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Sample records for agonist isoproterenol iso

  1. Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist.

    PubMed

    Sun, Ji-Min; Wang, Chun-Miao; Guo, Zeng; Hao, Yu-Yu; Xie, Yang-Jing; Gu, Jian; Wang, Ai-Ling

    2015-03-01

    Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP‑sensitive K+ (KATP) channel agonist was capable of reducing isoproterenol (Iso)‑induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left‑ventricular weight, and plasma B‑type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription‑polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The KATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the KATP channel agonist nicorandil. Addition of the KATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43. In conclusion, the present study indicated that chronic use of KATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43

  2. Effect of skin temperature on cutaneous vasodilator response to the β-adrenergic agonist isoproterenol

    PubMed Central

    Hodges, Gary J.; Johnson, John M.

    2015-01-01

    The vascular response to local skin cooling is dependent in part on a cold-induced translocation of α2C-receptors and an increased α-adrenoreceptor function. To discover whether β-adrenergic function might contribute, we examined whether β-receptor sensitivity to the β-agonist isoproterenol was affected by local skin temperature. In seven healthy volunteers, skin blood flow was measured from the forearm by laser-Doppler flowmetry and blood pressure was measured by finger photoplethysmography. Data were expressed as cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial blood pressure). Pharmacological agents were administered via intradermal microdialysis. We prepared four skin sites: one site was maintained at a thermoneutral temperature of 34°C (32 ± 10%CVCmax) one site was heated to 39°C (38 ± 11%CVCmax); and two sites were cooled, one to 29°C (22 ± 7%CVCmax) and the other 24°C (16 ± 4%CVCmax). After 20 min at these temperatures to allow stabilization of skin blood flow, isoproterenol was perfused in concentrations of 10, 30, 100, and 300 μM. Each concentration was perfused for 15 min. Relative to the CVC responses to isoproterenol at the thermoneutral skin temperature (34°C) (+21 ± 10%max), low skin temperatures reduced (at 29°C) (+17 ± 6%max) or abolished (at 24°C) (+1 ± 5%max) the vasodilator response, and warm (39°C) skin temperatures enhanced the vasodilator response (+40 ± 9%max) to isoproterenol. These data indicate that β-adrenergic function was influenced by local skin temperature. This finding raises the possibility that a part of the vasoconstrictor response to direct skin cooling could include reduced background β-receptor mediated vasodilation. PMID:25701007

  3. Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that selectively activates the MAPK/ERK pathway.

    PubMed

    Copik, Alicja J; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J; Fitch, Bill; Raymond, John R; Ford, Anthony P D W; Button, Donald; Milla, Marcos E

    2015-01-01

    The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e., not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK

  4. Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway

    PubMed Central

    Copik, Alicja. J.; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill; Raymond, John R.; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.

    2015-01-01

    The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK

  5. Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats

    EPA Science Inventory

    Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loa...

  6. Modulation of lung liquid clearance by isoproterenol in rat lungs.

    PubMed

    Saldías, F; Lecuona, E; Friedman, E; Barnard, M L; Ridge, K M; Sznajder, J I

    1998-05-01

    beta-Adrenergic agonists have been reported to increase lung liquid clearance by stimulating active Na+ transport across the alveolar epithelium. We studied mechanisms by which beta-adrenergic isoproterenol (Iso) increases lung liquid clearance in isolated perfused fluid-filled rat lungs. Iso perfused through the pulmonary circulation at concentrations of 10(-4) to 10(-8) M increased lung liquid clearance compared with that of control lungs (P < 0.01). The increase in lung liquid clearance was inhibited by the beta-antagonist propranolol (10(-5) M), the Na(+)-channel blocker amiloride (10(-4) M), and the antagonist of Na-K-ATPase, ouabain (5 x 10(-4) M). Colchicine, which inhibits cell microtubular transport of ion-transporting proteins to the plasma membrane, blocked the stimulatory effects of Iso on active Na+ transport, whereas the isomer lumicolchicine, which does not affect cell microtubular transport, did not inhibit Na+ transport. In parallel with these changes, the Na-K-ATPase alpha 1-subunit protein abundance and activity increased in alveolar type II cells stimulated by 10(-6) M Iso. Colchicine blocked the stimulatory effect of Iso and the recruitment of Na-K-ATPase alpha 1-protein to the basolateral membrane of alveolar type II cells. Accordingly, Iso increased active Na+ transport and lung liquid clearance by stimulation of beta-adrenergic receptors and probably by upregulation of apical Na+ channels and basolateral Na-K-ATPase mechanisms. Recruitment from intracellular pools and microtubular transport of Na+ pumps to the plasma membrane participate in beta-adrenergic stimulation of lung liquid clearance in rat lungs. PMID:9612284

  7. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy.

    PubMed

    Carll, Alex P; Haykal-Coates, Najwa; Winsett, Darrell W; Rowan, William H; Hazari, Mehdi S; Ledbetter, Allen D; Nyska, Abraham; Cascio, Wayne E; Watkinson, William P; Costa, Daniel L; Farraj, Aimen K

    2010-04-01

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were infused with isoproterenol (ISO; 2.5 mg/kg/day subcutaneous [sc]), a beta-adrenergic agonist, for 28 days and subsequently exposed to PM by inhalation. ISO induced tachycardia and hypotension throughout treatment followed by postinfusion decrements in heart rate, contractility, and blood pressures (systolic, diastolic, pulse), and fibrotic cardiomyopathy. Changes in heart rate and heart rate variability (HRV) 17 days after ISO cessation indicated parasympathetic dominance with concomitantly altered ventilation. Rats were subsequently exposed to filtered air or Harvard Particle 12 (HP12) (12 mg/m(3))--a metal-rich oil combustion-derived PM--at 18 and 19 days (4 h/day) after ISO infusion via nose-only inhalation to determine if cardio-impaired rats were more responsive to the effects of PM exposure. Inhalation of PM among ISO-pretreated rats significantly increased pulmonary lactate dehydrogenase, serum high-density lipoprotein (HDL) cholesterol, and heart-to-body mass ratio. PM exposure increased the number of ISO-pretreated rats that experienced bradyarrhythmic events, which occurred concomitantly with acute alterations of HRV. PM, however, did not significantly affect mean HRV in the ISO- or saline-pretreated groups. In summary, subchronic ISO treatment elicited some pathophysiologic and histopathological features of heart failure, including cardiomyopathy. The enhanced sensitivity to PM exposure in SHHF rats with ISO-accelerated cardiomyopathy suggests that this model may be useful for elucidating the mechanisms by which PM exposure exacerbates heart disease. PMID:20121584

  8. Desmodium gangeticum (Linn.) DC. exhibits antihypertrophic effect in isoproterenol-induced cardiomyoblasts via amelioration of oxidative stress and mitochondrial alterations.

    PubMed

    Sankar, Vandana; Pangayarselvi, Balasubramaniam; Prathapan, Ayyappan; Raghu, Kozhiparambil Gopalan

    2013-01-01

    Cardiac hypertrophy occurs in response to increased workload, such as hypertension or valvular heart disease. Oxidative stress has been implicated in cardiac hypertrophy and in its transition to heart failure. This study was taken up with the objective to evaluate the role of oxidative stress in cardiomyoblast hypertrophy and its modulation by Desmodium gangeticum (DG) that has been traditionally used in Ayurveda, an Indian system of medicine. The methanolic root extract was analyzed for total phenolic content and tested for antioxidant potential. Hypertrophy was induced by exposing H9c2 cell line to β-adrenergic receptor agonist, isoproterenol (ISO), for 96 hours. Analyses of reactive oxygen species (ROS) generation, mitochondrial transmembrane potential ([INCREMENT]Ψm), and integrity of permeability transition were performed in ISO as well as Desmodium and ISO-cotreated cells. The results demonstrated potent free radical scavenging activity of DG. Cell line studies showed significant increase in ROS generation, dissipation of [INCREMENT]Ψm, and permeability transition pore opening in ISO-treated cells. Desmodium was found to attenuate ISO-induced hypertrophy by reduction of ROS generation, restoration of [INCREMENT]Ψm, and prevention of permeability transition pore opening. This study is the first documentation of the modulatory effect of DG on cardiac hypertrophy. PMID:23052030

  9. Modulatory effect of semelil (ANGIPARS™) on isoproterenol induced cardiac injury

    PubMed Central

    Joukar, Siyavash; Najafipour, Hamid; Mirzaeipour, Fateme; Nasri, Hamidreza; Ahmadi, Mahboubeh Yeganeh Haj; Badinloo, Marziyeh

    2013-01-01

    Administration of semelil (ANGIPARS™) has been successful in the treatment of diabetic foot ulcer. Considering the improvement of blood flow and anti-inflammatory effect that are attributed to this drug, we investigated its effect on cardiovascular performance in rabbits with isoproterenol (ISO) induced myocardial injury. Animal groups included: control group; ISO group, received ISO 50 mg/kg s.c. for two consecutive days; S1+ISO, S5+ISO and S10+ISO groups, received semelil 1, 5, and 10 mg/kg/day i.p. respectively, 30 min before ISO. On the 3rd day, electrocardiogram (ECG) and hemodynamic parameters were recorded; blood samples were taken and hearts were removed for lab investigations. ISO induced heart injury, ECG disturbance, raise of cardiac troponin I and significant decrease in LVSP (p<0.05), +dp/dt max (p<0.01), -dp/dt max (p<0.05) along with increase of LVEDP (p<0.01). Semelil had no significant effects on ECG and plasma cardiac troponin I. Impairment of +dp/dt max and -dp/dt max was significantly improved in S5+ISO and S10+ISO groups (P<0.05 versus ISO). In addition, LVSP and LVEDP was somewhat recovered in these groups, although semelil (1 mg/kg/day) to some extent exacerbated the myocardial lesions induced by ISO (P<0.05). Therefore, in stressful conditions, semelil may improve myocardial contractility; however, it may aggravate the severity of injury. PMID:26417221

  10. Modulatory effect of semelil (ANGIPARS™) on isoproterenol induced cardiac injury.

    PubMed

    Joukar, Siyavash; Najafipour, Hamid; Mirzaeipour, Fateme; Nasri, Hamidreza; Ahmadi, Mahboubeh Yeganeh Haj; Badinloo, Marziyeh

    2013-01-01

    Administration of semelil (ANGIPARS™) has been successful in the treatment of diabetic foot ulcer. Considering the improvement of blood flow and anti-inflammatory effect that are attributed to this drug, we investigated its effect on cardiovascular performance in rabbits with isoproterenol (ISO) induced myocardial injury. Animal groups included: control group; ISO group, received ISO 50 mg/kg s.c. for two consecutive days; S1+ISO, S5+ISO and S10+ISO groups, received semelil 1, 5, and 10 mg/kg/day i.p. respectively, 30 min before ISO. On the 3(rd) day, electrocardiogram (ECG) and hemodynamic parameters were recorded; blood samples were taken and hearts were removed for lab investigations. ISO induced heart injury, ECG disturbance, raise of cardiac troponin I and significant decrease in LVSP (p<0.05), +dp/dt max (p<0.01), -dp/dt max (p<0.05) along with increase of LVEDP (p<0.01). Semelil had no significant effects on ECG and plasma cardiac troponin I. Impairment of +dp/dt max and -dp/dt max was significantly improved in S5+ISO and S10+ISO groups (P<0.05 versus ISO). In addition, LVSP and LVEDP was somewhat recovered in these groups, although semelil (1 mg/kg/day) to some extent exacerbated the myocardial lesions induced by ISO (P<0.05). Therefore, in stressful conditions, semelil may improve myocardial contractility; however, it may aggravate the severity of injury. PMID:26417221

  11. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  12. Attenuation of endoplasmic reticulum stress using the chemical chaperone 4-phenylbutyric acid prevents cardiac fibrosis induced by isoproterenol.

    PubMed

    Ayala, Pedro; Montenegro, José; Vivar, Raúl; Letelier, Alan; Urroz, Pablo Aránguiz; Copaja, Miguel; Pivet, Deisy; Humeres, Claudio; Troncoso, Rodrigo; Vicencio, José Miguel; Lavandero, Sergio; Díaz-Araya, Guillermo

    2012-02-01

    Increasing evidence indicates that endoplasmic reticulum (ER) stress is involved in various diseases. In the human heart, ischemia/reperfusion has been correlated to ER stress, and several markers of the unfolded protein response (UPR) participate during cardiac remodeling and fibrosis. Here, we used isoproterenol (ISO) injection as a model for in vivo cardiac fibrosis. ISO induced significant cardiomyocyte loss and collagen deposition in the damaged areas of the endocardium. These responses were accompanied by an increase in the protein levels of the luminal ER chaperones BIP and PDI, as well as an increase in the UPR effector CHOP. The use of the chemical chaperone 4-phenylbutyric acid (4-PBA) prevented the activation of the UPR, the increase in luminal chaperones and also, leads to decreased collagen deposition, cardiomyocyte loss into the damaged zones. Our results suggest that cardiac damage and fibrosis induced in vivo by the beta-adrenergic agonist ISO are tightly related to ER stress signaling pathways, and that increasing the ER luminal folding capacity with exogenously administrated 4-PBA is a powerful strategy for preventing the development of cardiac fibrosis. Additionally, 4-PBA might prevent the loss of cardiomyocytes. Our data suggests that the attenuation of ER stress pathways with pharmacological compounds such as the chemical chaperone 4-PBA can prevent the development of cardiac fibrosis and adverse remodeling. PMID:22101259

  13. Effects of isoproterenol on IL-2 and cAMP production in peripheral T cells from asthmatic and non-asthmatic subjects sensitive to Candida.

    PubMed

    Aihara, M; Dobashi, K; Horie, T; Iizuka, K; Nakazawa, T; Mori, M

    1999-09-01

    Immunity to Candida albicans (Candida) is characterized by a Th-1 type pattern of reactivity. Candida is rarely a cause antigen for bronchial asthma. Beta agonists have been found to inhibit secretion of IL-2 from T cells through intracellular cAMP elevation. We examined effects of isoproterenol (ISO) on Candida-stimulated T cells. Peripheral T cells obtained from six Candida-sensitive asthmatics, six Candida-sensitive non-asthmatic subjects, and six normal donors by Ficoll-Hypaque gradient centrifugation and nylon-wool column chromatography were incubated with Candida antigen or concanavalin A (Con A) in the absence or presence of ISO. Secretion of IL-2 and intracellular accumulation of cAMP were assayed by ELISA. Con A induced secretion of IL-2 in each of the three groups. Candida antigen induced IL-2 secretion in the normal and the non-asthmatic subjects, but not in the asthmatics. ISO, which reduced Con A-induced secretion of IL-2 in a dose-dependent manner, had no effect on Candida-induced secretion of IL-2. Although ISO increased the intracellular concentration of cAMP in untreated and Con A-treated T cells from all donors, cells from the normal and the non-asthmatic subjects, but not from the asthmatics, that were co-incubated with ISO and Candida had lower levels of cAMP than those treated with ISO alone. It is suggested that Candida antigen induces secretion of IL-2 and reduces ISO-inducible accumulation of cAMP in Candida-responsive IL-2 secreting cells, which may make Candida-induced secretion of IL-2 insensitive to ISO. PMID:10572628

  14. Role for the beta-adrenoceptor-coupled adenylate cyclase in the ontogenetic subsensitivity to isoproterenol in the embryonic chick ventricle

    SciTech Connect

    Smith, C.J.

    1985-01-01

    Isoproterenol (ISO) increases contractility and cyclic AMP content in ventricles of embryonic and hatched chicks. A transient decrease in beta-agonist sensitivity for both effects is seen in 18 day embryos (10E). Beta-adrenoceptor-coupled adenylate cylase (AC) and receptor binding were characterized in 14,000xg particulates and purified membranes from the ventricles of 10-11E, 17-19E and week-old chicks (5-6H). In crude particulates, the K/sub act/ for ISO (+100 ..mu..M Gpp(NH)p)-stimulated AC is greatest in the 17-19E. Maximal (ISO + Gpp(NH)p)-AC of the 11E is two-fold greater and NaF-AC is 30% greater than those of the 17-19E and 5-6 H. All age groups have comparable catalytic AC. All age groups have comparable K/sub d/'s for /sup 3/H-dihydroalprenolol (5-11 nM), while the 18E has 40% fewer receptors than the 11E and 5-6H. In particulates or membranes, K/sub act/ values for Gpp(NH)p, NaF, MnCl> and forskolin are unchanged with age. In membranes, K/sub act/ values for ISO plus guanine nucleotide (G) and maximal (ISO + G)-AC are similar in all ages. The net effect of ISO ((ISO + G) minus G) is least while that of G (G minus basal) is greatest in the 18E. Whereas /sup 32/P-labeling of a 42 kd protein by cholera toxin is lowest (25% decrease) in particulates of the 18E, labeling of a 39-41 kd doublet by pertussis toxin decreases continuously (by 50%) with age. All age groups have comparable K/sub d/'s (10-13 pM) for (/sup 125/I)-cyanopindolol (CYP). These data indicate that a transient decrease in receptor number and receptor-N/sub s/ (guanine nucleotide-sensitive) coupling in the 18E contribute to the subsensitivity to beta-agonist.

  15. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  16. Effectors of cyclic adenosine 5'-monophosphate up-regulating-oxytocin receptors in rabbit amnion cells: isoproterenol, parathyroid hormone-related protein, and potentiation by cortisol.

    PubMed

    Jeng, Y J; Hinko, A; Soloff, M S

    1995-11-01

    Forskolin (FSK; an activator of adenylyl cyclase) and cortisol synergistically increase the concentration of oxytocin receptors (OTRs) in rabbit amnion cells. The aims of this study were to characterize potential physiological regulators of OTR concentrations acting through adenylyl cyclase and to clarify the mechanisms of potentiation by cAMP and cortisol. Both isoproterenol (ISO) and parathyroid hormone-related protein (PTHrP) elevated amnion cell cAMP levels and OTR concentrations. The effects of ISO and PTHrP on OTR were potentiated by cortisol. Cortisol had no effect on the ability of ISO or PTHrP to stimulate adenylyl cyclase activity, and cAMP did not affect the number or affinity of glucocorticoid receptors in whole cells or in cytosol. Adenylyl cyclase activation, however, caused conversion of mifepristone (RU486) from a glucocorticoid antagonist to agonist. Thus, mifepristone elevated OTR receptor concentrations in the presence of FSK. In contrast, a structurally related glucocorticoid antagonist, onapristone (ZK98 299), was unaffected by cAMP. Because glucocorticoid receptors bound to mifepristone are capable of interacting with DNA, whereas onapristone-occupied receptors are not, we conclude that cAMP affects glucocoticoid receptor-DNA interactions, accounting for the synergistic effects of cAMP and cortisol on OTRs. PMID:8527507

  17. [Complex study of the rat heart at isoproterenol damage].

    PubMed

    Kapel'ko, V I; Lakomkin, V L; Lukoshkova, E V; Gramovich, V V; Vyborov, O N; Abramov, V S; Undrovinas, N A; Ermishkin, V V; Lakomkin, S V; Veselova, S P; Zhdanov, V S; Shirinskiĭ, V P

    2014-01-01

    Introduction of isoproterenol (an agonist of beta-adrenoreceptors) to rats is one of the widespread experimental models of cardiac failure. It is caused by damage of cardiomyocytes with the subsequent development of substitutive fibrosis. The purpose of the given work was the complex characteristic of cardiac function by means of invasive and noninvasive (echocardiography and impedansometry) methods of research. Isoproterenol was injected twice with a daily interval in dozes 85, 120, 150 or 180 mg/kg. Echocardiographic study of the heart in 2 weeks revealed obvious attributes of cardiac failure (left ventricular dilatation, lowered ejection fraction) in the groups which have received high cumulative dozes of isoproterenol (300-360 mg/kg). The catheterization of the left ventricle in these groups has shown raised enddiastolic pressure, decreased maximal rate of pressure development and fall, and also lowered indices of myocardial contractility and relaxability. In the groups which have received smaller isoproterenol dozes, apparent decrease in relaxability parameters (constants of isovolumic and auxovolumic relaxation) has been revealed at only slightly changed parameters of contractility. A strong correlation between echocardiographic and invasive parameters of myocardial contractility has been found. The phase analysis of the cardiac cycle has shown a lengthening of isometric phases of contraction and relaxation, as well as duration of ejection due to shortening duration of filling of both ventricles. Cardiomyocytes isolated from hearts with obvious cardiac failure responded to electrostimulation by arrhythmic contractions and also by much slowed and incomplete removal of free Ca++ from the myoplasm. Results allow to conclude that relatively smaller extent of myocardial damage is accompanied by decreased relaxability at slightly changed contractility, while at greater degree of damage both processes fail, but delay of relaxation still prevails. PMID:25102749

  18. Role of arachidonic acid metabolites in the action of a beta adrenergic agonist on human monocyte phagocytosis.

    PubMed

    Borda, E S; Tenenbaum, A; Sales, M E; Rumi, L; Sterin-Borda, L

    1998-02-01

    The mechanisms by which beta adrenergic stimulation regulates phagocytosis of Candida albicans by human peripheral monocytes (HPM) are characterized. Isoproterenol (ISO) inhibits phagocytosis in a concentration-dependent manner. This effect was blunted by propranolol, inhibitors of phospholipase A2 (PLA2), cyclooxygenase and verapamil, pointing to a participation of arachidonic acid (AA) metabolites and calcium in the phenomenon. Prostaglandin E2 (PGE2) and dibutyryl cyclic AMP (db-cAMP) also exerted the same inhibitory effect on phagocytosis. ISO interacts with beta adrenergic receptors of HPM increasing PGE2 and cAMP. We conclude that the mechanisms by which beta adrenergic stimulation regulates phagocytosis of Candida albicans by HPM appear to be secondary to beta adrenoceptor-mediated hydrolysis of AA accompanied by an increase in PGE2 generation and cAMP production. Both PGE2 and cAMP could act as mediators of the inhibitory action of beta agonists on the HPM-phagocytosis process. PMID:9578144

  19. Iloprost- and isoproterenol-induced increases in cAMP are regulated by different phosphodiesterases in erythrocytes of both rabbits and humans

    PubMed Central

    Adderley, Shaquria P.; Dufaux, Eileen A.; Sridharan, Meera; Bowles, Elizabeth A.; Hanson, Madelyn S.; Stephenson, Alan H.; Ellsworth, Mary L.; Sprague, Randy S.

    2009-01-01

    Activation of the G protein Gs results in increases in cAMP, a necessary step in the pathway for ATP release from rabbit and human erythrocytes. In all cells, the level of cAMP is the product of its synthesis by adenylyl cyclase and its hydrolysis by phosphodiesterases (PDEs). Both iloprost (Ilo), a PGI2 analog, and isoproterenol (Iso), a β-agonist, stimulate receptor-mediated increases in cAMP in rabbit and human erythrocytes. However, the specific PDEs associated with each of these signaling pathways in the erythrocyte have not been fully characterized. Previously, we reported that PDE3B is present in rabbit and human erythrocyte membranes and that PDE3 inhibitors potentiate Ilo-induced increases in cAMP. Here we report that inhibitors of either PDE2 or PDE4, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and rolipram, respectively, potentiate Iso-induced increases in cAMP in rabbit and human erythrocytes. Importantly, these inhibitors had no effect on cAMP increases associated with the incubation of erythrocytes with Ilo. In addition, we establish, for the first time, the presence of PDE2A protein in rabbit and human erythrocyte membranes. Finally, we determined that preincubation of human erythrocytes with EHNA and rolipram together potentiate Iso-induced ATP release, whereas preincubation with cilostazol enhances Ilo-induced release of ATP. These results are consistent with the hypothesis that, in rabbit and human erythrocytes, Ilo-induced increases in cAMP and ATP release are regulated by PDE3, whereas those associated with Iso are regulated by the activities of both PDE2 and PDE4. These studies demonstrate that PDE activity in these cells is localized to specific signaling pathways. PMID:19252089

  20. β2-Adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans

    PubMed Central

    Garovic, Vesna D; Joyner, Michael J; Dietz, Niki M; Boerwinkle, Eric; Turner, Stephen T

    2003-01-01

    Polymorphisms in the gene encoding the β2-adrenoceptor have been associated with interindividual differences in blood pressure and the diagnosis of hypertension. A common polymorphism resulting in a change from arginine to glycine at amino acid 16 (Arg16 → Gly) enhances agonist-promoted downregulation of receptor expression in vitro. It is unknown whether genotype-dependent differences in nitric oxide generation contribute to differences in vasodilator responses to β2-agonists in vivo. To address this question, venous occlusion plethysmography was used to measure forearm blood flow responses to graded brachial artery infusions of the β-agonist isoproterenol in 41 healthy normotensive Caucasian adults (mean age (± s.d.) = 29 ± 6 years), who were either Arg16 (n = 18) or Gly16 (n = 23) homozygotes. Compared to Arg16 homozygotes, Gly16 homozygotes demonstrated significantly greater blood flow responses to isoproterenol (P = 0.02). After inhibition of nitric oxide synthase by Nγ-monomethyl-l-arginine, blood flow responses did not differ significantly between genotype groups (P = 0.27). Consequently, effects of the Arg16 → Gly polymorphism on forearm blood flow responses to isoproterenol appear to be dependent on differences in endothelial generation of nitric oxide. In contrast to previous reports based on systemic infusions of β2-agonists, our findings indicate that regional blood flow responses to locally infused isoproterenol are significantly greater in Gly16 than in Arg16 homozygotes. PMID:12527744

  1. Protective effects of Astragalus polysaccharides against endothelial dysfunction in hypertrophic rats induced by isoproterenol.

    PubMed

    Han, Ronghui; Tang, Futian; Lu, Meili; Xu, Chonghua; Hu, Jin; Mei, Meng; Wang, Hongxin

    2016-09-01

    Astragalus polysaccharide (APS) is an important bioactive component extracted from Chinese herb Astragalus membranaceus. It has been widely used in treatment of cardiovascular diseases. We have previously reported that APS could inhibit isoproterenol-induced cardiac hypertrophy. The present study was designed to evaluate the protective effect of APS on vascular endothelia in cardiac hypertrophy rats induced by isoproterenol (ISO). ISO (10mg×kg(-1)) was intraperitoneally injected once daily for 2weeks to induce cardiac hypertrophy. APS (400 and 800mg×kg(-1)) was intragastrically injected once daily along with ISO. The results showed that combination with APS significantly ameliorates the endothelial dysfunction while attenuates cardiac hypertrophy induced by ISO. We found that administration with APS could attenuate the increase in number of circulating endothelial cell (CEC). APS also decreases the superoxide anion generation and the protein expression of p65 and the levels of TNF-α and IL-6; while increases the cGMP levels, an activity marker for nitric oxide (NO) in aortas. In addition, APS improves the relaxation dysfunction in isolated aortic rings and increases the protein expression of IκBα and Cu/Zn-SOD in aortas. In conclusion, our results suggested that APS had a protective effect against endothelial dysfunction in hypertrophic rats induced by ISO. The underlining mechanisms may be contributed to the anti-inflammatory effects and the improvement of the imbalance between reactive oxygen species (ROS) and NO. PMID:27344039

  2. Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress.

    PubMed

    Nagoor Meeran, M F; Jagadeesh, G S; Selvaraj, P

    2016-01-25

    Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats. PMID:26721194

  3. Effects of histidine and vitamin C on isoproterenol-induced acute myocardial infarction in rats

    PubMed Central

    Moradi-Arzeloo, Masoumeh; Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Asri-Rezaei, Siamak

    2016-01-01

    In the present study, we investigated the effects of histidine and vitamin C (alone or in combination) treatments against isoproterenol (a β-adrenergic receptor agonist)-induced acute myocardial infarction in rats. We used propranolol (a β-adrenergic receptor blocker) to compare the results. Rats were given intraperitoneal injections of histidine (40 mg kg-1) and vitamin C (40 mg kg-1) alone and combined daily for 21 days. Propranolol (10 mg kg-1) was orally administered daily for 10 days (from day 11 to day 21). Myocardial infarction was induced by subcutaneous injections of 150 mg kg-1 of isoproterenol at an interval of 24 hr on days 20 and 21. Blood and tissue samples were taken for histopathological and biochemical evaluations following electrocardiography recording on day 21. Isoproterenol elevated ST segment, increased heart weight, heart rate, serum activities of aspartate transaminase, lactate dehydrogenase, creatine kinase-MB and heart tissue content of malondialdehyde, and decreased R wave amplitude and superoxide dismutase and catalase activities of heart tissue. Necrosis, edema and inflammatory cells infiltration were observed in myocardial tissue sections. Our results indicated that histidine and vitamin C alone, and especially in combination prevent isoproterenol-induced cardiotoxicity and have similar protective effects with propranolol. Cardioprotective effects of histidine and vitamin C may be associated with their ability to reduce free radical-induced toxic effects. PMID:27226887

  4. Effects of histidine and vitamin C on isoproterenol-induced acute myocardial infarction in rats.

    PubMed

    Moradi-Arzeloo, Masoumeh; Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Asri-Rezaei, Siamak

    2016-01-01

    In the present study, we investigated the effects of histidine and vitamin C (alone or in combination) treatments against isoproterenol (a β-adrenergic receptor agonist)-induced acute myocardial infarction in rats. We used propranolol (a β-adrenergic receptor blocker) to compare the results. Rats were given intraperitoneal injections of histidine (40 mg kg(-1)) and vitamin C (40 mg kg(-1)) alone and combined daily for 21 days. Propranolol (10 mg kg(-1)) was orally administered daily for 10 days (from day 11 to day 21). Myocardial infarction was induced by subcutaneous injections of 150 mg kg(-1) of isoproterenol at an interval of 24 hr on days 20 and 21. Blood and tissue samples were taken for histopathological and biochemical evaluations following electrocardiography recording on day 21. Isoproterenol elevated ST segment, increased heart weight, heart rate, serum activities of aspartate transaminase, lactate dehydrogenase, creatine kinase-MB and heart tissue content of malondialdehyde, and decreased R wave amplitude and superoxide dismutase and catalase activities of heart tissue. Necrosis, edema and inflammatory cells infiltration were observed in myocardial tissue sections. Our results indicated that histidine and vitamin C alone, and especially in combination prevent isoproterenol-induced cardiotoxicity and have similar protective effects with propranolol. Cardioprotective effects of histidine and vitamin C may be associated with their ability to reduce free radical-induced toxic effects. PMID:27226887

  5. The Effects of Isoproterenol and Propranolol on Cytokine Profile Secretion by Cultured Tumor-infiltrating Lymphocytes Derived from Colorectal Cancer Patients

    PubMed Central

    Seyedi, Shahram; Andalib, Alireza; Rezaei, Abbas; Hosseini, Seyed Mohsen; Mohebbi, Seyed Reza; Zali, Mohammad Reza; Vafai, Mohamad; Behboo, Roubik; Tabatabaei, Seyed Abbas; Shahabi, Shahram

    2012-01-01

    Objective: Anti-tumor immunity and cytokine profiles have important roles in the development of cancer. Norepinephrine (NE) release due to sympathetic activation leads to a Th2 deviation via the beta-2 adrenergic receptor Beta-2 adrenergic receptor (β-2AR) and could increase cancer progression. This study intends to determine the effects of isoproterenol (ISO; beta-agonist) and propranolol (PRO; beta-antagonist) on the production of IFN-γ, IL-4, and IL-17. Cytokine levels have been examined in tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) of patients with colorectal cancer (CRC). The β-2AR expression on lymphocyte subsets was also assessed. Materials and Methods: In this experimental study, TILs were isolated from fresh CRC tissue and patient PBMCs were obtained just prior to surgery. The cells were cultured in medium for 72 hours. Concomitantly, cells were stimulated with 10 µg/ml phytohemagglutinin (PHA) alone or in the presence of either 1 µmol/L of PRO or 1 µmol/L ISO. The concentration of cytokines in the supernatants was measured by ELISA. Three-color flow cytometry was used to determine the expression of β-2AR on the lymphocyte subsets. Statistical analyses were performed via paired or independent t-test. Results: Levels of IFN-γ, IL-4 and IL-17 were elevated after PHA-stimulation of PBMCs and TILs. However, the elevation of IFN-γ and IL-17 production by TILs in response to PHA was significantly lower than PBMCs. In the presence of ISO, the IFN-γ/IL-4 ratio reduced in all groups, but this reduction was very low in TILs. Interestingly, the effects of PRO on cytokine production were, at least partially, comparable to those of ISO. Depressed levels of β-2AR expression were demonstrated on CD4+IFN-γ+ and CD4+IL-17+ lymphocytes in patients' PBMCs and TILs. Conclusion: This study has demonstrated the effects of ISO and PRO on cytokine production by TILs and determined β-2AR expression on these cells. ISO failed

  6. Cardioprotective potential of Punica granatum extract in isoproterenol-induced myocardial infarction in Wistar rats

    PubMed Central

    Mohan, Mahalaxmi; Patankar, Pankaj; Ghadi, Prakash; Kasture, Sanjay

    2010-01-01

    Objective: To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. Materials and Methods: The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. Results: Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. Conclusion: Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI. PMID:21808588

  7. Effects of Yohimbine and Tolazoline on Isoproterenol and Angiotensin 2-Induced Water Intake in Rats

    NASA Technical Reports Server (NTRS)

    Fregly, Melvin J.; Rowland, Neil E.; Greenleaf, John E.

    1983-01-01

    Subcutaneous administration of the alpha(sub 2)-adrenoreceptor antagonists, yohimbine and tolazoline, at doses up to 1000 micro-g/kg, had no effect on water intake of female rats. However, when these compounds were administered SC in combination with either the beta-adrenoreceptor agonist, isoproterenol (10 to 25 micro-g/kg, SC), or with angiotensin 2 (200 micro-g/kg, SC). water intake was enhanced. In contrast, intraventricular administration of either tolazoline (10 and 20 micro-g/kg) or yohimbine (300 micro-g/kg) failed to augment the dipsogenic response to angiotensin 2 (150 micro-g/kg, SC). Thus, the enhancing effect of these alpha(sub 2)-adrenoreceptor antagonists on isoproterenol- and angiotensin 2-induced water intakes appears to be manifested peripherally, rather than centrally. In view of the fact that clonidine, an alpha(sub 2)-adrenoreceptor agonist, has been shown to inhibit water intake induced by both isoproterenol and angiotensin 2, the results suggest that the alpha(sub 2)-adrenoreceptor may play a role in modulating water intake induced by these two dipsogenic agents.

