages (from 5-7th cent. to 18th cent.). Stable carbon and nitrogen isotope analysis on medieval populations indicated that individuals in studied sites in Lithuania were almost exclusively consuming C3 plants, C3 fed terrestrial animals, and some freshwater resources. Current investigation demonstrated social differences between elites and country people and is promising in paleodietary and daily life reconstruction. Acknowledgement I thank prof. dr. G. Grupe, Director of the Anthropological and Palaeoanatomical State Collection in Munich for providing the opportunity to work in her laboratory. The part of this work was funded by DAAD. Antanaitis-Jacobs, Indre, et al. "Diet in early Lithuanian prehistory and the new stable isotope evidence." Archaeologia Baltica 12 (2009): 12-30. Le Huray, Jonathan D., and Holger

  4. Unconditionally stable microwave Si-IMPATT amplifiers

    International Nuclear Information System (INIS)

    Seddik, M.M.

    1986-07-01

    The purpose of this investigation has been the development of an improved understanding of the design and analysis of microwave reflection amplifiers employing the negative resistance property of the IMPATT devices. Unconditionally stable amplifier circuit using a Silicon IMPATT diode is designed. The problems associated with the design procedures and the stability criterion are discussed. A computer program is developed to perform the computations. The stable characteristics of a reflection-type Si-IMPATT amplifier, such as gain, frequency and bandwidth are examined. It was found that at large signal drive levels, 7 dB gain with bandwidth of 800 MHz at 22,5 mA was obtained. (author)

  5. Drug metabolism in birds

    Science.gov (United States)

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  6. Metabolic imaging using SPECT

    International Nuclear Information System (INIS)

    Taki, Junichi; Matsunari, Ichiro

    2007-01-01

    In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123 I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. (orig.)

  7. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  8. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  9. Metabolic imaging using PET

    International Nuclear Information System (INIS)

    Kudo, Takashi

    2007-01-01

    There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

  10. Astrocytes and energy metabolism.

    Science.gov (United States)

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  11. petrography, compositional characteristics and stable isotope ...

    African Journals Online (AJOL)

    PROF EKWUEME

    Subsurface samples of the predominantly carbonate Ewekoro Formation, obtained from Ibese core hole within the Dahomey basin were used in this study. Investigations entail petrographic, elemental composition as well as stable isotopes (carbon and oxygen) geochemistry in order to deduce the different microfacies and ...

  12. Working conditions remain stable in the Netherlands

    NARCIS (Netherlands)

    Houtman, I.; Hooftman, W.

    2008-01-01

    Despite significant changes in the national questionnaires on work and health, the quality of work as well as health complaints in the Netherlands appear to be relatively stable. Pace of work seems to be on the increase again and more people are working in excess of their contractual hours.

  13. Thermally stable sintered porous metal articles

    International Nuclear Information System (INIS)

    Gombach, A.L.; Thellmann, E.L.

    1980-01-01

    A sintered porous metal article is provided which is essentially thermally stable at elevated temperatures. In addition, a method for producing such an article is also provided which method comprises preparing a blend of base metal particles and active dispersoid particles, forming the mixture into an article of the desired shape, and heating the so-formed article at sintering temperatures

  14. TOF for heavy stable particle identification

    International Nuclear Information System (INIS)

    Chang, C.Y.

    1983-01-01

    Searching for heavy stable particle production in a new energy region of hadron-hadron collisions is of fundamental theoretical interest. Observation of such particles produced in high energy collisions would indicate the existence of stable heavy leptons or any massive hadronic system carrying new quantum numbers. Experimentally, evidence of its production has not been found for PP collisions either at FNAL or at the CERN ISR for √S = 23 and 62 GeV respectively. However, many theories beyond the standard model do predict its existence on a mass scale ranging from 50 to a few hundred GeV. If so, it would make a high luminosity TeV collider an extremely ideal hunting ground for searching the production of such a speculated object. To measure the mass of a heavy stable charged particle, one usually uses its time of flight (TOF) and/or dE/dX information. For heavy neutral particle, one hopes it may decay at some later time after its production. Hence a pair of jets or a jet associated with a high P/sub t/ muon originated from some places other than the interacting point (IP) of the colliding beams may be a good signal. In this note, we examine the feasibility of TOF measurement on a heavy stable particle produced in PP collisions at √S = 1 TeV and a luminosity of 10 33 cm -2 sec -1 with a single arm spectrometer pointing to the IP

  15. Axisymmetric MHD stable sloshing ion distributions

    International Nuclear Information System (INIS)

    Berk, H.L.; Dominguez, N.; Roslyakov, G.V.

    1986-07-01

    The MHD stability of a sloshing ion distribution is investigated in a symmetric mirror cell. Fokker-Planck calculations show that stable configurations are possible for ion injection energies that are at least 150 times greater than the electron temperture. Special axial magnetic field profiles are suggested to optimize the favorable MHD properties

  16. Exact simulation of max-stable processes.

    Science.gov (United States)

    Dombry, Clément; Engelke, Sebastian; Oesting, Marco

    2016-06-01

    Max-stable processes play an important role as models for spatial extreme events. Their complex structure as the pointwise maximum over an infinite number of random functions makes their simulation difficult. Algorithms based on finite approximations are often inexact and computationally inefficient. We present a new algorithm for exact simulation of a max-stable process at a finite number of locations. It relies on the idea of simulating only the extremal functions, that is, those functions in the construction of a max-stable process that effectively contribute to the pointwise maximum. We further generalize the algorithm by Dieker & Mikosch (2015) for Brown-Resnick processes and use it for exact simulation via the spectral measure. We study the complexity of both algorithms, prove that our new approach via extremal functions is always more efficient, and provide closed-form expressions for their implementation that cover most popular models for max-stable processes and multivariate extreme value distributions. For simulation on dense grids, an adaptive design of the extremal function algorithm is proposed.

  17. Unconditionally stable integration of Maxwell's equations

    NARCIS (Netherlands)

    Verwer, J.G.; Bochev, Mikhail A.

    Numerical integration of Maxwell's equations is often based on explicit methods accepting a stability step size restriction. In literature evidence is given that there is also a need for unconditionally stable methods, as exemplified by the successful alternating direction implicit finite difference

  18. Unconditionally stable integration of Maxwell's equations

    NARCIS (Netherlands)

    J.G. Verwer (Jan); M.A. Botchev

    2008-01-01

    htmlabstractNumerical integration of Maxwell''s equations is often based on explicit methods accepting a stability step size restriction. In literature evidence is given that there is also a need for unconditionally stable methods, as exemplified by the successful alternating direction

  19. Unconditionally stable integration of Maxwell's equations

    NARCIS (Netherlands)

    J.G. Verwer (Jan); M.A. Botchev

    2009-01-01

    textabstractNumerical integration of Maxwell’s equations is often based on explicit methods accepting a stability step size restriction. In literature evidence is given that there is also a need for unconditionally stable methods, as exemplified by the successful alternating direction implicit –

  20. Method of producing thermally stable uranium carbonitrides

    International Nuclear Information System (INIS)

    Ugajin, M.; Takahashi, I.

    1975-01-01

    A thermally stable uranium carbonitride can be produced by adding tungsten and/or molybdenum in the amount of 0.2 wt percent or more, preferably 0.5 wt percent or more, to a pure uranium carbonitride. (U.S.)

  1. Champion Island, Galapagos Stable Oxygen Calibration Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Galapagos Coral Stable Oxygen Calibration Data. Sites: Bartolome Island: 0 deg, 17 min S, 90 deg 33 min W. Champion Island: 1 deg, 15 min S, 90 deg, 05 min W. Urvina...

  2. 26 S proteasomes function as stable entities

    DEFF Research Database (Denmark)

    Hendil, Klavs B; Hartmann-Petersen, Rasmus; Tanaka, Keiji

    2002-01-01

    , shuttles between a free state and the 26-S proteasome, bringing substrate to the complex. However, S5a was not found in the free state in HeLa cells. Besides, all subunits in PA700, including S5a, exchanged at similar low rates. It therefore seems that 26-S proteasomes function as stable entities during...

  3. Formal derivation of a stable marriage algorithm.

    NARCIS (Netherlands)

    Bijlsma, A.

    1991-01-01

    In this paper the well-known Stable Marriage Problem is considered once again. The name of this programming problem comes from the terms in which it was first described [2]: A certain community consists of n men and n women. Each person ranks those of the opposite sex in accordance with his or

  4. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  5. Biologically stable [18F]-labeled benzylfluoride derivatives

    International Nuclear Information System (INIS)

    Magata, Yasuhiro; Lang, Lixin; Kiesewetter, Dale O.; Jagoda, Elaine M.; Channing, Michael A.; Eckelman, William C.

    2000-01-01

    Use of the [ 18 F]-fluoromethyl phenyl group is an attractive alternative to direct fluorination of phenyl groups because the fluorination of the methyl group takes place under milder reaction conditions. However, we have found that 4-FMeBWAY showed femur uptake equal to that of fluoride up to 30 min in rat whereas 4-FMeQNB had a significantly lower percent injected dose per gram in femur up to 120 min. For these and other benzylfluoride derivatives, there was no clear in vivo structure-defluorination relationship. Because benzylchlorides (BzCls) are known alkylating agents, benzylfluorides may be alkylating agents as well, which may be the mechanism of defluorination. On this basis, the effects of substitution on chemical stability were evaluated by the 4-(4-nitro-benzyl)-pyridine (NBP) test, which is used to estimate alkylating activity with NBP. The effect of substitution on the alkylating activity was evaluated for nine BzCl derivatives: BzCl; 3- or 4-methoxy (electron donation) substituted BzCl; 2-, 3-, or 4-nitro (electron withdrawing) substituted BzCl; and 2-, 3-, or 4-chloro (electron withdrawing) substituted BzCl. Taken together, the alkylating reactivity of 3-chloro-BzCl was the weakest. This result was then applied to [ 18 F]-benzylfluoride derivatives and in vivo and in vitro stability were evaluated. Consequently, 3-chloro-[ 18 F]-benzylfluoride showed a 70-80% decrease of defluorination in both experiments in comparison with [ 18 F]-benzylfluoride, as expected. Moreover, a good linear relationship between in vivo femur uptake and in vitro hepatocyte metabolism was observed with seven 18 F-labeled radiopharmaceuticals, which were benzylfluorides, alkylfluorides, and arylfluorides. Apparently, the [ 18 F]-fluoride ion is released by metabolism in the liver in vivo. In conclusion, 3-chloro substituted BzCls are the most stable, which suggests that 3-chloro benzylfluorides will be the most chemically stable compound. This result should be important in

  6. The Nature of Stable Insomnia Phenotypes

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

    2015-01-01

    Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

  7. Strontium stable isotope behaviour accompanying basalt weathering

    Science.gov (United States)

    Burton, K. W.; Parkinson, I. J.; Gíslason, S. G. R.

    2016-12-01

    The strontium (Sr) stable isotope composition of rivers is strongly controlled by the balance of carbonate to silicate weathering (Krabbenhöft et al. 2010; Pearce et al. 2015). However, rivers draining silicate catchments possess distinctly heavier Sr stable isotope values than their bedrock compositions, pointing to significant fractionation during weathering. Some have argued for preferential release of heavy Sr from primary phases during chemical weathering, others for the formation of secondary weathering minerals that incorporate light isotopes. This study presents high-precision double-spike Sr stable isotope data for soils, rivers, ground waters and estuarine waters from Iceland, reflecting both natural weathering and societal impacts on those environments. The bedrock in Iceland is dominantly basaltic, d88/86Sr ≈ +0.27, extending to lighter values for rhyolites. Geothermal waters range from basaltic Sr stable compositions to those akin to seawater. Soil pore waters reflect a balance of input from primary mineral weathering, precipitation and litter recycling and removal into secondary phases and vegetation. Rivers and ground waters possess a wide range of d88/86Sr compositions from +0.101 to +0.858. Elemental and isotope data indicate that this fractionation primarily results from the formation or dissolution of secondary zeolite (d88/86Sr ≈ +0.10), but also carbonate (d88/86Sr ≈ +0.22) and sometimes anhydrite (d88/86Sr ≈ -0.73), driving the residual waters to heavier or lighter values, respectively. Estuarine waters largely reflect mixing with seawater, but are also be affected by adsorption onto particulates, again driving water to heavy values. Overall, these data indicate that the stability and nature of secondary weathering phases, exerts a strong control on the Sr stable isotope composition of silicate rivers. [1] Krabbenhöft et al. (2010) Geochim. Cosmochim. Acta 74, 4097-4109. [2] Pearce et al. (2015) Geochim. Cosmochim. Acta 157, 125-146.

  8. Magnesium stable isotope ecology using mammal tooth enamel

    Science.gov (United States)

    Martin, Jeremy E.; Vance, Derek; Balter, Vincent

    2015-01-01

    Geochemical inferences on ancient diet using bone and enamel apatite rely mainly on carbon isotope ratios (δ13C) and to a lesser extent on strontium/calcium (Sr/Ca) and barium/calcium (Ba/Ca) elemental ratios. Recent developments in nontraditional stable isotopes provide an unprecedented opportunity to use additional paleodietary proxies to disentangle complex diets such as omnivory. Of particular relevance for paleodietary reconstruction are metals present in large quantity in bone and enamel apatite, providing that biologically mediated fractionation processes are constrained. Calcium isotope ratios (δ44Ca) meet these criteria but exhibit complex ecological patterning. Stable magnesium isotope ratios (δ26Mg) also meet these criteria but a comprehensive understanding of its variability awaits new isotopic data. Here, 11 extant mammal species of known ecology from a single locality in equatorial Africa were sampled for tooth enamel and, together with vegetation and feces, analyzed for δ26Mg, δ13C, Sr/Ca, and Ba/Ca ratios. The results demonstrate that δ26Mg incorporated in tooth enamel becomes heavier from strict herbivores to omnivores/faunivores. Using data from experimentally raised sheep, we suggest that this 26Mg enrichment up the trophic chain is due to a 26Mg enrichment in muscle relative to bone. Notably, it is possible to distinguish omnivores from herbivores, using δ26Mg coupled to Ba/Ca ratios. The potential effects of metabolic and dietary changes on the enamel δ26Mg composition remain to be explored but, in the future, multiproxy approaches would permit a substantial refinement of dietary behaviors or enable accurate trophic reconstruction despite specimen-limited sampling, as is often the case for fossil assemblages.

  9. Stable ischemic heart disease in women: current perspectives

    Directory of Open Access Journals (Sweden)

    Samad F

    2017-09-01

    Full Text Available Fatima Samad,1 Anushree Agarwal,2 Zainab Samad3 1Aurora Cardiovascular Services, Aurora Sinai/Aurora St Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, WI, 2Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, 3Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m2, smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases. Diagnostic testing can be used effectively to risk stratify women. Guidelines-directed medical therapy including aspirin, statins, beta-blocker therapy, calcium channel blockers and ranolazine should be instituted for symptom and ischemia management. Despite robust evidence regarding the adverse outcomes seen in women with ischemic heart disease, knowledge gaps exist in several areas. Future research needs to be directed toward a greater understanding of the role of nontraditional risk factors for SIHD in women, gaining deeper insights into the sex differences in therapeutic effects and formulating a sex-specific algorithm for the

  10. Monitoring of the aerobe biodegradation of chlorinated organic solvents by stable isotope analysis

    Science.gov (United States)

    Horváth, Anikó; Futó, István; Palcsu, László

    2014-05-01

    Our chemical-biological basic research aims to eliminate chlorinated environmental contaminants from aquifers around industrial areas in the frame of research program supported by the European Social Fund (TÁMOP-4.2.2.A-11/1/KONV-2012-0043). The most careful and simplest way includes the in situ biodegradation with the help of cultured and compound specific strains. Numerous members of Pseudomonas bacteria are famous about function of bioremediation. They can metabolism the environmental hazardous chemicals like gas oils, dyes, and organic solvents. Our research based on the Pseudomonas putida F1 strain, because its ability to degrade halogenated hydrocarbons such as trichloroethylene. Several methods were investigated to estimate the rate of biodegradation, such as the measurement of the concentration of the pollutant along the contamination pathway, the microcosm's studies or the compound specific stable isotope analysis. In this area in the Transcarpathian basin we are pioneers in the stable isotope monitoring of biodegradation. The main goal is to find stable isotope fractionation factors by stable isotope analysis, which can help us to estimate the rate and effectiveness of the biodegradation. The subsequent research period includes the investigation of the method, testing its feasibility and adaptation in the environment. Last but not least, the research gives an opportunity to identify the producer of the contaminant based on the stable isotope composition of the contaminant.

  11. Trends in the use of stable isotopes in biochemistry and pharmacology

    International Nuclear Information System (INIS)

    Matwiyoff, N.A.; Walker, T.E.

    1977-01-01

    Recent trends in the use of the stable isotopes 13 C, 15 N and 18 O in biochemistry and pharmacology are reviewed with emphasis on the studies that have employed nuclear magnetic resonance (nmr) spectroscopy and mass spectrometry as analytical techniques. Pharmacological studies with drugs and other compounds labelled with stable isotopes have developed in parallel with the rapid progress in the enhancement of sensitivity and selectivity of gas chromatography - mass spectrometric analyses, and have been directed largely to an evaluation of pharmako-kinetics and drug metabolic pathways. In these studies, illustrated with selected samples, isotopically labelled compounds have been used to advantage as internal standards for the mass spectrometric analyses and as in vivo tracers for metabolites. In the broader discipline of biochemistry, stable isotopes and isotopically labelled compounds have been used increasingly in conjuction with both nmr spectroscopy and mass spectrometry in tracer and structural studies. The more recent trends in the use of stable isotopes in these biochemical studies are discussed in the context of the improvements in analytical techniques. Specific examples will be drawn from investigations of the biosynthesis of natural products by micro-organisms; the protein, fat and carbohydrate fluxes in humans; and the structure and function of enzymes, membranes and other macro-molecular assemblages. The potential for the future development of stable isotopes in biochemistry and pharmacology are considered briefly, together with some of the problems that must be solved if their considerable potential is to be realized. (author)

  12. Metabolism of elements in Japanese

    International Nuclear Information System (INIS)

    Uchiyama, Masafumi

    1990-01-01

    The metabolism of cesium and iodine in Japanese is reviewed regarding with assessing the internal dose from their radioisotopes. Cesium: A two-component model can depict the time-relating retention in the whole-body. The half-time in adult male is shorter for Japanese than for the ICRP Reference Man. The half-time is shorter in woman and shortest in infants. The difference in half-time between Japanese and Caucasian becomes larger with aging. The half-time is successfully related with other biological parameters. A use of the estimation model for biological half-time by Cryer and Baverstock is recommendable for Japanese. The cesium half-time has a wide difference as mush as 3 times among individuals even within the limited sexual and age-group. Iodine: ICRP recommended a model of iodine for Reference Man. However, uptake of iodine in thyroid depends on the concentration of iodine in blood in the same way as with the half-time. It is indicated that concentration of thyroxine in blood is kept constant when thyroid has an extraordinary amount of iodine supply. The amount of stable iodine in thyroid indicated no difference between Japanese and Caucasian. Considering these characteristic conditions for Japanese, a model was established in which another route for the release of inorganic iodine from thyroid is included beside those assumed in the ICRP model. The estimated half-time agreed with the observed values in Japanese who were administered iodine-131. The observed smaller uptake of iodine in thyroid for Japanese was also well explained. The uptake begins around 13 weeks after conception and increases with age upto the time of delivery. The rate of metabolism in newborn is 3 times higher than in adult. The biological half-time in thyroid increases with age. (author)

  13. Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX

    DEFF Research Database (Denmark)

    Sheykhzade, Majid; Abdolalizadeh, Bahareh; Koole, Cassandra

    2018-01-01

    receptors (CLR and RAMP1) were expressed in the artery. In rat cerebral membranes, binding affinities (pKi) of SAX and CGRP were 8.3 ± 0.19 and 9.3 ± 0.14. In human subcutaneous artery, SAX and CGRP induced vasodilation (pEC50 8.8 ± 0.18 and 9.5 ± 0.13), while pEC50s for cAMP production by human recombinant...

  14. Nitrogen acquisition, transport and metabolism in intact ectomycorrhizal associations studied by 15N stable isotope techniques

    International Nuclear Information System (INIS)

    Ek, H.

    1993-05-01

    The focus of this thesis is on the external mycelium and its role in nitrogen uptake, assimilation and translocation. Tree seedlings in association with ectomycorrhizal fungi were grown in observation chambers. The fungal mycelium were fed with 15-N ammonium or 15-N nitrate or a combination of both. The effects of Collembola on the ectomycorrhizal symbiosis were also studied. The results demonstrates an important role of the external mycelium of Paxillus involutus not only in the uptake but also in the assimilation of ammonium into a variety of different amino acids, primarily glutamine but also glutamic acid, aspartic acid, and alanine, immediately after uptake. The results indicate that ammonium is assimilated by GS and GOGAT or GDH in the mycelium at the uptake site. When nitrate was added to the mycelium as the sole nitrogen source nitrate was reduced in the mycelium and the product assimilated into amino acids. When ammonium nitrate was supplied to the fungal mycelium nitrate was taken up the fungus and transferred to the plant, however, apparently no assimilation of nitrate occurred in the external mycelium. Ammonium or an assimilation product, such as glutamine, probably represses nitrate reductase (NR) but not nitrate uptake and transfer in P. involutus. P. involutus nitrogen uptake and transfer to the associated mycorrhizal pine was up to 76% higher when low numbers of the Collembola Onychiurus armatus were present compared to when they were completely absent. This was probably an indirect effect as P. involutus hyphal growth rate and extramatrical biomass increased at a low Collembola density. At high Collembola densities P. involutus hyphal growth rate was retarded. (74 refs.)

  15. Surfactant Phosphatidylcholine Metabolism in Severe Neonatal Lung Disease: Studied with Stable Isotopes

    NARCIS (Netherlands)

    D.J.M.T. Janssen (Daphne)

    2003-01-01

    markdownabstract__Abstract__ Avery and Mead showed in 1959 that pulmonary surfactant deficiency is a major factor in the pathophysiology of respiratory distress syndrome (RDS). In 1980 Fujiwara et al. administered exogenous surfactant for the first time successfully to preterm infants with RDS

  16. Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism

    NARCIS (Netherlands)

    van Nimwegen, Lonneke J. M.; Storosum, Jitschak G.; Blumer, Regje M. E.; Allick, Gideon; Venema, Henk W.; de Haan, Lieuwe; Becker, Hiske; van Amelsvoort, Therese; Ackermans, Mariette T.; Fliers, Eric; Serlie, Mireille J. M.; Sauerwein, Hans P.

    2008-01-01

    OBJECTIVE: Our objective was to measure insulin sensitivity and body composition in antipsychotic-naive patients with DSM IV schizophrenia and/or schizoaffective disorder compared with matched controls. DESIGN: Seven antipsychotic medication-naive patients fulfilling the DSM IV A criteria for

  17. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  18. VRML metabolic network visualizer.

    Science.gov (United States)

    Rojdestvenski, Igor

    2003-03-01

    A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

  19. Human Body Exergy Metabolism

    OpenAIRE

    Mady, Carlos Eduardo Keutenedjian

    2013-01-01

    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  20. Development of a Safety Management Web Tool for Horse Stables.

    Science.gov (United States)

    Leppälä, Jarkko; Kolstrup, Christina Lunner; Pinzke, Stefan; Rautiainen, Risto; Saastamoinen, Markku; Särkijärvi, Susanna

    2015-11-12

    Managing a horse stable involves risks, which can have serious consequences for the stable, employees, clients, visitors and horses. Existing industrial or farm production risk management tools are not directly applicable to horse stables and they need to be adapted for use by managers of different types of stables. As a part of the InnoEquine project, an innovative web tool, InnoHorse, was developed to support horse stable managers in business, safety, pasture and manure management. A literature review, empirical horse stable case studies, expert panel workshops and stakeholder interviews were carried out to support the design. The InnoHorse web tool includes a safety section containing a horse stable safety map, stable safety checklists, and examples of good practices in stable safety, horse handling and rescue planning. This new horse stable safety management tool can also help in organizing work processes in horse stables in general.

  1. Basal metabolism in tropical birds: latitude, altitude, and the ‘pace of life’

    OpenAIRE

    Londoño, Gustavo Adolfo

    2015-01-01

    Life history varies across latitudes, with the ‘pace of life’ being ‘slower’ in tropical regions. Because life history is coupled to energy metabolism via allocation tradeoffs and links between performance capacity and energy use, low metabolic intensity is expected in tropical animals. Low metabolism has been reported for lowland tropical birds, but it is unclear if this is due to ‘slow’ life history or to a warm, stable environment. We measured basal metabolic rates (BMR) of 253 bird spe...

  2. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  3. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  4. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  5. The metabolic radiotherapy

    International Nuclear Information System (INIS)

    Begon, F.; Gaci, M.

    1993-01-01

    In this article, the authors recall the principles of the metabolic radiotherapy and present these main applications in the treatment of thyroid cancers, hyperthyroidism, polycythemia, arthritis, bone metastases, adrenergic neoplasms. They also present the radioimmunotherapy

  6. Engineering of metabolic control

    Science.gov (United States)

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  7. Microbial Metabolism in Serpentinite Fluids

    Science.gov (United States)

    Crespo-Medina, M.; Brazelton, W. J.; Twing, K. I.; Kubo, M.; Hoehler, T. M.; Schrenk, M. O.