  8. Preventive Effect of Phytic Acid on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

    PubMed Central

    Brindha, E.; Rajasekapandiyan, M.

    2015-01-01

    This study was aimed to evaluate the preventive role of phytic acid on membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na+ /K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with phytic acid (25 and 50 mg/kg, respectively) for a period of 56 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days. ISO-induced rats showed a significant decrease in the activity of Na+ /K+ ATPase and increase in the activities of Ca2+ and Mg2+ ATPase in the heart and a significant (P<0.05) increase in the levels of glycoproteins in serum and the heart were also observed in ISO-induced rats. Pretreatment with phytic acid for a period of 56 days exhibited a significant (P<0.05) effect and altered these biochemical parameters positively in ISO-induced rats. Thus, our study shows that phytic acid has cardioprotective role in ISO-induced MI in rats.

  9. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

    PubMed Central

    Karim, Nurul; Hossain, Md. Sabir; Alam, Nadia

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium. PMID:27294126

  10. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats.

    PubMed

    Afroz, Rizwana; Tanvir, E M; Karim, Nurul; Hossain, Md Sabir; Alam, Nadia; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium. PMID:27294126

  11. Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats

    PubMed Central

    Goyal, Sameer N.; Sharma, Charu; Mahajan, Umesh B.; Patil, Chandragouda R.; Agrawal, Yogeeta O.; Kumari, Santosh; Arya, Dharamvir Singh; Ojha, Shreesh

    2015-01-01

    Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities. PMID:26593900

  12. Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats.

    PubMed

    Goyal, Sameer N; Sharma, Charu; Mahajan, Umesh B; Patil, Chandragouda R; Agrawal, Yogeeta O; Kumari, Santosh; Arya, Dharamvir Singh; Ojha, Shreesh

    2015-01-01

    Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities. PMID:26593900

  13. Cell cycle control in isoproterenol-induced murine salivary acinar cell proliferation.

    PubMed

    Zeng, T; Yamamoto, H; Bowen, E; Broverman, R L; Nguyen, K H; Humphreys-Beher, M G

    1996-11-01

    The eukaryotic cell cycle is a summary of a complex network of signal transduction pathways resulting in both DNA replication and cell division. Cyclin-dependent kinases (CDKs) control the cell cycle in all eukaryotes, whereas other proteins, known as cyclins, act as their regulatory subunits. Chronic injection with isoproterenol (ISO) can induce acinar cell proliferation in rodent salivary glands. Cyclins and CDK proteins from control and ISO-treated murine parotid acinar cells were detected by using Western blotting techniques. By comparing the expression of these cell cycle regulatory kinases in the parotid acinar cell transition from a quiescent state to a hypertrophic state, we found rapid increases in the protein levels of all CDKs, cyclin D and proliferating cell nuclear antigen (PCNA). The highest protein levels for CDKs and cyclins appeared at about 72 hr of ISO stimulation and were coincident with the highest rate of increase in gland wet weight. After 72 hr, the increase of both cell cycle protein and gland wet weight began to subside. By using a co-immunoprecipitation method, the following cell cycle regulators (CDK-cyclin complexes) were detected, CDK4-cyclin D, CDK2-cyclin E, CDK2-cyclin A, and cdc2-cyclin B, along with an increase in kinase activity over control untreated animals. Additionally, we detected significant decreases in the newly isolated CDK inhibitor (CKI) p27kip but not Wee 1 kinase. The increased levels of CKI correlated with a decrease in kinase activity of CDK/cyclin complexes by 144 hr of chronic isoproterenol treatment. Our data suggest that the holoenzymes for cell cycle control (cyclin-CDK complexes) function as a final regulatory mechanism leading to salivary gland acinar cell proliferation. The gradual decline in protein levels of the CDKs and cyclins after 3 days of chronic treatment further indicates that ISO-induced proliferation of parotid acinar cells is self-limiting and non-tumorigenic. PMID:9375366

  14. L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways.

    PubMed

    Lin, Yan; Wang, Li-Na; Xi, Yu-Hui; Li, Hong-Zhu; Xiao, Feng-Gang; Zhao, Ya-Jun; Tian, Ye; Yang, Bao-Feng; Xu, Chang-Qing

    2008-08-01

    Polyamines (putrescine, spermidine and spermine) are essential for cell growth and differentiation. Nitric oxide exhibits antihypertrophic functions and inhibits cardiac remodelling. However, the metabolism of polyamines and the potential interactions with nitric oxide in cardiac hypertrophy remain unclear. We randomly divided Wistar rats into four treatment groups: controls, isoproterenol (ISO), ISO and L-arginine, and L-arginine. Isoproterenol (5 mg/kg/day, subcutaneously) and/or L-arginine (800 mg/kg/day, intraperitoneally) was administered once daily for 7 days. The expression of atrial natriuretic peptide mRNA was determined by reverse transcription-polymerase chain reaction, and fibrogenesis of heart was assessed by Van Gieson staining. Polyamines were measured with high-performance liquid chromatography, and plasma nitric oxide content and lactate dehydrogenase (LDH) activity were determined with a spectrophotometer. The expression levels of ornithine decarboxylase, spermidine/spermine N1-acetyltransferase (SSAT), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were analysed by Western blot. Heart-to-body weight ratio, left ventricle-to-body weight ratio, atrial natriuretic peptide mRNA expression, collagen fibres and LDH activity were elevated, both ornithine decarboxylase and SSAT proteins were up-regulated, and total polyamines were increased in the group treated with ISO. Additionally, the expression of iNOS was up-regulated, eNOS was down-regulated, and nitric oxide levels were low. Notably, cotreatment with L-arginine reversed most of these changes except for SSAT expression,which was further up-regulated. We propose that increased polyamines and decreased nitric oxide are involved in cardiac hypertrophy induced by ISO and suggest that L-arginine pre-treatment can attenuate cardiac hypertrophy through the regulation of key enzymes of the polyamine and nitric oxide pathways. PMID:18816294

  15. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model

    PubMed Central

    Wang, Jessica Jen-Chu; Rau, Christoph; Avetisyan, Rozeta; Ren, Shuxun; Romay, Milagros C.; Gong, Ke Wei; Wang, Yibin; Lusis, Aldons J.

    2016-01-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls. PMID:27385019

  16. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

    PubMed

    Wang, Jessica Jen-Chu; Rau, Christoph; Avetisyan, Rozeta; Ren, Shuxun; Romay, Milagros C; Stolin, Gabriel; Gong, Ke Wei; Wang, Yibin; Lusis, Aldons J

    2016-07-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls. PMID:27385019

  17. Isoproterenol potentiation of methyl mercury effects in vivo cardiac ATPasees and /sup 3/H-dopamine uptake

    SciTech Connect

    Ahammad-Sahib, K.I.; Moorthy, K.S.; Cameron, J.A.; Desaiah, D.

    1988-02-01

    Isoproterenol, a potent B-adrenergic receptor agonist, has been known to produce infarct-like myocardial lesions in rats characterized by swelling of endoplasmic reticulum. The swelling of this system is interpreted as an influx of large amount of extracellular fluid into myocardial cells by disturbances of the electrolyte metabolism. Isoproterenol is employed clinically as a bronchodilator in respiratory disorders and as a stimulant in heart block and cardiogenic shocks. In spite of its clinical use, possible drug-chemical interactions leading to adverse health effects are obvious when individuals on a regular isoproterenol treatment are exposed to an environmental contaminant such as methyl mercury. Consumption of fish and fish products is by far the most significant route of exposure to environmental mercury. In spite of such a possibility, little is know about isoproterenol-methyl mercury interaction. The present study forms the first of this kind to report such interactions and their effects on cardiac membrane bound enzymes such as Na/sup +/ -K/sup +/ and Ca/sup 2 +/-ATPases. Since Na/sup +/-K/sup +/ATPase has been implicated in uptake and release processes of catecholamines, the effects were also studied on /sup 3/H-dopamine uptake by sarcoplasmic reticulum. As a prelude to these proposed long-term chronic studies with non-lethal doses in the present report only single and sub-lethal doses were used for a shorter (48h) duration.

  18. Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway

    PubMed Central

    Al-rasheed, Nouf M; Al-Oteibi, Maha M; Al-Manee, Reem Z; Al-shareef, Sarah A; Al-Rasheed, Nawal M; Hasan, Iman H; Mohamad, Raeesa A; Mahmoud, Ayman M

    2015-01-01

    Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO)-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180–200 g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10 mg/kg body weight) for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg) intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW) ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of cardiac hypertrophy via modulation of the Janus kinase/signal transducer and activator of transcription-signaling pathway in the heart of ISO-administered animals. PMID:26150695

  19. Dietary Phenolic Acids of Macrotyloma uniflorum (Horse Gram) Protect the Rat Heart Against Isoproterenol-Induced Myocardial Infarction.

    PubMed

    Panda, Vandana; Laddha, Ankit; Nandave, Mukesh; Srinath, Sudhamani

    2016-07-01

    The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p-coumaric acid and ferulic acid) in isoproterenol (ISO)-induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO-elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C-reactive protein and malondialdehyde and a restoration of the levels of the ISO-depleted marker enzymes, reduced glutathione and the antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO-altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO-challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27091200

  20. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract

    PubMed Central

    Khalil, Md. Ibrahim; Ahmmed, Istiyak; Ahmed, Romana; Tanvir, E. M.; Afroz, Rizwana; Paul, Sudip; Gan, Siew Hua; Alam, Nadia

    2015-01-01

    We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats. PMID:26539517

  1. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract.

    PubMed

    Khalil, Md Ibrahim; Ahmmed, Istiyak; Ahmed, Romana; Tanvir, E M; Afroz, Rizwana; Paul, Sudip; Gan, Siew Hua; Alam, Nadia

    2015-01-01

    We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats. PMID:26539517

  2. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-12-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  3. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    PubMed Central

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-01-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis. PMID:26689945

  4. Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate.

    PubMed

    Li, Ping; Luo, Shike; Pan, Chunji; Cheng, Xiaoshu

    2015-12-01

    Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)‑induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator‑activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO‑induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO‑induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

  5. Effect of beta-ADrenergic Agonist on Cyclic AMP Synthesis in Chicken Skeletal Muscle Cells in Culture

    NASA Technical Reports Server (NTRS)

    Young, R. B.; Bridge, K. Y.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Because it seems logical that these agonists exert their action on muscle through stimulation of cAMP synthesis, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate cAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of cAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of cAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax levels were approximately 15-fold weaker than isoproterenol in stimulating the rate of cAMP synthesis. In addition, the EC50 values for isoproterenol, cimaterol, clenbuterol, epinephrine, and albuterol were 360 nM, 630 nM, 900 nM, 2,470 nM, and 3,650 nM, respectively. Finally, dose response curves show that the concentrations of cimaterol and clenbuterol in culture media at concentrations known to cause significant muscle hypertrophy in animals had no detectable effect on stimulation of CAMP accumulation in chicken skeletal muscle cells.

  6. Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR

    PubMed Central

    Yin, Qian; Yang, Chengzhi; Wu, Jimin; Lu, Haiyan; Zheng, Xiaohui; Zhang, Youyi; Lv, Zhizhen; Zheng, Xiaopu; Li, Zijian

    2016-01-01

    β-adrenergic receptors (β-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO) at the dose of 0.25 mg·kg−1·d−1 for 7days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB) is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling. PMID:27035432

  7. SIRT6 suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

    PubMed

    Lu, Jing; Sun, Duanping; Liu, Zhiping; Li, Min; Hong, Huiqi; Liu, Cui; Gao, Si; Li, Hong; Cai, Yi; Chen, Shaorui; Li, Zhuoming; Ye, Jiantao; Liu, Peiqing

    2016-06-01

    Reduction in autophagy has been reported to contribute to the pathogenesis of cardiac hypertrophy. However, the molecular pathways leading to impaired autophagy at the presence of hypertrophic stimuli remain to be elucidated. The present study aimed to investigate the role of sirtuin 6 (SIRT6), a sirtuin family member, in regulating cardiomyocyte autophagy, and its implication in prevention of cardiac hypertrophy. Primary neonatal rat cardiomyocytes (NRCMs) or Sprague-Dawley (SD) rats were submitted to isoproterenol (ISO) treatment, and then the hypertrophic responses and changes in autophagy activity were measured. The influence of SIRT6 on autophagy was observed in cultured NRCMs with gain- and loss-of-function approaches to regulate SIRT6 expression, and further confirmed in vivo by intramyocardial delivery of an adenovirus vector encoding SIRT6 cDNA. In addition, the involvement of SIRT6-mediated autophagy in attenuation of cardiomyocyte hypertrophy induced by ISO was determined basing on genetic or pharmaceutical disruption of autophagy, and the underlying mechanism was preliminarily explored. ISO-caused cardiac hypertrophy accompanying with a significant decrease in autophagy activity. SIRT6 overexpression enhanced autophagy in NRCMs and in rat hearts, whereas knockdown of SIRT6 by RNA interference led to suppression of cardiomyocyte autophagy. Furthermore, the protective effect of SIRT6 against ISO-stimulated hypertrophy was associated with induction of autophagy. SIRT6 promoted nuclear retention of forkhead box O3 transcription factor possibly via attenuating Akt signaling, which was responsible for autophagy activation. Our findings revealed that SIRT6 positively regulates autophagy in cardiomyocytes, which may help to ameliorate ISO-induced cardiac hypertrophy. PMID:27016702

  8. Protective effect of Tribulus terrestris L. fruit aqueous extracton lipid profile and oxidative stress in isoproterenol induced myocardial necrosis in male albino Wistar rats.

    PubMed

    Sailaja, K V; Shivaranjani, V Leela; Poornima, H; Rahamathulla, S B Md; Devi, K Lakshmi

    2013-01-01

    The objective of the present study was to evaluate the possible protective effects of Tribulus terrestris fruit aqueous extract (TTFAEt) on lipid profile and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in albino Wistar rats. Albino Wistar rats were divided into normal control, TTFAEt alone treated, ISO control and pretreated (TTFAEt+ISO) groups. The extract was administered at a dose of 50 mg/kg body weight for 40 days orally by gavage and ISO was administered at a dose of 85 mg/kg body weight for two consecutive days intraperitoneally at an interval of 24 h. ISO induced myocardial infarction (MI) was confirmed by disturbances in serum lipid profile, heart tissue lipid peroxidation and antioxidant enzyme levels. There was a significant increase in the levels of serum total cholesterol (32.60 %), triglycerides (41.30 %), very low density lipoproteins (81.81 %), low density lipoproteins (84%) and phospholipids (38.88 %) and a significant decrease in the levels of high density lipoproteins (33.33 %) in the ISO control group when compared to normal controls. Additionally, there is a significant decrease in the levels of heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and depletion of reduced glutathione, which indicates enhanced lipid peroxidation(172 %). Pretreatment with extract significantly showed a protective effect against ISO altered lipid profile, lipid peroxidation and antioxidant enzyme levels. The present study showed therapeutic effect of TTFAEt on lipid profile and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in experimental rats. PMID:26417233

  9. Effects of Lagenaria Sicessaria Fruit Juice on Lipid Profile and Glycoprotein Contents in Cardiotoxicity Induced by Isoproterenol in Rats

    PubMed Central

    Upaganlawar, Aman; Balaraman, R.

    2012-01-01

    This study investigated antihyperlipidemic effects of Lagenaria siceraria fruit juice (LSFJ) in isoproterenol (ISO)induced cardiotoxicity in rats. Rats treated with ISO (200 mg/kg, s.c.) showed a significant increase in the levels of triglycerides, cholesterol, and free fatty acids, in both serum and heart tissue. An increase in the levels of phospholipids, low-density lipoprotein, and very low-density lipoprotein-cholesterol, and decrease in high-density lipoprotein-cholesterol in serum and phospholipid levels in the heart were observed. ISO intoxicated rats also showed a significant decrease in the activities of lecithin: cholesterol acyl transferase, whereas lipoprotein lipase was found to be increased. Administration of LSFJ (400 mg/kg, p.o.) for 30 consecutive days and challenged with ISO on day 29th and 30th significantly attenuated these alterations and restored the levels of serum and heart lipids along with lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the protective effect of LSFJ during ISO-induced cardiotoxicity in rats. PMID:22736897

  10. Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

    NASA Technical Reports Server (NTRS)

    Young, R. B.; Bridge, K. Y.; Cureri, Peter A. (Technical Monitor)

    2002-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate cAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of cAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of cAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of cAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of cAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of cAMP by either epinephrine or isoproterenol.

  11. Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

    NASA Technical Reports Server (NTRS)

    Young, R. B.; Bridge, K. Y.

    2003-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate CAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of CAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of CAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of CAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of CAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of CAMP by either epinephrine or isoproterenol.

  12. Phorbol 12-myristate 13-acetate prevents isoproterenol-induced morphological change in cultured vascular smooth muscle cells

    SciTech Connect

    Nabika, Toru; Chaldakov, G.N.; Nara, Yasuo; Endo, Jiro; Yamori, Yukio )

    1988-10-01

    The effect of phorbol 12-myristate 13-acetate (PMA) on isoproterenol (ISO)- and dibutyryl cAMP (dBcAMP)-induced morphological change and cytoskeletal reorganization was studied in cultured vascular smooth muscle cells (VSMC) using the fluorescence staining of actin and microtubules. The treatment of VSMC with 1.0 {mu}M of ISO or with 1.0 mM of dBcAMP for 90 min induced the disruption of actin-containing stress fibers followed by cytoplasmic arborization. The addition of 100 nM of PMA prevented both the destruction of actin fibers and cell arborization induced either by ISO or by dBcAMP. These results indicated that the inhibition of arborization by PMA was mediated through the activation of protein kinase C. Colchicine at 5.0 {mu}M also had an inhibitory effect on ISO- and dBcAMP-induced cell arborization. However, immunofluorescence studies revealed that colchicine but not PMA elicited the reorganization of microtubules, suggesting that the effect of PMA was mediated through a mechanism different from that of colchicine. The observations indicated that the morphology of VSMC was regulated through the alteration of cytoskeletal organization induced by cAMP-mediated and by protein kinase C-dependent systems.

  13. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation

    PubMed Central

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  14. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation.

    PubMed

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  15. Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions.

    PubMed

    Easley, R B; Rodbard, D

    1977-12-01

    Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative "hyperdynamic beta-adrenergic state." PMID:200395

  16. PP2 prevents isoproterenol stimulation of cardiac pacemaker activity.

    PubMed

    Huang, Jianying; Lin, Yen-Chang; Hileman, Stan; Martin, Karen H; Hull, Robert; Yu, Han-Gang

    2015-02-01

    Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) using tyrosine kinase inhibitors for cancer therapy. We report here that a widely used selective inhibitor of Src tyrosine kinases, PP2, can inhibit and prevent isoproterenol stimulation of cardiac pacemaker activity. In dissected rat sinus node, PP2 inhibited and prevented isoproterenol stimulation of spontaneous beating rate. In isolated sinus node myocytes, PP2 suppressed the hyperpolarization-activated "funny" current (If) by negatively shifting the activation curve and decelerating activation kinetics, associated with decreased cell surface expression and reduced tyrosine phosphorylation of hyperpolarization-activated cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. In human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed isoproterenol stimulation of HCN4 and inhibited HCN4-573x, a cAMP-insensitive human HCN4 mutant. Isoprotenrenol had little effects on HCN4-573x. These results demonstrated that inhibition of presumably tyrosine Src kinase activity in heart by PP2 decreased and prevented the potential β-adrenergic stimulation of cardiac pacemaker activity. These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the key channel protein that controls the heart rate. PMID:25658311

  17. Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway.

    PubMed

    Han, Dandan; Wan, Changrong; Liu, Fenghua; Xu, Xiaolong; Jiang, Linshu; Xu, Jianqin

    2016-01-01

    Jujuboside A is a kind of the saponins isolated from the seeds of Ziziphus jujuba, which possesses multiple biological effects, such as antianxiety, antioxidant, and anti-inflammatory effects; however, its mediatory effect on isoproterenol-stimulated cardiomyocytes has not been investigated yet. In this study, we tried to detect the protective effect and potential mechanism of JUA on ISO-induced cardiomyocytes injury. H9C2 cells were treated with ISO to induce cell damage. Cells were pretreated with JUA to investigate the effects on the cell viability, morphological changes, light chain 3 conversion, and the activation of PI3K/Akt/mTOR signaling pathway. Results showed that ISO significantly inhibited the cell viability in a time- and dose-dependent manner. JUA pretreatment could reverse the reduction of cell viability and better the injury of H9C2 cells induced by ISO. Western blot analysis showed that JUA could accelerate the phosphorylation of PI3K, Akt, and mTOR. Results also indicated that JUA could significantly decrease the ratio of microtubule-associated protein LC3-II/I in H9C2 cells. Taken together, our research showed that JUA could notably reduce the damage cause by ISO via promoting the phosphorylation of PI3K, Akt, and mTOR and inhibiting LC3 conversion, which may be a potential choice for the treatment of heart diseases. PMID:27293469

  18. Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway

    PubMed Central

    Han, Dandan; Wan, Changrong; Liu, Fenghua; Xu, Xiaolong; Jiang, Linshu; Xu, Jianqin

    2016-01-01

    Jujuboside A is a kind of the saponins isolated from the seeds of Ziziphus jujuba, which possesses multiple biological effects, such as antianxiety, antioxidant, and anti-inflammatory effects; however, its mediatory effect on isoproterenol-stimulated cardiomyocytes has not been investigated yet. In this study, we tried to detect the protective effect and potential mechanism of JUA on ISO-induced cardiomyocytes injury. H9C2 cells were treated with ISO to induce cell damage. Cells were pretreated with JUA to investigate the effects on the cell viability, morphological changes, light chain 3 conversion, and the activation of PI3K/Akt/mTOR signaling pathway. Results showed that ISO significantly inhibited the cell viability in a time- and dose-dependent manner. JUA pretreatment could reverse the reduction of cell viability and better the injury of H9C2 cells induced by ISO. Western blot analysis showed that JUA could accelerate the phosphorylation of PI3K, Akt, and mTOR. Results also indicated that JUA could significantly decrease the ratio of microtubule-associated protein LC3-II/I in H9C2 cells. Taken together, our research showed that JUA could notably reduce the damage cause by ISO via promoting the phosphorylation of PI3K, Akt, and mTOR and inhibiting LC3 conversion, which may be a potential choice for the treatment of heart diseases. PMID:27293469

  19. Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol.

    PubMed

    Ishizuka, Kyoko; Hirukawa, Koji; Nakamura, Hiroshi; Togari, Akifumi

    2005-04-29

    The present study was designed to elucidate the mode of action of isoproterenol (Isp; adrenergic beta-agonist) and to characterize the effect of the calcitonin gene-related peptide (CGRP; sensory neuropeptide) on osteoclast formation induced by Isp in a mouse bone marrow culture system. Treatment of mouse bone marrow cells with Isp generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs) capable of excavating resorptive pits on dentine slices, and caused an increase in receptor activator of NF-kappaB ligand (RANKL) and a decrease in osteoprotegerin (OPG) production by the marrow cells. The osteoclast formation was significantly inhibited by OPG, suggesting the involvement of the RANKL-RANK system. CGRP inhibited the osteoclast formation caused by Isp or soluble RANKL (s-RANKL) but had no influence on RANKL or OPG production by the bone marrow cells treated with Isp, suggesting that CGRP inhibited the osteoclast formation by interfering with the action of RANKL produced by the Isp-treated bone marrow cells without affecting RANKL or OPG production. This in vitro data suggest the physiological interaction of sympathetic and sensory nerves in osteoclastogenesis in vivo. PMID:15814197

  20. Nonintracellular, cell-associated O-methylation of isoproterenol in the isolated rabbit thoracic aorta

    SciTech Connect

    Head, R.J.; Irvine, R.J.; Barone, S.; Stitzel, R.E.; de la Lande, I.S.

    1985-07-01

    The present study examines the subcellular site of catecholamine O-methylation in extraneuronal tissue. S-Adenosyl-l-methionine, a methyl donor that does not diffuse across biological membranes, was used to assess the participation of plasma membrane bound catechol-O-methyltransferase vs. cytoplasmic catechol-O-methyltransferase in the catecholamine O-methylating process. Segments of rabbit thoracic aorta incubated with (methyl-/sup 3/H)-S-adenosyl-l-methionine and isoproterenol generate (/sup 3/H)methoxy-isoproterenol. The formation of (/sup 3/H)methoxy-isoproterenol from (methyl-/sup 3/H)-S-adenosyl-l-methionine was proportional to the isoproterenol concentrations in the range of 0.1 to 1.0 microM. There was a marked preference for the O-methylation of the (+)- rather than the (-)-isomer of isoproterenol. The O-methylation of isoproterenol in the presence of (methyl-/sup 3/H)-S-adenosyl-l-methionine was stimulated as much as 8-fold by the removal of calcium ions from the incubation solutions. In contrast, the O-methylation of (+)-(/sup 3/H)isoproterenol by endogenous, intracellular S-adenosyl-l-methionine was only slightly inhibited by the removal of calcium ions from incubation solutions. The formation of (/sup 3/H)methoxy-isoproterenol from (methyl-/sup 3/H)-S-adenosyl-l-methionine and isoproterenol was not inhibited by pretreatment of tissues with phenoxybenzamine (32 microM) or treatment with metanephrine (27 mumol 1(-1) or deoxycorticosterone acetate (27 microM), i.e., drug treatments that inhibit the extraneuronal uptake and O-methylation of (/sup 3/H)-isoproterenol by endogenous intracellular S-adenosyl-l-methionine. The results of this study provide evidence for a nonintracellular, cell-associated site of O-methylation of isoproterenol in the rabbit aorta.

  1. Heart-type fatty acid-binding protein and its relation with morphological changes in rat myocardial damage model induced by isoproterenol.

    PubMed

    Hasić, Sabaheta; Jadrić, Radivoj; Cosović, Esad; Kiseljaković, Emina; Mornjaković, Zakira; Winterhalter-Jadrić, Mira

    2011-11-01

    We have investigated heart type fatty acid binding protein (H-FABP) rat serum values at different time point following subcutaneous (s.c) isoproterenol (ISO) administration and their correlation with severity of myocardial lesion. Thirty adult, male, Wistar rats were used for this study. Six rats per group were treated with a single dose of either ISO (ISO groups, dose 100 mg/kg, s.c.) at different time point (30', 60', 120', 240') or with saline (control group). Serum H-FABP was determined by enzyme-linked immunosorbent assay (ELISA) and histological analysis was performed by hematoxylin-eosin (HE) method of staining. The first serum H-FABP increase was obtained 30' following ISO administration, but maximal value was reached after 240'. Myocardial histological changes were time-dependent and correlated with serum H-FABP values (p<0.001). The results of the study suggest that H-FABP is sensitive marker for acute rat myocardial injury and its possible inclusion in myocardial injury screening studies in rats. PMID:22117831

  2. ISO radiation sterilization standards

    NASA Astrophysics Data System (ADS)

    Lambert, Byron J.; Hansen, Joyce M.

    1998-06-01

    This presentation provides an overview of the current status of the ISO radiation sterilization standards. The ISO standards are voluntary standards which detail both the validation and routine control of the sterilization process. ISO 11137 was approved in 1994 and published in 1995. When reviewing the standard you will note that less than 20% of the standard is devoted to requirements and the remainder is guidance on how to comply with the requirements. Future standards developments in radiation sterilization are being focused on providing additional guidance. The guidance that is currently provided in informative annexes of ISO 11137 includes: device/packaging materials, dose setting methods, and dosimeters and dose measurement, currently, there are four Technical Reports being developed to provide additional guidance: 1. AAMI Draft TIR, "Radiation Sterilization Material Qualification" 2. ISO TR 13409-1996, "Sterilization of health care products — Radiation sterilization — Substantiation of 25 kGy as a sterilization dose for small or infrequent production batches" 3. ISO Draft TR, "Sterilization of health care products — Radiation sterilization Selection of a sterilization dose for a single production batch" li]4. ISO Draft TR, "Sterilization of health care products — Radiation sterilization-Product Families, Plans for Sampling and Frequency of Dose Audits."

  3. A double-blind parallel study of acetylcysteine-isoproterenol and saline-isoproterenol in patients with chronic obstructive lung disease.

    PubMed

    Cato, A; Goldstein, I; Millman, M

    1977-01-01

    A double-blind parallel study in patients with asthma compared the safety and efficacy of saline-isoproterenol (SI) and acetylcysteine-isoproterenol (AI), when administered at home as an aerosol, over a one-week period, using a conventional nebulizer compressor. Measurements of pulmonary function revealed statistically significant differences between the two therapies for FEV1 and FVC in favour of AI. In the group treated with AI, the average sputum viscosity after six days of treatment was significantly less than pre-treatment values, or when compared to the results with SI treatment. No serious side-effects were reported during treatment with either therapy. These results indicate that acetylcysteine combined with a bronchodilator, such as isoproterenol, may be safe and of significant value in the treatment of patients with asthma who are also sputum producers. PMID:330289

  4. Protective effects of Labisia pumila var. alata on biochemical and histopathological alterations of cardiac muscle cells in isoproterenol-induced myocardial infarction rats.

    PubMed

    Dianita, Roza; Jantan, Ibrahim; Amran, Athirah Z; Jalil, Juriyati

    2015-01-01

    The study was designed to evaluate the cardioprotective effects of the standardized aqueous and 80% ethanol extracts of Labisia pumila var. alata (LPva) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The extracts were administered to Wistar rats orally for 28 days with three doses (100, 200 and 400 mg/kg of body weight) prior to ISO (85 mg/kg)-induced MI in two doses on day 29 and 30. The sera and hearts were collected for biochemical and histopathological analysis after the rats were sacrificed 48 h after the first induction. The main components of the extracts, gallic acid, alkylresorcinols and flavonoids were identified and quantitatively analyzed in the extracts by using a validated reversed phase HPLC method. The extracts showed significant protective effects as pretreated rats showed a significant dose-dependent decrease (p < 0.05) in cardiac enzyme activities, i.e., cardiac troponin I (cTnI), creatine kinase MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST), when compared with ISO-control rats. There were significant rises (p < 0.05) in the activity of oxidase enzymes, i.e., glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) of the pretreated rats, when compared with ISO-control group. Histopathological examination showed an improvement in membrane cell integrity in pre-treated rats compared to untreated rats. The major components of LPva extracts can be used as their biomarkers and contributed to the cardioprotective effects against ISO-induced MI rats. PMID:25786162

  5. ISOE Pilot Project Update

    SciTech Connect

    D. A. Hagemeyer D. E. Lewis

    2012-05-05

    This slide show introduces the Pilot Project to increase the value of Information System on Occupational Exposure (ISOE) data by increasing participation and amount of data reported from the U.S., reduce the hurdles and effort in participating, streamline the process of reporting and reduce time delay, and eliminate data entry and redundant effort.

  6. Analysis of ISO Data

    NASA Technical Reports Server (NTRS)

    Lambert, David L.

    2003-01-01

    A block grant supported several astronomers who executed observing programs using the Infrared Space Observatory (ISO). The ISO project in which Harriet Dinerstein participated was a study of sulfur and neon abundances in extragalactic H II regions using the ISO Short Wavelength Spectrometer (SWS). Evans and Jaffe, along with collaborators Ewine van Dishoeck and Wing-Fai Thi, and then graduate student Wenbin Li, carried out an in-depth study of the peripheral region of the molecular cloud L1204/S140, where the far ultraviolet radiation and the density are relatively low. Their observations test theories of photon-dominated regions (PDRs) in a regime that has been little explored. One ISO program was involved with PHT-32 observations of about a dozen young stars to search for extended emission that could be modeled with our dust-modeling-code at UT. The document reports on preliminary analysis of PHT 32 scanning of 10 pre-main-sequence stars at 50 and 100 microns. A small sample of R Coronae Borealis stars was observed with the SWS.

  7. The Infrared Space Observatory (ISO)

    NASA Technical Reports Server (NTRS)

    Helou, George; Kessler, Martin F.

    1995-01-01

    ISO, scheduled to launch in 1995, will carry into orbit the most sophisticated infrared observatory of the decade. Overviews of the mission, instrument payload and scientific program are given, along with a comparison of the strengths of ISO and SOFIA.

  8. Release of LHRH-activity from human fetal membranes upon exposure to PGE/sub 2/, oxytocin and isoproterenol

    SciTech Connect

    Poisner, A.M.; Poisner, R.; Becca, C.R.; Conn, P.M.

    1986-03-01

    The authors have previously reported that superfused chorion laeve (fetal membranes) release LHRH-like immunoreactivity upon exposure to angiotensin II. They have now studied the effects of other agonists on the release of LHRH-activity and something of its chemical nature. Fetal membranes were obtained from placentas delivered by cesarean section, the amnion stripped from the chorion, and the chorion superfused in an Amicon thin-channel device with the maternal surface facing up. The whole device was submerged in a 37 C water bath and perfused with a modified Locke's solution at 0.4 - 1.0 ml/min. LHRH-activity was measured by radioimmunoassay using three different antisera against LHRH. The release of LHRH-activity was stimulated by 6-10 min exposure to PGE/sub 2/, oxytocin, and isoproterenol. Extracts of chorion were studied using gel filtration on Sephacryl S-200 and ultrafiltration with Amicon PM-10 filters. The bulk of the LHRH-activity appeared as a higher molecular weight form (about 70,000 daltons). Since oxytocin has been reported to release PGE/sub 2/ from chorion, it may release LHRH-activity by virtue of liberating endogenous PGE/sub 2/. The chemical nature of the LHRH-activity is presently under investigation.