    2013-12-01

    Serpentinization is the process in which ultramafic rocks, characteristic of the upper mantle, react with water liberating mantle carbon and reducing power to potenially support chemosynthetic microbial communities. These communities may be important mediators of carbon and energy exchange between the deep Earth and the surface biosphere. Our work focuses on the Coast Range Ophiolite Microbial Observatory (CROMO) in Northern California where subsurface fluids are accessible through a series of wells. Preliminary analyses indicate that the highly basic fluids (pH 9-12) have low microbial diversity, but there is limited knowledge about the metabolic capabilities of these communties. Metagenomic data from similar serpentine environments [1] have identified Betaproteobacteria belonging to the order Burkholderiales and Gram-positive bacteria from the order Clostridiales as key components of the serpentine microbiome. In an effort to better characterize the microbial community, metabolism, and geochemistry at CROMO, fluids from two representative wells (N08B and CSWold) were sampled during recent field campaigns. Geochemical characterization of the fluids includes measurements of dissolved gases (H2, CO, CH4), dissolved inorganic and organic carbon, volatile fatty acids, and nutrients. The wells selected can be differentiated in that N08B had higher pH (10-11), lower dissolved oxygen, and cell counts ranging from 105-106 cells mL-1 of fluid, with an abundance of the betaproteobacterium Hydrogenophaga. In contrast, fluids from CSWold have slightly lower pH (9-9.5), DO, and conductivity, as well as higher TDN and TDP. CSWold fluid is also characterized for having lower cell counts (~103 cells mL-1) and an abundance of Dethiobacter, a taxon within the phylum Clostridiales. Microcosm experiments were conducted with the purpose of monitoring carbon fixation, methanotrophy and metabolism of small organic compounds, such as acetate and formate, while tracing changes in fluid

  8. Oxidative metabolism in muscle.

    OpenAIRE

    Ferrari, M; Binzoni, T; Quaresima, V

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  9. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  10. Fundamentals of the LISA stable flight formation

    International Nuclear Information System (INIS)

    Dhurandhar, S V; Nayak, K Rajesh; Koshti, S; Vinet, J-Y

    2005-01-01

    The joint NASA-ESA mission, LISA, relies crucially on the stability of the three-spacecraft constellation. Each of the spacecraft is in heliocentric orbit forming a stable triangle. In this paper we explicitly show with the help of the Clohessy-Wiltshire equations that any configuration of spacecraft lying in the planes making angles of ±60 0 with the ecliptic and given suitable initial velocities within the plane, can be made stable in the sense that the inter-spacecraft distances remain constant to first order in the dimensions of the configuration compared with the distance to the Sun. Such analysis would be useful in order to carry out theoretical studies on the optical links, simulators, etc

  11. A model for a stable coronal loop

    International Nuclear Information System (INIS)

    Hoven, G.V.; Chiuderi, C.; Giachetti, R.

    1977-01-01

    We present here a new plasma-physics model of a stable active-region arch which corresponds to the structure observed in the EUV. Pressure gradients are seen, so that the equilibrium magnetic field must depart from the force-free form valid in the surrounding corona. We take advantage of the data and of the approximate cylindrical symmetry to develop a modified form of the commonly assumed sheared-spiral structure. The dynamic MHD behavior of this new pressure/field model is then evaluated by the Newcomb criterion, taken from controlled-fusion physics, and the results show short-wavelength stability in a specific parameter range. Thus we demonstrate the possibility, for pressure profiles with widths of the order of the magnetic-field scale, that such arches can persist for reasonable periods. Finally, the spatial proportions and magnetic fields of a characteristic stable coronal loop are described

  12. Utilization of stable isotopes in medicine

    International Nuclear Information System (INIS)

    1980-11-01

    The ten lectures given at this round table are presented together with a discussion. Five lectures, relating to studies in which deuterium oxide was employed as a tracer of body water, dealt with pulmonary water measurements in man and animals, the total water pool in adipose subjects, and liquid compartments in children undergoing hemodyalisis. The heavy water is analysed by infrared spectrometry and a new double spectrodoser is described. Two studies using 13 C as tracer, described the diagnosis of liver troubles and diabetes respectively. A general review of the perspectives of the application of stable isotopes in clinical medicine is followed by a comparison of the use of stable and radioactive isotopes in France [fr

  13. Stable isotope enrichment: Current and future potential

    International Nuclear Information System (INIS)

    Tracy, J.G.; Aaron, W.S.

    1992-01-01

    Oak Ridge National Laboratory (ORNL) operates the Isotope Enrichment Facility for the purpose of providing enriched stable isotopes, selected radioactive isotopes (including the actinides), and isotope-related materials and services for use in various research applications. ORNL is responsible for isotope enrichment and the distribution of approximately 225 nongaseous stable isotopes from 50 multi-isotopic elements. Many enriched isotope products are of prime importance in the fabrication of nuclear targets and the subsequent production of special radionuclides. State-of-the-art techniques to achieve special isotopic, chemical, and physical requirements are performed at ORNL This report describes the status and capabilities of the Isotope Enrichment Facility and the Isotope Research Materials Laboratory as well as emphasizing potential advancements in enrichment capabilities

  14. On The Roman Domination Stable Graphs

    Directory of Open Access Journals (Sweden)

    Hajian Majid

    2017-11-01

    Full Text Available A Roman dominating function (or just RDF on a graph G = (V,E is a function f : V → {0, 1, 2} satisfying the condition that every vertex u for which f(u = 0 is adjacent to at least one vertex v for which f(v = 2. The weight of an RDF f is the value f(V (G = Pu2V (G f(u. The Roman domination number of a graph G, denoted by R(G, is the minimum weight of a Roman dominating function on G. A graph G is Roman domination stable if the Roman domination number of G remains unchanged under removal of any vertex. In this paper we present upper bounds for the Roman domination number in the class of Roman domination stable graphs, improving bounds posed in [V. Samodivkin, Roman domination in graphs: the class RUV R, Discrete Math. Algorithms Appl. 8 (2016 1650049].

  15. Design of optically stable image reflector system.

    Science.gov (United States)

    Tsai, Chung-Yu

    2013-08-01

    The design of a partially optically stable (POS) reflector system, in which the exit ray direction and image pose are unchanged as the reflector system rotates about a specific directional vector, was presented in an earlier study by the current group [Appl. Phys. B100, 883-890 (2010)]. The present study further proposes an optically stable image (OSI) reflector system, in which not only is the optical stability property of the POS system retained, but the image position and total ray path length are also fixed. An analytical method is proposed for the design of OSI reflector systems comprising multiple reflectors. The validity of the proposed approach is demonstrated by means of two illustrative examples.

  16. Formation of stable radicals during perfluoroalkane radiolysis

    International Nuclear Information System (INIS)

    Allayarov, S.R.; Demidov, S.V.; Kiryukhin, D.P.; Mikhajlov, A.I.; Barkalov, I.M.

    1984-01-01

    Accumulation and stabilization kinetics of perfluoroalkyls during α-radiolysis ( 60 Co) of perfluoralkanes (PFA) in a wide temperature range for different PFA fractions differing in the average molecular weight, is investigated. It is noted that low temperature (PFA) radiolysis (77 K) is of a linear nature of accumulation of stabilized radicals up to doses of approximately 700 KGy. In the case of PFA radiolysis at 300 K radiation yields of stable radicals are somewhat lower than at 47 K and at doses of 200-300 KGy, their accumulation ceases. It is shown that kinetics of formation and accumulation of stable radicals does not depend on molecular mass and PFA fraction viscosity. Perfluoroalkyl stability is explained by intra molecular conformation spheric insulation of the free valency. Perfluoroalkyl stability in different PFA fractions in a wide time range in different media is investigated

  17. Stable isotope enrichment - current and future potential

    International Nuclear Information System (INIS)

    Tracy, J.G.; Aaron, W.S.

    1993-01-01

    Oak Ridge National Laboratory (ORNL) operates the Isotope Enrichment Facility for the purpose of providing enriched stable isotopes, selected radioactive isotopes (including the actinides), and isotope-related materials and services for use in various research applications. ORNL is responsible for isotope enrichment and the distribution of approximately 225 nongaseous stable isotopes from 50 multi-isotopic elements. Many enriched isotope products are of prime importance in the fabrication of nuclear targets and the subsequent production of special radionuclides. State-of-the-art techniques to achieve special isotopic, chemical, and physical requirements are performed at ORNL. This report describes the status and capabilities of the Isotope Enrichment Facility and the Isotope Research Materials Laboratory as well as emphasizing potential advancements in enrichment capabilities. (orig.)

  18. Optimization of Parameters of Asymptotically Stable Systems

    Directory of Open Access Journals (Sweden)

    Anna Guerman

    2011-01-01

    Full Text Available This work deals with numerical methods of parameter optimization for asymptotically stable systems. We formulate a special mathematical programming problem that allows us to determine optimal parameters of a stabilizer. This problem involves solutions to a differential equation. We show how to chose the mesh in order to obtain discrete problem guaranteeing the necessary accuracy. The developed methodology is illustrated by an example concerning optimization of parameters for a satellite stabilization system.

  19. Multi-Stable Morphing Cellular Structures

    Science.gov (United States)

    2015-05-14

    stiffness on critical buckling load and arch stres - ses. It should be noted that although the arches in these studies snapped-through, they did not...switch roles in moving the VMT back from the second to the first stable equilibrium state. A prototype is designed and fabricated and the transition...pulling forward on the insert on the right blade and assisting its deployment. During this process the cable 3-4-1 goes slack and plays no role , but if

  20. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  1. Strongly stable real infinitesimally symplectic mappings

    NARCIS (Netherlands)

    Cushman, R.; Kelley, A.

    We prove that a mapA εsp(σ,R), the set of infinitesimally symplectic maps, is strongly stable if and only if its centralizerC(A) insp(σ,R) contains only semisimple elements. Using the theorem that everyB insp(σ,R) close toA is conjugate by a real symplectic map to an element ofC(A), we give a new

  2. A belief-based evolutionarily stable strategy

    OpenAIRE

    Deng, Xinyang; Wang, Zhen; Liu, Qi; Deng, Yong; Mahadevan, Sankaran

    2014-01-01

    As an equilibrium refinement of the Nash equilibrium, evolutionarily stable strategy (ESS) is a key concept in evolutionary game theory and has attracted growing interest. An ESS can be either a pure strategy or a mixed strategy. Even though the randomness is allowed in mixed strategy, the selection probability of pure strategy in a mixed strategy may fluctuate due to the impact of many factors. The fluctuation can lead to more uncertainty. In this paper, such uncertainty involved in mixed st...

  3. Juvenile life history of NE Atlantic orange roughy from otolith stable isotopes

    Science.gov (United States)

    Shephard, Samuel; Trueman, Clive; Rickaby, Rosalind; Rogan, Emer

    2007-08-01

    Otoliths of pre-recruit orange roughy ( Hoplostethus atlanticus) were sampled from different deep-water habitats ('flat' and 'hill') and areas (north and south) on the Porcupine Bank. Age-based profiles for stable isotopes of carbon (δ 13C) and oxygen (δ 18O) in these otoliths were developed, which provide a fish life-history record of water depth and metabolic activity. These profiles were consistent among all individuals implying endogenous (ontogenic) influences on the pattern. The data indicate that post-larval orange roughy are mesopelagic active foragers, early juvenile fish move into a low energy deep-demersal phase, and older pre-recruit orange roughy assume the habitat depth and metabolic rate typical of adults. Comparison of otolith stable isotope profiles among areas and habitats on the Porcupine Bank suggest that juvenile orange roughy from South 'hill' and 'flat' habitats experience differing temperature and metabolic status at certain life stages. This may reflect oceanographic and ecological divergence between the two environments and suggests fine-scale population structure that may reduce resilience to exploitation.

  4. Mechanical Properties of Stable Glasses Using Nanoindentation

    Science.gov (United States)

    Wolf, Sarah; Liu, Tianyi; Jiang, Yijie; Ablajan, Keyume; Zhang, Yue; Walsh, Patrick; Turner, Kevin; Fakhraai, Zahra

    Glasses with enhanced stability over ordinary, liquid quenched glasses have been formed via the process of Physical Vapor Deposition (PVD) by using a sufficiently slow deposition rate and a substrate temperature slightly below the glass transition temperature. These stable glasses have been shown to exhibit higher density, lower enthalpy, and better kinetic stability over ordinary glass, and are typically optically birefringent, due to packing and orientational anisotropy. Given these exceptional properties, it is of interest to further investigate how the properties of stable glasses compare to those of ordinary glass. In particular, the mechanical properties of stable glasses remain relatively under-investigated. While the speed of sound and elastic moduli have been shown to increase with increased stability, little is known about their hardness and fracture toughness compared to ordinary glasses. In this study, glasses of 9-(3,5-di(naphthalen-1-yl)phenyl)anthracene were deposited at varying temperatures relative to their glass transition temperature, and their mechanical properties measured by nanoindentation. Hardness and elastic modulus of the glasses were compared across substrate temperatures. After indentation, the topography of these films were studied using Atomic Force Microscopy (AFM) in order to further compare the relationship between thermodynamic and kinetic stability and mechanical failure. Z.F. and P.W. acknowledge funding from NSF(DMREF-1628407).

  5. Detonation of Meta-stable Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, Allen; Kuhl, Allen L.; Fried, Laurence E.; Howard, W. Michael; Seizew, Michael R.; Bell, John B.; Beckner, Vincent; Grcar, Joseph F.

    2008-05-31

    We consider the energy accumulation in meta-stable clusters. This energy can be much larger than the typical chemical bond energy (~;;1 ev/atom). For example, polymeric nitrogen can accumulate 4 ev/atom in the N8 (fcc) structure, while helium can accumulate 9 ev/atom in the excited triplet state He2* . They release their energy by cluster fission: N8 -> 4N2 and He2* -> 2He. We study the locus of states in thermodynamic state space for the detonation of such meta-stable clusters. In particular, the equilibrium isentrope, starting at the Chapman-Jouguet state, and expanding down to 1 atmosphere was calculated with the Cheetah code. Large detonation pressures (3 and 16 Mbar), temperatures (12 and 34 kilo-K) and velocities (20 and 43 km/s) are a consequence of the large heats of detonation (6.6 and 50 kilo-cal/g) for nitrogen and helium clusters respectively. If such meta-stable clusters could be synthesized, they offer the potential for large increases in the energy density of materials.

  6. Clinically stable angina pectoris is not necessarily associated with histologically stable atherosclerotic plaques

    NARCIS (Netherlands)

    van der Wal, A. C.; Becker, A. E.; Koch, K. T.; Piek, J. J.; Teeling, P.; van der Loos, C. M.; David, G. K.

    1996-01-01

    OBJECTIVE: To investigate the extent of plaque inflammation in culprit lesions of patients with chronic stable angina. DESIGN: Retrospective study. SETTING: Amsterdam reference centre. SUBJECTS: 89 consecutive patients who underwent directional coronary atherectomy, 58 of whom met the following

  7. Pharmacokinetics and Metabolism of 4R-Cembranoid

    OpenAIRE

    V?lez-Carrasco, Wanda; Green, Carol E.; Catz, Paul; Furimsky, Anna; O?Loughlin, Kathleen; Eterovi?, Vesna A.; Ferchmin, P. A.

    2015-01-01

    4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism ...

  8. Stable isotope studies of nicotine kinetics and bioavailability

    International Nuclear Information System (INIS)

    Benowitz, N.L.; Jacob, P. III; Denaro, C.; Jenkins, R.

    1991-01-01

    The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine

  9. Stable ischemic heart disease in women: current perspectives.

    Science.gov (United States)

    Samad, Fatima; Agarwal, Anushree; Samad, Zainab

    2017-01-01

    Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD) in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m 2 ), smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases. Diagnostic testing can be used effectively to risk stratify women. Guidelines-directed medical therapy including aspirin, statins, beta-blocker therapy, calcium channel blockers and ranolazine should be instituted for symptom and ischemia management. Despite robust evidence regarding the adverse outcomes seen in women with ischemic heart disease, knowledge gaps exist in several areas. Future research needs to be directed toward a greater understanding of the role of nontraditional risk factors for SIHD in women, gaining deeper insights into the sex differences in therapeutic effects and formulating a sex-specific algorithm for the management of SIHD in women.

  10. Fluorescein-labeled stable neurotensin derivatives.

    Science.gov (United States)

    Maes, Veronique; Hultsch, Christina; Kohl, Suzann; Bergmann, Ralf; Hanke, Thomas; Tourwé, Dirk

    2006-08-01

    Neurotensin(8-13) analogs containing a glycine or 5-aminovaleroyl spacer were labeled with fluorescein through formation of an N-terminal thiourea function. The receptor binding was measured in HT-29 cell cultures and showed a substantial decrease in affinity, especially for the metabolically stabilized [MeArg(9), Tle(11)] analog. Using fluorescence microscopy, the internalization of the fluorescent neurotensin analogs into HT-29 cells was observed. Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.

  11. Stable isotope fractionation during bacterial sulfate reduction is controlled by reoxidation of intermediates

    Science.gov (United States)

    Mangalo, Muna; Meckenstock, Rainer U.; Stichler, Willibald; Einsiedl, Florian

    2007-09-01

    Bacterial sulfate reduction is one of the most important respiration processes in anoxic habitats and is often assessed by analyzing the results of stable isotope fractionation. However, stable isotope fractionation is supposed to be influenced by the reduction rate and other parameters, such as temperature. We studied here the mechanistic basics of observed differences in stable isotope fractionation during bacterial sulfate reduction. Batch experiments with four sulfate-reducing strains ( Desulfovibrio desulfuricans, Desulfobacca acetoxidans, Desulfonatronovibrio hydrogenovorans, and strain TRM1) were performed. These microorganisms metabolize different carbon sources (lactate, acetate, formate, and toluene) and showed broad variations in their sulfur isotope enrichment factors. We performed a series of experiments on isotope exchange of 18O between residual sulfate and ambient water. Batch experiments were conducted with 18O-enriched (δ 18O water = +700‰) and depleted water (δ 18O water = -40‰), respectively, and the stable 18O isotope shift in the residual sulfate was followed. For Desulfovibrio desulfuricans and Desulfonatronovibrio hydrogenovorans, which are both characterized by low sulfur isotope fractionation ( ɛS > -13.2‰), δ 18O values in the remaining sulfate increased by only 50‰ during growth when 18O-enriched water was used for the growth medium. In contrast, with Desulfobacca acetoxidans and strain TRM1 ( ɛS factor ( ɛS exchange with water during sulfate reduction. However, this neither takes place in the sulfate itself nor during formation of APS (adenosine-5'-phosphosulfate), but rather in intermediates of the sulfate reduction pathway. These may in turn be partially reoxidized to form sulfate. This reoxidation leads to an incorporation of oxygen from water into the "recycled" sulfate changing the overall 18O isotopic composition of the remaining sulfate fraction. Our study shows that such incorporation of 18O is correlated with the

  12. Vertigo and metabolic disorders.

    Science.gov (United States)

    Santos, Maruska D' Aparecida; Bittar, Roseli Saraiva Moreira

    2012-01-01

    Metabolic disorders are accepted by many authors as being responsible for balance disorders. Because of the importance of metabolic disorders in the field of labyrinthine dysfunction, we decided to assess the prevalence of carbohydrates, lipids and thyroid hormones disorders in our patients with vestibular diseases. The study evaluates the metabolic profile of 325 patients with vertigo who sought the Otolaryngology Department of the University of São Paulo in the Hospital das Clínicas da Universidade de São Paulo. The laboratory tests ordered according to the classical research protocol were: low-density lipoprotein cholesterol fraction, TSH, T3, T4 and fasting blood sugar level. The metabolic disorders found and the ones that were observed in the general population were compared. The high level of low-density lipoprotein cholesterol, the altered levels of thyroid hormones, the higher prevalence of diabetes mellitus were the most significant changes found in the group of study. The higher amount of metabolic disorders in patients with vertigo disease reinforces the hypothesis of its influence on the etiopathogenesis of cochleovestibular symptoms.

  13. Metabolic surgery: quo vadis?

    Science.gov (United States)

    Ramos-Leví, Ana M; Rubio Herrera, Miguel A

    2014-01-01

    The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  14. Nuclear magnetic resonance studies of metabolic regulation

    International Nuclear Information System (INIS)

    Sillerud, L.O.; Han, C.H.; Whaley, T.W.

    1983-01-01

    Nuclear magnetic resonance (NMR) techniques for the detection of the metabolic transformations of biological compounds labeled with stable isotopes, particularly carbon-13 have been explored. We have studied adipose tissue in the intact rat, the exteriorized epididymal fat pad, and the isolated adipocyte. Triacylglycerol metabolism in adipose tissue is regulated by lipogenic factors (insulin, corticosterone, thyroxine, and growth hormone) and lipolytic factors (glucagon and catecholamines). The synthesis of triglyceride from 5.5 mM glucose was stimulated by about 4-fold by 10 nM insulin. Triglyceride synthesis from glucose in the presence of insulin occurred at a rate of 330 nmol/hr/10 6 cells. Since the NMR signals from free and esterified fatty acids and glycerol are distinct, we could directly measure the rate of hormone-stimulated lipolysis. Epinephrine (10 μM) gave a lipolytic rate of 0.30 μmol/hr/10 6 cells as monitored by free-glycerol appearance in the medium. 13 C NMR provides a superior method for the measurement of triglyceride metabolism since it directly measures the changes in the substrates and products in situ

  15. Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation.

    Directory of Open Access Journals (Sweden)

    Hugo I Contreras-Treviño

    Full Text Available Species A rotavirus non-structural protein 3 (NSP3 is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A binding protein (PABP from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3'-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD. We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E, whereas one mutation had the opposite effects (Y192A. Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.

  16. Stable isogeometric analysis of trimmed geometries

    Science.gov (United States)

    Marussig, Benjamin; Zechner, Jürgen; Beer, Gernot; Fries, Thomas-Peter

    2017-04-01

    We explore extended B-splines as a stable basis for isogeometric analysis with trimmed parameter spaces. The stabilization is accomplished by an appropriate substitution of B-splines that may lead to ill-conditioned system matrices. The construction for non-uniform knot vectors is presented. The properties of extended B-splines are examined in the context of interpolation, potential, and linear elasticity problems and excellent results are attained. The analysis is performed by an isogeometric boundary element formulation using collocation. It is argued that extended B-splines provide a flexible and simple stabilization scheme which ideally suits the isogeometric paradigm.

  17. The observation of a stable dibaryon

    International Nuclear Information System (INIS)

    Shakhbazyan, B.A.; Sashin, V.A.; Kecheryan, A.O.; Martynov, A.S.

    1989-01-01

    V 0 -particle which is unambiguously interpreted as a weak decay of the stable dibaryon value of cross section H→p+Σ - ,Σ→n+π - is observed. Its mass is M H =(2218+-12) MeV c 2 with a standard deviation S=12 MeV/c 2 and the error of the mean σ=2.8 MeV/c 2 . The investigation has been performed at the Laboratory of High energies, JINR. 10 refs.; 1 fig.; 3 tabs

  18. Protein labelling with stable isotopes: strategies

    International Nuclear Information System (INIS)

    Lirsac, P.N.; Gilles, N.; Jamin, N.; Toma, F.; Gabrielsen, O.; Boulain, J.C.; Menez, A.

    1994-01-01

    A protein labelling technique with stable isotopes has been developed at the CEA: a labelled complete medium has been developed, performing as well as the Luria medium, but differing from it because it contains not only free aminated acids and peptides, but also sugars (96% of D-glucopyrannose) and labelled nucleosides. These precursors are produced from a labelled photosynthetic micro-organisms biomass, obtained with micro-algae having incorporated carbon 13, nitrogen 15 and deuterium during their culture. Labelling costs are reduced. 1 fig., 1 tab., 3 refs

  19. Metabolism of phencyclidine

    International Nuclear Information System (INIS)

    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s)

  20. Progresses in the stable isotope studies of microbial processes associated with wetland methane production

    International Nuclear Information System (INIS)

    Li Qing; Lin Guanghui

    2013-01-01

    Methane emissions from wetlands play a key role in regulating global atmospheric methane concentration, so better understanding of microbial processes for the methane emission in wetlands is critical for developing process models and reducing uncertainty in global methane emission inventory. In this review, we describe basic microbial processes for wetland methane production and then demonstrate how stable isotope fractionation and stable isotope probing can be used to investigate the mechanisms underlying different methanogenic pathways and to quantify microbial species involved in wetland methane production. When applying stable isotope technique to calculate contributions of different pathways to the total methane production in various wetlands, the technical challenge is how to determine isotopic fractionation factors for the acetate derived methane production and carbon dioxide derived methane production. Although the application of stable isotope probing techniques to study the actual functions of different microbial organisms to methane production process is significantly superior to the traditional molecular biology method, the combination of these two technologies will be crucial for direct linking of the microbial community and functional structure with the corresponding metabolic functions, and provide new ideas for future studies. (authors)

  1. Metabolic changes in malnutrition.

    Science.gov (United States)

    Emery, P W

    2005-10-01

    This paper is concerned with malnutrition caused by inadequate intake of all the major nutrients rather than deficiency diseases relating to a single micronutrient. Three common situations are recognised: young children in third world countries with protein-energy malnutrition; adults in the same countries who are chronically adapted to subsisting on marginally inadequate diets; and patients who become malnourished as a result of chronic diseases. In all these situations infectious diseases are often also present, and this complicates the interpretation of biochemical and physiological observations. The metabolic response to starvation is primarily concerned with maintaining a supply of water-soluble substrates to supply energy to the brain. Thus there is an initial rise in metabolic rate, reflecting gluconeogenic activity. As fasting progresses, gluconeogenesis is suppressed to minimise muscle protein breakdown and ketones become the main fuel for the brain. With chronic underfeeding the basal metabolic rate per cell appears to fall, but the mechanistic basis for this is not clear. The main adaptation to chronic energy deficiency is slow growth and low adult body size, although the reduction in energy requirement achieved by this is partially offset by the preservation of the more metabolically active organs at the expense of muscle, which has a lower metabolic rate. The interaction between malnutrition and the metabolic response to trauma has been studied using an animal model. The rise in energy expenditure and urinary nitrogen excretion following surgery were significantly attenuated in malnourished rats, suggesting that malnutrition impairs the ability of the body to mobilise substrates to support inflammatory and reparative processes. However, the healing process in wounded muscle remained unimpaired in malnutrition, suggesting that this process has a high biological priority.