  9. ISO: Isochrone construction

    NASA Astrophysics Data System (ADS)

    Dotter, Aaron

    2016-01-01

    ISO transforms MESA history files into a uniform basis for interpolation and then constructs new stellar evolution tracks and isochrones from that basis. It is written in Fortran and requires MESA (ascl:1010.083), primarily for interpolation. Though designed to ingest MESA star history files, tracks from other stellar evolution codes can be incorporated by loading the tracks into the data structures used in the codes.

  10. Inhibitory GTP binding protein G/sub i/ regulates US -adrenoceptor affinity towards US -agonists

    SciTech Connect

    Marbach, I.; Levitzki, A.

    1987-05-01

    Treatment of S-49 lymphoma cell membranes with pertussis toxin (PT) causes a three-fold reduction of US -adrenoceptor (US AR) affinity towards isoproterenol. A similar treatment with cholera toxin (CT) does not cause such a modulation. The effects were studied by the detailed analysis of SVI-cyanopindolol (CYP) binding curves in the absence and presence of increasing agonist concentrations. Thus, the authors were able to compare in detail the effects of G/sub s/ and G/sub i/ on the agonist-associated state of the US AR. In contrast to these findings, PT treatment does not have any effect on the displacement of SVI-CYP by (-)isoproterenol. These results demonstrate that the inhibitory GTP protein G/sub i/ modulates the US AR affinity towards US -agonists. This might be due to the association of G/sub i/ with the agonist-bound US AR x G/sub s/ x C complex within the membrane. This hypothesis, as well as others, is under investigation.

  11. Increased 4-hydroxy-2-nonenal-induced proteasome dysfunction is correlated with cardiac damage in streptozotocin-injected rats with isoproterenol infusion.

    PubMed

    Deshpande, Mandar; Mali, Vishal R; Pan, Guodong; Xu, Jiang; Yang, Xiao-Ping; Thandavarayan, Rajarajan A; Palaniyandi, Suresh Selvaraj

    2016-07-01

    Increase in 4-hydroxy-2-nonenal (4HNE) due to oxidative stress has been observed in a variety of cardiac diseases such as diabetic cardiomyopathy. 4HNE exerts a damaging effect in the myocardium by interfering with subcellular organelles like mitochondria by forming adducts. Therefore, we hypothesized that increased 4HNE adduct formation in the heart results in proteasome inactivation in isoproterenol (ISO)-infused type 1 diabetes mellitus (DM) rats. Eight-week-old male Sprague Dawley rats were injected with streptozotocin (STZ, 65 mg kg(-1) ). The rats were infused with ISO (5 mg kg(-1) ) for 2 weeks by mini pumps, after 8 weeks of STZ injection. We studied normal control (n = 8) and DM + ISO (n = 10) groups. Cardiac performance was assessed by echocardiography and Millar catheter at the end of the protocol at 20 weeks. Initially, we found an increase in 4HNE adducts in the hearts of the DM + ISO group. There was also a decrease in myocardial proteasomal peptidase (chymotrypsin and trypsin-like) activity. Increases in cardiomyocyte area (446 ± 32·7 vs 221 ± 10·83) (µm(2) ), per cent area of cardiac fibrosis (7·4 ± 0·7 vs 2·7 ± 0·5) and cardiac dysfunction were also found in DM + ISO (P < 0·05) relative to controls. We also found increased 4HNE adduct formation on proteasomal subunits. Furthermore, reduced aldehyde dehydrogenase 2 activity was observed in the myocardium of the DM + ISO group. Treatment with 4HNE (100 μM) for 4 h on cultured H9c2 cardiomyocytes attenuated proteasome activity. Therefore, we conclude that the 4HNE-induced decrease in proteasome activity may be involved in the cardiac pathology in STZ-injected rats infused with ISO. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27273517

  12. Aegle marmelos fruit extract attenuates isoproterenol-induced oxidative stress in rats

    PubMed Central

    Krushna, Gadham Setty Saayi; Kareem, Mohammed Abdul; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Hussain, Shaik Althaf; Devi Kodidhela, Lakshmi

    2012-01-01

    Myocardial infarction is a major public health concern and the leading cause of death throughout the world. The present study investigates the ability of Aegle marmelos fruit extract to prevent pathological changes and oxidative stress after isoproterenol induced myocardial infarction in rats. In vitro studies showed that Aegle marmelos fruit extract possesses antioxidant activity. Administration of isoproterenol (85 mg/kg body weight) to rats resulted in significantly elevated plasma transaminases, lactate dehydrogenase and creatine kinase, however, cardiac tissue analyses showed decreased activity of the above enzymes compared to experimental control rats. Further, isoproterenol administration significantly increased plasma and cardiac tissue thiobarbituric acid reactive substances and lowered the activities of cardiac tissue superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and glutathione-S-transferase when compared to control groups. Pretreatment with Aegle marmelos fruit extract at a dose of 150 mg/kg body weight for a period of 45 days significantly prevented the observed alterations. Our data suggest that Aegle marmelos fruit extract exerts its protective effect by decreasing thiobarbituric acid reactive substances and elevating antioxidants status in isoproterenol treated rats. Both biochemical and histopathological results in the isoproterenol-induced myocardial infarction model emphasize the beneficial action of Aegle marmelos fruit extract as a cardioprotective agent. PMID:22573921

  13. Aqueous extract of Saussurea lappa root ameliorate oxidative myocardial injury induced by isoproterenol in rats

    PubMed Central

    Saleem, T. S. Mohamed; Lokanath, N.; Prasanthi, A.; Madhavi, M.; Mallika, G.; Vishnu, M. N.

    2013-01-01

    Saussurea lappa Clarke (Compositae), is commonly known as Kushta. In Ayurvedha, it is mentioned that the aqueous extract of the root S. lappa was used for treatment of angina pectoris. The present study was designed to investigate the cardioprotective effect of aqueous extract of root of S. lappa against isoproterenol induced myocardial injury. Myocardial injury in rat was induced by the administration of isoproterenol at a dose of 85 mg/kg, i.p., The rats were pretreated with the aqueous extract of S. lappa (AESL) in three different doses (100, 200 and 300 mg/kg, p.o.) through the oral route. Isoproterenol alone-treated rats showed increased serum concentration of lactate dehydrogenase (LDH), creatinine kinase (CK), and aspartate transaminase (AST), increased myocardial thiobarbituric acid reactive substances (TBARS) level, and decreased myocardial glutathione (GSH) level due to myocardial damage produced by isoproterenol. This is further conformed by histopathological changes. Chronic oral administration of AESL in three different doses significantly restored the level of myocardial LDH, CK, AST, TBARS, and GSH. The extract effect was compared with the reference standard α-tocopherol which also offered similar protection in biochemical and histopathological changes. The overall beneficial effect which was observed with the dose of 200 mg/kg indicated that AESL produced significant dose-dependent activity against isoproterenol induced myocardial injury. PMID:23833749

  14. USGIN ISO metadata profile

    NASA Astrophysics Data System (ADS)

    Richard, S. M.

    2011-12-01

    The USGIN project has drafted and is using a specification for use of ISO 19115/19/39 metadata, recommendations for simple metadata content, and a proposal for a URI scheme to identify resources using resolvable http URI's(see http://lab.usgin.org/usgin-profiles). The principal target use case is a catalog in which resources can be registered and described by data providers for discovery by users. We are currently using the ESRI Geoportal (Open Source), with configuration files for the USGIN profile. The metadata offered by the catalog must provide sufficient content to guide search engines to locate requested resources, to describe the resource content, provenance, and quality so users can determine if the resource will serve for intended usage, and finally to enable human users and sofware clients to obtain or access the resource. In order to achieve an operational federated catalog system, provisions in the ISO specification must be restricted and usage clarified to reduce the heterogeneity of 'standard' metadata and service implementations such that a single client can search against different catalogs, and the metadata returned by catalogs can be parsed reliably to locate required information. Usage of the complex ISO 19139 XML schema allows for a great deal of structured metadata content, but the heterogenity in approaches to content encoding has hampered development of sophisticated client software that can take advantage of the rich metadata; the lack of such clients in turn reduces motivation for metadata producers to produce content-rich metadata. If the only significant use of the detailed, structured metadata is to format into text for people to read, then the detailed information could be put in free text elements and be just as useful. In order for complex metadata encoding and content to be useful, there must be clear and unambiguous conventions on the encoding that are utilized by the community that wishes to take advantage of advanced metadata

  15. ISO 9000 Quality Management System

    NASA Astrophysics Data System (ADS)

    Hadjicostas, Evsevios

    The ISO 9000 series describes a quality management system applicable to any organization. In this chapter we present the requirements of the standard in a way that is as close as possible to the needs of analytical laboratories. The sequence of the requirements follows that in the ISO 9001:2008 standard. In addition, the guidelines for performance improvement set out in the ISO 9004 are reviewed. Both standards should be used as a reference as well as the basis for further elaboration.

  16. ISO 50001 Energy Management Standard

    SciTech Connect

    2013-08-12

    This powerful standard from the International Organization for Standardization (ISO) provides an internationally recognized framework for organizations to voluntarily implement an energy management system.

  17. 21 CFR 201.305 - Isoproterenol inhalation preparations (pressurized aerosols, nebulizers, powders) for human use...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... completely to other forms of therapy until use of the isoproterenol inhalation preparation was discontinued...) On the basis of the above information and after discussion with and concurrence of the Respiratory... such instances the use of this preparation be discontinued immediately and alternative...

  18. 21 CFR 201.305 - Isoproterenol inhalation preparations (pressurized aerosols, nebulizers, powders) for human use...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... completely to other forms of therapy until use of the isoproterenol inhalation preparation was discontinued...) On the basis of the above information and after discussion with and concurrence of the Respiratory... such instances the use of this preparation be discontinued immediately and alternative...

  19. 21 CFR 201.305 - Isoproterenol inhalation preparations (pressurized aerosols, nebulizers, powders) for human use...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... completely to other forms of therapy until use of the isoproterenol inhalation preparation was discontinued...) On the basis of the above information and after discussion with and concurrence of the Respiratory... such instances the use of this preparation be discontinued immediately and alternative...

  20. 21 CFR 201.305 - Isoproterenol inhalation preparations (pressurized aerosols, nebulizers, powders) for human use...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... completely to other forms of therapy until use of the isoproterenol inhalation preparation was discontinued...) On the basis of the above information and after discussion with and concurrence of the Respiratory... such instances the use of this preparation be discontinued immediately and alternative...

  1. 21 CFR 201.305 - Isoproterenol inhalation preparations (pressurized aerosols, nebulizers, powders) for human use...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... completely to other forms of therapy until use of the isoproterenol inhalation preparation was discontinued...) On the basis of the above information and after discussion with and concurrence of the Respiratory... such instances the use of this preparation be discontinued immediately and alternative...

  2. Isoproterenol stimulates phosphorylation of the insulin-regulatable glucose transporter in rat adipocytes

    SciTech Connect

    James, D.E.; Hiken, J.; Lawrence, J.C. Jr. )

    1989-11-01

    The authors have examined the acute effect of insulin and isoproterenol on the phosphorylation state of the insulin-regulatable glucose transporter (IRGT) in rat adipocytes. The IRGT was immunoprecipitated from either detergent-solubilized whole-cell homogenates or subcellular fraction of {sup 32}P-labeled fat cells and subjected to sodium dodecyl sulfate/polyarcylamide gel electrophoresis. The {sup 32}P-labeled IRGT was detected by autoradiography as a species of apparent M{sub r} 46,000. Insulin stimulated translocation of the IRGT from low-density microsomes to the plasma membrane but did not affect phosphorylation of the transporter in either fraction. Isoproterenol inhibited insulin-stimulated glucose transport by 40% but was without effect on the subcellar distribution of the transporter in either the presence or absence of insulin. Isoproterenol stimulated phosphorylation of the IRGT 2-fold. Incubating cells with dibutyryl-cAMP and 8-bromo-cAMP also stimulated phosphorylation 2-fold, and the transporter was phosphorylated in vitro when IRGT-enriched vesicles were incubated with cAMP-dependent protein kinase and ({gamma}-{sup 32}P)ATP. These results suggest that isoproterenol stimulates phosphorylation of the IRGT via a cAMP-dependent pathway and that phosphorylation of the transporter may modulate its ability to transport glucose.

  3. Acute effects of inhaled isoproterenol on the mechanical characteristics of the lungs in normal man

    PubMed Central

    McFadden, E. R.; Newton-Howes, Jan; Pride, N. B.

    1970-01-01

    We investigated the effects of isoproterenol on the pulmonary mechanics of eight healthy male subjects. We measured the flow-volume, pressure-volume, resistance-volume, and pressure-flow relationships of the lungs of our subjects in addition to the forced expiratory volume (FEV1). The results of this study confirm earlier observations that isoproterenol produces a considerable decrease in airway resistance but only small changes in maximum expiratory flow. Measurements of static pressure-volume curves showed that isoproterenol caused a temporary decrease in the elastic recoil pressure of the lungs. In five men there were mean falls in recoil pressure of 4.1 cm H2O at 85% total lung capacity (TLC), 2.6 cm H2O at 75% TLC, and 1.5 cm H2O at 50% TLC. We postulate that the reason for the relatively small increments in maximum expiratory flow after isoproterenol is primarily that the effects of airway dilatation are in large part negated by the reduction in lung recoil pressure, which results in a fall in the maximum effective driving force for expiratory air flow, and secondly that there is an increase in the compliance of the flow-limiting airways. These studies emphasize that tests of maximum flow and of airway resistance should not be regarded as invariably interchangeable in the assessment of airway reactions or mild disease of the airways. PMID:5443178

  4. Diosmin exhibits anti-hyperlipidemic effects in isoproterenol induced myocardial infarcted rats.

    PubMed

    Queenthy, S Sharmila; John, Babu

    2013-10-15

    The aim of the present study was to evaluate the protective effects of diosmin on experimentally induced myocardial infarcted rats. Diosmin (5 and 10mg/kg body weight) was administered orally as pretreatment daily for a period of 10 days. Then isoproterenol (100mg/kg) was injected subcutaneously into rats at an interval of 24h for 2 days (on 11th and 12th day). Isoproterenol-induced myocardial infarcted rats showed significant changes in electrocardiogram and an increase in the levels of cardiac markers, compared with normal rats. Additionally, increased plasma lipid peroxidation products and altered lipid metabolism in the plasma were observed in the isoproterenol-induced myocardial infarcted rats. Pretreatment with diosmin (5 and 10mg/kg body weight) minimized the electrocardiographic changes, decreased the levels of serum cardiac marker enzymes reduced plasma lipid peroxidation and minimized the alterations in the lipid metabolism of isoproterenol-induced myocardial infarcted rats. Also, diosmin inhibited the enhanced activity of liver HMG CoA reductase. The in vitro study revealed the free radical scavenging activity of diosmin. The free radical scavenging and anti-hyperlipidaemic effects are the reasons for the cardioprotective effects of diosmin. PMID:24036254

  5. The ISO Spacecraft

    NASA Astrophysics Data System (ADS)

    Ximenez de Ferrin, S.

    1995-11-01

    ESA's Infrared Space Observatory (ISO) consists of two modules: the Payload module, which includes the telescope and the scientific instruments, and the Service Module, which houses the instruments electronics, the hydrazine propellant tank and all other classical spacecraft subsystems. To ensure that the telescope is kept near absolute zero and thus is the least disturbed by the effects of the infrared emissions from other elements of the system, the telescope is enclosed in a helium-cooled cryostat. The cryostat in turn is shaded by a Sun-shield to protect it from the heat of the direct Sun. The shield has a covering of solar cells that provide the electrical power needed for the mission.

  6. Quality Assurance through ISO 9000.

    ERIC Educational Resources Information Center

    Zuckerman, Amy

    2000-01-01

    Created in 1987 by the International Organization for Standardization, in Geneva, Switzerland, ISO 9000 is attempting to develop a world standard to help companies and other institutions measure and monitor their quality-control efforts. This article describes four school districts' successful efforts to secure ISO 9000 certification. (MLH)

  7. ISO 9000: The Librarian's Role.

    ERIC Educational Resources Information Center

    Dobson, Chris; Ernst, Carolyn

    1999-01-01

    Describes the special library's role in implementing ISO 9000 (i.e., a series of international quality-assurance standards developed by the International Organization of Standards). Topics discussed include document and data control, keeping the standards current, documentation of procedures, the ISO 9000 audit, and benefits for the library. (MES)

  8. Skeletal muscle beta-receptors and isoproterenol-stimulated vasodilation in canine heart failure

    SciTech Connect

    Frey, M.J.; Lanoce, V.; Molinoff, P.B.; Wilson, J.R. )

    1989-11-01

    To investigate whether heart failure alters beta-adrenergic receptors on skeletal muscle and its associated vasculature, the density of beta-adrenergic receptors, isoproterenol-stimulated adenylate cyclase activity, and coupling of the guanine nucleotide-binding regulatory protein were compared in 18 control dogs and 16 dogs with heart failure induced by 5-8 wk of ventricular pacing at 260 beats/min. Hindlimb vascular responses to isoproterenol were compared in eight controls and eight of the dogs with heart failure. In dogs with heart failure, the density of beta-receptors on skeletal muscle was reduced in both gastrocnemius (control: 50 +/- 5; heart failure: 33 +/- 8 fmol/mg of protein) and semitendinosus muscle (control: 43 +/- 9; heart failure: 27 +/- 9 fmol/mg of protein, both P less than 0.05). Receptor coupling to the ternary complex, as determined by isoproterenol competition curves with and without guanosine 5'-triphosphate (GTP), was unchanged. Isoproterenol-stimulated adenylate cyclase activity was significantly decreased in semitendinosus muscle (control: 52.4 +/- 4.6; heart failure: 36.5 +/- 9.5 pmol.mg-1.min-1; P less than 0.05) and tended to be decreased in gastrocnemius muscle (control: 40.1 +/- 8.5; heart failure: 33.5 +/- 4.5 pmol.mg-1.min-1; P = NS). Isoproterenol-induced hindlimb vasodilation was not significantly different in controls and in dogs with heart failure. These findings suggest that heart failure causes downregulation of skeletal muscle beta-adrenergic receptors, probably due to receptor exposure to elevated catecholamine levels, but does not reduce beta-receptor-mediated vasodilation in muscle.

  9. Effects of aging on responses to isoproterenol tilt-table testing in patients with syncope.

    PubMed

    Sheldon, R

    1994-09-01

    The diagnosis of neuromediated syncope is often established with isoproterenol head-up tilt-table testing. Previous work has demonstrated changes in autonomic nervous system function with progressive age, suggesting that responses to tilt-table testing may depend on the age of the patient. The purpose of this study was to assess the effects of age on the clinical and hemodynamic responses to isoproterenol tilt testing in patients with syncope of undetermined etiology. Accordingly, 85 patients with syncope of undetermined etiology underwent tilt testing with infusions of 0, 2, and 5 micrograms/min of isoproterenol in 3 successive stages. Of 85 patients tested, 66 had a positive outcome. The proportions of patients with a positive test and with tests ending in syncope declined significantly with age, with positive outcomes seen in 100%, 86%, 69%, and 61% of patients aged 12 to 20, 21 to 35, 36 to 60, and 61 to 88 years, respectively (p = 0.033, chi-square). Presyncope developed more slowly in patients aged 61 to 88 years (half-time to presyncope 2.5 minutes) than in younger patients (half-times to presyncope 0.7 to 0.9 minute). There were no significant age-related changes in peak and trough systolic blood pressures and rate-pressure products, but trough heart rate increased significantly with age (r = 0.40, p = 0.003). In conclusion, the likelihood of a positive outcome to isoproterenol tilt-table testing declines with age. Older patients take longer to develop presyncope, are less likely to develop syncope, and are less able to develop a relative bradycardia. These results guide interpretation of isoproterenol tilt-table testing. PMID:8059726

  10. Differential Signaling of the Endogenous Agonists at the β2-Adrenergic Receptor*

    PubMed Central

    Reiner, Susanne; Ambrosio, Manuela; Hoffmann, Carsten; Lohse, Martin J.

    2010-01-01

    The concept of “functional selectivity” or “biased signaling” suggests that a ligand can have distinct efficacies with regard to different signaling pathways. We have investigated the question of whether biased signaling may be related to distinct agonist-induced conformational changes in receptors using the β2-adrenergic receptor (β2AR) and its two endogenous ligands epinephrine and norepinephrine as a model system. Agonist-induced conformational changes were determined in a fluorescently tagged β2AR FRET sensor. In this β2AR sensor, norepinephrine caused signals that amounted to only ≈50% of those induced by epinephrine and the standard “full” agonist isoproterenol. Furthermore, norepinephrine-induced changes in the β2AR FRET sensor were slower than those induced by epinephrine (rate constants, 47 versus 128 ms). A similar partial β2AR activation signal was revealed for the synthetic agonists fenoterol and terbutaline. However, norepinephrine was almost as efficient as epinephrine (and isoproterenol) in causing activation of Gs and adenylyl cyclase. In contrast, fenoterol was quite efficient in triggering β-arrestin2 recruitment to the cell surface and its interaction with β2AR, as well as internalization of the receptors, whereas norepinephrine caused partial and slow changes in these assays. We conclude that partial agonism of norepinephrine at the β2AR is related to the induction of a different active conformation and that this conformation is efficient in signaling to Gs and less efficient in signaling to β-arrestin2. These observations extend the concept of biased signaling to the endogenous agonists of the β2AR and link it to distinct conformational changes in the receptor. PMID:20837485

  11. [Correction of isoproterenol-induced myocardial injury with magnesium salts in magnesium-deficient rats].

    PubMed

    Kharitonova, M V; Zheltova, A A; Spasov, A A; Smirnov, A V; Pan'shin, N G; Iezhitsa, I N

    2013-01-01

    The effect of Mg L-asparaginate (Mg-L-Asp), Mg chloride (MgCl2) and Mg sulfate (MgSO4) on the severity of isoproterenol-induced myocardial injury in Mg-deficient rats has been evaluated. To induce Mg deficiency, twenty-eight rats were placed on a low Mg diet (Mg content < 15 mg/kg) and demineralized water for 10 weeks. Twelve control rats were fed a basal control diet (Mg content = 500 mg/kg) and water (with Mg content 20 mg/l) for equal duration. On day 49 of low Mg diet, Mg-deficient rats were randomly divided into four groups: 1) group that continued to receive low Mg diet; 2) low Mg diet plus oral MgSO4; 3) low Mg diet plus oral Mg-L-Asp and 4) low Mg diet plus oral MgCl2 (50 mg of Mg per kg of body weight). Isoproterenol was injected subcutaneously (30 mg/kg BW, twice, at an interval of 24 hours) on the day 70 of the study, when plasma and erythrocyte Mg level in rats fed a low Mg diet were significantly decreased by 47% and 45% compared to intact animals. Twenty-four hours after second injection of isoproterenol, tests for activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were run and histopathological study was carried out. Administration of isoproterenol to rats resulted in significantly elevated plasma CK, LDH and AST, however analyses in Mg deficient group demonstrated more dramatically increased activity of CK and AST compared to control rats (3,06 and 4,67 fold in Mg-deficient group vs. 1,91 and 3,92 fold in intact group). Increased leakage of cardiac injury markers was concomitant to increased volume of fuchsinophilic cardiomyocytes (54.2 +/- 1.7% in Mg-deficient group and 38.9 +/- 1.9% in intact group, p < 0.05). However, pretreatment with of MgCl2, MgSO4 and Mg-L-Asp during 21 days favorably decreased sensitivity of myocardium to isoproterenol-induced ischemic injury. All evaluated salts significantly decreased myocyte marker enzymes as well as protected myocardium against isoproterenol

  12. Cardioprotective potential of N,α-L-rhamnopyranosyl vincosamide, an indole alkaloid, isolated from the leaves of Moringa oleifera in isoproterenol induced cardiotoxic rats: in vivo and in vitro studies.

    PubMed

    Panda, Sunanda; Kar, Anand; Sharma, Pratibha; Sharma, Ashok

    2013-02-15

    Hitherto unknown protective effect of N,α-L-rhamnopyranosyl vincosamide (VR), isolated from Moringa oleifera leaves in isoproterenol (ISO)-induced cardiac toxicity was evaluated in rats. Oral administration of VR at 40 mg/kg for 7 days markedly reduced the ISO-induced increase in the levels of serum cardiac markers such as troponin-T, creatine kinase-MB, lactate dehydrogenase and glutamate pyruvate transaminase as well as cardiac lipid peroxidation with a parallel increase in the cellular antioxidants suggesting its cardio-protective and free radical scavenging potential, which was latter confirmed by in vitro study. Rats treated with test compound also improved the ISO-induced abnormal changes in ECG as well as in cardiac histology. A reduction in myocardial necrosis was further evidenced by the tri-phenyl tetrazolium chloride (TTC) stain in isolated test drug pretreated rats. These findings suggest the cardio-protective potential of the isolated alkaloid and possibly the beneficial action is mediated through its free radical scavenging property. PMID:23321560

  13. Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice.

    PubMed

    Vergaro, Giuseppe; Prud'homme, Mathilde; Fazal, Loubina; Merval, Regine; Passino, Claudio; Emdin, Michele; Samuel, Jane-Lise; Cohen Solal, Alain; Delcayre, Claude

    2016-03-01

    Galectin-3 (Gal-3) is involved in inflammation, fibrogenesis, and cardiac remodeling. Previous evidence shows that Gal-3 interacts with aldosterone in promoting macrophage infiltration and vascular fibrosis and that Gal-3 genetic and pharmacological inhibition prevents remodeling in a pressure-overload animal model of heart failure. We aimed to explore the contribution of Gal-3 and aldosterone in mechanisms leading to heart failure in a murine model. Male mice with cardiac-specific hyperaldosteronism underwent isoproterenol subcutaneous injections, to be then randomized to receive placebo, a Gal-3 inhibitor (modified citrus pectin [MCP]), an aldosterone antagonist (potassium canrenoate), or MCP+canrenoate for 14 days. Isoproterenol induced a rapid and persistent decrease in left ventricular fractional shortening (-20% at day 14); this was markedly improved by treatment with either MCP or canrenoate (both P<0.001 versus placebo). MCP and canrenoate also reduced cardiac hypertrophy and fibrosis and the expression of genes involved in fibrogenesis (Coll-1 and Coll-3) and macrophage infiltration (CD-68 and MCP-1). After isoproterenol, Gal-3 gene expression (P<0.05 versus placebo) and protein levels (-61% and -69% versus placebo) were decreased by both canrenoate and MCP. The combined use of antagonists of Gal-3 and aldosterone resulted in more pronounced effects on cardiac hypertrophy, inflammation, and fibrosis, when compared with either MCP or canrenoate alone. Inhibition of Gal-3 and aldosterone can reverse isoproterenol-induced left ventricular dysfunction, by reducing myocardial inflammation and fibrogenesis. Gal-3 likely participates in mechanisms of aldosterone-mediated myocardial damage in a heart failure murine model with cardiac hyperaldosteronism. Gal-3 inhibition may represent a new promising therapeutic option in heart failure. PMID:26781273

  14. Acute Myocardial Histopathology in Normal and Arteriosclerotic Rats During Isoproterenol-induced Infarction

    PubMed Central

    Wexler, B. C.; Judd, J. T.

    1970-01-01

    Arteriosclerotic and non-arteriosclerotic, male Sprague-Dawley rats were given 2 s.c. injections of isoproterenol known to produce extensive myocardial infarction. The appearance of positive fuchsinophilia was used as an index of focal myocardial acidosis and of anaerobic metabolism. After one injection of isoproterenol, positive fuchsinophilia appeared within 30 min., reached a zenith at 4 hr and then promptly disappeared. Following the second injection of isoproterenol, fuchsinophilia reappeared briefly but was not as intense. The arteriosclerotic animals showed markedly less evidence of heart failure outwardly and less evidence of fuchsinophilia, histopathologically. Apparently, the first episode of cardiac stimulation caused only temporary cardiac ischaemia, positive fuchsinophilia and anaerobic cardiac metabolism. After the second injection, however, irreversible cardiac damage occurred and despite an abortive attempt towards anaerobic metabolic readjustment overt cardiac necrosis became dominant. ImagesFigs. 9-10Figs. 11-12Figs. 1-2Figs. 13-14Figs. 7-8Figs. 5-6Figs. 3-4 PMID:4099593

  15. Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca2+ overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats

    PubMed Central

    Liu, Yue-Tao; Zhou, Chao; Jia, Hong-Mei; Chang, Xing; Zou, Zhong-Mei

    2016-01-01

    Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca2+ overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca2+ overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network. PMID:27457884

  16. Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca(2+) overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats.

    PubMed

    Liu, Yue-Tao; Zhou, Chao; Jia, Hong-Mei; Chang, Xing; Zou, Zhong-Mei

    2016-01-01

    Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca(2+) overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca(2+) overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network. PMID:27457884

  17. [ISO 15189 medical laboratory accreditation].

    PubMed

    Aoyagi, Tsutomu

    2004-10-01

    This International Standard, based upon ISO/IEC 17025 and ISO 9001, provides requirements for competence and quality that are particular to medical laboratories. While this International Standard is intended for use throughout the currently recognized disciplines of medical laboratory services, those working in other services and disciplines will also find it useful and appropriate. In addition, bodies engaged in the recognition of the competence of medical laboratories will be able to use this International Standard as the basis for their activities. The Japan Accreditation Board for Conformity Assessment (AB) and the Japanese Committee for Clinical Laboratory Standards (CCLS) are jointly developing the program of accreditation of medical laboratories. ISO 15189 requirements consist of two parts, one is management requirements and the other is technical requirements. The former includes the requirements of all parts of ISO 9001, moreover it includes the requirement of conformity assessment body, for example, impartiality and independence from any other party. The latter includes the requirements of laboratory competence (e.g. personnel, facility, instrument, and examination methods), moreover it requires that laboratories shall participate proficiency testing(s) and laboratories' examination results shall have traceability of measurements and implement uncertainty of measurement. Implementation of ISO 15189 will result in a significant improvement in medical laboratories management system and their technical competence. The accreditation of medical laboratory will improve medical laboratory service and be useful for patients. PMID:15624503

  18. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  19. CRM 1-Mediated Degradation and Agonist-Induced Down-Regulation of β-Adrenergic Receptor mRNAs

    PubMed Central

    Bai, Ying; Lu, Huafei; Machida, Curtis A.

    2006-01-01

    SUMMARY The β1-adrenergic receptor (β1-AR) mRNAs are post-transcriptionally regulated at the level of mRNA stability and undergo accelerated agonist-mediated degradation via interaction of its 3' untranslated region (UTR) with RNA binding proteins, including the HuR nuclear protein. In a previous report [Kirigiti et al. (2001). Mol. Pharmacol. 60:1308-1324), we examined the agonist-mediated down-regulation of the rat β1-AR mRNAs, endogenously expressed in the rat C6 cell line and ectopically expressed in transfectant hamster DDT1MF2 and rat L6 cells. In this report, we determined that isoproterenol treatment of neonatal rat cortical neurons, an important cell type expressing β1-ARs in the brain, results in significant decreases in β1-AR mRNA stability, while treatment with leptomycin B, an inhibitor of the nuclear export receptor CRM 1, results in significant increases in β1-AR mRNA stability and nuclear retention. UV-crosslinking/immunoprecipitation and glycerol gradient fractionation analyses indicate that the β1-AR 3' UTR recognize complexes composed of HuR and multiple proteins, including CRM 1. Cell-permeable peptides containing the leucine-rich nuclear export signal (NES) were used as inhibitors of CRM 1-mediated nuclear export. When DDT1MF2 transfectants were treated with isoproterenol and peptide inhibitors, only the co-addition of the NES inhibitor reversed the isoproterenol-induced reduction of β1-AR mRNA levels. Our results suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation and agonist-mediated down-regulation of the β1-AR mRNAs. PMID:16997396

  20. Canstatin inhibits isoproterenol-induced apoptosis through preserving mitochondrial morphology in differentiated H9c2 cardiomyoblasts.

    PubMed

    Okada, Muneyoshi; Morioka, Suiri; Kanazawa, Hiroki; Yamawaki, Hideyuki

    2016-08-01

    Canstatin, a non-collagenous fragment, is cleaved from type IV collagen α2 chain, an essential component of basement membrane surrounding cardiomyocytes. Although canstatin is known as an endogenous anti-angiogenic factor, its effects on cardiomyocytes have not been clarified. This study examined the effects of canstatin on isoproterenol-induced apoptosis in differentiated H9c2 cardiomyoblasts. Retinoic acid was used to differentiate H9c2 myoblast to cardiomyocyte-like phenotype. Cell viability was determined by a cell counting assay. Western blotting was performed to detect expression of cleaved casepase-3 and phosphorylation of dynamin related protein (Drp)1 at Ser637 which regulates mitochondrial fission. Mito Sox Red staining was performed to examine a mitochondria-dependent production of reactive oxygen species (ROS). Mitochondrial morphology was detected by Mito Tracker Red staining. Isoproterenol (100 μM, 48 h) significantly decreased cell viability and increased cleaved caspase-3 expression, which were inhibited by canstatin (10-250 ng/ml) in a concentration-dependent manner. Canstatin suppressed the isoproterenol-induced mitochondrial fission but not ROS. Canstatin also inhibited the isoproterenol-induced dephosphorylation of Drp1 at Ser637. In conclusion, canstatin inhibits isoproterenol-induced apoptosis through the inhibition of mitochondrial fission via the suppression of dephosphorylation of Drp1 at Ser637 in differentiated H9c2 cardiomyoblasts. PMID:27315818

  1. Andrographis paniculata extract protect against isoproterenol-induced myocardial injury by mitigating cardiac dysfunction and oxidative injury in rats.