  2. Urea metabolism in plants.

    Science.gov (United States)

    Witte, Claus-Peter

    2011-03-01

    Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Nitrile Metabolizing Yeasts

    Science.gov (United States)

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing

  4. Remarks on stable and quasi-stable k-strings at large N

    International Nuclear Information System (INIS)

    Armoni, A.; Shifman, M.

    2003-01-01

    We discuss k-strings in the large-N Yang-Mills theory and its supersymmetric extension. Whereas the tension of the bona fide (stable) QCD string is expected to depend only on the N-ality of the representation, tensions that depend on specific representation R are often reported in the lattice literature. In particular, adjoint strings are discussed and found in certain simulations. We clarify this issue by systematically exploiting the notion of the quasi-stable strings which becomes well-defined at large N. The quasi-stable strings with representation-dependent tensions decay, but the decay rate (per unit length per unit time) is suppressed as Λ 2 F(N) where F(N) falls off as a function of N. It can be determined on the case-by-case basis. The quasi-stable strings eventually decay into stable strings whose tension indeed depends only on the N-ality. We also briefly review large-N arguments showing why the Casimir formula for the string tension cannot be correct, and present additional arguments in favor of the sine formula. Finally, we comment on the relevance of our estimates to Euclidean lattice measurements

  5. The medical effects of radioactive fall-out: role of stable end-products

    International Nuclear Information System (INIS)

    Burrows, B.A.; Cardarelli, J.C.; Boling, E.A.; Sinex, F.M.

    1980-01-01

    To summarize, from preliminary observations on the possible effects of radioactive fall-out, it may be inferred that in addition to the secondary products of ionizing irradiation per se, the stable end-products of the transmutation of certain radionuclides may adversely influence cellular metabolism, including mutagenesis. The discussion of the possible role of intracellular barium as an end-product of 137Cs decay is offered as an example of an unpredictable number of broad ecological, as well as the more limited medical, effects that may be of both clinical and climatological significance

  6. Heat-stable, FE-dependent alcohol dehydrogenase for aldehyde detoxification

    Science.gov (United States)

    Elkins, James G.; Clarkson, Sonya

    2018-04-24

    The present invention relates to microorganisms and polypeptides for detoxifying aldehydes associated with industrial fermentations. In particular, a heat-stable, NADPH- and iron-dependent alcohol dehydrogenase was cloned from Thermoanaerobacter pseudethanolicus 39E and displayed activity against a number of aldehydes including inhibitory compounds that are produced during the dilute-acid pretreatment process of lignocellulosic biomass before fermentation to biofuels. Methods to use the microorganisms and polypeptides of the invention for improved conversion of bio mass to biofuel are provided as well as use of the enzyme in metabolic engineering strategies for producing longer-chain alcohols from sugars using thermophilic, fermentative microorganisms.

  7. Hypothyroidism in metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2012-01-01

    Full Text Available Aim: Metabolic syndrome (MetS and hypothyroidism are well established forerunners of atherogenic cardiovascular disease. Considerable overlap occurs in the pathogenic mechanisms of atherosclerotic cardiovascular disease by metabolic syndrome and hypothyroidism. Insulin resistance has been studied as the basic pathogenic mechanism in metabolic syndrome. [1] This cross sectional study intended to assess thyroid function in patients with metabolic syndrome and to investigate the association between hypothyroidism and metabolic syndrome. Materials and Methods: One hundred patients with metabolic syndrome who fulfilled the National Cholesterol Education Program- Adult Treatment Panel (NCEP-ATP III criteria [ 3 out of 5 criteria positive namely blood pressure ≥ 130/85 mm hg or on antihypertensive medications, fasting plasma glucose > 100 mg/dl or on anti-diabetic medications, fasting triglycerides > 150 mg/dl, high density lipoprotein cholesterol (HDL-C 102 cms in men and 88 cms in women] were included in the study group. [2] Fifty patients who had no features of metabolic syndrome (0 out of 5 criteria for metabolic syndrome were included in the control group. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions and lipid levels and those who are under treatment for any thyroid related disorder were excluded from the study. Acutely ill patients were excluded taking into account sick euthyroid syndrome. Patients were subjected to anthropometry, evaluation of vital parameters, lipid and thyroid profile along with other routine laboratory parameters. Students t-test, Chi square test and linear regression, multiple logistic regression models were used for statistical analysis. P value < 0.05 was considered significant. Results: Of the 100 patients in study group, 55 were females (55% and 45 were males (45%. Of the 50

  8. Metabolic complications in oncology

    International Nuclear Information System (INIS)

    Sycova-Mila, Z.

    2012-01-01

    Currently, a lot of space and time is devoted to the therapy of oncologic diseases itself. To reach the good therapy results, complex care of the oncologic patient is needed. Management of complications linked with the disease itself and management of complications emerged after administration of chemotherapy, radiotherapy or targeted therapy, plays a significant role. In addition to infectious, hematological, neurological, cardiac or other complications, metabolic complications are relatively extensive and serious. One of the most frequent metabolic complications in oncology is tumor lysis syndrome, hyperuricemia, hypercalcaemia and syndrome of inappropriate secretion of antidiuretic hormone. (author)

  9. Prokaryote metabolism activity

    OpenAIRE

    Biederman, Lori

    2017-01-01

    I wrote this activity to emphasize that prokaryotic organisms can carry out 6 different types of metabolisms (as presented in Freeman’s Biological Science textbook) and this contrasts to eukaryotes, which can only use 2 metabolism pathways (photoautotroph and heterotroph).    For in class materials I remove the  red box (upper right corner) and print slides 3-10, place them back-to-back and laminate them.  The students get a key (slide 2) and a two-sided organism sheet...

  10. Stable isotope measurements of atmospheric CO2

    International Nuclear Information System (INIS)

    White, J.W.C.; Ferretti, D.F.; Vaughn, B.H.; Francey, R.J.; Allison, C.E.

    2002-01-01

    The measurement of stable carbon isotope ratios of atmospheric carbon dioxide, δ 13 CO 2 are useful for partitioning surface-atmospheric fluxes into terrestrial and oceanic components. δC 18 OO also has potential for segregating photosynthetic and respiratory fluxes in terrestrial ecosystems. Here we describe in detail the techniques for making these measurements. The primary challenge for all of the techniques used to measure isotopes of atmospheric CO 2 is to achieve acceptable accuracy and precision and to maintain them over the decades needed to observe carbon cycle variability. The keys to success such an approach are diligent intercalibrations of laboratories from around the world, as well as the use of multiple techniques such as dual inlet and GC-IRMS and the intercomparison of such measurements. We focus here on two laboratories, the Stable Isotope Lab at the Institute for Arctic and Alpine Research (INSTAAR) at the University of Colorado is described and the Commonwealth Scientific and Industrial Research Organisation - Atmospheric Research (CSIRO). Different approaches exist at other laboratories (e.g. programs operated by Scripps Institution of Oceanography (SIO) and The Center for Atmospheric and Oceanic Studies, Toboku University (TU)) however these are not discussed here. Finally, we also discuss the recently developed Gas Chromatography - Isotope Ratio Mass Spectrometry (GC-IRMS) technique which holds significant promise for measuring ultra-small samples of gas with good precision. (author)

  11. Stable statistical representations facilitate visual search.

    Science.gov (United States)

    Corbett, Jennifer E; Melcher, David

    2014-10-01

    Observers represent the average properties of object ensembles even when they cannot identify individual elements. To investigate the functional role of ensemble statistics, we examined how modulating statistical stability affects visual search. We varied the mean and/or individual sizes of an array of Gabor patches while observers searched for a tilted target. In "stable" blocks, the mean and/or local sizes of the Gabors were constant over successive displays, whereas in "unstable" baseline blocks they changed from trial to trial. Although there was no relationship between the context and the spatial location of the target, observers found targets faster (as indexed by faster correct responses and fewer saccades) as the global mean size became stable over several displays. Building statistical stability also facilitated scanning the scene, as measured by larger saccadic amplitudes, faster saccadic reaction times, and shorter fixation durations. These findings suggest a central role for peripheral visual information, creating context to free resources for detailed processing of salient targets and maintaining the illusion of visual stability.

  12. Color stable manganese-doped phosphors

    Science.gov (United States)

    Lyons, Robert Joseph [Burnt Hills, NY; Setlur, Anant Achyut [Niskayuna, NY; Deshpande, Anirudha Rajendra [Twinsburg, OH; Grigorov, Ljudmil Slavchev [Sofia, BG

    2012-08-28

    A process for preparing color stable Mn.sup.+4 doped phosphors includes providing a phosphor of formula I; A.sub.x[MF.sub.y]:Mn.sup.+4 I and contacting the phosphor in particulate form with a saturated solution of a composition of formula II in aqueous hydrofluoric acid; A.sub.x[MF.sub.y]; II wherein A is Li, Na, K, Rb, Cs, NR.sub.4 or a combination thereof; M is Si, Ge, Sn, Ti, Zr, Al, Ga, In, Sc, Y, La, Nb, Ta, Bi, Gd, or a combination thereof; R is H, lower alkyl, or a combination thereof; x is the absolute value of the charge of the [MF.sub.y] ion; and y is 5, 6 or 7. In particular embodiments, M is Si, Ge, Sn, Ti, Zr, or a combination thereof. A lighting apparatus capable of emitting white light includes a semiconductor light source; and a phosphor composition radiationally coupled to the light source, and which includes a color stable Mn.sup.+4 doped phosphor.

  13. Multivariate Max-Stable Spatial Processes

    KAUST Repository

    Genton, Marc G.

    2014-01-06

    Analysis of spatial extremes is currently based on univariate processes. Max-stable processes allow the spatial dependence of extremes to be modelled and explicitly quantified, they are therefore widely adopted in applications. For a better understanding of extreme events of real processes, such as environmental phenomena, it may be useful to study several spatial variables simultaneously. To this end, we extend some theoretical results and applications of max-stable processes to the multivariate setting to analyze extreme events of several variables observed across space. In particular, we study the maxima of independent replicates of multivariate processes, both in the Gaussian and Student-t cases. Then, we define a Poisson process construction in the multivariate setting and introduce multivariate versions of the Smith Gaussian extremevalue, the Schlather extremal-Gaussian and extremal-t, and the BrownResnick models. Inferential aspects of those models based on composite likelihoods are developed. We present results of various Monte Carlo simulations and of an application to a dataset of summer daily temperature maxima and minima in Oklahoma, U.S.A., highlighting the utility of working with multivariate models in contrast to the univariate case. Based on joint work with Simone Padoan and Huiyan Sang.

  14. Multivariate Max-Stable Spatial Processes

    KAUST Repository

    Genton, Marc G.

    2014-01-01

    Analysis of spatial extremes is currently based on univariate processes. Max-stable processes allow the spatial dependence of extremes to be modelled and explicitly quantified, they are therefore widely adopted in applications. For a better understanding of extreme events of real processes, such as environmental phenomena, it may be useful to study several spatial variables simultaneously. To this end, we extend some theoretical results and applications of max-stable processes to the multivariate setting to analyze extreme events of several variables observed across space. In particular, we study the maxima of independent replicates of multivariate processes, both in the Gaussian and Student-t cases. Then, we define a Poisson process construction in the multivariate setting and introduce multivariate versions of the Smith Gaussian extremevalue, the Schlather extremal-Gaussian and extremal-t, and the BrownResnick models. Inferential aspects of those models based on composite likelihoods are developed. We present results of various Monte Carlo simulations and of an application to a dataset of summer daily temperature maxima and minima in Oklahoma, U.S.A., highlighting the utility of working with multivariate models in contrast to the univariate case. Based on joint work with Simone Padoan and Huiyan Sang.

  15. Shifts in rotifer life history in response to stable isotope enrichment: testing theories of isotope effects on organismal growth

    Science.gov (United States)

    2017-01-01

    In ecology, stable isotope labelling is commonly used for tracing material transfer in trophic interactions, nutrient budgets and biogeochemical processes. The main assumption in this approach is that the enrichment with a heavy isotope has no effect on the organism growth and metabolism. This assumption is, however, challenged by theoretical considerations and experimental studies on kinetic isotope effects in vivo. Here, I demonstrate profound changes in life histories of the rotifer Brachionus plicatilis fed 15N-enriched algae (0.4–5.0 at%); i.e. at the enrichment levels commonly used in ecological studies. These findings support theoretically predicted effects of heavy isotope enrichment on growth, metabolism and ageing in biological systems and underline the importance of accounting for such effects when using stable isotope labelling in experimental studies. PMID:28405367

  16. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  17. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  18. Wall-crossing between stable and co-stable ADHM data

    Science.gov (United States)

    Ohkawa, Ryo

    2018-06-01

    We prove formula between Nekrasov partition functions defined from stable and co-stable ADHM data for the plane following method by Nakajima and Yoshioka (Kyoto J Math 51(2):263-335, 2011) based on the theory of wall-crossing formula developed by Mochizuki (Donaldson type invariants for algebraic surfaces: transition of moduli stacks, Lecture notes in mathematics, vol 1972, Springer, Berlin, 2009). This formula is similar to conjectures by Ito et al. [J High Energy Phys 2013(5):045, 2013, (4.1), (4.2)] for A1 singularity.

  19. SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

    Science.gov (United States)

    Gougat, Jean; Ferrari, Bernard; Sarran, Lionel; Planchenault, Claudine; Poncelet, Martine; Maruani, Jeanne; Alonso, Richard; Cudennec, Annie; Croci, Tiziano; Guagnini, Fabio; Urban-Szabo, Katalin; Martinolle, Jean-Pierre; Soubrié, Philippe; Finance, Olivier; Le Fur, Gérard

    2004-05-01

    The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.

  20. Neonatal nutrition and metabolism

    National Research Council Canada - National Science Library

    Thureen, Patti J; Hay, William W

    2006-01-01

    ..., the volume highlights the important longterm effects of fetal and neonatal growth on health in later life. In addition, there are very practical chapters on methods and techniques for assessing nutritional status, body composition, and evaluating metabolic function. Written by an authoritative, international team of cont...

  1. Insect flight muscle metabolism

    NARCIS (Netherlands)

    Horst, D.J. van der; Beenakkers, A.M.Th.; Marrewijk, W.J.A. van

    1984-01-01

    The flight of an insect is of a very complicated and extremely energy-demanding nature. Wingbeat frequency may differ between various species but values up to 1000 Hz have been measured. Consequently metabolic activity may be very high during flight and the transition from rest to flight is

  2. Sleep and metabolic function.

    Science.gov (United States)

    Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.

  3. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  4. Metabolism of femoxetine

    International Nuclear Information System (INIS)

    Larsson, H.; Lund, J.

    1981-01-01

    The metabolism of femoxetine, a serotonin uptake inhibitor, has been investigated in rats, dogs, monkeys, and human subjects using two 14 C-femoxetine compounds with labelling in different positions. The metabolic pathways were oxidations (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolised, and the same metabolites were found in urine from all four species. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N-oxide than monkey and man, while most of the radioactivity (60-100%) in these two species was excreted as two hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in these two species as one metabolite, formed by demethylation of a methoxy group. A demethylation of a N-CH 3 group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0 to 18% of the dose between individuals. Most of the radioactivity was excreted with the faeces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in the metabolic pattern. No dose dependency was observed in any of the three animal species investigated. (author)

  5. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Metabolic Diseases of Muscle

    Science.gov (United States)

    ... here and still get the great care and treatment I received in Michigan.” MDA Is Here to Help You T he Muscular Dystrophy Association offers a vast array of services to help you and your family deal with metabolic diseases of muscle. The staff at your local MDA office is ...

  7. Measurement of the bio-availability in man of a pharmaceutic form of magnesium, by the means of stable isotopes

    International Nuclear Information System (INIS)

    Benech, H.; Pruvost, A.; Grognet, J.M.; Morge, X.

    1994-01-01

    A method for measuring the absolute bio-availability, in man, of an oral magnesium pharmaceutic form by the means of the simultaneous utilization of two stable magnesium isotopes, 25 Mg and 26 Mg, by oral or intra-venous administrations in order to study the metabolism of magnesium in the human body, is presented. Fecal elimination and urinary excretion of magnesium are recorded. 10 refs

  8. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    OpenAIRE

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p

  9. Fat metabolism during exercise in patients with mitochondrial disease

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Orngreen, Mette Cathrine; Van Hall, Gerrit

    2009-01-01

    . Fat metabolism was determined by means of indirect calorimetry and stable isotope technique in patients and healthy subjects. Patients carried various types and loads (mean [SE], 72% [5%]) of mitochondrial DNA (mtDNA) mutations in skeletal muscle. All subjects exercised at the same absolute workload......OBJECTIVE: To determine whether patients with defects of the respiratory chain have metabolic adaptations that promote a preferential use of fats or carbohydrates, similar to what is observed in metabolic myopathies affecting glycolysis or fat oxidation. DESIGN: Causation and case-control study...... (mean [SE], 65 [10] W), corresponding to 72% (in patients) and 30% (in healthy subjects) of maximum oxygen consumption. SETTING: Neuromuscular research unit. PARTICIPANTS: Ten patients with mtDNA mutations and 10 sex-matched healthy subjects. MAIN OUTCOME MEASURES: Fat turnover, plasma concentrations...

  10. [Carbohydrates metabolism disturbances when simulating prenatal alcohol intoxication].

    Science.gov (United States)

    Kurch, N M; Vysokogorskiĭ, V E

    2013-01-01

    The influence of prenatal alcohol intoxication on carbohydrate metabolism markers has been investigated at different terms of postnatal offspring development (15, 30 and 60 days). Plasma glucose decreased as compared with the same in control group was detected. In the liver homogenates an increase of phosphorylase activity and a decrease of glucose-6-phosphatase, aldolase and glucose-6-phosphate dehydrogenase activities were found. These changes were accompanied by the incease in the lactate/pyruvate index attributed to increased lactate content in the liver tissue. The obtained data indicate essential disturbances of carbohydrate metabolism markers in prenatal alcoholized offspring, which include stable hypoglycemia, suppression of glycolytic and pentosephosphate pathways of glucose metabolism and lactate accumulation in the liver.

  11. Dysregulated metabolism contributes to oncogenesis

    Science.gov (United States)

    Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

    2015-01-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  12. Stable CSR in storage rings: A model

    International Nuclear Information System (INIS)

    Sannibale, Fernando; Byrd, John M.; Loftsdottir, Agusta; Venturini, Marco; Abo-Bakr, Michael; Feikes, Jorge; Holldack, Karsten; Kuske, Peter; Wustefeld, Godehart; Hubers, Heinz-Willerm; Warnock, Robert

    2005-01-01

    A comprehensive historical view of the work done on coherent synchrotron radiation (CSR) in storage rings is given in reference [1]. Here we want just to point out that even if the issue of CSR in storage rings was already discussed over 50 years ago, it is only recently that a considerable number of observations have been reported. In fact, intense bursts of coherent synchrotron radiation with a stochastic character were measured in the terahertz frequency range, at several synchrotron light source storage rings [2-8]. It has been shown [8-11], that this bursting emission of CSR is associated with a single bunch instability, usually referred as microbunching instability (MBI), driven by the fields of the synchrotron radiation emitted by the bunch itself. Of remarkably different characteristics was the CSR emission observed at BESSY II in Berlin, when the storage ring was tuned into a special low momentum compaction mode [12, 13]. In fact, the emitted radiation was not the quasi-random bursting observed in the other machines, but a powerful and stable flux of broadband CSR in the terahertz range. This was an important result, because it experimentally demonstrated the concrete possibility of constructing a stable broadband source with extremely high power in the terahertz region. Since the publication of the first successful experiment using the ring as a CSR source [14], BESSY II has regular scheduled user s shifts dedicated to CSR experiments. At the present time, several other laboratories are investigating the possibility of a CSR mode of operation [15-17] and a design for a new ring optimized for CSR is at an advanced stage [18]. In what follows, we describe a model that first accounts for the BESSY II observations and then indicates that the special case of BESSY II is actually quite general and typical when relativistic electron storage rings are tuned for short bunches. The model provides a scheme for predicting and optimizing the performance of ring

  13. Stable CSR in Storage Rings: A Model

    International Nuclear Information System (INIS)

    Sannibale, F.

    2005-01-01

    A comprehensive historical view of the work done on coherent synchrotron radiation (CSR) in storage rings is given in reference [1]. Here we want just to point out that even if the issue of CSR in storage rings was already discussed over 50 years ago, it is only recently that a considerable number of observations have been reported. In fact, intense bursts of coherent synchrotron radiation with a stochastic character were measured in the terahertz frequency range, at several synchrotron light source storage rings [2-8]. It has been shown [8-11], that this bursting emission of CSR is associated with a single bunch instability, usually referred as microbunching instability (MBI), driven by the fields of the synchrotron radiation emitted by the bunch itself. Of remarkably different characteristics was the CSR emission observed at BESSY II in Berlin, when the storage ring was tuned into a special low momentum compaction mode [12, 13]. In fact, the emitted radiation was not the quasi-random bursting observed in the other machines, but a powerful and stable flux of broadband CSR in the terahertz range. This was an important result, because it experimentally demonstrated the concrete possibility of constructing a stable broadband source with extremely high power in the terahertz region. Since the publication of the first successful experiment using the ring as a CSR source [14], BESSY II has regular scheduled user's shifts dedicated to CSR experiments. At the present time, several other laboratories are investigating the possibility of a CSR mode of operation [15-17] and a design for a new ring optimized for CSR is at an advanced stage [18]. In what follows, we describe a model that first accounts for the BESSY II observations and then indicates that the special case of BESSY II is actually quite general and typical when relativistic electron storage rings are tuned for short bunches. The model provides a scheme for predicting and optimizing the performance of ring

  14. Tukey max-stable processes for spatial extremes

    KAUST Repository

    Xu, Ganggang; Genton, Marc G.

    2016-01-01

    We propose a new type of max-stable process that we call the Tukey max-stable process for spatial extremes. It brings additional flexibility to modeling dependence structures among spatial extremes. The statistical properties of the Tukey max

  15. Cerebral ketone body metabolism.

    Science.gov (United States)

    Morris, A A M

    2005-01-01

    Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

  16. A Metabolic Race

    Directory of Open Access Journals (Sweden)

    A.M.S. Costa et al.

    2017-07-01

    Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

  17. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.

    Directory of Open Access Journals (Sweden)

    Eleanor C Saunders

    2014-01-01

    Full Text Available Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13C-stable isotope resolved metabolomics and (2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

  18. Chance and stability stable distributions and their applications

    CERN Document Server

    Uchaikin, Vladimir V

    1999-01-01

    An introduction to the theory of stable distributions and their applications. It contains a modern outlook on the mathematical aspects of the theory. The authors explain numerous peculiarities of stable distributions and describe the principle concept of probability theory and function analysis. A significant part of the book is devoted to applications of stable distributions. Another notable feature is the material on the interconnection of stable laws with fractals, chaos and anomalous transport processes.

  19. Stable orbits for lunar landing assistance

    Science.gov (United States)

    Condoleo, Ennio; Cinelli, Marco; Ortore, Emiliano; Circi, Christian

    2017-10-01

    To improve lunar landing performances in terms of mission costs, trajectory determination and visibility the use of a single probe located over an assistance orbit around the Moon has been taken into consideration. To this end, the properties of two quasi-circular orbits characterised by a stable behaviour of semi-major axis, eccentricity and inclination have been investigated. The analysis has demonstrated the possibility of using an assistance probe, located over one of these orbits, as a relay satellite between lander and Earth, even in the case of landings on the far side of the Moon. A comparison about the accuracy in retrieving the lander's state with respect to the use of a probe located in the Lagrangian point L2 of the Earth-Moon system has also been carried out.

  20. The Search for Stable, Massive, Elementary Particles

    International Nuclear Information System (INIS)

    Kim, Peter C.