    PubMed

    Ojha, Shreesh; Bharti, Saurabh; Golechha, Mahaveer; Sharma, Ashok K; Rani, Neha; Kumari, Santosh; Arya, Dharamvir Singh

    2012-01-01

    Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart. PMID:22568041

  2. Our Application of ISO 9000.

    ERIC Educational Resources Information Center

    Hammond, Jane

    2000-01-01

    Since a large, underfunded urban Colorado district initiated ISO 9000 reforms, administrators and staff have reviewed 14 central-office departments' processes to improve efficiency and enhance student outcomes. Jefferson County has saved $900,000 annually on purchasing processes, developed a quality curriculum-development process, and improved…

  3. Combinational effect of resveratrol and atorvastatin on isoproterenol-induced cardiac hypertrophy in rats

    PubMed Central

    Chakraborty, Songjukta; Pujani, Mukta; Haque, Syed Ehtaishamul

    2015-01-01

    Introduction: Resveratrol is a natural polyphenol present mainly in grapes. It has been shown to offer strong cardio protection in animal models due to its ability to correct lipid peroxidation and maintain antioxidants level. Atorvastatin, a HMG-CoA reductase inhibitor, lowers cholesterol level and is commonly prescribed to heart patients. Our aim in this study was to see the combination effect of these two drugs against Isoproterenol-induced cardiac hypertrophy in rats. Materials and Methods: Wister Albino rats were treated with resveratrol (20 mg/kg/day, p.o), atorvastatin (20 mg/kg/day, p.o) and in combination (resveratrol [10 mg/kg/day, p.o] + atorvastatin [10 mg/kg/day, p.o]) for a period of 25 days and from 15th till 25th day Isoproterenol (5 mg/kg/day, s.c) was co-administered to rats to induce cardiac hypertrophy. Results: A significant increase in creatine kinase, lactate dehydrogenase, aspartate transaminase and lipid peroxidation with the significant decrease in reduced glutathione, superoxide dismutase and catalase were observed in Isoproterenol treated rats. Resveratrol, atorvastatin and their combination significantly reversed the effect. The histopathological studies and myocardial infarct size evaluation also confirmed the protection. Conclusion: Comparing the data we came to this conclusion that atorvastatin although showed the protection along all the parameters, the extent of protection offered by resveratrol alone and in combination were more effective. Hence, it can be concluded that resveratrol, an herbal nutritional supplement, alone and in combination is better against cardiac hypertrophy. PMID:26229360

  4. Effect of the adrenergic beta 3-agonist, BRL37344, on heat production by brown adipocytes in obese and in older rats.

    PubMed

    Yamakawa, A; Tanaka, E; Nakano, S

    1994-12-01

    Heat production by isolated brown adipocytes, from hypothalamic obese rats and from older rats, was investigated by microcalorimetry. The obese and older rats were 12 and 40 weeks-old, respectively. The basal heat production by the brown adipocytes was significantly less in the obese and older rats than in control rats 12 weeks of age. Isoproterenol and a novel adrenergic beta 3-agonist, BRL37344, increased heat production in a concentration-dependent manner in all rats. The effects of isoproterenol were significantly less in the obese group than in the controls, while BRL37344 stimulated heat production in all rats almost identically. These results suggest that (1) the heat producing capacity of brown adipocytes is reduced by hypothalamic obesity and aging, and (2) BRL37344 might be useful as an anti-obesity drug. PMID:7570685

  5. Flow injection spectrophotometric determination of isoproterenol using an avocado (Persea americana) crude extract immobilized on controlled-pore silica reactor.

    PubMed

    Lupetti, Karina Omuro; Vieira, Iolanda Cruz; Fatibello-Filho, Orlando

    2002-04-22

    An enzymatic reactor was constructed by the immobilization of polyphenol oxidase (PPO) from avocado (Persea americana) crude extract in an inorganic support of controlled pore silica (CPS), after a previous step of silanization. This inorganic support has been used as an excellent carrier to immobilize this enzyme and the enzymatic reactor was used in a flow injection system for the determination of isoproterenol in pharmaceutical products. The procedure is based on the oxidation reaction of this drug with immobilized PPO and the product obtained was monitored at 492 nm. This system presented an analytical curve from 1.23x10(-4) to 7.38x10(-4) mol l(-1) isoproterenol with a detection limit of 6.25x10(-5) mol l(-1). Recoveries of isoproterenol between 98.5 and 103.1%, a relative standard deviation (R.S.D.) less than 1% (n=10) and 36 determinations per h were obtained. PMID:18968613

  6. ISOs: The new antitrust regulators?

    SciTech Connect

    Raskin, D.B.

    1998-04-01

    Fear of seller market power in emerging electricity markets has led regulators to sanction use of independent system operators as private market police. A more restrained approach is likely to yield better results without the chilling effects of private regulation. This new industry regulatory paradigm has received little critical attention to date. This is unfortunate because ISO antitrust regulation raises serious legal and policy concerns. The California and New England Power Pool (NEPOOL) plans are quite intrusive. They require the ISO to make difficult distinctions between acceptable and unacceptable market behavior. They create considerable risk that desirable competitive behavior will be chilled and that market participants will incur significant explicit and implicit costs to meet regulatory requirements.

  7. 75 FR 7581 - RTO/ISO Performance Metrics; Notice Requesting Comments on RTO/ISO Performance Metrics

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-22

    ... Energy Regulatory Commission RTO/ISO Performance Metrics; Notice Requesting Comments on RTO/ ISO..., work with regional transmission organizations (RTO), Independent System Operators (ISO), stakeholders and other experts to develop standardized measures that track the performance of RTO/ISO...

  8. Deletion of CXCR4 in cardiomyocytes exacerbates cardiac dysfunction following isoproterenol administration.

    PubMed

    Wang, E R; Jarrah, A A; Benard, L; Chen, J; Schwarzkopf, M; Hadri, L; Tarzami, S T

    2014-05-01

    Altered alpha- and beta-adrenergic receptor signaling is associated with cardiac hypertrophy and failure. Stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 have been reported to mediate cardioprotection after injury through the mobilization of stem cells into injured tissue. However, little is known regarding whether SDF-1/CXCR4 induces acute protection following pathological hypertrophy and if so, by what molecular mechanism. We have previously reported that CXCR4 physically interacts with the beta-2 adrenergic receptor and modulates its downstream signaling. Here we have shown that CXCR4 expression prevents beta-adrenergic receptor-induced hypertrophy. Cardiac beta-adrenergic receptors were stimulated with the implantation of a subcutaneous osmotic pump administrating isoproterenol and CXCR4 expression was selectively abrogated in cardiomyocytes using Cre-loxP-mediated gene recombination. CXCR4 knockout mice showed worsened fractional shortening and ejection fraction. CXCR4 ablation increased susceptibility to isoproterenol-induced heart failure, by upregulating apoptotic markers and reducing mitochondrial function; cardiac function decreases whereas fibrosis increases. In addition, CXCR4 expression was rescued with the use of cardiotropic adeno-associated viral-9 vectors. CXCR4 gene transfer reduced cardiac apoptotic signaling, improved mitochondrial function and resulted in a recovered cardiac function. Our results represent the first evidence that SDF-1/CXCR4 signaling mediates acute cardioprotection through modulating beta-adrenergic receptor signaling in vivo. PMID:24646609

  9. Exocyst subunits are involved in isoproterenol-induced amylase release from rat parotid acinar cells.

    PubMed

    Imai, Akane; Yoshie, Sumio; Haga-Tsujimura, Maiko; Nashida, Tomoko; Shimomura, Hiromi

    2012-04-01

    Exocytosis of secretory granules in parotid acinar cells requires multiple events: tethering, docking, priming, and fusion with a luminal plasma membrane. The exocyst complex, which is composed of eight subunits (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84) that are conserved in yeast and mammalian cells, is thought to participate in the exocytotic pathway. However, to date, no exocyst subunit has been identified in salivary glands. In the present study, we investigated the expression and function of exocyst subunits in rat parotid acinar cells. The expression of mRNA for all eight exocyst subunits was detected in parotid acinar cells by RT-PCR, and Sec6 and Sec8 proteins were localized on the luminal plasma membrane. Sec6 interacted with Sec8 after 5 min of stimulation with isoproterenol. In addition, antibodies to-Sec6 and Sec8 inhibited isoproterenol-induced amylase release from streptolysin O-permeabilized parotid acinar cells. These results suggest that an exocyst complex of eight subunits is required for amylase release from parotid acinar cells. PMID:22409218

  10. Coconut Haustorium Maintains Cardiac Integrity and Alleviates Oxidative Stress in Rats Subjected to Isoproterenol-induced Myocardial Infarction

    PubMed Central

    Chikku, A. M.; Rajamohan, T.

    2012-01-01

    The present study evaluates the effect of aqueous extract of coconut haustorium on isoproterenol-induced myocardial infarction in Sprague Dawley rats. Rats were pretreated with aqueous extract of coconut haustorium (40 mg/100 g) orally for 45 days. After pretreatment, myocardial infarction was induced by injecting isoproterenol subcutaneously (20 mg/100 g body weight) twice at an interval of 24 h. Activity of marker enzymes like lactate dehydrogenase, creatinine kinase-MB, aspartate transaminase and alanine transaminase were increased in the serum and decreased in the heart of isoproterenol treated rats indicating cardiac damage. These changes were significantly reduced in haustorium pretreated rats. Moreover, an increase in the activities of antioxidant enzymes and decrease in the levels of peroxidation products were observed in the myocardium of coconut haustorium pretreated rats. Histopathology of the heart of these rats showed almost normal tissue morphology. From these results, it is clear that aqueous extract of coconut haustorium possess significant cardioprotective and antioxidant properties during isoproterenol-induced myocardial infarction in rats. PMID:23716867

  11. Beta-Adrenergic Agonists

    PubMed Central

    Barisione, Giovanni; Baroffio, Michele; Crimi, Emanuele; Brusasco, Vito

    2010-01-01

    Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β2-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β2-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β2-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised.

  12. Regulation of cardiac sodium-calcium exchanger by beta-adrenergic agonists.

    PubMed Central

    Fan, J; Shuba, Y M; Morad, M

    1996-01-01

    Na+-Ca2+ exchanger and Ca2+ channel are two major sarcolemmal Ca2+-transporting proteins of cardiac myocytes. Although the Ca2+ channel is effectively regulated by protein kinase A-dependent phosphorylation, no enzymatic regulation of the exchanger protein has been identified as yet. Here we report that in frog ventricular myocytes, isoproterenol down-regulates the Na+-Ca2+ exchanger, independent of intracellular Ca2+ and membrane potential, by activation of the beta-receptor/adenylate-cyclase/cAMP-dependent cascade, resulting in suppression of transmembrane Ca2+ transport via the exchanger and providing for the well-documented contracture-suppressant effect of the hormone on frog heart. The beta-blocker propranolol blocks the isoproterenol effect, whereas forskolin, cAMP, and theophylline mimic it. In the frog heart where contractile Ca2+ is transported primarily by the Na+-Ca2+ exchanger, the beta-agonists' simultaneous enhancement of Ca2+ current, ICa, and suppression of Na+-Ca2+ exchanger current, INa-Ca would enable the myocyte to develop force rapidly at the onset of depolarization (enhancement of ICa) and to decrease Ca2+ influx (suppression of INa-Ca) later in the action potential. This unique adrenergically induced shift in the Ca2+ influx pathways may have evolved in response to paucity of the sarcoplasmic reticulum Ca2+-ATPase/phospholamban complex and absence of significant intracellular Ca2+ release pools in the frog heart. PMID:8643609

  13. Nicorandil enhances the efficacy of mesenchymal stem cell therapy in isoproterenol-induced heart failure in rats.

    PubMed

    Mohamed, Sarah S; Ahmed, Lamiaa A; Attia, Wael A; Khattab, Mahmoud M

    2015-12-01

    Stem cell transplantation has emerged as a promising technique for regenerative medicine in cardiovascular therapeutics. However, the results have been less than optimal. The aim of the present study was to investigate whether nicorandil could offer an additional benefit over bone marrow-derived mesenchymal stem cell therapy in isoproterenol-induced myocardial damage and its progression to heart failure in rats. Isoproterenol was injected subcutaneously for 2 consecutive days at doses of 85 and 170 mg/kg/day, respectively. Nicorandil (3 mg/kg/day) was then given orally with or without a single intravenous bone marrow-derived mesenchymal stem cell administration. Electrocardiography and echocardiography were recorded 2 weeks after the beginning of treatment. Rats were then sacrificed and the ventricle was isolated for estimation of tumor necrosis factor-alpha, vascular endothelial growth factor and transforming growth factor-beta. Moreover, protein expressions of caspase-3, connexin-43 as well as endothelial and inducible nitric oxide synthases were evaluated. Finally, histological studies of myocardial fibrosis and blood vessel density were performed and cryosections were done for estimation cell homing. Combined nicorandil/bone marrow-derived mesenchymal stem cell therapy provided an additional improvement compared to cell therapy alone toward reducing isoproterenol-induced cardiac hypertrophy, fibrosis and inflammation. Notably, combined therapy induced significant increase in angiogenesis and cell homing and prevented isoproterenol-induced changes in contractility and apoptotic markers. In conclusion, combined nicorandil/bone marrow-derived mesenchymal stem cell therapy was superior to cell therapy alone toward preventing isoproterenol-induced heart failure in rats through creation of a supportive environment for mesenchymal stem cells. PMID:26453143

  14. Enhancing Technology Education Students' Understanding of ISO 9000.

    ERIC Educational Resources Information Center

    Harding, Kerry A.; Tesolowski, Dennis G.; Simmons, J. Bryan

    2000-01-01

    Defines ISO 9000, the quality control standard of the International Organization for Standardization (ISO), and looks at the benefits of ISO certification. Looks at the four levels of ISO 9000 and discusses the construction of training courses to prepare ISO documentation. (JOW)

  15. Documenting an ISO 9000 Quality System.

    ERIC Educational Resources Information Center

    Fisher, Barry

    1995-01-01

    Discusses six steps to follow when documenting an ISO 9000 quality system: using ISO 9000 to develop a quality system, identifying a company's business processes, analyzing the business processes; describing the procedures, writing the quality manual, and working to the documented procedures. (SR)

  16. Maximizing Value for Training with ISO 9000.

    ERIC Educational Resources Information Center

    Russo, C. W. Russ; Russo, Tracy Callaway

    1996-01-01

    The International Organization for Standardization (ISO) has created quality assurance guidelines that help technology trainers and educators manage and organize training programs. This article briefly outlines program design principles, emphasizing needs analysis and outcome evaluation, performance documentation, and process management. ISO 9000…

  17. [Merits of acquiring ISO15189 accreditation].

    PubMed

    Kitagawa, Masami

    2010-01-01

    In Japan, an ISO15189 accreditation system was started in 2005. To date, 47 hospitals have been accredited. In this session, I will present the merits of acquiring accreditation regarding ISO15189 based on our experience. Our hospital has 263 beds. The Clinical Examination Section consists of 12 staff (including 5 part-time workers): 7 in change of sample examination and 5 in charge of physiological examination. The annual number of samples is approximately 150,000. Samples collected on health checkups account for 90%. To improve the quality and service, assessment by third persons has been positively utilized in our hospital. Accreditation regarding ISO9001, ISO14001, ISO27001, privacy mark, hospital function assessment, the functional assessment of "ningen-dock"/health checkup hospitals, labor/hygiene service function assessment, and ISO15189 has been acquired. Patients may not recognize ISO. So, it must be utilized, considering that the acquisition of accreditation is not a goal but a starting point. Furthermore, cost-performance should be improved to achieve utilization-related merits. It is important to not only acquire accreditation but also help clinical staff and patients become aware of some changes/merits. Patients may consult a hospital for the following reasons: confidence in the hospital, and the staffs kind/polite attitudes. Long-term management strategies should be established without pursuing only short-term profits. I will introduce several merits of acquiring accreditation regarding ISO15189. Initially, incidental conditions for bids and appeal points include accreditation regarding ISO15189. Our corporation has participated in some competitive bids regarding health checkup business. In some companies, the bid conditions included ISO acquisition. In our hospital, clinical trials have been positively carried out. For participation in trials, hospitals must pass an institutional examination. However, ISO acquisition facilitates the preparation of

  18. Activation of β1-adrenoceptor triggers oxidative stress mediated myocardial membrane destabilization in isoproterenol induced myocardial infarcted rats: 7-hydroxycoumarin and its counter action.

    PubMed

    Jagadeesh, Govindan Sangaran; Nagoor Meeran, Mohamed Fizur; Selvaraj, Palanisamy

    2016-04-15

    Activation of β1-adrenoceptor stimulates myocardial membrane destabilization in isoproterenol induced rats. Male albino Wistar rats were pre and co-treated with 7-hydroxycoumarin (16mg/kg body weight) daily for 8 days. Myocardial infarction was induced into rats by the subcutaneous administration of isoproterenol (100mg/kg body weight) at an interval of 24h daily for a period of two days (7th and 8th day). The levels/activities of serum cardiac troponin-T, lactate dehydrogenase and the concentrations of heart lipid peroxidation products were significantly increased and the antioxidant status was significantly decreased in isoproterenol induced rats. Furthermore, the activity of sodium/potassium-dependent adenosine triphosphatase was significantly decreased and the activities of calcium and magnesium-dependent adenosine triphosphatases were significantly increased in the heart of isoproterenol induced myocardial infarcted rats. Isoproterenol induced rats also revealed increased concentrations of sodium and calcium and decreased concentrations of potassium in the heart. 7-hydroxycoumarin pre- and co-treatment showed considerable impact on all biochemical parameters assessed. Also, 7-HC greatly reduced the infarct size of the myocardium. The in vitro study confirmed its potent free radical scavenging activity. Thus, the present study revealed that 7-HC attenuates myocardial membrane destabilization by reinstating the activities/levels of adenosine triphosphatases and minerals in isoproterenol induced rats by inhibiting oxidative stress. These effects are attributed to the membrane stabilizing and free radical scavenging properties of 7-hydroxycoumarin. PMID:26930228

  19. Cardioprotective Effects of Essential Oil of Lavandula angustifolia on Isoproterenol-induced Acute Myocardial Infarction in Rat

    PubMed Central

    Ziaee, Mojtaba; Khorrami, Arash; Ebrahimi, Maryam; Nourafcan, Hassan; Amiraslanzadeh, Masoumeh; Rameshrad, Maryam; Garjani, Mehraveh; Garjani, Alireza

    2015-01-01

    Myocardial infarction (MI) is a common presentation of the ischemic heart disease. Lavandula angustifolia is an herbaceous plant with antioxidative effects. This study was designed to investigate the cardioprotective effects of lavandula angustifolia essential oil against isoproterenol-induced MI in rats. The dried sample was subjected to hydrodistillation by using a Clevenger and the oils were dried over anhydrous Na2SO4. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the essential oil. MI was induced by subcutaneous injection of Isoproterenol (100 mg/Kg) for 3 consecutive days at an interval of 24 h. The essential oil was given intraperitoneally every 24 h started at MI induction. Following anesthesia, hemodynamic parameters were measured. After sacrificing the animals, the hearts were removed to measure the heart to body weight ratio and histopathological examination. Myeloperoxidase (MPO) and Malondialdehyde (MDA) were measured in heart tissues for evaluating the activity of neutrophils and lipid peroxidation, respectively. The essential oil amended ECG pattern by suppressing ST-segment elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly decreased heart to body weight ratio (P<0.001) and the elevation of MDA and MPO in myocardium, it also increased dp/dtmax from 2793 ± 210 to 4488 ± 253 mmHg/sec (P<0.001), and 20 mg/Kg of it significantly lowered LVEDP from 14 ± 3.43 to 4.3 ± 0.83 mmHg (P<0.001).The results demonstrated that L. angustifolia protects myocardium against isoproterenol-induced MI that it could be related to its antioxidant properties. PMID:25561934

  20. Cardioprotective Effects of Essential Oil of Lavandula angustifolia on Isoproterenol-induced Acute Myocardial Infarction in Rat.

    PubMed

    Ziaee, Mojtaba; Khorrami, Arash; Ebrahimi, Maryam; Nourafcan, Hassan; Amiraslanzadeh, Masoumeh; Rameshrad, Maryam; Garjani, Mehraveh; Garjani, Alireza

    2015-01-01

    Myocardial infarction (MI) is a common presentation of the ischemic heart disease. Lavandula angustifolia is an herbaceous plant with antioxidative effects. This study was designed to investigate the cardioprotective effects of lavandula angustifolia essential oil against isoproterenol-induced MI in rats. The dried sample was subjected to hydrodistillation by using a Clevenger and the oils were dried over anhydrous Na2SO4. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the essential oil. MI was induced by subcutaneous injection of Isoproterenol (100 mg/Kg) for 3 consecutive days at an interval of 24 h. The essential oil was given intraperitoneally every 24 h started at MI induction. Following anesthesia, hemodynamic parameters were measured. After sacrificing the animals, the hearts were removed to measure the heart to body weight ratio and histopathological examination. Myeloperoxidase (MPO) and Malondialdehyde (MDA) were measured in heart tissues for evaluating the activity of neutrophils and lipid peroxidation, respectively. The essential oil amended ECG pattern by suppressing ST-segment elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly decreased heart to body weight ratio (P<0.001) and the elevation of MDA and MPO in myocardium, it also increased dp/dtmax from 2793 ± 210 to 4488 ± 253 mmHg/sec (P<0.001), and 20 mg/Kg of it significantly lowered LVEDP from 14 ± 3.43 to 4.3 ± 0.83 mmHg (P<0.001).The results demonstrated that L. angustifolia protects myocardium against isoproterenol-induced MI that it could be related to its antioxidant properties. PMID:25561934

  1. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat

    PubMed Central

    Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

    2015-01-01

    Baicalin belongs to glucuronic acid glycosides and after hydrolysisbaicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. PMID:26617721

  2. Cardioprotective effect of methanolic extract of Marrubium vulgare L. on isoproterenol-induced acute myocardial infarction in rats.

    PubMed

    Yousefi, Keyvan; Soraya, Hamid; Fathiazad, Fatemeh; Khorrami, Arash; Hamedeyazdan, Sanaz; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2013-08-01

    Isoproterenol injection (100 mg/kg; sc) produced changes in ECG pattern including ST-segment elevation and suppressed R-amplitude. The methanolic extract of M. vulgare at doses of 10, 20, and 40 mg/kg significantly amended the ECG changes. A severe myocardial necrosis and edematous along with a sharp reduction in the arterial blood pressure, left ventricular contractility (LVdP/dt(max or min)), but a marked increase in the left ventricular end-diastolic pressure (LVEDP) were seen in the isoproterenol group. All parameters were significantly improved by the extract treatment. The extract (10 mg/kg) strongly increased LVdP/dt(max). Similarly, treatment with 40 mg/kg of M. vulgare lowered the elevated LVEDP and the heart to body weight ratio. In addition to in vitro antioxidant activity, the extract suppressed markedly the elevation of malondialdehyde levels both in serum and in myocardium. The results demonstrate that M. vulgare protects myocardium against isoproterenol-induced acute myocardial infarction and suggest that the effects could be related to antioxidant activities. PMID:24228389

  3. The universe as seen by ISO'

    NASA Astrophysics Data System (ADS)

    1998-10-01

    Nearly 400 hundred infrared astronomers will attend a conference in Paris from October the 20th to the 23rd to review and discuss the latest results from the European Infrared Space Telescope, ISO. This will be the first major scientific conference devoted to ISO since the end of its in-orbit mission last May. Thus, it's a long-awaited occasion for the scientists to come to conclusions and start picturing the infrared face of the universe in detail. The meeting, entitled "The Universe as seen by ISO", will be held at UNESCO, Place de Fontenoy, 75007-PARIS where nearly 300 scientific papers ranging over all fields of Astronomy, from Solar System to Cosmology, will be presented and analysed by infrared astronomers. Press interested in the ISO results presentations are invited to attend the conference and to contact Monica Salomone, the ISO press representative at the registration desk. For further information, please contact: ESA Public Relations Division Tel: +33(0)1.53.69.7155 Fax: +33(0)1.53.69.7690 Background The infrared universe is relatively poorly known because infrared light comes from dusty and cold regions that are invisible to other telescopes. ISO, the best infrared space telescope so far, finally has swept away the dust and seen all the way through. ISO scientists, therefore, are ready for surprises. The recent discovery by ISO of the presence of water throughout the universe was already a hint of what is still to come. More findings can be expected from this meeting, and a few results are already summarized below. Rings of Andromeda "ISO unveils the hidden rings of Andromeda " The Andromeda galaxy, one of the closest companions of our own galaxy, has been hiding from the astronomers' eyes one of its secrets: while always considered a typical spiral galaxy, ISO sees it now as a spectacular ringed galaxy. Andromeda is thus structured in multiple concentric rings, made of very cold dust --at about -260 degree C--. The cold dust cannot be seen by optical

  4. Introduction to the Infrared Space Observatory (ISO)

    NASA Technical Reports Server (NTRS)

    Kessler, M. F.; Sibille, F.

    1989-01-01

    The Infrared Space Observatory (ISO) is an astronomical satellite, which will operate at infrared wavelengths (2.5 to 200 microns) for a period of at least 18 months. Imaging, spectroscopic, photometric and polarimetric observations will be obtained by four scientific instruments in the focal plane of its 60-cm diameter, cryogenically-cooled telescope. Two-thirds of ISO's observing time will be available to the astronomical community. ISO is a fully approved and funded project of the European Space Agency (ESA) with a foreseen launch date of May 1993.

  5. ISAP: ISO Spectral Analysis Package

    NASA Astrophysics Data System (ADS)

    Ali, Babar; Bauer, Otto; Brauher, Jim; Buckley, Mark; Harwood, Andrew; Hur, Min; Khan, Iffat; Li, Jing; Lord, Steve; Lutz, Dieter; Mazzarella, Joe; Molinari, Sergio; Morris, Pat; Narron, Bob; Seidenschwang, Karla; Sidher, Sunil; Sturm, Eckhard; Swinyard, Bruce; Unger, Sarah; Verstraete, Laurent; Vivares, Florence; Wieprecht, Ecki

    2014-03-01

    ISAP, written in IDL, simplifies the process of visualizing, subsetting, shifting, rebinning, masking, combining scans with weighted means or medians, filtering, and smoothing Auto Analysis Results (AARs) from post-pipeline processing of the Infrared Space Observatory's (ISO) Short Wavelength Spectrometer (SWS) and Long Wavelength Spectrometer (LWS) data. It can also be applied to PHOT-S and CAM-CVF data, and data from practically any spectrometer. The result of a typical ISAP session is expected to be a "simple spectrum" (single-valued spectrum which may be resampled to a uniform wavelength separation if desired) that can be further analyzed and measured either with other ISAP functions, native IDL functions, or exported to other analysis package (e.g., IRAF, MIDAS) if desired. ISAP provides many tools for further analysis, line-fitting, and continuum measurements, such as routines for unit conversions, conversions from wavelength space to frequency space, line and continuum fitting, flux measurement, synthetic photometry and models such as a zodiacal light model to predict and subtract the dominant foreground at some wavelengths.

  6. ISO 14001 ENVIRONMENTAL MANAGEMENT SYSTEMS FOR GOVERNMENT

    EPA Science Inventory

    This presentation provides an overview of the document, ISO 14001 - A Tool for Supporting Government Environmental Programs and Policies, recently published by USEPA/s Office of Research and Development. It is an informational document, explaining the backjground and development ...

  7. The New ISO Standard for Solar Filters

    NASA Astrophysics Data System (ADS)

    Chou, B. R.

    2015-11-01

    The contents of the new ISO standard for solar filters are reviewed and the rationale for its transmittance requirements are presented. The standard is scheduled for a final approval ballot in late 2014.

  8. Cardioprotective Effects of Lagenaria siceraria Fruit Juice on Isoproterenol-induced Myocardial Infarction in Wistar Rats: A Biochemical and Histoarchitecture Study

    PubMed Central

    Upaganlawar, A; Balaraman, R

    2011-01-01

    The present study was designed to evaluate the cardioprotective effects of Lagenaria siceraria fruit juice in isoproterenol-induced myocardial infarction. Rats injected with isoproterenol (200 mg/kg, s.c.) showed a significant increase in the levels of serum uric acid, tissue Na++ and Ca++ ions and membrane-bound Ca+2-ATPase activity. A significant decrease in the levels of serum protein, tissue K+ ion, vitamin E level, and the activities of Na+/K+-ATPase and mg+2-ATPase was observed. Isoproterenol injected rats also showed a significant increase in the intensity of lactate dehydrogenase isoenzyme and histopathologic alterations in the heart. Treatment with L. siceraria fruit juice (400 mg/kg/day, p.o.) for 30 days and administration of isoproterenol on 29th and 30th days showed a protective effect on altered biochemical and histopathologic changes. These findings indicate the cardioprotective effect of L. siceraria fruit juice in isoproterenol-induced myocardial infarction in rats. PMID:22224036

  9. Calcium and zinc dyshomeostasis during isoproterenol-induced acute stressor state

    PubMed Central

    Shahbaz, Atta U.; Zhao, Tieqiang; Zhao, Wenyuan; Johnson, Patti L.; Ahokas, Robert A.; Bhattacharya, Syamal K.; Sun, Yao; Gerling, Ivan C.

    2011-01-01

    Acute hyperadrenergic stressor states are accompanied by cation dyshomeostasis, together with the release of cardiac troponins predictive of necrosis. The signal-transducer-effector pathway accounting for this pathophysiological scenario remains unclear. We hypothesized that a dyshomeostasis of extra- and intracellular Ca2+ and Zn2+ occurs in rats in response to isoproterenol (Isop) including excessive intracellular Ca2+ accumulation (EICA) and mitochondrial [Ca2+]m-induced oxidative stress. Contemporaneously, the selective translocation of Ca2+ and Zn2+ to tissues contributes to their fallen plasma levels. Rats received a single subcutaneous injection of Isop (1 mg/kg body wt). Other groups of rats received pretreatment for 10 days with either carvedilol (C), a β-adrenergic receptor antagonist with mitochondrial Ca2+ uniporter-inhibiting properties, or quercetin (Q), a flavonoid with mitochondrial-targeted antioxidant properties, before Isop. We monitored temporal responses in the following: [Ca2+] and [Zn2+] in plasma, left ventricular (LV) apex, equator and base, skeletal muscle, liver, spleen, and peripheral blood mononuclear cells (PBMC), indices of oxidative stress and antioxidant defenses, mitochondrial permeability transition pore (mPTP) opening, and myocardial fibrosis. We found ionized hypocalcemia and hypozincemia attributable to their tissue translocation and also a heterogeneous distribution of these cations among tissues with a preferential Ca2+ accumulation in the LV apex, muscle, and PBMC, whereas Zn2+ declined except in liver, where it increased corresponding with upregulation of metallothionein, a Zn2+-binding protein. EICA was associated with a simultaneous increase in tissue 8-isoprostane and increased [Ca2+]m accompanied by a rise in H2O2 generation, mPTP opening, and scarring, each of which were prevented by either C or Q. Thus excessive [Ca2+]m, coupled with the induction of oxidative stress and increased mPTP opening, suggests that this

  10. Calcium and zinc dyshomeostasis during isoproterenol-induced acute stressor state.

    PubMed

    Shahbaz, Atta U; Zhao, Tieqiang; Zhao, Wenyuan; Johnson, Patti L; Ahokas, Robert A; Bhattacharya, Syamal K; Sun, Yao; Gerling, Ivan C; Weber, Karl T

    2011-02-01

    Acute hyperadrenergic stressor states are accompanied by cation dyshomeostasis, together with the release of cardiac troponins predictive of necrosis. The signal-transducer-effector pathway accounting for this pathophysiological scenario remains unclear. We hypothesized that a dyshomeostasis of extra- and intracellular Ca2+ and Zn2+ occurs in rats in response to isoproterenol (Isop) including excessive intracellular Ca2+ accumulation (EICA) and mitochondrial [Ca2+]m-induced oxidative stress. Contemporaneously, the selective translocation of Ca2+ and Zn2+ to tissues contributes to their fallen plasma levels. Rats received a single subcutaneous injection of Isop (1 mg/kg body wt). Other groups of rats received pretreatment for 10 days with either carvedilol (C), a β-adrenergic receptor antagonist with mitochondrial Ca2+ uniporter-inhibiting properties, or quercetin (Q), a flavonoid with mitochondrial-targeted antioxidant properties, before Isop. We monitored temporal responses in the following: [Ca2+] and [Zn2+] in plasma, left ventricular (LV) apex, equator and base, skeletal muscle, liver, spleen, and peripheral blood mononuclear cells (PBMC), indices of oxidative stress and antioxidant defenses, mitochondrial permeability transition pore (mPTP) opening, and myocardial fibrosis. We found ionized hypocalcemia and hypozincemia attributable to their tissue translocation and also a heterogeneous distribution of these cations among tissues with a preferential Ca2+ accumulation in the LV apex, muscle, and PBMC, whereas Zn2+ declined except in liver, where it increased corresponding with upregulation of metallothionein, a Zn2+-binding protein. EICA was associated with a simultaneous increase in tissue 8-isoprostane and increased [Ca2+]m accompanied by a rise in H2O2 generation, mPTP opening, and scarring, each of which were prevented by either C or Q. Thus excessive [Ca2+]m, coupled with the induction of oxidative stress and increased mPTP opening, suggests that this

  11. ISO 9000 and Creativity: Potential Advantages of Implementing ISO in Community Colleges

    ERIC Educational Resources Information Center

    Alkeaid, Adel

    2007-01-01

    The purpose of this paper is to examine the relationship between the ISO 9000 standard and creativity. In this paper, the researcher tries to answer the following questions: Which learning theories best foster creative thought? Is creativity more behaviorist or constructivist? Where does ISO 9000 fit in the continuum from behaviorism to…

  12. Isoproterenol regulates CD44 expression in gastric cancer cells through STAT3/MicroRNA373 cascade.

    PubMed

    Wei, Bo; Sun, Xiaoyan; Geng, Zhijun; Shi, Ming; Chen, Zhida; Chen, Lin; Wang, Yongan; Fu, Xiaobing

    2016-10-01

    Gastric cancer is a heterogeneous disease, and stem cells are thought to be the cell of origin contributed to this malignancy. However, studies with breast and intestinal cancer models show non-stem cancer cells can change their surface phenotype and convert into tumor-initiating cells induced by the signals emanating from surrounding tumor microenvironment. Here, we show that CD44 was expressed at different levels in gastric metastases compared with primary tumors, and also negatively correlated with the expression of miR-373. By using a panel of human gastric cancer cell lines and analysis of archived data from The Cancer Genomics Altas (TCGA) database, we verified the inverse correlation between CD44 and miR-373. Furthermore, the stress-associated hormone, isoproterenol, could increase the expression levels of "stem"-related proteins, such as CD44, Nanog, and Rex-1, and induce chemoresistance in gastric cancer cells. Transfection with miR-373, however, reversed not only the effect of isoproterenol on phenotypic conversion but also its effect on drug sensitivity. Isoproterenol triggered downstream target STAT3 mainly through β2-adrenergic receptors (β2-ARs). Activated STAT3 functioned as a miR-373 suppressor by binding to its promoter, which forms a positive feedback circuit to maintain CD44 activity and direct the phenotypic conversion from CD44(low) to CD44(hi) expression. Our data suggest an important role of β2-AR/STAT3/miR-373 signaling on the transformation of gastric cancer cells. This study also suggests a potential therapeutic or preventive treatment for gastric cancer patients who are especially prone to psychosocial stress. PMID:27512943

  13. Effects of caffeine, halothane, succinylcholine, phenylephrine and isoproterenol on myocardial force of contraction of malignant hyperthermia susceptible swine.

    PubMed

    Scholz, J; Roewer, N; Rum, U; Schmitz, W; Scholz, H; Schulte am Esch, J

    1991-05-01

    The effects of caffeine, halothane, succinylcholine, phenylephrine and isoproterenol on force of contraction were studied in electrically driven (0.2 Hz) trabeculae isolated from the right ventricles of the hearts of malignant hyperthermia susceptible (MHS) and healthy control (nMHS) swine. Caffeine (0.1-10 mmol/l) had positive inotropic effects, amounting to 275 +/- 35% of control in nMHS and 268 +/- 34% in MHS (n = 16). Halothane (0.25-4 vol%) decreased the force of contraction maximally to 52 +/- 4% in nMHS and 51 +/- 5% of control in MHS (n = 16). Propranolol did not change these effects. Succinylcholine (0.1-10000 mumol/l) had a small positive inotropic effect in both groups, which was blocked by propranolol. Phenylephrine (0.1-300 mumol/l) increased the force of contraction maximally to 188 +/- 24% of control in nMHS and to 193 +/- 23% in MHS (n = 16). The inotropic effect was blocked by prazosin but not by succinylcholine (1 mmol/l). Isoproterenol (0.01-10 mumol/l) had a positive inotropic effect of maximally 275 +/- 21% of control in nMHS and 396 +/- 31% in MHS (n = 17) (P less than 0.05). Succinylcholine potentiated this effect, and propranolol shifted the concentration-response curves to the right. We conclude that caffeine, halothane, succinylcholine and phenylephrine have similar inotropic effects in the hearts of nMHS and MHS, whereas isoproterenol has a significantly greater effect in MHS than in nMHS. PMID:1853693

  14. Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats.

    PubMed

    Abbas, Amr M

    2016-09-01

    Myocardial infarction (MI) is a common cause of mortality worldwide. Isorhapontigenin is a derivative of stilbene with chemical structure similar to resveratrol. The omega-3 fatty acids (FA) have beneficial effects on neurodegenerative, inflammatory, and cardiovascular diseases. The aim of this study was to investigate the effects of pretreatment with isorhapontigenin and omega-3 FA on rat model of isoproterenol-induced MI. Fifty-six rats were divided into seven groups: normal, normal + isorhapontigenin, normal + omega-3 FA, MI, MI + isorhapontigenin, MI + omega-3 FA, and MI + isorhapontigenin + omega-3 FA. Serum levels of cardiac marker enzymes [lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)], cardiac troponin I (cTnI), inflammatory markers [tumor necrosis factor-alpha (TNF-α) and interleukin-6], and lipid profile [triglycerides, total cholesterol (T.Ch), high and low density lipoproteins (HDL, LDL), and phospholipids] as well as cardiac levels of malondialdehyde and anti-oxidants [reduced glutathione (GSH), superoxide dismutase (SOD), and catalase)] were measured in all rats. ECG and histopathological examination were performed. Isoproterenol caused a significant elevation of ST segment, decreased R wave amplitude, HDL, and anti-oxidants, and increased LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, triglycerides, T.Ch, LDL, and phospholipids. Omega-3 FA or isorhapontigenin significantly decreased the ST segment elevation, LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, and phospholipids and increased R wave amplitude and anti-oxidants. The effects of combined omega-3 FA and isorhapontigenin were more significant than either of them alone. Therefore, we conclude that omega-3 FA and isorhapontigenin have a cardioprotective effect on rats with isoproterenol-induced MI through their anti-oxidant and anti-inflammatory actions. PMID:27193109

  15. Transgenic overexpression of transient receptor potential vanilloid subtype 1 attenuates isoproterenol-induced myocardial fibrosis in mice.

    PubMed

    Wang, Qiang; Zhang, Yunrong; Li, De; Zhang, Yan; Tang, Bing; Li, Gang; Yang, Yongjian; Yang, Dachun

    2016-08-01

    Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel with high permeability to Ca2+. Intracellular Ca2+ signaling is an essential regulator of endothelial nitric oxide (NO) synthase (eNOS) that plays a beneficial role in myocardial fibrosis. The aim of the present study was to determine the role of TRPV1 in isoproterenol-induced myocardial fibrosis. Transgenic mice overexpressing TRPV1 were generated on a C57BL/6J genetic background. An animal model of myocardial fibrosis was created by subcutaneously injecting the mice with isoproterenol. We found that the wild-type mice exhibited a significant increase in heart/body weight ratio, left ventricle/body weight ratio, left ventricular end-diastolic pressure (LVEDP), the cardiac fibrotic lesion area and collagen content, as well as a marked decrease in eNOS phosphorylation and NO/cyclic guanosine monophosphate (cGMP) levels at 2 weeks after the administration of isoproterenol (all p<0.01). However, these changes were significantly attenuated in the TRPV1 transgenic mice (p<0.05 or p<0.01). Moreover, the beneficial effects on myocardial fibrosis exerted by the overexpression of TRPV1 were attenuated by the administration of the eNOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) (all p<0.05). Similar anti-fibrotic effects were observed in in vitro experiments with primary cultured cardiac fibroblasts. The findings of our study suggest that TRPV1 overexpression attenuates isoproterenol‑induced myocardial fibrosis. PMID:27314441

  16. Hemodynamic and regional blood flow distribution responses to dextran, hydralazine, isoproterenol and amrinone during experimental cardiac tamponade

    SciTech Connect

    Millard, R.W.; Fowler, N.O.; Gabel, M.

    1983-06-01

    Four different interventions were examined in dogs with cardiac tamponade. Infusion of 216 to 288 ml saline solution into the pericardium reduced cardiac output from 3.5 +/- 0.3 to 1.7 +/- 0.2 liters/min as systemic vascular resistance increased from 4,110 +/- 281 to 6,370 +/- 424 dynes . s . cm-5. Left ventricular epicardial and endocardial blood flows were 178 +/- 13 and 220 +/- 12 ml/min per 100 g, respectively, and decreased to 72 +/- 14 and 78 +/- 11 ml/min per 100 g with tamponade. Reductions of 25 to 65% occurred in visceral and brain blood flows and in a composite brain sample. Cardiac output during tamponade was significantly increased by isoproterenol, 0.5 microgram/kg per min intravenously; hydralazine, 40 mg intravenously; dextran infusion or combined hydralazine and dextran, but not by amrinone. Total systemic vascular resistance was reduced by all interventions. Left ventricular epicardial flow was increased by isoproterenol, hydralazine and the hydralazine-dextran combination. Endocardial flow was increased by amrinone and the combination of hydralazine and dextran. Right ventricular myocardial blood flow increased with all interventions except dextran. Kidney cortical and composite brain blood flows were increased by both dextran alone and by the hydralazine-dextran combinations. Blood flow to small intestine was increased by all interventions as was that to large intestine by all except amrinone and hydralazine. Liver blood flow response was variable. The most pronounced hemodynamic and tissue perfusion improvements during cardiac tamponade were effected by combined vasodilation-blood volume expansion with a hydralazine-dextran combination. Isoproterenol had as dramatic an effect but it was short-lived. Amrinone was the least effective intervention.

  17. Agonist-trafficking and hallucinogens.

    PubMed

    González-Maeso, Javier; Sealfon, Stuart C

    2009-01-01

    Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT(2A) receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs. PMID:19275609

  18. Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats

    PubMed Central

    2012-01-01

    Background and the purpose of the study The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil) on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI). Methods The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG's TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used to induce MI. Results Phytochemical screening indicated the presence of phenolic compounds (5.36%) and flavonoids (1.86%). Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium. Conclusion The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities. PMID:23351503

  19. Agonist binding to β-adrenergic receptors on human airway epithelial cells inhibits migration and wound repair.

    PubMed

    Peitzman, Elizabeth R; Zaidman, Nathan A; Maniak, Peter J; O'Grady, Scott M

    2015-12-15

    Human airway epithelial cells express β-adrenergic receptors (β-ARs), which regulate mucociliary clearance by stimulating transepithelial anion transport and ciliary beat frequency. Previous studies using airway epithelial cells showed that stimulation with isoproterenol increased cell migration and wound repair by a cAMP-dependent mechanism. In the present study, impedance-sensing arrays were used to measure cell migration and epithelial restitution following wounding of confluent normal human bronchial epithelial (NHBE) and Calu-3 cells by electroporation. Stimulation with epinephrine or the β2-AR-selective agonist salbutamol significantly delayed wound closure and reduced the mean surface area of lamellipodia protruding into the wound. Treatment with the β-AR bias agonist carvedilol or isoetharine also produced a delay in epithelial restitution similar in magnitude to epinephrine and salbutamol. Measurements of extracellular signal-regulated kinase phosphorylation following salbutamol or carvedilol stimulation showed no significant change in the level of phosphorylation compared with untreated control cells. However, inhibition of protein phosphatase 2A activity completely blocked the delay in wound closure produced by β-AR agonists. In Calu-3 cells, where CFTR expression was inhibited by RNAi, salbutamol did not inhibit wound repair, suggesting that β-AR agonist stimulation and loss of CFTR function share a common pathway leading to inhibition of epithelial repair. Confocal images of the basal membrane of Calu-3 cells labeled with anti-β1-integrin (clone HUTS-4) antibody showed that treatment with epinephrine or carvedilol reduced the level of activated integrin in the membrane. These findings suggest that treatment with β-AR agonists delays airway epithelial repair by a G protein- and cAMP-independent mechanism involving protein phosphatase 2A and a reduction in β1-integrin activation in the basal membrane. PMID:26491049

  20. [Update to ISO 15189:2012, and future prospects].

    PubMed

    Shimoda, Katsuji; Kubono, Katsuo

    2014-06-01

    ISO (the International Organization for Standardization) is a worldwide federation of national standard bodies (ISO member bodies). The work of preparing international standards is normally carried out through ISO technical committees. ISO 15189 was prepared by Technical Committee ISO/TC 212, clinical laboratory testing, and in vitro diagnostic test systems. This third edition replaces the second edition (ISO 15189:2007), which was technically revised. Medical laboratory services are essential for patient care and, therefore, have to be available to meet the needs of all patients and the clinical personnel responsible for the care of those patients. PMID:25151783

  1. Protective Effects of Berberine on Isoproterenol-Induced Acute Myocardial Ischemia in Rats through Regulating HMGB1-TLR4 Axis

    PubMed Central

    Zhang, Tianzhu; Yang, Shihai; Du, Juan

    2014-01-01

    Berberine, an isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis (Huanglian), has been shown to display a wide array of pharmacological activities. The present study was to investigate the effects of berberine against myocardial ischemia produced in rats by isoproterenol. 50 male Sprague-Dawley rats were randomized equally into five groups: a control group, an untreated model group, berberine (30, 60 mg/kg) treatment, or propranolol (30 mg/kg). Rats were treated for 12 days and then given isoproterenol, 85 mg/kg for 2 consecutive days by subcutaneous injection. ST-segment elevation was measured after the last administration. Serum levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured after the rats were sacrificed. The hearts were excised for determining heart weight index, microscopic examination, high mobility group box 1 (HMGB1), toll-like receptor (TLR4), prodeath protein (Bax), antideath protein (Bcl-2), and tumor necrosis factor (TNF-α) protein were determined by western blot. Berberine decreased the ST elevation induced by acute myocardial ischemia, and decreased serum levels of CK-MB, LDH, TNF-α, and IL-6. Berberine increased total superoxide dismutase (T-SOD) activity and decreased malondialdehyde (MDA) content in myocardial tissue. Berberine can regulate HMGB1-TLR4 axis to protect myocardial ischemia. PMID:25477998

  2. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

    PubMed

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-01-01

    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations. PMID:27138239

  3. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors

    PubMed Central

    Koshimizu, Taka-aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-01-01

    Reducing Na+ in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na+-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na+ sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na+ increased cell surface [3H]AVP binding and decreased receptor internalization. Substitution of Na+ by Cs+ or NH4+ inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na+ over Cs+. Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations. PMID:27138239

  4. Yeast mutants overproducing iso-cytochromes c

    SciTech Connect

    Sherman, F.; Cardillo, T.S.; Errede, B.; Friedman, L.; McKnight, G.; Stiles, J.I.

    1980-01-01

    For over 15 years, the iso-cytochrome c system in the yeast Saccharomyces cerevisiae has been used to investigate a multitude of problems in genetics and molecular biology. More recently, attention has been focused on using mutants for examining translation and transcriptional processes and for probing regulatory regions governing gene expression. In an effort to explore regulatory mechanisms and to investigate mutational alterations that lead to increased levels of gene products, we have isolated and characterized mutants that overproduce cytochrome c. In this paper we have briefly summarized background information of some essential features of the iso-cytochrome c system and we have described the types of mutants that overproduce iso-1-cytochrome c or iso-2-cytochrome c. Genetic procedures and recombinant DNA procedures were used to demonstrate that abnormally high amounts of gene products occur in mutants as result of duplications of gene copies or of extended alteration of regulatory regions. The results summarized in this paper point out the requirements of gross mutational changes or rearrangements of chromosomal segments for augmenting gene products.

  5. Infrared Space Observatory (ISO) Data Analysis

    NASA Technical Reports Server (NTRS)

    Joseph, Robert D.; Sanders, David B.; Stockton, Alan; Hu, Esther

    1999-01-01

    Joseph is an ISO Co-Investigator. His Guaranteed Time Observations include both a major programme for which he is the Principal Investigator, and a number of other prgrammes in collaboration with other ISPHOT Co-Investigators, David Sanders, Alan Stockton, and Esther Hu.

  6. Enthusiasm for Europe's space telescope ISO

    NASA Astrophysics Data System (ADS)

    1996-11-01

    "Are the most luminous galaxies powered by extreme rates of star formation, or do they harbour black-hole-powered active nuclei as well?" Scientists lead by Reinhard Genzel at Max Planck Institut fur extra terrestrische Physik in Garching, Germany, have used ISO's Short Wavelength Spectrometer to give an answer. Writing in the London journal Nature, an independent commentator, Gerry Gilmore of the Institute of Astronomy in Cambridge, considers that their papers in Astronomy and Astrophysics give a clear answer to this question. The "remarkable result" according to Gilmore is that none of three ultra-luminous infrared galaxies studied by ISO requires an active nucleus to account for the emissions, which arise from rapid star formation. About another ISO target Gilmore writes: "In one lovely example, of two intersecting disk galaxies known as the Antennae, it is even possible to resolve the spot where the two disks currently cross, and to see the progression of star formation across the disk as the two galaxies orbit through each other." (Nature, 21 November 1996, p. 211) One year after its launch, ISO is exceptionally popular among astronomers, not only in Europe but worldwide. A panel of American astronomers, reporting to NASA on the scientific merits of eight astrophysical space missions, gives ISO the highest ranking and calls it "the major infrared mission of the decade". At a time when NASA is reducing its budgets for some astrophysical missions, its funding of ISO-related research is increasing. The demand for a share in ISO's unique view of the infrared universe is insatiable. ESA has been overwhelmed by new proposals for observations, coming from 511 groups of astronomers in ESA's own Member States and in the USA and Japan. Although ISO is extremely efficient, performing an average of 45 observations a day, it could not cope with 16,000 observations requested as additions to ISO's already busy programme for 1997. The time allocation committee has had to turn

  7. Regulation of Activator Protein-1 by 8-iso-Prostaglandin E{sub 2} in a Thromboxane A{sub 2} Receptor-Dependent and -Independent Manner

    SciTech Connect

    Weber, Thomas J.; Markillie, Lye MENG.

    2003-05-01

    The thromboxane A{sub 2} (TXA{sub 2}) receptor (TP) is represented by two alternatively spliced forms, termed the platelet/placental (TP-P) and endothelial (TP-E) type receptors. Experimental evidence suggests that TP isoforms may be regulated by novel ligands termed the isoprostanes, which paradoxically act as TP agonists in smooth muscle and TP antagonists in platelet preparations. Here we have investigated whether prototypical isoprostanes (8-iso-PG{sub 2{sub {alpha}}} and 8-iso-PGE{sub 2}) regulate the activity of TP isoforms expressed in Chinese Hamster Ovary (CHO) cells using activator protein-1 (AP-1)-luciferase activity as a reporter. AP-1-luciferase activity was increased by a TP agonist (U46619) in CHO cells transfected with the human TP-P and TP-E receptors and this response was fully inhibited by TP antagonists (ISAP, SQ29,548). AP-1-luciferase activity was potently (nM) increased by 8-iso-PGE2 in CHO TP-P and TP-E cells, and this response was partially inhibited by cotreatment of cells with TP antagonists, while 8-iso-PGF{sub 2{sub {alpha}}} was without effect. Cyclooxygenase inhibitors did not abolish 8-iso-PGE{sub 2} mediated AP-1-luciferase activity, indicating that this response is not dependent on de novo TXA2 biosynthesis. Interestingly, 8-iso-PGE{sub 2}-mediated AP-1-luciferase activity was near maximal in naive cells between 1-10 nM concentrations, and this response was not inhibited by TP antagonist or reproduced by agonists for TP or EP1/EP3 receptors. These observations (1) support a role for novel ligands in the regulation of TP-dependent signaling, (2) indicate that TP-P and TP-E couple to AP-1, (3) provide further evidence that isoprostanes function as TP agonists in a cell-type specific fashion, and (4) indicate that additional targets regulated by 8-iso-PGE{sub 2} couple to AP-1.

  8. The Relationship between the Training Function and ISO-9000 Registration.

    ERIC Educational Resources Information Center

    Maxwell, Randy C.; Jost, Karen L.

    ISO 9000 is one of a series of international standards providing guidelines and governing quality of products and services. The ISO 9000 certification demonstrates the capability of a supplier to control the processes that determine the acceptability of the product or service being supplied. This paper focuses on the training aspects of ISO 9000…

  9. First Results from the ISO-IRAS Faint Galaxy Survey

    NASA Technical Reports Server (NTRS)

    Wolstencroft, R. D.; Wehrle, A. E.; Levine, D. A.

    1997-01-01

    We present the first result from the ISO-IRAS Faint Galaxy Survey (IIFGS), a program designed to obtain ISO observations of the most distant and luminous galaxies in the IRAS Faint Source Survey by filling short gaps in the ISO observing schedule with pairs of 12um ISOCAM AND 90um ISOPHOT observation.

  10. ISO's analysis of Comet Hale-Bopp

    NASA Astrophysics Data System (ADS)

    1997-03-01

    The European Space Agency's Infrared Space Observatory ISO inspected Comet Hall-Bopp during the spring and autumn of 1996. The need to keep ISO's telescope extremely cold restricts the spacecraft's pointing in relation to the Sun and the Earth and it ruled out observations at other times. The analyses of the 1996 observations are not yet complete, but already they give new insight into the nature of comets. Comet Hale-Bopp is believed to be a large comet with a nucleus up to 40 kilometres wide. It was discovered in July 1995 by two American astronomers working independently, Alan Hale and Thomas Bopp. At that time, the comet was a billion kilometres away from the Sun, but 200 times brighter than Halley's Comet was, when at a comparable distance. Comet Hale-Bopp will make its closest approach to the Earth on 22 March, and its closest approach to the Sun (perihelion) on 1 April 1997. Some scientific results from ISO The discovery of Comet Hale-Bopp occurred before ISO's launch in November 1995. When first observed by ISO in March and April 1996, the comet was still 700 million kilometres from the Sun, and almost as far from the Earth and ISO. With its privileged view of infrared wavebands inaccessible from the Earth's surface, ISO's photometer ISOPHOT discovered that carbon dioxide was an important constituent of the comet's emissions of vapour.ISOPHOT measured the temperature of the dust cloud around Comet Hale-Bopp. In March 1996, when the comet was still more than 700 million kilometres from the Sun, the dust cloud was at minus 120 degrees C. When ISOPHOT made similar observations in October 1996, the comet was 420 million kilometres from the Sun, and the dust cloud had warmed to about minus 50 degrees C. Intensive observations of Comet Hale-Bopp were also made by ISO's Short-Wave Spectrometer SWS, the Long-Wave Spectrometer LWS, and the ISOPHOT spectrometer PHOT-S. Results are due for publication at the end of March. They will give details about the composition

  11. ISO Results Presented at International Astronomical Union

    NASA Astrophysics Data System (ADS)

    1997-08-01

    Some of the work being presented is collected in the attached ESA Information Note N 25-97, ISO illuminates our cosmic ancestry. A set of six colour images illustrating various aspects have also been released and are available at http://www.estec.esa.nl/spdwww/iso1808.htm or in hard copy from ESA Public Relations Paris (fax:+33.1.5369.7690). These pictures cover: 1. Distant but powerful infrared galaxies 2. A scan across the milky way 3. Helix nebula: the shroud of a dead star 4. Supernova remnant Cassiopeia A 5. Trifid nebula: a dusty birthplace of stars 6. Precursors of stars and planets The International Astronomical Union provides a forum where astronomers from all over the world can develop astronomy in all its aspects through international co-operation. General Assemblies are held every three years. It is expected that over 1600 astronomers will attend this year's meeting, which is being held in Kyoto, Japan from 18-30 August. Further information on the meeting can be found at: www.tenmon.or.jp/iau97/ . ISO illuminates our cosmic ancestry The European Space Agency's Infrared Space Observatory, ISO, is unmatched in its ability to explore and analyse many of the universal processes that made our existence possible. We are children of the stars. Every atom in our bodies was created in cosmic space and delivered to the Sun's vicinity in time for the Earth's formation, during a ceaseless cycle of birth, death and rebirth among the stars. The most creative places in the sky are cool and dusty, and opaque even to the Hubble Space Telescope. Infrared rays penetrating the dust reveal to ISO hidden objects, and the atoms and molecules of cosmic chemistry. "ISO is reading Nature's recipe book," says Roger Bonnet, ESA's director of science. "As the world's only telescope capable of observing the Universe over a wide range of infrared wavelengths, ISO plays an indispensable part in astronomical discoveries that help to explain how we came to exist." This Information Note

  12. Compositional changes in (iso)flavonoids and estrogenic activity of three edible Lupinus species by germination and Rhizopus-elicitation.

    PubMed

    Aisyah, Siti; Vincken, Jean-Paul; Andini, Silvia; Mardiah, Zahara; Gruppen, Harry

    2016-02-01

    The effects of germination and elicitation on (iso)flavonoid composition of extracts from three edible lupine species (Lupinus luteus, Lupinus albus, Lupinus angustifolius) were determined by RP-UHPLC-MS(n). The total (iso)flavonoid content of lupine increased over 10-fold upon germination, with the total content and composition of isoflavonoids more affected than those of flavonoids. Glycosylated isoflavones were the most predominant compounds found in lupine seedlings. Lesser amounts of isoflavone aglycones, including prenylated ones, were also accumulated. Elicitation with Rhizopus oryzae, in addition to germination, raised the content of isoflavonoids further: the total content of 2'-hydroxygenistein derivatives was increased considerably, without increasing that of genistein derivatives. Elicitation by fungus triggered prenylation of isoflavonoids, especially of the 2'-hydroxygenistein derivatives. The preferred positions of prenylation differed among the three lupine species. The change in isoflavone composition increased the agonistic activity of the extracts towards the human estrogen receptors, whereas no antagonistic activity was observed. PMID:26749476

  13. ISO Results Presented at International Astronomical Union

    NASA Astrophysics Data System (ADS)

    1997-08-01

    Some of the work being presented is collected in the attached ESA Information Note N 25-97, ISO illuminates our cosmic ancestry. A set of six colour images illustrating various aspects have also been released and are available at http://www.estec.esa.nl/spdwww/iso1808.htm or in hard copy from ESA Public Relations Paris (fax:+33.1.5369.7690). These pictures cover: 1. Distant but powerful infrared galaxies 2. A scan across the milky way 3. Helix nebula: the shroud of a dead star 4. Supernova remnant Cassiopeia A 5. Trifid nebula: a dusty birthplace of stars 6. Precursors of stars and planets The International Astronomical Union provides a forum where astronomers from all over the world can develop astronomy in all its aspects through international co-operation. General Assemblies are held every three years. It is expected that over 1600 astronomers will attend this year's meeting, which is being held in Kyoto, Japan from 18-30 August. Further information on the meeting can be found at: www.tenmon.or.jp/iau97/ . ISO illuminates our cosmic ancestry The European Space Agency's Infrared Space Observatory, ISO, is unmatched in its ability to explore and analyse many of the universal processes that made our existence possible. We are children of the stars. Every atom in our bodies was created in cosmic space and delivered to the Sun's vicinity in time for the Earth's formation, during a ceaseless cycle of birth, death and rebirth among the stars. The most creative places in the sky are cool and dusty, and opaque even to the Hubble Space Telescope. Infrared rays penetrating the dust reveal to ISO hidden objects, and the atoms and molecules of cosmic chemistry. "ISO is reading Nature's recipe book," says Roger Bonnet, ESA's director of science. "As the world's only telescope capable of observing the Universe over a wide range of infrared wavelengths, ISO plays an indispensable part in astronomical discoveries that help to explain how we came to exist." This Information Note

  14. Promoting Strong ISO 50001 Outcomes with Supportive National Infrastructure

    SciTech Connect

    McKane, Aimee, T.; Siciliano, Graziella; de los Reyes, Pamela

    2015-08-04

    The ISO 50001 standard is a key mechanism for reducing greenhouse gas emissions and improving energy efficiency globally. An increasing number of companies are seeking certification, creating the need for personnel that are competent to conduct ISO 50001 certification audits. The growth of ISO 50001 is expected to accelerate as more companies integrate ISO 50001 into their corporate sustainability strategies and supplier requirements. Robust implementation of ISO 50001 represents an important tool for countries with climate change mitigation goals. Because of its dual focus on continual improvement of an organization’s energy management system (EnMS) and its energy performance improvement, ISO 50001 requires skills of both implementers and certification auditors that are not well-supported by current credentials and training. This paper describes an effort to address skill gaps of certification auditors, a critical factor to ensure that ISO 50001 implementations are robust and result in continued energy performance improvement. A collaboration of governments through the Energy Management Working Group (EMWG), formerly under Global Superior Energy Performance (GSEP), has formed to build workforce capacity for ISO 50001 certification audits. The EMWG is leading the development of an internationally-relevant certification scheme for ISO 50001 Lead Auditor that meets requirements for ISO/IEC 17024 accreditation and ISO 50003 for defining ISO 50001 Lead Auditor competency. Wider availability of competent ISO 50001 Lead Auditors will ultimately increase the impact and market value of ISO 50001 certification and improve consistency of ISO 50001 certification outcomes by establishing a standardized and high level of knowledge and skills globally.

  15. Marrubium vulgare L. methanolic extract inhibits inflammatory response and prevents cardiomyocyte fibrosis in isoproterenol-induced acute myocardial infarction in rats

    PubMed Central

    Yousefi, Keyvan; Fathiazad, Fatemeh; Soraya, Hamid; Rameshrad, Maryam; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2014-01-01

    Introduction: Nowadays, finding new therapeutic compounds from natural products for treatment and prevention of a variety of diseases including cardiovascular disorders is getting a great deal of attention. This approach would result in finding new drugs which are more effective and have fewer side effects than the conventional medicines. The present study was designed to investigate the anti-inflammatory effect of the methanolic extract of Marrubiumvulgare, a popular traditional medicinal herb, on isoproterenol-induced myocardial infarction (MI) in rat model. Methods: Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for two consecutive days was used to induce MI. Then, histopathological changes and inflammatory markers were evaluated. Results: Isoproterenol injection increased inflammatory response, as shown by a significant increase in peripheral neutrophil count, myocardial myeloperoxidase (MPO) activity and serum levels of creatinine kinase-MB (CK-MB) and TNF-α (p<0.001). In the groups treated with 10, 20 and 40 mg/kg of M.vulgare extract serum CK-MB was subsided by 55.4%, 52.2% and 69%, respectively. Also treatment with the extract (40 mg/kg) significantly reduced (p<0.001) MPO activity in MI group. The levels of TNF-α was also considerably declined in the serums of MI group (p<0.001). In addition, peripheral neutrophil count, was significantly lowered by all doses of the extract (p<0.001). Interstitial fibrosis significantly was attenuated in treated groups compared with control MI group. Conclusion: The results of study demonstrate that the M. vulgare extract has strong protective effects against isoproterenol-induced myocardial infarction and it seems possible that this protection is due to its anti-inflammatory effects. PMID:24790895

  16. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat

    PubMed Central

    Sun, Shen-Jie; Wu, Xiao-Peng; Song, Heng-Liang; Li, Gui-Qi

    2015-01-01

    Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, anti-inflammation, etc. The aim of this study was to investigate the potential cardioprotective effects of baicalin ameliorates isoproterenol-induced acute myocardial infarction (AMI) through inducible nitric oxide synthase (iNOS), inflammation, oxidative stress and P38MAPK passageway in rat. Rat model of AMI was induced by isoproterenol (100 mg/kg) and then treated baicalin (various does of baicalin: 1 mg/kg, 10 mg/kg and 100 mg/kg, respectively) for 24 h. Infarct size, the heart weight to body weight ratio and creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) of rats with AMI induced by isoproterenol were used to evaluate curative effect of baicalin on AMI. Meanwhile, iNOS and phosphorylation-p38 MAPK (p-p38) protein expressions, inflammatory factor and oxidative stress were inspected using western blot and commercial kits, respectively. In the present study, pre-treatment with baicalin (10 or 100 mg/kg) significantly ameliorated infarct size, the heart weight to body weight ratio and CK, CK-MB, LDH and cTnT levels in rats with AMI induced by isoproterenol. iNOS protein expression, the serum TNF-α, IL-6, MDA and SOD levels and p-38 protein expressions were significantly suppressed by treatment with baicalin (10 or 100 mg/kg). These results suggest that acute treatment with baicalin ameliorates AMI, iNOS, inflammation, oxidative stress and P38MAPK pathway in rat with AMI induced by isoproterenol. PMID:26885181

  17. Incorporating ISO Metadata Using HDF Product Designer

    NASA Technical Reports Server (NTRS)

    Jelenak, Aleksandar; Kozimor, John; Habermann, Ted

    2016-01-01

    The need to store in HDF5 files increasing amounts of metadata of various complexity is greatly overcoming the capabilities of the Earth science metadata conventions currently in use. Data producers until now did not have much choice but to come up with ad hoc solutions to this challenge. Such solutions, in turn, pose a wide range of issues for data managers, distributors, and, ultimately, data users. The HDF Group is experimenting on a novel approach of using ISO 19115 metadata objects as a catch-all container for all the metadata that cannot be fitted into the current Earth science data conventions. This presentation will showcase how the HDF Product Designer software can be utilized to help data producers include various ISO metadata objects in their products.

  18. ISO TC211 standards on Provenance for Earth science

    NASA Astrophysics Data System (ADS)

    Di, L.; Deng, M.

    2014-12-01

    Data provenance, also called lineage, records the derivation history of a data product. The history could include the algorithms used, the process steps taken, the computing environment run, data sources input to the processes, the organization/person responsible for the product, etc. Provenance provides important information to data users for them to determine the usability and reliability of the product. In the science domain, the data provenance is especially important since scientists need to use the information to determine the scientific validity of a data product and to decide if such a product can be used as the basis for further scientific analysis. Provenance is a kind of metadata. In Earth science domain, the International Organization for Standardization (ISO) Technical Committee 211 (ISO TC 211) have set geospatial metadata standards for geospatial data, including ISO 19115:2003-Metadata, ISO 19115-2:2009-Metadata-Part 2: Extensions for imagery and gridded data, and ISO 19115-1:2014 - Metadata -- Part 1: Fundamentals. ISO 19115 and ISO 19115-1 define the fundamental metadata for documenting geospatial data products, and ISO 19115-2 provides additional metadata classes for imagery and gridded data. ISO 19115-1:2014 is the revised version of ISO 19115:2003. ISO 19115 and ISO 19115-1 define fundamental lineage information classes and subclasses. They miss some key information classes needed for documenting the provenance in the Web service environment, such as the running environment, the algorithms, and software executables. However, ISO 19115-2 extends the lineage model in ISO 19115 and provides additional metadata classes needed for documenting provenance information. The combination of lineage models in ISO 19115 and ISO 19115-2 provides a comprehensive provenance information model needed for the web service environment. Currently the ISO Provence standard is not compatible with W3C Prov standard. The revision of ISO 19115-2 will be started in

  19. Updates to ISO 21348 (determining solar irradiances)

    NASA Astrophysics Data System (ADS)

    Tobiska, W. Kent

    2012-07-01

    The ISO 21348 (Determining Solar Irradiances) International Standard is going through a document update. A consensus solar spectrum, solar indices/proxies descriptions, solar model descriptions, and solar measurement descriptions are among the Annexes that are proposed to the standard. These topics will be reviewed and described. The International Standards Organization (ISO) published IS 21348 in 2007 after 7 years of development by the international scientific community. In ISO, documents are reviewed on a regular basis and reaffirmed, updated, or deleted according to the votes of national delegations represented in ISO. IS 21348 provides guidelines for specifying the process of determining solar irradiances. Solar irradiances are reported through products such as measurement sets, reference spectra, empirical models, theoretical models and solar irradiance proxies or indices. These products are used in scientific and engineering applications to characterize within the natural space environment solar irradiances that are relevant to space systems and materials. Examples of applications using input solar irradiance energy include the determination of atmospheric densities for spacecraft orbit determination, attitude control and re-entry calculations, as well as for debris mitigation and collision avoidance activity. Direct and indirect pressure from solar irradiance upon spacecraft surfaces also affects attitude control separately from atmospheric density effects. Solar irradiances are used to provide inputs for a) calculations of ionospheric parameters, b) photon-induced radiation effects, and c) radiative transfer modeling of planetary atmospheres. Input solar irradiance energy is used to characterize material properties related to spacecraft thermal control, including surface temperatures, reflectivity, absorption and degradation. Solar energy applications requiring a standard process for determining solar irradiance energy include i) solar cell power

  20. ISO 55000: Creating an asset management system.

    PubMed

    Bradley, Chris; Main, Kevin

    2015-02-01

    In the October 2014 issue of HEJ, Keith Hamer, group vice-president, Asset Management & Engineering at Sodexo, and marketing director at Asset Wisdom, Kevin Main, argued that the new ISO 55000 standards present facilities managers with an opportunity to create 'a joined-up, whole lifecycle approach' to managing and delivering value from assets. In this article, Kevin Main and Chris Bradley, who runs various asset management projects, examine the process of creating an asset management system. PMID:26268021

  1. Revision of ISO 15859 Aerospace Fluid Standards

    NASA Technical Reports Server (NTRS)

    Greene, Benjamin; McClure, Mark B.