    2001-01-01

    In this paper we review the experimental and observational searches for stable, massive, elementary particles other than the electron and proton. The particles may be neutral, may have unit charge or may have fractional charge. They may interact through the strong, electromagnetic, weak or gravitational forces or through some unknown force. The purpose of this review is to provide a guide for future searches--what is known, what is not known, and what appear to be the most fruitful areas for new searches. A variety of experimental and observational methods such as accelerator experiments, cosmic ray studies, searches for exotic particles in bulk matter and searches using astrophysical observations is included in this review

  1. The production of stable isotopes in Spain

    Energy Technology Data Exchange (ETDEWEB)

    Urgel, M; Iglesias, J; Casas, J; Saviron, J M; Quintanilla, M

    1965-07-01

    The activities developed in the field of the production of stable isotopes by means of ion-exchange chromatography and thermal diffusion techniques are reported. The first method was used to study the separation of the nitrogen and boron isotopes, whereby the separation factor was determined by the break through method. Values ranging from 1,028 to 1,022 were obtained for the separation factor of nitrogen by using ammonium hydroxide solutions while the corresponding values as obtained for boron amounted to 1,035-1,027 using boric acid solutions. Using ammonium chloride or acetate and sodium borate, respectively, resulted in the obtention of values for the separation factor approaching unity. The isotopic separation has been carried out according to the method of development by displacement. The separation of the isotopes of the noble gases, oxygen, nitrogen and carbon has been accomplished resorting to the method of thermal diffusion. (Author) 16 refs.

  2. Multivariate max-stable spatial processes

    KAUST Repository

    Genton, Marc G.; Padoan, S. A.; Sang, H.

    2015-01-01

    Max-stable processes allow the spatial dependence of extremes to be modelled and quantified, so they are widely adopted in applications. For a better understanding of extremes, it may be useful to study several variables simultaneously. To this end, we study the maxima of independent replicates of multivariate processes, both in the Gaussian and Student-t cases. We define a Poisson process construction and introduce multivariate versions of the Smith Gaussian extreme-value, the Schlather extremal-Gaussian and extremal-t, and the Brown–Resnick models. We develop inference for the models based on composite likelihoods. We present results of Monte Carlo simulations and an application to daily maximum wind speed and wind gust.

  3. Bounded excursion stable gravastars and black holes

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, P [Instituto de Fisica, Universidade Federal Fluminense, Avenida Litoranea, s/n, Boa Viagem 24210-340, Niteroi, RJ (Brazil); Miguelote, A Y; Chan, R [Coordenacao de Astronomia e Astrofisica, Observatorio Nacional, Rua General Jose Cristino, 77, Sao Cristovao 20921-400, Rio de Janeiro, RJ (Brazil); Da Silva, M F; Wang, Anzhong [Departamento de Fisica Teorica, Instituto de Fisica, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier 524, Maracana 20550-900, Rio de Janeiro-RJ (Brazil); Santos, N O, E-mail: pedrosennarocha@gmail.com, E-mail: yasuda@on.br, E-mail: chan@on.br, E-mail: mfasnic@gmail.com, E-mail: N.O.Santos@qmul.ac.uk, E-mail: anzhong_wang@baylor.edu [LERMA/CNRS-FRE 2460, Universite Pierre et Marie Curie, ERGA, Boite 142, 4 Place Jussieu, 75005 Paris Cedex 05 (France)

    2008-06-15

    Dynamical models of prototype gravastars were constructed in order to study their stability. The models are the Visser-Wiltshire three-layer gravastars, in which an infinitely thin spherical shell of stiff fluid divides the whole spacetime into two regions, where the internal region is de Sitter, and the external one is Schwarzschild. It is found that in some cases the models represent the 'bounded excursion' stable gravastars, where the thin shell is oscillating between two finite radii, while in other cases they collapse until the formation of black holes occurs. In the phase space, the region for the 'bounded excursion' gravastars is very small in comparison to that of black holes, but not empty. Therefore, although the possibility of the existence of gravastars cannot be excluded from such dynamical models, our results indicate that, even if gravastars do indeed exist, that does not exclude the possibility of the existence of black holes.

  4. Use of stable isotopes in agriculture

    International Nuclear Information System (INIS)

    Ali, F. K.

    2011-01-01

    Scientific research is considered to be one of the most important steps to achieve sustainable agriculture development. This paper is focused on the role of stable isotopes and their applications in agriculture for plant and animal production, and to study the relationship between soil, plant, air, water, nutrients and agricultural pests. Symbiotic N 2 fixation and efficient use of chemical and organic N fertilizers using 15 N were reported. Factors affecting 13 C values and application of carbon isotope discrimination to physiological and eco-physiological studies and selection of genotypes with improved water-use efficiency and drought tolerance and the recent progress in this field are reviewed. Moreover, the use of carbon isotope compositions in monitoring environmental changes and its various applications in food technology, animal production and entomology are discussed. (author)

  5. Multivariate max-stable spatial processes

    KAUST Repository

    Genton, Marc G.

    2015-02-11

    Max-stable processes allow the spatial dependence of extremes to be modelled and quantified, so they are widely adopted in applications. For a better understanding of extremes, it may be useful to study several variables simultaneously. To this end, we study the maxima of independent replicates of multivariate processes, both in the Gaussian and Student-t cases. We define a Poisson process construction and introduce multivariate versions of the Smith Gaussian extreme-value, the Schlather extremal-Gaussian and extremal-t, and the Brown–Resnick models. We develop inference for the models based on composite likelihoods. We present results of Monte Carlo simulations and an application to daily maximum wind speed and wind gust.

  6. Perceptually stable regions for arbitrary polygons.

    Science.gov (United States)

    Rocha, J

    2003-01-01

    Zou and Yan have recently developed a skeletonization algorithm of digital shapes based on a regularity/singularity analysis; they use the polygon whose vertices are the boundary pixels of the image to compute a constrained Delaunay triangulation (CDT) in order to find local symmetries and stable regions. Their method has produced good results but it is slow since its complexity depends on the number of contour pixels. This paper presents an extension of their technique to handle arbitrary polygons, not only polygons of short edges. Consequently, not only can we achieve results as good as theirs for digital images, but we can also compute skeletons of polygons of any number of edges. Since we can handle polygonal approximations of figures, the skeletons are more resilient to noise and faster to process.

  7. Stable Oxygen-18 and Deuterium Isotopes

    DEFF Research Database (Denmark)

    Müller, Sascha

    The application of stable Oxygen-18 (18O) and Deuterium (2H) isotopes, as a tracer for fluxes between different compartments of the water cycle was subject of the present PhD-thesis. During a three year period, temporal data from a wide range of water cycle constituents was collected from...... the Skjern River catchment, Denmark. The presented applications focused on studying the isotopic 'input signal' to the hydrosphere in the form of precipitation, the isotopic 'output signal' with its related dynamic processes at a coastal saltwater-freshwater interface (groundwater isotopes) and the temporal...... development within a given lowland headwater catchment (stream water isotopes). Based on our investigations on the precipitation isotopic composition a local meteoric water line (LMWL) was constructed and expressed as: δ2H=7.4 δ18O + 5.36‰. Moreover, we showed that under maritime temperature climate influence...

  8. A belief-based evolutionarily stable strategy.

    Science.gov (United States)

    Deng, Xinyang; Wang, Zhen; Liu, Qi; Deng, Yong; Mahadevan, Sankaran

    2014-11-21

    As an equilibrium refinement of the Nash equilibrium, evolutionarily stable strategy (ESS) is a key concept in evolutionary game theory and has attracted growing interest. An ESS can be either a pure strategy or a mixed strategy. Even though the randomness is allowed in mixed strategy, the selection probability of pure strategy in a mixed strategy may fluctuate due to the impact of many factors. The fluctuation can lead to more uncertainty. In this paper, such uncertainty involved in mixed strategy has been further taken into consideration: a belief strategy is proposed in terms of Dempster-Shafer evidence theory. Furthermore, based on the proposed belief strategy, a belief-based ESS has been developed. The belief strategy and belief-based ESS can reduce to the mixed strategy and mixed ESS, which provide more realistic and powerful tools to describe interactions among agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Stable computation of generalized singular values

    Energy Technology Data Exchange (ETDEWEB)

    Drmac, Z.; Jessup, E.R. [Univ. of Colorado, Boulder, CO (United States)

    1996-12-31

    We study floating-point computation of the generalized singular value decomposition (GSVD) of a general matrix pair (A, B), where A and B are real matrices with the same numbers of columns. The GSVD is a powerful analytical and computational tool. For instance, the GSVD is an implicit way to solve the generalized symmetric eigenvalue problem Kx = {lambda}Mx, where K = A{sup {tau}}A and M = B{sup {tau}}B. Our goal is to develop stable numerical algorithms for the GSVD that are capable of computing the singular value approximations with the high relative accuracy that the perturbation theory says is possible. We assume that the singular values are well-determined by the data, i.e., that small relative perturbations {delta}A and {delta}B (pointwise rounding errors, for example) cause in each singular value {sigma} of (A, B) only a small relative perturbation {vert_bar}{delta}{sigma}{vert_bar}/{sigma}.

  10. Stable carbides in transition metal alloys

    International Nuclear Information System (INIS)

    Piotrkowski, R.

    1991-01-01

    In the present work different techniques were employed for the identification of stable carbides in two sets of transition metal alloys of wide technological application: a set of three high alloy M2 type steels in which W and/or Mo were total or partially replaced by Nb, and a Zr-2.5 Nb alloy. The M2 steel is a high speed steel worldwide used and the Zr-2.5 Nb alloy is the base material for the pressure tubes in the CANDU type nuclear reactors. The stability of carbide was studied in the frame of Goldschmidt's theory of interstitial alloys. The identification of stable carbides in steels was performed by determining their metallic composition with an energy analyzer attached to the scanning electron microscope (SEM). By these means typical carbides of the M2 steel, MC and M 6 C, were found. Moreover, the spatial and size distribution of carbide particles were determined after different heat treatments, and both microstructure and microhardness were correlated with the appearance of the secondary hardening phenomenon. In the Zr-Nb alloy a study of the α and β phases present after different heat treatments was performed with optical and SEM metallographic techniques, with the guide of Abriata and Bolcich phase diagram. The α-β interphase boundaries were characterized as short circuits for diffusion with radiotracer techniques and applying Fisher-Bondy-Martin model. The precipitation of carbides was promoted by heat treatments that produced first the C diffusion into the samples at high temperatures (β phase), and then the precipitation of carbide particles at lower temperature (α phase or (α+β)) two phase field. The precipitated carbides were identified as (Zr, Nb)C 1-x with SEM, electron microprobe and X-ray diffraction techniques. (Author) [es

  11. Stable isotopes as tracers for radionuclides

    International Nuclear Information System (INIS)

    Giussani, A.; Bartolo, D. de; Cantone, M.C.; Zilker, T.; Greim, H.; Roth, P.; Werner, E.

    2000-01-01

    The assessment of internal dose after incorporation of radionuclides requires as input data the knowledge of the uptake into the systemic circulation, the distribution and retention in selected organs, the excretion pathways. Realistic biokinetic models are needed for reliable estimates, correct interpretation of bioassay measurements, appropriate decision-making in radiological emergencies. For many radionuclides, however, the biokinetic models currently recommended are often generic, with very few specific parameters, due to the lack of experimental human data. The use of stable isotopes as tracers enables to determine important biokinetic parameters such as the fractional uptake, the clearance from the transfer compartment, the excretion patterns under experimentally controlled conditions. The subjects investigated are not exposed to any radiation risk, so this technique enables to obtain biokinetic information also for sensitive groups of the population, such as children or pregnant women, and to determine age- and gender-specific model parameters. Sophisticated analytical method, able to discriminate and quantitate different isotopes of the same element in complex matrices such as biological fluids, have to be purposely developed and optimized. Activation analysis and mass spectrometry are the most proper techniques of choice. Experiments were conducted with molybdenum, tellurium, ruthenium and zirconium. Activation analysis with protons, thermal ionization mass spectrometry and inductively coupled mass spectrometry were employed for the determination of stable isotopes of these elements in blood plasma and urine samples. Several deviations from the predictions of the ICRP models were observed. For example, modifications to the current model for molybdenum have been suggested on the basis of these results. The dose coefficients to the target regions calculated with this proposed model are even of one order of magnitude different than the ICRP estimates

  12. Can you boost your metabolism?

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000893.htm Can you boost your metabolism? To use the sharing ... boosting metabolism than tactics that work. Some myths can backfire. If you think you are burning more ...

  13. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

  14. A Note on Interpolation of Stable Processes | Nassiuma | Journal of ...

    African Journals Online (AJOL)

    Interpolation procedures tailored for gaussian processes may not be applied to infinite variance stable processes. Alternative techniques suitable for a limited set of stable case with index α∈(1,2] were initially studied by Pourahmadi (1984) for harmonizable processes. This was later extended to the ARMA stable process ...

  15. Stable cycling in discrete-time genetic models.

    OpenAIRE

    Hastings, A

    1981-01-01

    Examples of stable cycling are discussed for two-locus, two-allele, deterministic, discrete-time models with constant fitnesses. The cases that cycle were found by using numerical techniques to search for stable Hopf bifurcations. One consequence of the results is that apparent cases of directional selection may be due to stable cycling.

  16. Stable cycling in discrete-time genetic models.

    Science.gov (United States)

    Hastings, A

    1981-11-01

    Examples of stable cycling are discussed for two-locus, two-allele, deterministic, discrete-time models with constant fitnesses. The cases that cycle were found by using numerical techniques to search for stable Hopf bifurcations. One consequence of the results is that apparent cases of directional selection may be due to stable cycling.