    2012-01-01

    A detailed review of ISO 15859 "Space Systems - Fluid Characteristics, Sampling and Test Methods" was performed An approach to revising Parts 1-9 and 11-13 was developed and concurred by the NASA Technical Standards Program Office. The approach was to align them with the highest level source documents, and not to program-specific requirements. The updated documents were prepared and presented.

  2. Voltammmetric Determination of Captopril Using Multiwall Carbon Nanotubes Paste Electrode in the Presence of Isoproterenol as a Mediator

    PubMed Central

    Akbari chermini, Sadeghi; Krimi, Hasan; Keyvanfard, Mohsen; Alizad, Khadijeh

    2016-01-01

    The electrocatalytic oxidation of captopril (CAP) was studied by modified carbon nanotubes paste electrode in the presence of isoproterenol (ISPT) using cyclic voltammetry (CV), chronoamperometry and square wave voltammetry (SWV). Also, the values of catalytic rate constant (k), and electron transfer coefficient (α) for CAP were calculated. The mechanism of CA electrochemical behavior at the modified electrode surface was analyzed by various electrochemical methods in the presence of mediator. The prepared modified electrode showed voltammetric responses with high sensitivity for CAP, making it very suitable for the detection of CAP at trace levels. Under the optimized conditions, the peak current was linear to CAP concentration over the concentration range of 0.3 to 90 μmol L−1 using SWV. The detection limit was 0.1 μmol L−1. The proposed method was successfully applied for the determination of CAP in the urine, tablet and patient urine samples. PMID:27610151

  3. Voltammmetric Determination of Captopril Using Multiwall Carbon Nanotubes Paste Electrode in the Presence of Isoproterenol as a Mediator.

    PubMed

    Akbari Chermini, Sadeghi; Krimi, Hasan; Keyvanfard, Mohsen; Alizad, Khadijeh

    2016-01-01

    The electrocatalytic oxidation of captopril (CAP) was studied by modified carbon nanotubes paste electrode in the presence of isoproterenol (ISPT) using cyclic voltammetry (CV), chronoamperometry and square wave voltammetry (SWV). Also, the values of catalytic rate constant (k), and electron transfer coefficient (α) for CAP were calculated. The mechanism of CA electrochemical behavior at the modified electrode surface was analyzed by various electrochemical methods in the presence of mediator. The prepared modified electrode showed voltammetric responses with high sensitivity for CAP, making it very suitable for the detection of CAP at trace levels. Under the optimized conditions, the peak current was linear to CAP concentration over the concentration range of 0.3 to 90 μmol L(-1) using SWV. The detection limit was 0.1 μmol L(-1). The proposed method was successfully applied for the determination of CAP in the urine, tablet and patient urine samples. PMID:27610151

  4. ISO's analysis of Comet Hale-Bopp

    NASA Astrophysics Data System (ADS)

    1997-03-01

    The European Space Agency's Infrared Space Observatory ISO inspected Comet Hall-Bopp during the spring and autumn of 1996. The need to keep ISO's telescope extremely cold restricts the spacecraft's pointing in relation to the Sun and the Earth and it ruled out observations at other times. The analyses of the 1996 observations are not yet complete, but already they give new insight into the nature of comets. Comet Hale-Bopp is believed to be a large comet with a nucleus up to 40 kilometres wide. It was discovered in July 1995 by two American astronomers working independently, Alan Hale and Thomas Bopp. At that time, the comet was a billion kilometres away from the Sun, but 200 times brighter than Halley's Comet was, when at a comparable distance. Comet Hale-Bopp will make its closest approach to the Earth on 22 March, and its closest approach to the Sun (perihelion) on 1 April 1997. Some scientific results from ISO The discovery of Comet Hale-Bopp occurred before ISO's launch in November 1995. When first observed by ISO in March and April 1996, the comet was still 700 million kilometres from the Sun, and almost as far from the Earth and ISO. With its privileged view of infrared wavebands inaccessible from the Earth's surface, ISO's photometer ISOPHOT discovered that carbon dioxide was an important constituent of the comet's emissions of vapour.ISOPHOT measured the temperature of the dust cloud around Comet Hale-Bopp. In March 1996, when the comet was still more than 700 million kilometres from the Sun, the dust cloud was at minus 120 degrees C. When ISOPHOT made similar observations in October 1996, the comet was 420 million kilometres from the Sun, and the dust cloud had warmed to about minus 50 degrees C. Intensive observations of Comet Hale-Bopp were also made by ISO's Short-Wave Spectrometer SWS, the Long-Wave Spectrometer LWS, and the ISOPHOT spectrometer PHOT-S. Results are due for publication at the end of March. They will give details about the composition

  5. Internet sites help untangle ISO 14000

    SciTech Connect

    Bishop, J.

    1996-03-01

    The coming of ISO 14000, the Environmental Quality standard being developed by the International Organization for Standardization, will carry a critical message to manufacturers worldwide: domestic political and regulatory issues inevitably will become secondary to the demands of the international marketplace. In the US, the struggle underway between the Clinton administration and the Republican majority over environmental regulation promises to ease industry`s regulatory burden and lower compliance cost. However, a victory by those fighting for more lenient rules could be a hollow one for US business if the international community, through such mechanisms as ISO 14000, demands compliance with a more stringent environmental standard. Confining one`s business to domestic transactions will not do the trick of avoiding the issue, as manufacturers formally adhering to the international standard likely will demand equally strict compliance from their suppliers. Thus, few companies may be able to escape ISO 14000`s impact, even if they are not involved directly in selling to foreign buyers.

  6. Terminalia arjuna (Roxb.) Wight & Arn. augments cardioprotection via antioxidant and antiapoptotic cascade in isoproterenol induced cardiotoxicity in rats.

    PubMed

    Shukla, Santosh K; Sharma, Suman B; Singh, Usha R; Ahmad, Sayeed; Dwivedi, Shridhar

    2015-12-01

    Worldwide, Ischemic heart disease (IHD) affects a large population. Implication of myocardial infarction (MI) and its multiple pathophysiology in cardiac function is well known. Further, isoproterenol (ISP) is known to induce MI. Today, there is an urgent need for effective drug that could limit the myocardial injury. Therapeutic intervention with antioxidants has been shown useful in preventing the deleterious changes produced by ISP. Here, we investigated the protective effects of oral pre-treatment of hydroalcoholic extract of bark of Terminalia arjuna (HETA) on biochemical and apoptotic changes during cardiotoxicity induced by isoproterenol (ISP) in rats. HETA was orally administered at a dose of 100, 200 and 400 mg/kg body wt., for 30 days with concurrent administration of ISP (85 mg/kg body wt.) on days 28th and 29th at an interval of 24 h. ISP caused deleterious changes in the myocardium and significantly increased (P < 0.05) malondialdehyde, serum glutamate oxaloacitate transaminase, creatine kinase-MB, lactate dehydrogenase and troponin-I. However, it significantly decreased (P < 0.05) glutathione and superoxide dismutase compared to healthy control. Oral pre-treatment of HETA for 30 days significantly decreased (P < 0.05) the biochemical parameters of oxidative stress and cardiac markers as compared to ISP control. Histopathological findings also revealed that architecture of the myocardium was restored towards normal in HETA pre-treated group. Overall, the present study has shown that the hydroalcoholic extract of bark of T. arjuna (HETA) attenuates oxidative stress, apoptosis and improves antioxidant status in ISP-induced cardiotoxicity in rats. PMID:26742326

  7. Synthesis, Pharmacological Characterization, and Structure–Activity Relationship Studies of Small Molecular Agonists for the Orphan GPR88 Receptor

    PubMed Central

    2014-01-01

    GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorders. The signal transduction pathway and receptor functions of GPR88, however, are still largely unknown due to the lack of endogenous and synthetic ligands. In this paper, we report the synthesis of a GPR88 agonist 2-PCCA and its pure diastereomers, which were functionally characterized in both transiently and stably expressing GPR88 HEK293 cells. 2-PCCA inhibited isoproterenol-stimulated cAMP accumulation in a concentration-dependent manner in cells expressing GPR88 but not in the control cells, suggesting that the observed cAMP inhibition is mediated through GPR88 and that GPR88 is coupled to Gαi. 2-PCCA did not induce calcium mobilization in GPR88 cells, indicating no Gαq-mediated response. A structure–activity relationship (SAR) study of 2-PCCA was also conducted to explore the key structural features for GPR88 agonist activity. PMID:24793972

  8. Nedd4 Mediates Agonist-dependent Ubiquitination, Lysosomal Targeting, and Degradation of the β2-Adrenergic Receptor*S⃞

    PubMed Central

    Shenoy, Sudha K.; Xiao, Kunhong; Venkataramanan, Vidya; Snyder, Peter M.; Freedman, Neil J.; Weissman, Allan M.

    2008-01-01

    Agonist-stimulated β2-adrenergic receptor (β2AR) ubiquitination is a major factor that governs both lysosomal trafficking and degradation of internalized receptors, but the identity of the E3 ubiquitin ligase regulating this process was unknown. Among the various catalytically inactive E3 ubiquitin ligase mutants that we tested, a dominant negative Nedd4 specifically inhibited isoproterenol-induced ubiquitination and degradation of the β2AR in HEK-293 cells. Moreover, siRNA that down-regulates Nedd4 expression inhibited β2AR ubiquitination and lysosomal degradation, whereas siRNA targeting the closely related E3 ligases Nedd4-2 or AIP4 did not. Interestingly, β2AR as well as β-arrestin2, the endocytic and signaling adaptor for the β2AR, interact robustly with Nedd4 upon agonist stimulation. However, β2AR-Nedd4 interaction is ablated when β-arrestin2 expression is knocked down by siRNA transfection, implicating an essential E3 ubiquitin ligase adaptor role for β-arrestin2 in mediating β2AR ubiquitination. Notably, β-arrestin2 interacts with two different E3 ubiquitin ligases, namely, Mdm2 and Nedd4 to regulate distinct steps in β2AR trafficking. Collectively, our findings indicate that the degradative fate of the β2AR in the lysosomal compartments is dependent upon β-arrestin2-mediated recruitment of Nedd4 to the activated receptor and Nedd4-catalyzed ubiquitination. PMID:18544533

  9. Total synthesis and evaluation of iso-duocarmycin SA and iso-yatakemycin.

    PubMed

    MacMillan, Karen S; Nguyen, Trinh; Nguyen, Trihn; Hwang, Inkyu; Boger, Dale L

    2009-01-28

    The total synthesis and evaluation of iso-duocarmycin SA (5) and iso-yatakemycin (6), representing key analogues of the corresponding natural products incorporating an isomeric alkylation subunit, are detailed. This pyrrole isomer of the natural alkylation subunit displayed an enhanced reaction regioselectivity and a 2-fold diminished stability. Although still exceptionally potent, the iso-duocarmycin SA derivatives and natural product analogues exhibited a corresponding approximate 3-5-fold reduction in cytotoxic activity [L1210 IC(50) for (+)-iso-duocarmycin SA = 50 pM and for (+)-iso-yatakemycin = 15 pM] consistent with their placement on a parabolic relationship correlating activity with reactivity. The DNA alkylation selectivity of the resulting key natural product analogues was unaltered by the structure modification in spite of the minor-groove presentation of a potential H-bond donor. Additionally, a unique ortho-spirocyclization with such derivatives was explored via the preparation, characterization, and evaluation of 34 that is incapable of the more conventional para-spirocyclization. Although 34 proved sufficiently stable for isolation and characterization, it displayed little stability in protic solvents (t(1/2) = 0.19 h at pH 3, t(1/2) = 0.20 h at pH 7), a pH-independent (H(+) independent) solvolysis rate profile at pH 3/4-7, and a much reduced cytotoxic potency, but a DNA alkylation selectivity and efficiency comparable to those of duocarmycin SA and iso-duocarmycin SA. The implications of these observations on the source of the DNA alkylation selectivity and catalysis for this class of natural products are discussed. PMID:19154178

  10. ISO 639-1 and ISO 639-2: International Standards for Language Codes. ISO 15924: International Standard for Names of Scripts.

    ERIC Educational Resources Information Center

    Byrum, John D.

    This paper describes two international standards for the representation of the names of languages. The first (ISO 639-1), published in 1988, provides two-letter codes for 136 languages and was produced primarily to meet terminological needs. The second (ISO 639-2) appeared in late 1998 and includes three-letter codes for 460 languages. This list…

  11. Kappa Opioid Receptor Agonist and Brain Ischemia

    PubMed Central

    Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

    2014-01-01

    Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

  12. Catalogue of ISO LWS observations of asteroids

    NASA Astrophysics Data System (ADS)

    Hormuth, F.; Müller, T. G.

    2009-04-01

    Context: The long wavelength spectrometer (LWS) onboard the infrared space observatory (ISO) observed the four large main-belt asteroids (1) Ceres, (2) Pallas, (4) Vesta, and (10) Hygiea multiple times. The photometric and spectroscopic data cover the wavelength range between 43 and 197 μm, and are a unique dataset for future investigations and detailed characterisations of these bodies. Aims: The standard ISO archive products, produced through the last post-mission LWS pipeline, were still affected by instrument artefacts. Our goal was to provide the best possible data products to exploit the full scientific potential of these observations. Methods: For all asteroid observations we analysed in detail the dark current, the calibration reference flashes, the space environment effects (glitches), memory effects, tracking influences, and various other sources of uncertainty. We performed a refined reduction of all measurements, corrected for the various effects, and re-calibrated the data. We outline the data reduction process and give an overview of the available data and the quality of the observations. We apply a thermophysical model to the flux measurements to derive far-IR based diameter and albedo values of the asteroids. The measured thermal rotational lightcurve of (4) Vesta is compared to model predictions. Results: The catalogue of LWS (long wavelength spectrometer) observations of asteroids contains 57 manually reduced datasets, including seven non-standard observations, which as such did not have final pipeline products available before. In total, the archive now contains 11 spectral scans and 46 fixed grating measurements with a simultaneous observation at 10 key wavelengths distributed over the full LWS range. The new data products are now accessible via the ISO data archive as highly processed data products (HPDP). Conclusions: The quality of the data products was checked against state-of-the-art thermophysical model predictions and an excellent

  13. Analysis of data from ISO CORRAG program

    SciTech Connect

    Dean, S.W.; Reiser, D.B.

    1998-12-31

    An analysis of the flat panel corrosion rates from the one-year exposures in the ISO CORRAG program has been carried out to determine the extent of correlation between the four metals used in this study. The corrosion rates all showed highly significant correlations when compared on a logarithmic basis. This conversion was necessary to eliminate bias from the correlation of standard deviation with average values. Residual analysis showed that times of wetness accelerated steel, zinc, and copper corrosion more than aluminum. Sulfur dioxide accelerated zinc more than copper, and chloride accelerated steel more than zinc and aluminum, and copper more than aluminum.

  14. Procedure preparation for ISO 9000 certification

    SciTech Connect

    Klement, R.E.

    1995-11-01

    The Kansas City Division (KCD) produces nonnuclear components for nuclear weapons. The company has operated the plant for the US Department of Energy since 1949. Throughout the history of the plant, procedures were written to reflect the nuclear weapons industry best practices, and the facility built a reputation for producing high quality products. In 1991 a critical process team was asked to use Just In Time principles to determine a better way to administrate procedures. By 1992 the team was successful in implementing a full-time centralized procedure group to handle the creation, coordination, review, resolution, and publication of plant-wide administrative and operating procedures. In 1993 AlliedSignal was commissioned by its President and CEO Larry Bossidy to register all of the world-wide sites under the ISO 9000 quality standard. This presented a formidable challenge for the Kansas City Division. Though the independent third-party auditors conceded during a preassessment that the company did in fact build high quality products, the procedures and procedure system did not accurately reflect the current business practices. The purpose of this paper is to share information about the successful implementation of centralized procedure administration and the re-engineering of the procedure system, leading to successful ISO 9001 certification at AlliedSignal Inc., Kansas City Division.

  15. New Dust Features Observed with ISO

    NASA Technical Reports Server (NTRS)

    Tielens, Alexander G. G. M.; Young, Richard E. (Technical Monitor)

    1997-01-01

    This paper will review our current knowledge of circumstellar and interstellar dust with the emphasis on infrared spectroscopy with ISO. Objects embedded in or located behind molecular clouds show a wealth of absorption features due to simple molecules in an icy mantle. The SWS on ISO has provided us, for the first time, with complete 3-45 um spectra which allow an inventory of interstellar ice. Among the species identified are H2O, CH3OH, CH4, CO2, CO, and OCS. These species are formed through simple reactions among gas phase species accreted on grain surfaces, possibly modified by FUV photolysis and warm-up (ie., outgassing). The implications of the observations for our understanding of these processes will be reviewed. The IR spectra of many UV bright objects are dominated by strong emission features at 3.3, 6.2, 7.7, and 11.3 micrometers. These are generally attributed to Polycyclic Aromatic Hydrocarbons (PAHs) molecules. The observational evidence will be reviewed. The emphasis will be on recent data which show widespread spectral variations, particularly among protoplanetary and planetary nebulae, and their implications. One of the most exciting, recent discoveries on interstellar and circumstellar dust has been the detection of spectral structure due to crystalline olivine and enstatite in a variety of objects surrounded by circumstellar silicates. These spectra will be reviewed and circumstellar silicate mineralogy will be discussed.

  16. Experience with ISO quality control in assisted reproductive technology.

    PubMed

    Alper, Michael M

    2013-12-01

    Assisted reproductive technology (ART) programs are complex organizations requiring the integration of multiple disciplines. ISO 9001:2008 is a quality management system that is readily adaptable to an ART program. The value that ISO brings to the entire organization includes control of documents, clear delineation of responsibilities of staff members, documentation of the numerous processes and procedures, improvement in tracking and reducing errors, and overall better control of systems. A quality ART program sets quality objectives and monitors their progress. ISO provides a sense of transparency within the organization and clearer understanding of how service is provided to patients. Most importantly, ISO provides the framework to allow for continual improvement. PMID:24112531

  17. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    PubMed

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  18. Analysis of ISO NE Balancing Requirements: Uncertainty-based Secure Ranges for ISO New England Dynamic Inerchange Adjustments

    SciTech Connect

    Etingov, Pavel V.; Makarov, Yuri V.; Wu, Di; Hou, Zhangshuan; Sun, Yannan; Maslennikov, S.; Luo, X.; Zheng, T.; George, S.; Knowland, T.; Litvinov, E.; Weaver, S.; Sanchez, E.

    2013-01-31

    The document describes detailed uncertainty quantification (UQ) methodology developed by PNNL to estimate secure ranges of potential dynamic intra-hour interchange adjustments in the ISO-NE system and provides description of the dynamic interchange adjustment (DINA) tool developed under the same contract. The overall system ramping up and down capability, spinning reserve requirements, interchange schedules, load variations and uncertainties from various sources that are relevant to the ISO-NE system are incorporated into the methodology and the tool. The DINA tool has been tested by PNNL and ISO-NE staff engineers using ISO-NE data.

  19. Iso 19011:2002--a combined auditing standard for quality and environmental management systems.

    PubMed

    Johnson, G L

    2000-01-01

    In a precedent-setting decision in 1998, the International Organization for Standardization (ISO) directed ISO Technical Committee (TC) 176 on Quality Management and ISO TC 207 on Environmental Management to develop jointly a single guideline standard for auditing quality and environmental management systems. When approved, this standard would replace ISO 10011-1, ISO 10011-2, and ISO 10011-3 on quality auditing and ISO 14010, ISO 14011, and ISO 14012 on environmental auditing. A Joint Working Group (JWG) was established comprising experts from both TC 176 and TC 207 to develop the new standard, ISO 19011, Guidelines on Quality and/or Environmental Management Systems Auditing, and to incorporate lessons learned from efforts to improve compatibility between ISO 9001/9004 and ISO 14001/14004, the standards for quality and environmental management systems, respectively. Work is proceeding on the development of ISO 19011 with an expected completion in early 2002. PMID:12008882

  20. Beta-agonists and animal welfare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  1. Twenty new ISO standards on dosimetry for radiation processing

    NASA Astrophysics Data System (ADS)

    Farrar, H., IV

    2000-03-01

    Twenty standards on essentially all aspects of dosimetry for radiation processing were published as new ISO standards in December 1998. The standards are based on 20 standard practices and guides developed over the past 14 years by Subcommittee E10.01 of the American Society for Testing and Materials (ASTM). The transformation to ISO standards using the 'fast track' process under ISO Technical Committee 85 (ISO/TC85) commenced in 1995 and resulted in some overlap of technical information between three of the new standards and the existing ISO Standard 11137 Sterilization of health care products — Requirements for validation and routine control — Radiation sterilization. Although the technical information in these four standards was consistent, compromise wording in the scopes of the three new ISO standards to establish precedence for use were adopted. Two of the new ISO standards are specifically for food irradiation applications, but the majority apply to all forms of gamma, X-ray, and electron beam radiation processing, including dosimetry for sterilization of health care products and the radiation processing of fruit, vegetables, meats, spices, processed foods, plastics, inks, medical wastes, and paper. Most of the standards provide exact procedures for using individual dosimetry systems or for characterizing various types of irradiation facilities, but one covers the selection and calibration of dosimetry systems, and another covers the treatment of uncertainties using the new ISO Type A and Type B evaluations. Unfortunately, nine of the 20 standards just adopted by the ISO are not the most recent versions of these standards and are therefore already out of date. To help solve this problem, efforts are being made to develop procedures to coordinate the ASTM and ISO development and revision processes for these and future ASTM-originating dosimetry standards. In the meantime, an additional four dosimetry standards have recently been published by the ASTM but

  2. The ISO View of Star Forming Galaxies

    NASA Technical Reports Server (NTRS)

    Helou, George

    1999-01-01

    ISO studies of normal galaxies in the local Universe have revealed basic new properties whose significant implications for the star formation process and cosmology are only starting to be understood. This review will touch on the general results of a statistical nature, and provide a quick summary of the profusion of exciting results on individual objects. In the mid-infrared, PHT-S has established that the spectra of star forming galaxies between 6 and-13microns are dominated by the Aromatic Features in Emission (AFE), and show little variation as a function of the heating intensity. The Carriers of the AFE (CAFE) are thus a universal component of dust with standard properties, and contribute between 10 and 25% of the total dust luminosity. In addition to AFE, the spectra show a low-level continuum detectable at wavelengths longer than 3.5microns whose origin is still under investigation. The mid-infrared colors formed as the ratio of flux densities in the 6.75micron and the 15micron bands of ISO-CAM remain essentially constant and near unity for quiescent and mildly active galaxies. As dust heating increases further, the 15micron flux increases steeply compared to 6.75microns, indicating that dust heated to 100KISO-PHOT is starting to constrain the distribution of dust temperatures at the low end of the temperature scale. From LWS data, the far-infrared fine-structure lines of [CII] and [OI], which provide most of the cooling for warm atomic gas, show variations that have remained controversial in their interpretation. In particular, as the galaxy become more active in star formation, its [CII] flux weakens relative to total dust emission while the [OI] does not. This behavior has attracted much interest because it extrapolates to the most active galaxies, making them weaker in [CII

  3. Mitochondrial ATP-sensitive potassium channel opening inhibits isoproterenol-induced cardiac hypertrophy by preventing oxidative damage.

    PubMed

    Lemos Caldas, Francisco Rodrigo; Rocha Leite, Iago Mateus; Tavarez Filgueiras, Ana Beatriz; de Figueiredo Júnior, Isaias Lima; Gomes Marques de Sousa, Tereza Amália; Martins, Pamela Reis; Kowaltowski, Alicia Juliana; Fernandes Facundo, Heberty di Tarso

    2015-04-01

    Cardiac hypertrophy is a chronic complex disease that occurs in response to hemodynamic load and is accompanied by oxidative stress and mitochondrial dysfunction. Mitochondrial ATP-sensitive K channels (mitoKATPs) have previously been shown to prevent oxidative cardiac damage under conditions of ischemia/reperfusion. However, the effect of these channels on cardiac hypertrophy has not been tested to date. In this study, we show that treatment of Swiss mice with isoproterenol (30 mg·kg·d) induces cardiac hypertrophy while significantly decreasing the levels of reduced protein thiols, glutathione, catalase, and superoxide dismutase activity, indicative of a condition of oxidative imbalance. Treatment with diazoxide (a mitoKATP opener, 5 mg·kg·d) normalized the levels of protein thiols and reduced glutathione, rescued superoxide dismutase activity, and significantly prevented cardiac hypertrophy. The protective effects of diazoxide were mitigated by the mitoKATP blockers 5-hydroxydecanoate (5 mg·kg·d) and glibenclamide (3 mg·kg·d), demonstrating that they were related to activation of the channel. Taken together, our results establish that mitoKATP activation promotes very robust prevention of cardiac hypertrophy and associated oxidative imbalance and suggest that these channels can be important drug targets for the pharmacological control of cardiac hypertrophy. PMID:25850726

  4. Eugenia jambolana pretreatment prevents isoproterenol-induced myocardial damage in rats: evidence from biochemical, molecular, and histopathological studies.

    PubMed

    Shukla, Santosh Kumar; Sharma, Suman Bala; Singh, Usha Rani; Ahmad, Sayeed; Maheshwari, Ankur; Misro, Manmohan; Dwivedi, Shridhar

    2014-02-01

    Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated. Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h. Ischemic control group exhibited significant increases in oxidative stress parameters, markers of inflammation, cardiac damage markers, and apoptotic markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided cardioprotective activity by decreasing levels of malondialdehyde, cardiac markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor alpha); and increased levels of superoxide dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw). Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated rats, which was further confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The present study provides evidence that pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves cardiac architecture in ISP-induced rats and, hence, is cardioprotective. PMID:24325453

  5. Eugenia jambolana Pretreatment Prevents Isoproterenol-Induced Myocardial Damage in Rats: Evidence from Biochemical, Molecular, and Histopathological Studies

    PubMed Central

    Shukla, Santosh Kumar; Singh, Usha Rani; Ahmad, Sayeed; Maheshwari, Ankur; Misro, Manmohan; Dwivedi, Shridhar

    2014-01-01

    Abstract Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated. Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h. Ischemic control group exhibited significant increases in oxidative stress parameters, markers of inflammation, cardiac damage markers, and apoptotic markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided cardioprotective activity by decreasing levels of malondialdehyde, cardiac markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor alpha); and increased levels of superoxide dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw). Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated rats, which was further confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The present study provides evidence that pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves cardiac architecture in ISP-induced rats and, hence, is cardioprotective. PMID:24325453

  6. Amelioration of inflammation by phenolic rich methanolic extract of Ocimum sanctum Linn. leaves in isoproterenol induced myocardial infarction.

    PubMed

    Kavitha, S; John, Febi; Indira, M

    2015-10-01

    Myocardial infarction (MI) is one of the leading causes of death worldwide. Oxidative stress and inflammation play vital role in the development of MI. The Indian basil or Tulsi (Ocimum sanctum Linn.), owing to its antioxidant potential, is used in the traditional system of Indian medicine to treat various disorders. We evaluated methanolic extract of O. sanctum (Tulsi) leaves on inflammation in isoproterenol (ISP) induced MI in rats. ISP-induced MI increased the levels of cardiac markers, phospholipases and phospholipid content. However, the same were reduced on pre-treatment with methanolic extract of O. sanctum leaves. The activities of 5-lipoxygenase and cycloxygenase-2 and levels of leukotriene B4 and thromboxane B2 were also elevated in ISP-treated rats, which were significantly decreased (P < 0.001) in extract pre-treated rats. The enhanced mRNA expressions of nuclear factor kappa-B, 5-lipoxygenase activating protein and receptor for leukotriene B4 on MI induction, were considerably reduced (P < 0.001) on extract pre-treatment. Histopathological analysis also confirmed the findings. The results also revealed the high phenolic content of methanolic extract of O. sanctum leaves. The study demonstrated that methanolic extract of Tulsi leaves can decrease inflammation in the cardiac tissue of ISP-induced MI in rats and its effect may be through downregulation of oxidative stress and arachidonic acid pathway. This cardioprotective effect may be due to the high phenolic content of methanolic extract of O. sanctum leaves. PMID:26665293

  7. β2-agonist therapy in lung disease.

    PubMed

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  8. METADATA REGISTRY, ISO/IEC 11179

    SciTech Connect

    Pon, R K; Buttler, D J

    2008-01-03

    ISO/IEC-11179 is an international standard that documents the standardization and registration of metadata to make data understandable and shareable. This standardization and registration allows for easier locating, retrieving, and transmitting data from disparate databases. The standard defines the how metadata are conceptually modeled and how they are shared among parties, but does not define how data is physically represented as bits and bytes. The standard consists of six parts. Part 1 provides a high-level overview of the standard and defines the basic element of a metadata registry - a data element. Part 2 defines the procedures for registering classification schemes and classifying administered items in a metadata registry (MDR). Part 3 specifies the structure of an MDR. Part 4 specifies requirements and recommendations for constructing definitions for data and metadata. Part 5 defines how administered items are named and identified. Part 6 defines how administered items are registered and assigned an identifier.

  9. ISO/IEC's image interchange facility

    NASA Astrophysics Data System (ADS)

    Blum, Christof; Hofmann, Georg R.

    1992-04-01

    This paper gives a technical description of the Image Interchange Facility (IIF), which comprises both a formate definition and a functional gateway specification. IIF is a part of the first International Image Processing and Interchange Standard (IPI), which is under elaboration by ISO/IEC JTC1/SC24. This paper reflects the related committee work performed up until January 1992. Considering the deficiencies and drawbacks of existing formats and current practices in exchanging digital images, the need for a new and more general approach to image interchange can be seen. This paper describes the requirements and design principles of the IIF data format and the IIF gateway. Furthermore, it explains the relation to the reference model for open communication (OSI) as well as the relation to the other parts of the IPI standard.

  10. The Strengths and Weaknesses of ISO 9000 in Vocational Education

    ERIC Educational Resources Information Center

    Bevans-Gonzales, Theresa L.; Nair, Ajay T.

    2004-01-01

    ISO 9000 is a set of quality standards that assists an organization to identify, correct and prevent errors, and to promote continual improvement. Educational institutions worldwide are implementing ISO 9000 as they face increasing external pressure to maintain accountability for funding. Similar to other countries, in the United States vocational…

  11. Evaluating Education Quality in Terms of ISO9000 Standards

    ERIC Educational Resources Information Center

    Fengchun, Cheng; Vogel, Linda R.; Zhaoyu, Zheng

    2014-01-01

    While nations measure the quality of educational systems by different standards, many nations, such as China, have adopted the ISO9000 quality standards to assess the quality of schools. This article explores the various elements of the the ISO9000 standards and how each element relates to the various groups that are consumers or stakeholders in…

  12. ISO 14001 ENVIRONMENTL MANAGEMENT SYSTEMS IN GOVERNMENT AND INDUSTRY

    EPA Science Inventory

    Two new USEPA documents address environmental management systems (EMS) from the perspectives of government and industry and are offered as tools for understanding the process of the ISO 14000 Standards development and usefulness of an EMS approach. The first document, ISO 14001 -...

  13. Quality Systems and ISO 9000 in Higher Education.

    ERIC Educational Resources Information Center

    Lundquist, Robert

    1997-01-01

    Examines quality assurance systems in higher education in general and of ISO 9000, a set of international quality standards, in particular. Reports on a survey of 23 institutions worldwide concerning implementation of quality systems and application of the ISO 9000 standards. Concludes that while institutions have found the quality assurance…

  14. Manufacturing Bms/Iso System Review

    NASA Technical Reports Server (NTRS)

    Gomez, Yazmin

    2004-01-01

    The Quality Management System (QMS) is one that recognizes the need to continuously change and improve an organization s products and services as determined by system feedback, and corresponding management decisions. The purpose of a Quality Management System is to minimize quality variability of an organization's products and services. The optimal Quality Management System balances the need for an organization to maintain flexibility in the products and services it provides with the need for providing the appropriate level of discipline and control over the processes used to provide them. The goal of a Quality Management System is to ensure the quality of the products and services while consistently (through minimizing quality variability) meeting or exceeding customer expectations. The GRC Business Management System (BMS) is the foundation of the Center's ISO 9001:2000 registered quality system. ISO 9001 is a quality system model developed by the International Organization for Standardization. BMS supports and promote the Glenn Research Center Quality Policy and wants to ensure the customer satisfaction while also meeting quality standards. My assignment during this summer is to examine the manufacturing processes used to develop research hardware, which in most cases are one of a kind hardware, made with non conventional equipment and materials. During this process of observation I will make a determination, based on my observations of the hardware development processes the best way to meet customer requirements and at the same time achieve the GRC quality standards. The purpose of my task is to review the manufacturing processes identifying opportunities in which to optimize the efficiency of the processes and establish a plan for implementation and continuous improvement.

  15. The Ice Survey Opportunity of ISO

    NASA Astrophysics Data System (ADS)

    Dartois, Emmanuel

    2005-08-01

    The instruments on board the Infrared Space Observatory have for the first time allowed a complete low (PHOT, CVF) to medium resolution (SWS) spectroscopic harvest, from 2.5 to 45 μm, of interstellar dust. Amongst the detected solids present in starless molecular clouds surrounding recently born stellar and still embedded objects or products of the chemistry in some mass loss envelopes, the so-called “ice mantles” are of specific interest. They represent an interface between the very refractory carbonaceous and silicates materials that built the first grains with the rich chemistry taking place in the gas phase. Molecules condense, react on ices, are subjected to UV and cosmic ray irradiation at low temperatures, participating efficiently to the evolution toward more complex molecules, being in constant interaction in an ice layer. They also play an important role in the radiative transfer of molecular clouds and strongly affect the gas phase chemistry. ISO results shed light on many other species than H2O ice. The detection of these van der Waal's solids is mainly performed in absorption. Each ice feature observed by ISO spectrometer is an important species, with abundance in the 10-4-10-7 range with respect to H2. Such high abundances represent a substantial reservoir of matter that, once released later on, replenishes the gas phase and feeds the ladder of molecular complexity. Medium resolution spectroscopy also offers the opportunity to look at individual line profiles of the ice features, and therefore to progressively reveal the interactions taking place in the mantles. This article will give a view on selected results to avoid to overlap with the numerous reviews the reader is invited to consult (e.g. van Dishoeck, in press; Gibb et al., 2004.).

  16. The ISO-IRAS Faint Galaxy Survey

    NASA Technical Reports Server (NTRS)

    Smith, Harding E.

    1999-01-01

    As part of the ISO-IRAS Faint Galaxy Survey ISO Satellite observations of over 600 IRAS sources have been obtained with the ISOCAM instrument. Because our survey strategy involved relatively short integrations, great care was required in developing analysis software including cosmic-ray and transient removal and calibration. These observations have now been through final pipeline processing at IPAC and ground-based follow-up is ongoing. The observations are for sources from two samples: a " Filler' sample selected to be at z greater than 0.1 and a fainter sample which selected for the highest redshift galaxies in the IRAS survey, with redshifts 0.2 less than z less than 1.0. I now have obtained ground-based follow-up spectrophotometry at Lick and Palomar observatories for 100 LFIRGs with 0.1 less than z less than 0.7. Our observations have confirmed that these systems are comparable to nearby LFIRGs such as Arp 220, with L (sub -)(fir) greater than 10(exp 11) L(sub -) sun and typically HII/Liner optical excitation. About 10% of the galaxies show true AGN (Sy2) excitation. Based on our work on a nearby complete sample of LFIRGS, we believe that the majority of these systems are luminous Starbursts, thus this project is tracing the luminous end of the galaxy star-forming luminosity function - the (infrared) star-formation history of the Universe to z approx. 1, a topic of some considerable recent interest. A by-product of these ISOCAM observations is approximately 1 square degree of deep 2 microns pointings outside the IRAS error boxes, allowing us an independent estimate of the mid-infrared log N - log S relation. Ground-based observations of this sample are continuing.

  17. Objectives And Structures Of The International Organization For Standardization (ISO)

    NASA Astrophysics Data System (ADS)

    Reihlen, Helmut

    1989-04-01

    I am certainly pleased to be with you here today, and to speak to you on the subject of international standardization. The work of some of the ISO technical committees, such as ISO/TC 36 "Cinematography", ISO/TC 42 "Photograhy" and, of course, ISO/TC 172 "Optics and optical instruments" may be familiar to many of you and their activities will be presented in your technical sessions. Rather than going into the detail of these technical committees it might be appropriate that, in my capacity as Vice-President of ISO, I present to you an overview of the organization, what it aims to do, with what means, what its achievements are and how it does its job in practice.

  18. Biodegradability Evaluation of Polymers by ISO 14855-2

    PubMed Central

    Funabashi, Masahiro; Ninomiya, Fumi; Kunioka, Masao

    2009-01-01

    Biodegradabilities of polymers and their composites in a controlled compost were described. Polycaprolactone (PCL) and poly(lactic acid) (PLA) were employed as biodegradable polymers. Biodegradabilities of PCL and PLA samples in a controlled compost were measured using a Microbial Oxidative Degradation Analyzer (MODA) according to ISO 14855-2. Sample preparation method for biodegradation test according to ISO/DIS 10210 was also described. Effects of sizes and shapes of samples on biodegradability were studied. Reproducibility of biodegradation test of ISO 14855-2 by MODA was confirmed. Validity of sample preparation method for polymer pellets, polymer film, and polymer products of ISO/DIS 10210 for ISO 14855-2 was confirmed. PMID:20111676

  19. Biodegradability evaluation of polymers by ISO 14855-2.

    PubMed

    Funabashi, Masahiro; Ninomiya, Fumi; Kunioka, Masao

    2009-10-01

    Biodegradabilities of polymers and their composites in a controlled compost were described. Polycaprolactone (PCL) and poly(lactic acid) (PLA) were employed as biodegradable polymers. Biodegradabilities of PCL and PLA samples in a controlled compost were measured using a Microbial Oxidative Degradation Analyzer (MODA) according to ISO 14855-2. Sample preparation method for biodegradation test according to ISO/DIS 10210 was also described. Effects of sizes and shapes of samples on biodegradability were studied. Reproducibility of biodegradation test of ISO 14855-2 by MODA was confirmed. Validity of sample preparation method for polymer pellets, polymer film, and polymer products of ISO/DIS 10210 for ISO 14855-2 was confirmed. PMID:20111676

  20. Usability evaluation of mobile applications using ISO 9241 and ISO 25062 standards.

    PubMed

    Moumane, Karima; Idri, Ali; Abran, Alain

    2016-01-01

    This paper presents an empirical study based on a set of measures to evaluate the usability of mobile applications running on different mobile operating systems, including Android, iOS and Symbian. The aim is to evaluate empirically a framework that we have developed on the use of the Software Quality Standard ISO 9126 in mobile environments, especially the usability characteristic. To do that, 32 users had participated in the experiment and we have used ISO 25062 and ISO 9241 standards for objective measures by working with two widely used mobile applications: Google Apps and Google Maps. The QUIS 7.0 questionnaire have been used to collect measures assessing the users' level of satisfaction when using these two mobile applications. By analyzing the results we highlighted a set of mobile usability issues that are related to the hardware as well as to the software and that need to be taken into account by designers and developers in order to improve the usability of mobile applications. PMID:27190747

  1. Aspirin metabolites are GPR35 agonists.

    PubMed

    Deng, Huayun; Fang, Ye

    2012-07-01

    Aspirin is widely used as an anti-inflammatory, anti-platelet, anti-pyretic, and cancer-preventive agent; however, the molecular mode of action is unlikely due entirely to the inhibition of cyclooxygenases. Here, we report the agonist activity of several aspirin metabolites at GPR35, a poorly characterized orphan G protein-coupled receptor. 2,3,5-Trihydroxybenzoic acid, an aspirin catabolite, was found to be the most potent GPR35 agonist among aspirin metabolites. Salicyluric acid, the main metabolite of aspirin, was also active. These results suggest that the GPR35 agonist activity of certain aspirin metabolites may contribute to the clinical features of aspirin. PMID:22526472

  2. ISO Spectroscopy of Proto-Planetary Nebulae

    NASA Technical Reports Server (NTRS)

    Hrivnak, Bruce J.

    2000-01-01

    The goal of this program was to determine the chemical properties of the dust shells around protoplanetary nebulae (PPNs) through a study of their short-wavelength (6-45 micron) infrared spectra. PPNs are evolved stars in transition from the asymptotic giant branch to the planetary nebula stages. Spectral features in the 10 to 20 gm region indicate the chemical nature (oxygen- or carbon-rich), and the strengths of the features relate to the physical properties of the shells. A few bright carbon-rich PPNs have been observed to show PAH features and an unidentified 21 micron emission feature. We used the Infrared Space Observatory (ISO) to observe a sample of IRAS sources that have the expected properties of PPNs and for which we have accurate positions. Some of these have optical counterparts (proposal SWSPPN01) and some do not (SWSPPN02). We had previously observed these from the ground with near-infrared photometry and, for those with visible counterparts, visible photometry and spectroscopy, which we have combined with these new ISO data in the interpretation of the spectra. We have completed a study of the unidentified emission feature at 21 micron in eight sources. We find the shape of the feature to be the same in all of the sources, with no evidence of any substructure. The ratio of the emission peak to continuum ranges from 0.13 to 1.30. We have completed a study of seven PPNs and two other carbon-rich objects for which we had obtained ISO 2-45 micron observations. The unidentified emission features at 21 and 30 micron were detected in six sources, including four new detections of the 30 micron feature. This previously unresolved 30 micron feature was resolved and found to consist of a broad feature peaking at 27.2 micron (the "30 micron" feature) and a narrower feature peaking at 25.5 micron (the "26 micron" feature). This new 26 micron feature is detected in eight sources and is particularly strong in IRAS Z02229+6208 and 16594-4656. The unidentified

  3. Monoterpenoid agonists of TRPV3

    PubMed Central

    Vogt-Eisele, A K; Weber, K; Sherkheli, M A; Vielhaber, G; Panten, J; Gisselmann, G; Hatt, H

    2007-01-01

    Background and purpose: Transient receptor potential (TRP) V3 is a thermosensitive ion channel expressed predominantly in the skin and neural tissues. It is activated by warmth and the monoterpene camphor and has been hypothesized to be involved in skin sensitization. A selection of monoterpenoid compounds was tested for TRPV3 activation to establish a structure-function relationship. The related channel TRPM8 is activated by cool temperatures and a number of chemicals, among them the monoterpene (-)-menthol. The overlap of the receptor pharmacology between the two channels was investigated. Experimental approach: Transfected HEK293 cells were superfused with the test substances. Evoked currents were measured in whole cell patch clamp measurements. Dose-response curves for the most potent agonists were obtained in Xenopus laevis oocytes. Key results: Six monoterpenes significantly more potent than camphor were identified: 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol and (+)-borneol. Their EC50 is up to 16 times lower than that of camphor. All of these compounds carry a ring-located hydroxyl group and neither activates TRPM8 to a major extent. Conclusions and implications: Terpenoids have long been recognized as medically and pharmacologically active compounds, although their molecular targets have only partially been identified. TRPV3 activation may be responsible for several of the described effects of terpenoids. We show here that TRPV3 is activated by a number of monoterpenes and that a secondary hydroxyl-group is a structural requirement. PMID:17420775

  4. IsoCombretaQuinazolines: Potent Cytotoxic Agents with Antitubulin Activity.

    PubMed

    Soussi, Mohamed Ali; Provot, Olivier; Bernadat, Guillaume; Bignon, Jérome; Desravines, Déborah; Dubois, Joëlle; Brion, Jean-Daniel; Messaoudi, Samir; Alami, Mouad

    2015-08-01

    A series of novel isocombretaquinazolines (isoCoQ) 4 were quickly prepared by coupling N-toluenesulfonylhydrazones with 4-chloroquinazolines under palladium catalysis. These compounds, which can be regarded as isocombretastatin A-4 (isoCA-4) analogues that lack the 3,4,5-trimethoxyphenyl ring, displayed nanomolar-level cytotoxicity against various human cancer cell lines and were observed to effectively inhibit tubulin polymerization. The isoCoQ compounds 2-methoxy-5-(1-(2-methylquinazolin-4-yl)vinyl)phenol (4 b), 4-[1-(3-fluoro-4-methoxyphenyl)vinyl]-2-methylquinazoline (4 c), and 2-methoxy-5-(1-(2-methylquinazolin-4-yl)vinyl)aniline (4 d), which respectively bear the greatest resemblance to isoCA-4, isoFCA-4, and isoNH2 CA-4, are able to arrest HCT116 cancer cells in the G2 /M cell-cycle phase at very low concentrations. Preliminary in vitro antivascular assay results show that 4 d is able to disrupt a network of capillary-like structures formed by human umbilical vein endothelial cells on Matrigel. All these results clearly demonstrate that replacement of the 3,4,5-trimethoxyphenyl ring of isoCA-4 with a quinazoline nucleus is a feasible approach toward new and highly promising derivatives with the potential for further development as antitubulin agents. PMID:26076053

  5. Assessment of Indian Rosewood (Dalbergia sissoo) Standardized Leaf Extract on Isoproterenol-Induced Myocardial Injury in Rats.

    PubMed

    Kasa, Jaya Kiran; Singh, Thakur Uttam; Parida, Subhashree; Addison, M Pule; Darzi, Sajad Ahmad; Choudhury, Soumen; Kandasamy, Kannan; Singh, Vishakha; Dash, Jeevan Ranjan; Shanker, Karuna; Mishra, Santosh Kumar

    2015-07-01

    The present study was undertaken to evaluate the effect of alcoholic extract of Dalbergia sissoo leaf extract (DSE) on isoproterenol (ISP)-induced myocardial injury in rats. Evaluation of three doses (30, 100 and 300 mg/kg of body weight) of DSE was done in ISP-treated rats. ISP was used at 85 mg/kg body weight by subcutaneous route for two subsequent days to induce myocardial injury in rats. Assessment of myocardial injury was done by estimation of different cardiac injury markers like LDH, CK-MB. Serum cholesterol, LDL, HDL, triglycerides in serum, myocardial infarcted area, oxidative stress and histopathology in heart tissue were also assessed in rats. Mean arterial pressure and heart rate were recorded in all the groups. Rats pretreated with DSE (30, 100 and 300 mg/kg of body weight) showed significant (p < 0.05-0.001) improvement in the heart weight/body weight ratio, myocardial infarcted areas, heart rate and mean arterial pressure in ISP-induced myocardial injury. DSE showed significant (p < 0.05-0.001) improvement in serum LDH, CK-MB, cholesterol, LDL and triglyceride levels at all the dose levels. However, DSE pretreatment had no significant effect on serum HDL level. Pretreatment with DSE (30, 100 and 300 mg/kg body weight) showed significant (p < 0.001) reduction in MDA level in comparison with myocardial injured rats. Further, antioxidant potential was also improved in terms of improved activities of reduced glutathione, superoxide dismutase and catalase with the DSE pretreatment. Histopathology also showed significant improvement in heart tissue. The study suggests that DSE showed beneficial effect in ISP-induced myocardial injury in rats. PMID:25420456

  6. Differentiation of human adipocytes at physiological oxygen levels results in increased adiponectin secretion and isoproterenol-stimulated lipolysis

    PubMed Central

    Famulla, Susanne; Schlich, Raphaela; Sell, Henrike; Eckel, Jürgen

    2012-01-01

    Adipose tissue (AT) hypoxia occurs in obese humans and mice. Acute hypoxia in adipocytes causes dysregulation of adipokine secretion with an increase in inflammatory factors and diminished adiponectin release. O2 levels in humans range between 3 and 11% revealing that conventional in vitro culturing at ambient air and acute hypoxia treatment (1% O2) are performed under non-physiological conditions. In this study, we mimicked physiological conditions by differentiating human primary adipocytes under 10% or 5% O2 in comparison to 21% O2. Induction of differentiation markers was comparable between all three conditions. Adipokine release by adipocytes differentiated at lower oxygen levels was altered, with a marked upregulation of adiponectin, IL-6 and DPP4 secretion, and reduced leptin levels compared with adipocytes differentiated at 21% O2. Isoproterenol-induced lipolysis was significantly elevated in adipocytes differentiated at 10% and 5% compared with 21% O2. This effect was accompanied by increased protein expression of β-1 and -2 adrenergic receptor, HSL and perilipin. Conditioned medium (CM) of adipocytes differentiated at the three different conditions was generated for stimulation of human skeletal muscle cells (SkMC) or smooth muscle cells (SMC). CM-induced insulin resistance in SkMC was comparable for the different CMs. However, the SMC proliferative effect of CM from adipocytes differentiated at 10% O2 was significantly reduced compared with 21% O2. This study demonstrates that oxygen levels during adipogenesis are important factors altering adipocyte functionality such as adipokine release, in particular adiponectin secretion, as well as the hormone-induced lipolytic pathway. PMID:23700522

  7. Moringa oleifera leaf extract prevents isoproterenol-induced myocardial damage in rats: evidence for an antioxidant, antiperoxidative, and cardioprotective intervention.

    PubMed

    Nandave, Mukesh; Ojha, Shreesh Kumar; Joshi, Sujata; Kumari, Santosh; Arya, Dharamvir Singh

    2009-02-01

    The present study evaluated cardioprotective effect of lyophilized hydroalcoholic extract of Moringa oleifera in the isoproterenol (ISP)-induced model of myocardial infarction. Wistar albino male rats were divided into three groups and orally fed saline once daily alone (sham) or with ISP (ISP control) or ISP with M. oleifera (200 mg/kg), respectively, for 1 month. On days 29 and 30 of administration, rats of the ISP control and M. oleifera-ISP groups were administered ISP (85 mg/kg, s.c.) at an interval of 24 hours. On day 31, hemodynamic parameters (mean arterial pressure [MAP], heart rate [HR], left ventricular end-diastolic pressure [LVEDP], and left ventricular peak positive [(+) LV dP/dt] and negative [(-) LV dP/dt] pressures were recorded. At the end of the experiment, the animals were sacrificed, and hearts were excised and processed for biochemical, histopathological, and ultrastructural studies. Chronic treatment with M. oleifera demonstrated mitigating effects on ISP-induced hemodynamic [HR, (+) LV dP/dt, (-) LV dP/dt, and LVEDP] perturbations. Chronic M. oleifera treatment resulted in significant favorable modulation of the biochemical enzymes (superoxide dismutase, catalase, glutathione peroxidase, lactate dehydrogenase, and creatine kinase-MB) but failed to demonstrate any significant effect on reduced glutathione compared to the ISP control group. Moringa treatment significantly prevented the rise in lipid peroxidation in myocardial tissue. Furthermore, M. oleifera also prevented the deleterious histopathological and ultrastructural perturbations caused by ISP. Based on the results of the present study, it can be concluded that M. oleifera extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, antiperoxidative, and myocardial preservative properties. PMID:19298195

  8. Piperidine derivatives as nonprostanoid IP receptor agonists.

    PubMed

    Hayashi, Ryoji; Sakagami, Hideki; Koiwa, Masakazu; Ito, Hiroaki; Miyamoto, Mitsuko; Isogaya, Masafumi

    2016-05-01

    The discovery of a new class of nonprostanoid prostaglandin I2 receptor (IP receptor) agonists is reported. Among them, the unique piperidine derivative 31b (2-((1-(2-(N-(4-tolyl)benzamido)ethyl)piperidin-4-yl)oxy)acetic acid) was a good IP receptor agonist and was 50-fold more selective for the human IP receptor than for other human prostanoid receptors. This compound showed good pharmacokinetic properties in dog. PMID:26996371

  9. The ISO SWS on-line system

    NASA Technical Reports Server (NTRS)

    Roelfsema, P. R.; Kester, D. J. M.; Wesselius, P. R.; Wieprech, E.; Sym, N.

    1992-01-01

    The software which is currently being developed for the Short Wavelength Spectrometer (SWS) of the Infrared Space Observatory (ISO) is described. The spectrometer has a wide range of capabilities in the 2-45 micron infrared band. SWS contains two independent gratings, one for the long and one for the short wavelength section of the band. With the gratings a spectral resolution of approximately 1000 to approximately 2500 can be obtained. The instrument also contains two Fabry-Perault's yielding a resolution between approximately 1000 and approximately 20000. Software is currently being developed for the acquisition, calibration, and analysis of SWS data. The software is firstly required to run in a pipeline mode without human interaction, to process data as they are received from the telescope. However, both for testing and calibration of the instrument as well as for evaluation of the planned operating procedures the software should also be suitable for interactive use. Thirdly the same software will be used for long term characterization of the instrument. The software must work properly within the environment designed by the European Space Agency (ESA) for the spacecraft operations. As a result strict constraints are put on I/O devices, throughput etc.

  10. First light with ISO and its instruments

    NASA Astrophysics Data System (ADS)

    1995-12-01

    On 28 November, the first infrared images were taken with the ISOCAM instrument. The target was the beautiful spiral galaxy, M51, also known as the Whirlpool Galaxy. Images were taken in two infrared colours, at wavelengths of 7 and 15 microns, and at two resolutions, namely 3 and 6 arc seconds. Figure 1 shows the 7 micron ISOCAM image with a spatial resolution of 6 arc seconds. Spiral structure in galaxies was first discovered by observations of M51 taken in 1845 by the third Earl of Rosse in Ireland. At a distance of 20 million light years, M51 is not one of our nearest neighbors in space but it is one of the most spectacular, as it presents its spiral structure face-on to us. M51 is smaller and - at a mass of 50000 million suns - less massive than our galaxy. However, due to intense recent star formation, it is much brighter. While very detailed images have been available for some time in the optical and radio wavelength range, infrared data in the ISO range has been very limited. Figure 2 shows the data from the previous infrared satellite - the American/Dutch/British satellite IRAS; where, in a similar wavelength range, there is not even a hint of the spiral structure. For ISOCAM, with its higher spatial resolution and greater sensitivity, not only the spiral structure but also details within are easily visible, even in a raw first light image. Images from ISOCAM data will be compared with maps at other wavelengths to reveal information about the star formation processes in galaxies. First light for the ISOPHOT instrument was obtained on 29 November 1995 from the star Gamma Draconis. A huge signal was measured in a narrow band filter at 3.29 microns (figure 3). The optical axis of the instrument was found by this observation to be as close as 15 arc seconds to the predicted position. The next target was the interacting galaxy, NGC6090, which was clearly detected for the first time at the longest wavelengths, 120 - 240 microns, exclusively available on ISO

  11. International environmental management standards (ISO 9000`s less tractable siblings)

    SciTech Connect

    Cascio, J.

    1994-12-31

    Before the advent of ISO 9000 Quality Management standards, the International Organization for Standardization`s (ISO) nearly exclusive focus was on international technical and safety standards. Then, some ten years ago, this staid, Geneva based world standards harmonizer took a fateful step into a more exciting, through considerably less solid realm by impaneling a new technical committee (TC 176) to develop Quality Management standards for organizations. With that, it entered the relatively soft science of organizational management. This initial gamble paid off and resulted in the ISO 9000 series of Quality standards which have won adherents throughout the world and have (in some regions) become requirements of trade. Now, ISO has launched its second sally into the organizational management field by forming Technical Committee 207 to develop yet another set of management standards, this time focusing on the considerably less tractable subject of environmental protection activities within organizations.

  12. Standardization by ISO to Ensure the Sustainability of Space Activities

    NASA Astrophysics Data System (ADS)

    Kato, A.; Lazare, B.; Oltrogge, D.; Stokes, H.

    2013-08-01

    The ISO / Technical Committee 20 / Sub-committee 14 develops debris-related standards and technical reports to mitigate debris and help ensure mission and space sustainability. While UN Guidelines and the IADC Guidelines encourage national governments and agencies to promote debris mitigation design and operation, the ISO standards will help the global space industry promote and sustain its space-related business. In this paper the scope and status of each ISO standard is discussed within an overall framework. A comparison with international guidelines is also provided to demonstrate the level of consistency. Finally, as a case study, the ISO standards are applied to a CubeSat mission, thus demonstrating their usability on a relatively recent and popular class of satellite.

  13. Applicability of ISO 16697 Data to Spacecraft Fire Fighting Strategies

    NASA Technical Reports Server (NTRS)

    Hirsch, David B.; Beeson, Harold D.

    2012-01-01

    Presentation Agenda: (1) Selected variables affecting oxygen consumption during spacecraft fires, (2) General overview of ISO 16697, (3) Estimated amounts of material consumed during combustion in typical ISS enclosures, (4) Discussion on potential applications.

  14. INVITATION : Latest astronomical results from ISO: Press briefing in London

    NASA Astrophysics Data System (ADS)

    1998-03-01

    Representatives of the media are invited to attend the briefing at the Institute of Physics, which will commence with registration and demonstrations at 10:00 a.m. London time. As of 10:30, Paul Murdin, Head of Astronomy at PPARC will initiate the briefing on behalf of PPARC. Reinhard Genzel, a German astronomer and Director of the Max Planck Institute, will make an independent assessment of ISO's achievements and announce some recent discoveries. Martin Kessler, the European Space Agency's project scientist, will summarize the extent of ISO's observations and describe the continuing work of analysis. At 11:45 (after questions) ISO scientists will be available for interviews, with quiet rooms for radio interviews and a scale model of ISO as backdrop for TV interviews and still pictures. Other facilities will include digital images from ISO, and a demonstration of educational project work. To coincide with the event, ESA will distribute a video news release, an Information Note, and new pictures from ISO. After the briefing there will be a buffet lunch. The nearest underground stations to the Institute of Physics are Great Portland Street and Regent's Park. Representatives of the media wishing to attend are requested to return by fax (+33(0)1.53.69.76.90) the attached accreditation form. For further information, please contact : ESA Public Relations Division Tel : +33(0)1.53.69.71.55 Fax : +33(0)1.53.69.76.90

  15. 77 FR 11532 - Notice of Attendance at ISO New England and NEPOOL Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ... Federal Energy Regulatory Commission Notice of Attendance at ISO New England and NEPOOL Meetings The... Commission staff may attend upcoming ISO New England Inc. (ISO-NE) and New England Power Pool (NEPOOL... Commission staff may monitor the various meetings posted on the ISO-NE Web site. NEPOOL...

  16. Iso-geometric analysis for neutron diffusion problems

    SciTech Connect

    Hall, S. K.; Eaton, M. D.; Williams, M. M. R.

    2012-07-01

    Iso-geometric analysis can be viewed as a generalisation of the finite element method. It permits the exact representation of a wider range of geometries including conic sections. This is possible due to the use of concepts employed in computer-aided design. The underlying mathematical representations from computer-aided design are used to capture both the geometry and approximate the solution. In this paper the neutron diffusion equation is solved using iso-geometric analysis. The practical advantages are highlighted by looking at the problem of a circular fuel pin in a square moderator. For this problem the finite element method requires the geometry to be approximated. This leads to errors in the shape and size of the interface between the fuel and the moderator. In contrast to this iso-geometric analysis allows the interface to be represented exactly. It is found that, due to a cancellation of errors, the finite element method converges more quickly than iso-geometric analysis for this problem. A fuel pin in a vacuum was then considered as this problem is highly sensitive to the leakage across the interface. In this case iso-geometric analysis greatly outperforms the finite element method. Due to the improvement in the representation of the geometry iso-geometric analysis can outperform traditional finite element methods. It is proposed that the use of iso-geometric analysis on neutron transport problems will allow deterministic solutions to be obtained for exact geometries. Something that is only currently possible with Monte Carlo techniques. (authors)

  17. beta2-Agonists at the Olympic Games.

    PubMed

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  18. First light with ISO and its instruments

    NASA Astrophysics Data System (ADS)

    1995-12-01

    On 28 November, the first infrared images were taken with the ISOCAM instrument. The target was the beautiful spiral galaxy, M51, also known as the Whirlpool Galaxy. Images were taken in two infrared colours, at wavelengths of 7 and 15 microns, and at two resolutions, namely 3 and 6 arc seconds. Figure 1 shows the 7 micron ISOCAM image with a spatial resolution of 6 arc seconds. Spiral structure in galaxies was first discovered by observations of M51 taken in 1845 by the third Earl of Rosse in Ireland. At a distance of 20 million light years, M51 is not one of our nearest neighbors in space but it is one of the most spectacular, as it presents its spiral structure face-on to us. M51 is smaller and - at a mass of 50000 million suns - less massive than our galaxy. However, due to intense recent star formation, it is much brighter. While very detailed images have been available for some time in the optical and radio wavelength range, infrared data in the ISO range has been very limited. Figure 2 shows the data from the previous infrared satellite - the American/Dutch/British satellite IRAS; where, in a similar wavelength range, there is not even a hint of the spiral structure. For ISOCAM, with its higher spatial resolution and greater sensitivity, not only the spiral structure but also details within are easily visible, even in a raw first light image. Images from ISOCAM data will be compared with maps at other wavelengths to reveal information about the star formation processes in galaxies. First light for the ISOPHOT instrument was obtained on 29 November 1995 from the star Gamma Draconis. A huge signal was measured in a narrow band filter at 3.29 microns (figure 3). The optical axis of the instrument was found by this observation to be as close as 15 arc seconds to the predicted position. The next target was the interacting galaxy, NGC6090, which was clearly detected for the first time at the longest wavelengths, 120 - 240 microns, exclusively available on ISO

  19. Introduction of a single isomer beta agonist.

    PubMed

    Rau, J L

    2000-08-01

    The release of levalbuterol offers the first approved single-isomer beta agonist for oral inhalation. Data from in vitro studies support the concept that S albuterol is not inactive and may have properties antagonistic to bronchodilation. There is some variability in the results of clinical studies with the separate isomers of albuterol, which suggests the need for further study. The introduction of levalbuterol into general clinical use in managing asthma and chronic obstructive disease should begin to offer additional information on the effects of a single isomer beta agonist in comparison to previous racemic mixtures. PMID:10963321

  20. Implementing ISO standard-compliant freeform component drawings

    NASA Astrophysics Data System (ADS)

    Youngworth, Richard N.; Kiontke, Sven R.; Aikens, David M.

    2016-07-01

    Successful fabrication of aspheres requires all parts of the process chain including design, production, and measurements. Aspheres now are well-established and accepted as an equal optical element, when done properly. Research and industry have now started to focus efforts to develop the next element that propels the field forward in capability, namely the optical freeform surface. An essential factor enabling wide use of freeforms is communicating requirements. This paper discusses form description and tolerancing additions to ISO 10110 to accommodate freeform surfaces. Information stating how ISO 10110 and related standards documents such as ISO 14999-4 are being continually developed to meet the requirements for specifying freeform surfaces is also provided. This paper further provides an example monolithic freeform element using the recently updated relevant parts of ISO 10110. The first manufacturing of this component has been successful, and this paper shows the role the ISO standard has played in success. Definitions for toleranced parameters, such as surface registration (centration) and form deviation (irregularity, slope, Zernike, PV, and PVr), are also indicated. The monolithic example also shows how to use the defined data and definitions for metrology and data handling. Metrology results for the freeform surface are given.

  1. Regulation of activator protein-1 by 8-iso-prostaglandin E2 in a thromboxane A2 receptor-dependent and -independent manner

    SciTech Connect

    Weber, Thomas J.; Markillie, Lye MENG.

    2003-05-01

    The thromboxane (TX) A{sub 2} receptor (TP) encompasses two alternatively spliced forms, termed the platelet/placental (TP-P) and endothelial (TP-E) type receptors. Experimental evidence suggests that TP activity may be modulated by novel ligands, termed the isoprostanes, that paradoxically act as TP agonists in smooth muscle and TP antagonists in platelet preparations. Here we have investigated whether prototypical isoprostanes 8-iso-prostaglandin (PG)F{sub 2{alpha}} and 8-iso-PGE{sub 2} regulate the activity of TP isoforms expressed in Chinese hamster ovary (CHO) cells using activator protein-1 (AP-1)-luciferase activity as a reporter. AP-1-luciferase activity was increased by a TP agonist [9,11-dideoxy-9{alpha},11{alpha}-methanoepoxy PGF{sub 2{alpha}} (U46619)] in CHO cells transfected with the human TP-P and TP-E receptors, and this response was fully inhibited by TP antagonists [1S-[1{alpha},2{beta}(Z),3{alpha},5{alpha}

  2. Reciprocity of agonistic support in ravens

    PubMed Central

    Fraser, Orlaith N.; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim’s likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID:22298910

  3. Multiple tyrosine metabolites are GPR35 agonists

    PubMed Central

    Deng, Huayun; Hu, Haibei; Fang, Ye

    2012-01-01

    Both kynurenic acid and 2-acyl lysophosphatidic acid have been postulated to be the endogenous agonists of GPR35. However, controversy remains whether alternative endogenous agonists exist. The molecular targets accounted for many nongenomic actions of thyroid hormones are mostly unknown. Here we report the agonist activity of multiple tyrosine metabolites at the GPR35. Tyrosine metabolism intermediates that contain carboxylic acid and/or catechol functional groups were first selected. Whole cell dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor were then used to characterize their agonist activity in native HT-29. Molecular assays including β-arrestin translocation, ERK phosphorylation and receptor internalization confirmed that GPR35 functions as a receptor for 5,6-dihydroxyindole-2-carboxylic acid, 3,3′,5′-triiodothyronine, 3,3′,5-triiodothyronine, gentisate, rosmarinate, and 3-nitrotyrosine. These results suggest that multiple tyrosine metabolites are alternative endogenous ligands of GPR35, and GPR35 may represent a druggable target for treating certain diseases associated with abnormality of tyrosine metabolism. PMID:22523636

  4. Small molecule TSHR agonists and antagonists.

    PubMed

    Neumann, S; Gershengorn, M C

    2011-04-01

    TSH activates the TSH receptor (TSHR) thereby stimulating the function of thyroid follicular cells (thyrocytes) leading to biosynthesis and secretion of thyroid hormones. Because TSHR is involved in several thyroid pathologies, there is a strong rationale for the design of small molecule "drug-like" ligands. Recombinant human TSH (rhTSH, Thyrogen(®)) has been used in the follow-up of patients with thyroid cancer to increase the sensitivity for detection of recurrence or metastasis. rhTSH is difficult to produce and must be administered by injection. A small molecule TSHR agonist could produce the same beneficial effects as rhTSH but with greater ease of oral administration. We developed a small molecule ligand that is a full agonist at TSHR. Importantly for its clinical potential, this agonist elevated serum thyroxine and stimulated thyroidal radioiodide uptake in mice after its absorption from the gastrointestinal tract following oral administration. Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate TSHR. We identified the first small molecule TSHR antagonists that inhibited TSH- and TSAb-stimulated signalling in primary cultures of human thyrocytes. Our results provide proof-of-principle for effectiveness of small molecule agonists and antagonists for TSHR. We suggest that these small molecule ligands are lead compounds for the development of higher potency ligands that can be used as probes of TSHR biology with therapeutic potential. PMID:21511239

  5. Reciprocity of agonistic support in ravens.

    PubMed

    Fraser, Orlaith N; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID:22298910

  6. ISO 9001 benefits and pitfalls: the path to successful certification.

    PubMed

    Krause, M S

    1996-09-01

    The lifeblood of a business is developing and commercializing new products with minimum cost and time and maximum quality. Implementation of a quality management system is often used to achieve these goals, and the ISO 9001 standard for a business quality system is rapidly becoming the model of choice. The existence of an ISO-compliant system is a key to meeting the forthcoming regulatory requirements in the European Union and the US Food and Drug Administrations's proposed good management practices. DuPont has demonstrated leadership in the achievement of ISO registration. I describe the path to these successful registrations along with key lessons from the experience. Elements of success are management commitment, adequate resources, education, communication, total organizational involvement, and auditing of system performance. For the system to flourish and provide benefits to the users, sufficient time must be allocated for the organization to change. PMID:8787731

  7. Metal-Size Influence in Iso-Selective Lactide Polymerization**

    PubMed Central

    Bakewell, Clare; White, Andrew J P; Long, Nicholas J; Williams, Charlotte K

    2014-01-01

    Iso-selective initiators for the ring-opening polymerization (ROP) of rac-lactide are rare outside of Group 13. We describe the first examples of highly iso-selective lutetium initiators. The phosphasalen lutetium ethoxide complex shows excellent iso-selectivity, with a Pi value of 0.81–0.84 at 298 K, excellent rates, and high degrees of polymerization control. Conversely, the corresponding La derivative exhibits moderate heteroselectivity (Ps=0.74, 298 K). Thus, the choice of metal center is shown to be crucial in determining the level and mode of stereocontrol. The relative order of rates for the series of complexes is inversely related to metallic covalent radius: that is, La>Y>Lu. PMID:25044165

  8. IAL SPACE: A test laboratory for the ISO cryogenic payload

    NASA Technical Reports Server (NTRS)

    Cucchiaro, A.; Henrist, M.; Macau, J. P.; Ninane, N.; Blanpain, R.