  17. Malaria infection during pregnancy in area of stable transmission ...

    African Journals Online (AJOL)

    Malaria infection during pregnancy in area of stable transmission. ... (LBW), a leading cause of neonatal death in areas of stable malaria transmission. ... areas of stable malaria transmission and the effective strategies for prevention and control. Keywords: malaria, pregnancy, semi-immune women, anaemia, low birthweight

  18. Sleep and Metabolism: An Overview

    OpenAIRE

    Sharma, Sunil; Kavuru, Mani

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways i...

  19. Energy Metabolism in the Liver

    OpenAIRE

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, p...

  20. Identification of glucose-fermenting bacteria present in an in vitro model of the human intestine by RNA-stable isotope probing

    NARCIS (Netherlands)

    Egert, M.; Graaf, A.A. de; Maathuis, A.; Waard, P. de; Plugge, C.M.; Smidt, H.; Deutz, N.E.P.; Dijkema, C.; Vos, W.M. de; Venema, K.

    2007-01-01

    16S rRNA-based stable isotope probing (SIP) and nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling were used to identify bacteria fermenting glucose under conditions simulating the human intestine. The TIM-2 in vitro model of the human intestine was inoculated with a GI tract

  1. Identification of glucose-fermenting bacteria present in an in-vitro model of the human inetstine by RNA-stable isotope probing

    NARCIS (Netherlands)

    Egert, M.G.G.; Graaf, de A.A.; Maathuis, A.; Waard, de P.; Plugge, C.M.; Smidt, H.; Deutz, N.E.P.; Dijkema, C.; Vos, de W.M.; Venema, K.

    2007-01-01

    16S rRNA-based stable isotope probing (SIP) and nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling were used to identify bacteria fermenting glucose under conditions simulating the human intestine. The TIM-2 in vitro model of the human intestine was inoculated with a GI tract

  2. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    International Nuclear Information System (INIS)

    Cohen, G.M.

    1990-01-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity

  3. Stable isotopes in human nutrition research. Final report on an IAEA co-ordinated research programme, Vienna, Austria, 1993

    International Nuclear Information System (INIS)

    1993-01-01

    The Co-ordinated Research Programme (CRP) on Applications of Stable Isotope Tracers in Human Nutrition Research was established by the Agency in October 1988 and was completed in 1992. At various times during this period the CRP encompassed 16 participants in 16 countries. Its general objective was to help establish competence in the use of stable isotope techniques, particularly in developing countries, and particularly with reference to applications of 2 H, 13 C, 15 N, and 18 O in human nutrition research. Thereby it was hoped that it would be possible (i) to identify centres and scientists throughout the developing world who could use stable isotopes in human nutrition research, (ii) to assess the need for methodological adaptations for isotope-based methods in developing countries, and (iii) to advance the competence of the participants in using stable isotopes as tracers of human metabolism. In addition it was expected that the CRP would make a study of some major questions which have been identified by international groups of nutrition experts, particularly in areas relating to energy and protein metabolism. This document comprises copies of the working papers submitted by all CRP participants who contributed a final report on their project. These reports include details of the rationale, methods, results and interpretations from each of the respective studies. Refs, figs and tabs

  4. HTSSIP: An R package for analysis of high throughput sequencing data from nucleic acid stable isotope probing (SIP experiments.

    Directory of Open Access Journals (Sweden)

    Nicholas D Youngblut

    Full Text Available Combining high throughput sequencing with stable isotope probing (HTS-SIP is a powerful method for mapping in situ metabolic processes to thousands of microbial taxa. However, accurately mapping metabolic processes to taxa is complex and challenging. Multiple HTS-SIP data analysis methods have been developed, including high-resolution stable isotope probing (HR-SIP, multi-window high-resolution stable isotope probing (MW-HR-SIP, quantitative stable isotope probing (qSIP, and ΔBD. Currently, there is no publicly available software designed specifically for analyzing HTS-SIP data. To address this shortfall, we have developed the HTSSIP R package, an open-source, cross-platform toolset for conducting HTS-SIP analyses in a straightforward and easily reproducible manner. The HTSSIP package, along with full documentation and examples, is available from CRAN at https://cran.r-project.org/web/packages/HTSSIP/index.html and Github at https://github.com/buckleylab/HTSSIP.

  5. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    Directory of Open Access Journals (Sweden)

    Marin de Mas Igor

    2011-10-01

    Full Text Available Abstract Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate. The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose

  6. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ..., both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.

  7. Post-accident action for radiation protection: Reducing the transfer of radioiodine to milk in cows by adding stable iodine to the forage

    International Nuclear Information System (INIS)

    Kiefer, P.; Voigt, G.

    1999-01-01

    The publication summarizes the activities for the study and reports the measured results achieved. The usefulness of stable iodine administration to cows for reducing the radioiodine transfer to the milk is explained. It was found that enhanced stable radioiodine doses have an effect on the metabolism of dairy cows that has to be taken into account. Initially, a literature study was carried out, which then served as a basis for defining subsequent studies and experiments. The evaluation of the results yields information about the effects of stable iodine on the radioiodine transfer as well as the metabolic pathways of iodine in dairy cows. In order to achieve a clear transfer-reducing effect (by a factor of 2), doses of 1g/d have to be administered to a cow. This dose will lead to a stable iodine concentration in the milk of about 10 mg/kg. The WHO recommends a daily maximum of 0.5 mg of stable iodine in order to safely prevent adverse health effects in man. Ingestion of more than 2 mg/d may induce in man thyroid disorders and other metabolic disorders. In some countries, the reference level for dairy milk accepted is 0.5 mg of iodine/kg of milk. (orig./CB) [de

  8. Microglia energy metabolism in metabolic disorder.

    Science.gov (United States)

    Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

    2016-12-15

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Applications of stable isotopes of 2H, 13C and 15N to clinical problems

    International Nuclear Information System (INIS)

    Klein, P.D.; Szczepanik, P.A.; Hachey, D.L.

    1974-01-01

    The function of the Argonne Program is to provide synthetic, analytical instrumental capability in a core facility for the clinical investigator who needs to use 2 H, 13 C, or 15 N labelled compounds for metabolic or clinical research on pregnant women, newborn infants, young children, or for mass screening. To carry out such application development, there were six stages which were recurrent steps in every application. Five fundamental strategies should be adopted to establish the use of stable isotopes in clinical work. The instrument required for measurements was a combined gas chromatograph-mass spectrometer, and its use was schematically illustrated. Some of the successful experiences with compounds labelled by stable isotopes, such as deuterium labelled chenodeoxycholic acid, and respective 13 C and 15 N-labelled glycine were described. Deutrium labelled bile acid enabled easy and safe determination of the size of the bile acid pool and the replacement rate, providing clearer diagnoses for cholestatic liver disease and gallstones. 13 C and 15 N labelled compounds were used in clinical studies, of children with genetic disorders of amino acid metabolism, i.e., non ketotic hyperflycinemia, B 12 -responsive methyl malonic acidemia, and Lesch-Nyhan syndrome. 15 N-labelled glycine was also studied in a child with Lesch-Nyhan syndrome. (Mukohata, S.)

  10. Stable isotope sup 15 N-urea and clinical research in nephrology

    Energy Technology Data Exchange (ETDEWEB)

    Sugino, Nobuhiro; Arai, Junko; Akimoto, Mitsuko; Miwa, Toichiro; Takuma, Takehide (Tokyo Women' s Medical Coll. (Japan))

    1990-08-01

    Stable isotope {sup 15}N-compound, {sup 15}N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. {sup 15}N-urea incorporation into plasma albumin in addition to plasma {sup 15}N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered {sup 15}N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through {sup 15}N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal. Therefore, administration of {sup 15}N-compound to human subjects may contribute to provide us the important informations on nitrogen metabolism. For instance, urea kinetics are described in the endstage chronic renal failure in this review. However, less expensive {sup 15}N-compounds should be provided and more simple but accurate measurement of {sup 15}N activity should be developed for the further clinical application of the stable isotope. (author).

  11. Stable isotope 15N-urea and clinical research in nephrology

    International Nuclear Information System (INIS)

    Sugino, Nobuhiro; Arai, Junko; Akimoto, Mitsuko; Miwa, Toichiro; Takuma, Takehide

    1990-01-01

    Stable isotope 15 N-compound, 15 N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. 15 N-urea incorporation into plasma albumin in addition to plasma 15 N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered 15 N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through 15 N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal. Therefore, administration of 15 N-compound to human subjects may contribute to provide us the important informations on nitrogen metabolism. For instance, urea kinetics are described in the endstage chronic renal failure in this review. However, less expensive 15 N-compounds should be provided and more simple but accurate measurement of 15 N activity should be developed for the further clinical application of the stable isotope. (author)

  12. Influence of horse stable environment on human airways.

    Science.gov (United States)

    Elfman, Lena; Riihimäki, Miia; Pringle, John; Wålinder, Robert

    2009-05-25

    Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. The horse stable environment and stable-workers (n = 13) in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function. Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-beta-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated. Biomarkers involved in the development of airway diseases have been studied in relation to environmental exposure levels in equine stables. Respirable dust and 1

  13. Stability properties of nonlinear dynamical systems and evolutionary stable states

    Energy Technology Data Exchange (ETDEWEB)

    Gleria, Iram, E-mail: iram@fis.ufal.br [Instituto de Física, Universidade Federal de Alagoas, 57072-970 Maceió-AL (Brazil); Brenig, Leon [Faculté des Sciences, Université Libre de Bruxelles, 1050 Brussels (Belgium); Rocha Filho, Tarcísio M.; Figueiredo, Annibal [Instituto de Física and International Center for Condensed Matter Physics, Universidade de Brasília, 70919-970 Brasília-DF (Brazil)

    2017-03-18

    Highlights: • We address the problem of equilibrium stability in a general class of non-linear systems. • We link Evolutionary Stable States (ESS) to stable fixed points of square quasi-polynomial (QP) systems. • We show that an interior ES point may be related to stable interior fixed points of QP systems. - Abstract: In this paper we address the problem of stability in a general class of non-linear systems. We establish a link between the concepts of asymptotic stable interior fixed points of square Quasi-Polynomial systems and evolutionary stable states, a property of some payoff matrices arising from evolutionary games.

  14. Influence of horse stable environment on human airways

    Directory of Open Access Journals (Sweden)

    Pringle John

    2009-05-01

    Full Text Available Abstract Background Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. Methods The horse stable environment and stable-workers (n = 13 in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function. Results Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-β-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated. Conclusion Biomarkers involved in the development of airway diseases have been studied in relation to

  15. Metabolic syndrome in hyperprolactinemia

    DEFF Research Database (Denmark)

    Andersen, Marianne; Glintborg, Dorte

    2018-01-01

    The metabolic syndrome (MetS) is a conglomerate of clinical findings that convey into increased morbidity and mortality from type 2 diabetes mellitus (T2D) and cardiovascular disease. Hyperprolactinemia (hyperPRL) is associated with components of MetS, especially during pregnancy. Endogenous levels...... in patients with T2D. HyperPRL is a biomarker for decreased dopaminergic tonus in the hypothalamic-pituitary circuit. Patients with a prolactinoma, patients with schizophrenia and/or T2D often have disturbances in this balance and the finding of lower prolactin (PRL) levels in polycystic ovary syndrome (PCOS......) may indicate increased dopaminergic tonus. Recent studies supported that PRL levels within or above reference range may be differently related to MetS. In healthy study populations and in PCOS, PRL levels were inversely associated with metabolic risk markers. Ongoing research on PRL fragments...

  16. Calcium metabolism in birds.

    Science.gov (United States)

    de Matos, Ricardo

    2008-01-01

    Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

  17. Spectrum of metabolic myopathies.

    Science.gov (United States)

    Angelini, Corrado

    2015-04-01

    Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  18. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  19. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  20. Stable isotope analysis in primatology: a critical review.

    Science.gov (United States)

    Sandberg, Paul A; Loudon, James E; Sponheimer, Matt

    2012-11-01

    Stable isotope analysis has become an important tool in ecology over the last 25 years. A wealth of ecological information is stored in animal tissues in the relative abundances of the stable isotopes of several elements, particularly carbon and nitrogen, because these isotopes navigate through ecological processes in predictable ways. Stable carbon and nitrogen isotopes have been measured in most primate taxonomic groups and have yielded information about dietary content, dietary variability, and habitat use. Stable isotopes have recently proven useful for addressing more fine-grained questions about niche dynamics and anthropogenic effects on feeding ecology. Here, we discuss stable carbon and nitrogen isotope systematics and critically review the published stable carbon and nitrogen isotope data for modern primates with a focus on the problems and prospects for future stable isotope applications in primatology. © 2012 Wiley Periodicals, Inc.