    1990-01-01

    The ESA Infrared Space Observatory (ISO) satellite is a 3 axes pointed platform designed to make accurate pointed observations of astronomical objects and sources in the wavelength range between 2.5 and 200 microns. ISO is composed of a service module and a payload module which is a large cylindrical vacuum vessel. The vessel is in fact a cryostat (capacity of 2250 l of liquid He II) which contains the telescope and the four focal scientific instruments. The latter being cooled up to a temperature less than 4 K. The qualification of the payload requires the measurement respectively of: the image quality of the telescope through wave front error (WFE) measurements; and the optical alignment of the scientific instruments with respect to the telescope axis and the telescope focus, and this under cryogenic conditions. Consequently, since 1988, the FOCAL 5 IAL Space facility has been upgraded in order to perform the cryogenic optical tests of the ISO optical subsystems.

  9. Snooker Structure-Based Pharmacophore Model Explains Differences in Agonist and Blocker Binding to Bitter Receptor hTAS2R39

    PubMed Central

    Roland, Wibke S. U.; Sanders, Marijn P. A.; van Buren, Leo; Gouka, Robin J.; Gruppen, Harry; Vincken, Jean-Paul; Ritschel, Tina

    2015-01-01

    The human bitter taste receptor hTAS2R39 can be activated by many dietary (iso)flavonoids. Furthermore, hTAS2R39 activity can be blocked by 6-methoxyflavanones, 4’-fluoro-6-methoxyflavanone in particular. A structure-based pharmacophore model of the hTAS2R39 binding pocket was built using Snooker software, which has been used successfully before for drug design of GPCRs of the rhodopsin subfamily. For the validation of the model, two sets of compounds, both of which contained actives and inactives, were used: (i) an (iso)flavonoid-dedicated set, and (ii) a more generic, structurally diverse set. Agonists were characterized by their linear binding geometry and the fact that they bound deeply in the hTAS2R39 pocket, mapping the hydrogen donor feature based on T5.45 and N3.36, analogues of which have been proposed to play a key role in activation of GPCRs. Blockers lack hydrogen-bond donors enabling contact to the receptor. Furthermore, they had a crooked geometry, which could sterically hinder movement of the TM domains upon receptor activation. Our results reveal characteristics of hTAS2R39 agonist and bitter blocker binding, which might facilitate the development of blockers suitable to counter the bitterness of dietary hTAS2R39 agonists in food applications. PMID:25729848

  10. Snooker structure-based pharmacophore model explains differences in agonist and blocker binding to bitter receptor hTAS2R39.

    PubMed

    Roland, Wibke S U; Sanders, Marijn P A; van Buren, Leo; Gouka, Robin J; Gruppen, Harry; Vincken, Jean-Paul; Ritschel, Tina

    2015-01-01

    The human bitter taste receptor hTAS2R39 can be activated by many dietary (iso)flavonoids. Furthermore, hTAS2R39 activity can be blocked by 6-methoxyflavanones, 4'-fluoro-6-methoxyflavanone in particular. A structure-based pharmacophore model of the hTAS2R39 binding pocket was built using Snooker software, which has been used successfully before for drug design of GPCRs of the rhodopsin subfamily. For the validation of the model, two sets of compounds, both of which contained actives and inactives, were used: (i) an (iso)flavonoid-dedicated set, and (ii) a more generic, structurally diverse set. Agonists were characterized by their linear binding geometry and the fact that they bound deeply in the hTAS2R39 pocket, mapping the hydrogen donor feature based on T5.45 and N3.36, analogues of which have been proposed to play a key role in activation of GPCRs. Blockers lack hydrogen-bond donors enabling contact to the receptor. Furthermore, they had a crooked geometry, which could sterically hinder movement of the TM domains upon receptor activation. Our results reveal characteristics of hTAS2R39 agonist and bitter blocker binding, which might facilitate the development of blockers suitable to counter the bitterness of dietary hTAS2R39 agonists in food applications. PMID:25729848

  11. Progress report on the management of the NEA ISOE system

    SciTech Connect

    Lazo, E.

    1995-03-01

    The Information System on Occupational Exposure (ISOE) was launched by the Organization for Economic Cooperation and Development (OECD), Nuclear Energy Agency (NEA) on 1 January, 1992, to facilitate the communication of dosimetric and ALARA implementation data among nuclear utilities around the world. After two years of operation the System has become a mature interactive network for transfer of data and experience. Currently, 37 utilities from 12 countries, representing 289 power plants, and 12 national regulatory authorities participate in ISOE. Agreements for cooperation also exist between the NEA and the Commission of the European Communities (CEC), and the Paris Center of the WOrld Association of Nuclear Operators (WANO-PC). In addition, the International Atomic Energy Agency (IAEA) is acting as a co-sponsor of ISOE for the participation of non-NEA member countries. Three Regional Technical Centres, Europe, Asia, and Non-NEA member countries, serve to administer the system. The ISOE Network is comprised of three data bases and a communications network at several levels. The three ISOE data bases include the following types of information: NEA1 - annual plant dosimetric information; NEA2 - plant operational characteristics for dose and dose rate reduction; and NEA3 - job specific ALARA practices and experiences. The ISOE communications network has matured greatly during 1992 and 1993. In addition to having access to the above mentioned data bases, participants may now solicit information on new subjects, through the Technical Centres, from all other participants on a real-time basis. Information Sheets on these studies are produced for distribution to all participants. In addition, Topical Reports on areas of interest are produced, and Topical Meetings are held annually.

  12. ISO celebrates its prolonged life with a video of Jupiter

    NASA Astrophysics Data System (ADS)

    1997-07-01

    This is excellent news for astronomers and especially for the multinational teams, with leaders in France, Germany, the Netherlands and the United Kingdom, who spent many years devising the four instruments served by ISO's telescope. The camera ISOCAM, the photometer ISOPHOT, the Short Wavelength Spectrometer and the Long Wavelength Spectrometer span between them an unprecedented range of infrared wavelengths from 2 to 200 microns. The atmosphere of Jupiter is one of the cool and cloudy places attracting ISO's attention, and ESA today releases a video of unprecedented images of Jupiter. The planet changes its appearance drastically as the camera ISOCAM scans a range of 90 different infrared wavelengths. Picture by picture, ISOCAM picks out different features of the atmosphere's composition and behaviour. These and other results from ISO will enable scientists to sharpen their ideas about how Jupiter's weather works. "ISO is giving us a new impression of the giant planets of the Solar System," comments Roger Bonnet, ESA's director of science. "Not just Jupiter, but Saturn, Uranus and Neptune too. By observing the planets across its very wide range of infrared wavelengths, ISO can see features overlooked even by spacecraft visiting the planets. The remarkable movie of Jupiter released today represents only a few per cent of ISO's wavelength range, yet every image tells its own story." More information about the Jupiter video appears later in this Information Note. How ISO's cold telescope beat the calendar The need to keep ISO's telescope and instruments chilled to a very low temperature sets a limit to their useful operating life. ISO was supplied with more than 2000 litres of superfluid helium to cool it. Slow evaporation maintains key parts of the spacecraft at temperatures close to absolute zero, below minus 271 degrees C. The rate of loss of helium was expected to be about 3 litres a day, but the cryogenic system could not be tested in exactly the conditions

  13. New water and remote galaxies complete ISO's observations

    NASA Astrophysics Data System (ADS)

    ISO's operational teams at ESA's ground station at Villafranca near Madrid have been hurrying to provide the world's astronomers with as many observations as possible. They have long anticipated the exhaustion of ISO's vital supply of liquid helium, which cooled the infrared telescope and its instruments to their operating temperatures, close to absolute zero. Two weeks after ISO was put into orbit on 17 November 1995 by an Ariane 44P launcher, the external parts of the cooling system had settled to the operating temperature. The specification required that ISO should then operate for at least 18 months -- implying that operations might have to end in May 1997. Thanks to superb engineering by European industry, which built the spacecraft and its super-cool telescope, ISO has given astronomers almost a year longer than that. During the extra time the count of ISO's observations of cosmic objects has risen from 16,000 to about 26,000. Among the benefits of ISO's longevity has been the chance to examine an important region of the sky, in and around the constellation of Orion. This was not accessible in the nominal mission but has now been observed in two periods. Four inter national teams, supported by national funding agencies, supplied the instruments to analyse the infrared rays received by ISO's telescope. The principal investigators leading the teams are Dietrich Lemke (Heidelberg, Germany) for the versatile photometer ISOPHOT, Catherine Cesarsky (Saclay, France) for the camera ISOCAM, Thijs de Graauw (Groningen, the Netherlands) for the Short Wavelength Spectrometer SWS, and Peter Clegg (London, UK) for the Long Wavelength Spectrometer LWS. Water vapour on Titan A big difference between ISO and the only previous infrared astronomy satellite (IRAS 1983) has been its ability to examine individual objects across a wide range of accurately defined infrared wavelengths. Many spectra showing patterns of intensities at the different wavelengths have enabled astronomers

  14. Launching the chaotic realm of iso-fractals: A short remark

    SciTech Connect

    O'Schmidt, Nathan; Katebi, Reza; Corda, Christian

    2015-03-10

    In this brief note, we introduce the new, emerging sub-discipline of iso-fractals by highlighting and discussing the preliminary results of recent works. First, we note the abundance of fractal, chaotic, non-linear, and self-similar structures in nature while emphasizing the importance of studying such systems because fractal geometry is the language of chaos. Second, we outline the iso-fractal generalization of the Mandelbrot set to exemplify the newly generated Mandelbrot iso-sets. Third, we present the cutting-edge notion of dynamic iso-spaces and explain how a mathematical space can be iso-topically lifted with iso-unit functions that (continuously or discretely) change; in the discrete case examples, we mention that iteratively generated sequences like Fibonacci’s numbers and (the complex moduli of) Mandelbrot’s numbers can supply a deterministic chain of iso-units to construct an ordered series of (magnified and/or de-magnified) iso-spaces that are locally iso-morphic. Fourth, we consider the initiation of iso-fractals with Inopin’s holographic ring (IHR) topology and fractional statistics for 2D and 3D iso-spaces. In total, the reviewed iso-fractal results are a significant improvement over traditional fractals because the application of Santilli’s iso-mathematics arms us an extra degree of freedom for attacking problems in chaos. Finally, we conclude by proposing some questions and ideas for future research work.

  15. CM and DM in an ISO R and D Environment

    NASA Technical Reports Server (NTRS)

    Crowley, Sandra L.

    2000-01-01

    ISO 9000 - a common buzz word in industry is making inroads to government agencies. The National Aeronautics and Space Agency (NASA) achieved ISO 9001 certification at each of its nine (9) Centers and Headquarters in 1998-1999. NASA Glenn Research Center (GRC) was recommended for certification in September 1999. Since then, each of the Centers has been going through the semi-annual surveillance audits. Growing out of the manufacturing industry, successful application of the international quality standard to a research and development (R&D) environment has had its challenges. This paper will address how GRC applied Configuration Management (CM) and Data (or Document) Management (DM) to meet challenges to achieve ISO certification. One of the first challenges was to fit the ISO 9001-1994 elements to the GRC environment. Some of the elements fit well-Management Responsibility (4.1), Internal Audits (4.17), Document and Data Control (4.5). Other elements were not suited or applied easily to the R&D environment-Servicing (4.19), Statistical Techniques (4.20). Since GRC "builds" only one or two items at a time, these elements were considered not applicable to the environment.

  16. Procedure for calculating general aircraft noise based on ISO 3891

    SciTech Connect

    Hediger, J.R.

    1982-01-01

    The standard ISO-3891 specifies the presentation of aircraft noise heard on the ground or of noise exposure by succession of aircraft, without giving any details on different parameters required to their calculation. The following study provides some of these parameters considering acoustic measurements as well as laboratory analysis realized in co-operation with the Swiss Federal Office for Civil Aviation.

  17. Information Asymmetries as Trade Barriers: ISO 9000 Increases International Commerce

    ERIC Educational Resources Information Center

    Potoski, Matthew; Prakash, Aseem

    2009-01-01

    Spatial, cultural, and linguistic barriers create information asymmetries between buyers and sellers that impede international trade. The International Organization for Standardization's ISO 9000 program is designed to reduce these information asymmetries by providing assurance about the product quality of firms that receive its certification.…

  18. Covenants with Weak Swords: ISO 14001 and Facilities' Environmental Performance

    ERIC Educational Resources Information Center

    Potoski, Matthew; Prakash, Aseem

    2005-01-01

    Voluntary environmental programs are codes of progressive environmental conduct that firms pledge to adopt. This paper investigates whether ISO 14001, a voluntary program with a weak sword--a weak monitoring and sanctioning mechanism--can mitigate shirking and improve participants' environmental performance. Sponsored by the International…

  19. A digital ISO expansion technique for digital cameras

    NASA Astrophysics Data System (ADS)

    Yoo, Youngjin; Lee, Kangeui; Choe, Wonhee; Park, SungChan; Lee, Seong-Deok; Kim, Chang-Yong

    2010-01-01

    Market's demands of digital cameras for higher sensitivity capability under low-light conditions are remarkably increasing nowadays. The digital camera market is now a tough race for providing higher ISO capability. In this paper, we explore an approach for increasing maximum ISO capability of digital cameras without changing any structure of an image sensor or CFA. Our method is directly applied to the raw Bayer pattern CFA image to avoid non-linearity characteristics and noise amplification which are usually deteriorated after ISP (Image Signal Processor) of digital cameras. The proposed method fuses multiple short exposed images which are noisy, but less blurred. Our approach is designed to avoid the ghost artifact caused by hand-shaking and object motion. In order to achieve a desired ISO image quality, both low frequency chromatic noise and fine-grain noise that usually appear in high ISO images are removed and then we modify the different layers which are created by a two-scale non-linear decomposition of an image. Once our approach is performed on an input Bayer pattern CFA image, the resultant Bayer image is further processed by ISP to obtain a fully processed RGB image. The performance of our proposed approach is evaluated by comparing SNR (Signal to Noise Ratio), MTF50 (Modulation Transfer Function), color error ~E*ab and visual quality with reference images whose exposure times are properly extended into a variety of target sensitivity.

  20. ISO 9000 Quality Systems: Application to Higher Education.

    ERIC Educational Resources Information Center

    Clery, Roger G.

    This paper describes and explains the 20 elements of the International Organization for Standards 9000 (ISO 9000) series, a model for quality assurance in the business processes of design/development, production, installation and servicing. The standards were designed in 1987 to provide a common denominator for business quality particularly to…

  1. Congenital isolated Iso-Kikuchi syndrome in a newborn.

    PubMed

    Valerio, Enrico; Favot, Francesca; Mattei, Ilaria; Cutrone, Mario

    2015-10-01

    Classic CO (also called Iso-Kikuchi syndrome) represents a benign, isolated condition associated with normal patient outcome. Nevertheless, clinical follow-up and/or further clinically-based tests are needed to exclude other nail diseases associated with multisystem pathology; complete family history is also important to determine sporadic or hereditary transmission of such condition. PMID:26509026

  2. Application of ISO 9000 Standards to Education and Training.

    ERIC Educational Resources Information Center

    Van den Berghe, Wouter

    1998-01-01

    ISO 9000 certification has the advantages of a measurable framework for quality efforts, continuous improvement, and better customer service. Drawbacks for education and training providers include volume of paperwork, ongoing cost, risk of a growing bureaucracy, and the difficulty of making changes quickly. (SK)

  3. Participation in the ISO Key Project - IPAC Project

    NASA Technical Reports Server (NTRS)

    Lo, Kwok-Yung

    2001-01-01

    This program used guaranteed ISO time to observe the interstellar medium in nearby galaxies. The goals of the program are to determine the origin of the infrared emission, to quantify the physical conditions of the interstellar medium, and to study the heating and physical properties of interstellar dust. This program has been carried out successfully, and produced a number of publications reporting the results.

  4. ISO observations of Titan with SWS/grating

    NASA Technical Reports Server (NTRS)

    Coustenis, A.; Encrenaz, T.; Salama, A.; Lellouch, E.; Gautier, D.; Kessler, M. F.; deGraauw, T.; Samuelson, R. E.; Bjoraker, G.; Orton, G.

    1997-01-01

    The observations of Titan performed by the Infrared Space Observatory (ISO) short wavelength spectrometer (SWS), in the 2 micrometer to 45 micrometer region using the grating mode, are reported on. Special attention is given to data from Titan concerning 7 micrometer to 45 micrometer spectral resolution. Future work for improving Titan's spectra investigation is suggested.

  5. The Challenge of ISO 9000 Certification in Higher Education.

    ERIC Educational Resources Information Center

    Crawford, Lachlan E. D.; Shutler, Paul M. E.

    1998-01-01

    Describes requirements for ISO 9000 certification in industry, using a factory example. Shows how requirements might be applied in higher education, with "product" being the actual learning outcome and "customer" anyone who purchases educational services. Addresses issues of continuous improvement in higher education. (SK)

  6. HERG1 Channel Agonists and Cardiac Arrhythmia

    PubMed Central

    Sanguinetti, Michael

    2014-01-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  7. HERG1 channel agonists and cardiac arrhythmia.

    PubMed

    Sanguinetti, Michael C

    2014-04-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  8. Foam-stabilizing effects and cling formation patterns of iso-alpha-acids and reduced iso-alpha-acids in lager beer.

    PubMed

    Kunimune, Takeshi; Shellhammer, Thomas H

    2008-09-24

    Foam-stabilizing properties and cling formation patterns of iso-alpha-acids and reduced iso-alpha-acids were investigated using an unhopped lager beer. Unhopped beer was dosed with iso-alpha-acid (Iso), rho-iso-alpha-acid (Rho), tetrahydro-iso-alpha-acid (Tetra), and hexahydro-iso-alpha-acid (Hexa), separately, over a range of concentrations from 2 to 10 ppm. A uniform foam was created by Inpack 2000 Flasher Head and was measured by a NIBEM Foam Stability Tester (NIBEM-TPH) followed by a NIBEM Cling Meter (NIBEM-CLM) to determine the relationship between the concentration and NIBEM-30 and the cling formation ability of each compound. The foam-stabilizing power was determined to be Tetra, Hexa, Iso, and Rho from the strongest to weakest. Linear regression models were created using the NIBEM-TPH data set, and on the basis of 95% confidence intervals, the foam stability of Tetra or Hexa became significantly larger than that of Iso when 2.4 or 4.2 ppm of Tetra or Hexa was used as a replacement for Iso, respectively. Cling formation patterns could be categorized into three groups: "ring", "mesh", and "powdery". The control beer had the lowest foam stability and did not yield any foam cling. PMID:18729457

  9. [Efforts to achieve and effects of acquiring ISO 15189 in Tokushima University Hospital].

    PubMed

    Shono, Kazuko; Kishi, Misako; Satou, Mituyo; Nagamine, Yasunori; Doi, Tosio

    2009-12-01

    The medical laboratory of Tokushima University Hospital acquired ISO 15189, an international standard for medical laboratories, on July 6th, 2007, resulting in it achieving the 24th place in Japan and 5th place among national university hospitals. The first surveillance was just performed on October 6th, 2008. Tokushima University Hospital, in which our medical laboratory is included as one section, already succeeded in acquiring ISO 9001, PrivacyMark System, and Quality Health Care ver. 5 before accomplishing ISO 15189. To achieve ISO 15189, we prepared documents based on ISO 9001 without any consultation, resulting in a review of the difference between ISO 9001 and ISO 15189 after the preliminary survey. Although achieving ISO 15189 resulted in an improvement in the reliability of laboratory results and accuracy, leading to the development of our technical skills and awareness, and sharing of knowledge, we consider that the considerable investment of time to prepare the requirements remains to be overcome. PMID:20077817

  10. 75 FR 16096 - New England Power Generators Association Inc., Complainant v. ISO New England Inc., Respondent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission New England Power Generators Association Inc., Complainant v. ISO New... Generators Association Inc. (Complainant) filed a formal complaint against ISO New England Inc....

  11. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

    Scheel, David; Godfrey-Smith, Peter; Lawrence, Matthew

    2016-02-01

    Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits. PMID:26832440

  12. Melanocortin 1 Receptor Agonists Reduce Proteinuria

    PubMed Central

    Ebefors, Kerstin; Johansson, Martin E.; Stefánsson, Bergur; Granqvist, Anna; Arnadottir, Margret; Berg, Anna-Lena; Nyström, Jenny; Haraldsson, Börje

    2010-01-01

    Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown. Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P < 0.01). Furthermore, treatment with MC1R agonists improved podocyte morphology and reduced oxidative stress. In summary, podocytes express MC1R, and MC1R agonism reduces proteinuria, improves glomerular morphology, and reduces oxidative stress in nephrotic rats with PHN. These data may explain the proteinuria-reducing effects of ACTH observed in patients with membranous nephropathy, and MC1R agonists may provide a new therapeutic option for these patients. PMID:20507942

  13. Cosmic water traced by Europe's space telescope ISO

    NASA Astrophysics Data System (ADS)

    1996-05-01

    In retracing this history, ISO also observes water in the form of ice in cooler regions around the stars, and in the dust surrounding young stars, from which planets could evolve. Comets represent an intermediate stage in planet-building, and they contain much water ice. According to one hypothesis the newly formed Earth received some of its water directly from impacting comets. Water vapour in the Earth's atmosphere has prevented telescopes on the ground from detecting the water vapour among the stars, except in very unusual circumstances. ISO orbiting in space escapes the impediment of the atmosphere. Excellent onboard instruments register the characteristic infrared signatures of water vapour, water ice and many other materials. When ISO scrutinizes selected objects, it detects emissions or absorptions of infrared rays at particular wavelengths, or "lines" in a spectrum, which reveal the presence of identifiable atoms, molecules and solids. The Short Wavelength Specrometer and the Long Wavelength Spectrometer provide detailed chemical diagnoses, and the photometer ISOPHOT and camera ISOCAM also have important spectroscopic capabilities. Examples of water detection were among many topics reviewed at the First ISO Science Workshop held at ESA's Research and Technology Centre (ESTEC) in Noordwijk, the Netherlands (29-31 May) when 300 astronomers from Europe, the USA and Japan gathered to assess results from ISO since its launch on 17 November 1995. The Long Wavelength Spectrometer has made remarkable observations of water-vapour lines in the vicinity of dying stars and in star-forming regions. So has the Short Wavelength Spectrometer, which also detects water ice. The photometer lSOPHOT has registered water ice in a large number of objects. Although fascinated by the natural history of water in the cosmos, astronomers have more technical reasons for welcoming ISO's observations. They can use thc details in a spectrum to reduce the abundance of water and its

  14. 78 FR 38027 - ISO New England Inc.; Notice of Initiation of Proceeding and Refund Effective Date

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ... Energy Regulatory Commission ISO New England Inc.; Notice of Initiation of Proceeding and Refund... determine the justness and reasonableness of section III.A.15 of Appendix A of ISO New England Inc.'s existing tariff. Dominion Energy Marketing, Inc. and ISO New England Inc., 143 FERC ] 61,233 (2013)....

  15. Iso-vector form factors of the delta and nucleon in QCD sum rules

    SciTech Connect

    Ozpineci, A.

    2012-10-23

    Form factors are important non-perturbative properties of hadrons. They give information about the internal structure of the hadrons. In this work, iso-vector axial-vector and iso-vector tensor form factors of the nucleon and the iso-vector axial-vector {Delta}{yields}N transition form factor calculations in QCD Sum Rules are presented.

  16. New water and remote galaxies complete ISO's observations

    NASA Astrophysics Data System (ADS)

    ISO's operational teams at ESA's ground station at Villafranca near Madrid have been hurrying to provide the world's astronomers with as many observations as possible. They have long anticipated the exhaustion of ISO's vital supply of liquid helium, which cooled the infrared telescope and its instruments to their operating temperatures, close to absolute zero. Two weeks after ISO was put into orbit on 17 November 1995 by an Ariane 44P launcher, the external parts of the cooling system had settled to the operating temperature. The specification required that ISO should then operate for at least 18 months -- implying that operations might have to end in May 1997. Thanks to superb engineering by European industry, which built the spacecraft and its super-cool telescope, ISO has given astronomers almost a year longer than that. During the extra time the count of ISO's observations of cosmic objects has risen from 16,000 to about 26,000. Among the benefits of ISO's longevity has been the chance to examine an important region of the sky, in and around the constellation of Orion. This was not accessible in the nominal mission but has now been observed in two periods. Four inter national teams, supported by national funding agencies, supplied the instruments to analyse the infrared rays received by ISO's telescope. The principal investigators leading the teams are Dietrich Lemke (Heidelberg, Germany) for the versatile photometer ISOPHOT, Catherine Cesarsky (Saclay, France) for the camera ISOCAM, Thijs de Graauw (Groningen, the Netherlands) for the Short Wavelength Spectrometer SWS, and Peter Clegg (London, UK) for the Long Wavelength Spectrometer LWS. Water vapour on Titan A big difference between ISO and the only previous infrared astronomy satellite (IRAS 1983) has been its ability to examine individual objects across a wide range of accurately defined infrared wavelengths. Many spectra showing patterns of intensities at the different wavelengths have enabled astronomers

  17. Tachykinin NK(3) receptor agonists induced microvascular leakage hypersensitivity in the guinea-pig airways.

    PubMed

    Daoui, S; Ahnaou, A; Naline, E; Emonds-Alt, X; Lagente, V; Advenier, C

    2001-12-21

    Microvascular leakage hypersensitivity is a main component of neurogenic inflammation and of tachykinin effects. The aim of this study was to examine the ability of neurokinin B and of the tachykinin NK(3) receptor agonists, [MePhe(7)]neurokinin B or senktide, to potentiate when given by aerosol the microvascular leakage induced by histamine in guinea-pig airways and to compare their effects to those of tachykinin NK(1) (substance P, [Sar(9),Met(O(2))(11)]substance P) or tachykinin NK(2) (neurokinin A, [betaAla(8)]neurokinin A (4-10)) receptor agonists. Guinea-pigs were pretreated successively for 10 min with aerolized salbutamol and phosphoramidon; 15 min later, they were exposed for 30 min to an aerosolized solution of tachykinin receptor agonists; 24 h later, the animals were anaesthetized and vascular permeability was quantified by extravasation of Evans blue dye. Neurokinin B, [MePhe(7)]neurokinin B and senktide (3 x 10(-6)-3 x 10(-5)M) induced a potentiation of the effects of histamine on the vascular permeability in the trachea and main bronchi. Compared to other tachykinin NK(1) and NK(2) receptor agonists, the order of potency was: senktide>neurokinin B=[Sar(9),Met(O(2))(11)]substance P=[betaAla(8)]neurokinin A (4-10)=[MePhe(7)]neurokinin B>neurokinin A>substance P. The potentiation by [MePhe(7)]neurokinin B of histamine-induced microvascular leakage was abolished by the tachykinin NK(1) receptor antagonist SR140333 ([(S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)piperidin-3-yl]etyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane, chloride]) or the tachykinin NK(3) receptor antagonists SR 142801 ([(R)-(N)-(1-(3-(l-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl) propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide]) and SB 223412 ([(S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide]). In conclusion, these results suggest that tachykinin NK(3) receptors might be involved in the potentiation of histamine-induced increase in microvascular

  18. Testing the Generalizability of the ISO Model for Nursing Diagnoses

    PubMed Central

    Harris, Marcelline; Kim, Hyeoneui; Rhudy, Lori; Savova, Guergana; Chute, Christopher

    2003-01-01

    The purpose of this study was to explore whether the ISO reference terminology model for nursing diagnoses could be generalized to the MDS data set that, like nursing terminologies standardizes expressions of the concepts within and relevant to the domain of nursing practice. We first constructed paraphrased expressions of the rubrics from the data set. Next we dissected those expressions into the reference model domains of focus and judgment, recorded any qualifiers required for either domain, and semantic links required to represent associative relations. Our findings demonstrate that the ISO model for nursing diagnoses is generalizable to the MDS data set, however expansions to the model are required if the model is to be used to represent objects rather than terms. PMID:14728177

  19. Space qualification of the ISO cryogenic rupture discs

    NASA Astrophysics Data System (ADS)

    Ettlinger, E.; Ruediger, H.; Wanner, M.

    1990-03-01

    Space cryostats, like the model to be used in the Infrared Space Observatory (ISO), require safety components to protect the satellite, the launcher, and the personnel against overpressure in the helium system. The ISO cryostat, which carries 2250 cu dm of liquid helium, will be equipped with a rupture disk as the ultimate safety component in case of loss of the insulation vacuum. Because it will have to operate under conditions of zero gravity and low pressure drop, the rupture disk has to be located directly on the helium tank and may thus release up to 5 kg/s of helium at a differential pressure of 2.6 bar directly into the insulation vacuum space. The selection and design of the rupture disk, as well as the test and qualification philosophy, are described.

  20. Dyonic ISO(7) supergravity and the duality hierarchy

    NASA Astrophysics Data System (ADS)

    Guarino, Adolfo; Varela, Oscar

    2016-02-01

    Motivated by its well defined higher dimensional origin, a detailed study of D = 4 {N}=8 supergravity with a dyonically gauged ISO(7)=SO(7)ltimes {{R}}^7 gauge group is performed. We write down the Lagrangian and describe the tensor and duality hierarchies, focusing on an interesting subsector with closed field equations and supersymmetry transformations. We then truncate the {N}=8 theory to some smaller sectors with {N}=2 and {N}=1 supersymmetry and SU(3), G2 and SO(4) bosonic symmetry. Canonical and superpotential formulations for these sectors are given, and their vacuum structure and spectra is analysed. Unlike the purely electric ISO(7) gauging, the dyonic gauging displays a rich structure of vacua, all of them AdS. We recover all previously known ones and find a new {N}=1 vacuum with SU(3) symmetry and various non-supersymmetric vacua, all of them stable within the full {N}=8 theory.

  1. Participation in the Infrared Space Observatory (ISO) Mission

    NASA Technical Reports Server (NTRS)

    Joseph, Robert D.

    2002-01-01

    All the Infrared Space Observatory (ISO) data have been transmitted from the ISO Data Centre, reduced, and calibrated. This has been rather labor-intensive as new calibrations for both the ISOPHOT and ISOCAM data have been released and the algorithms for data reduction have improved. We actually discovered errors in the calibration in earlier versions of the software. However the data reduction improvements have now converged and we have a self-consistent, well-calibrated database. It has also been a major effort to obtain the ground-based JHK imaging, 450 micrometer and 850 micrometer imaging and the 1-2.5 micrometer near-infrared spectroscopy for most of the sample galaxies.

  2. Why did ISO 9001:2008 system fail to deliver?

    PubMed

    Langford, Melvyn

    2014-02-01

    This article is based on an actual investigation undertaken, and summarises the subsequent report's findings and observations. It has been anonymised for obvious reasons. In May 2013 an analysis was undertaken by a multidisciplinary team that compared an NHS Trust estates department's managerial systems against the NHS national recommendations. The conclusions stated that: 'There was a systemic failure across a large number of topics generating intolerable/substantial risks to the organisation, its staff, and patients; this despite the department's managerial systems being accredited to the International Standard ISO 9001:2008'. The natural question raised when presented with this demonstrable and auditable evidence was: 'Why did the ISO 9001:2008 system fail?' PMID:24620489

  3. ISO(4,1) symmetry in the EFT of inflation

    SciTech Connect

    Creminelli, Paolo; Emami, Razieh; Simonović, Marko; Trevisan, Gabriele E-mail: emami@mail.ipm.ir E-mail: gtrevi@sissa.it

    2013-07-01

    In DBI inflation the cubic action is a particular linear combination of the two, otherwise independent, cubic operators π-dot {sup 3} and π-dot (∂{sub i}π){sup 2}. We show that in the Effective Field Theory (EFT) of inflation this is a consequence of an approximate 5D Poincar and apos;e symmetry, ISO(4,1), non-linearly realized by the Goldstone π. This symmetry uniquely fixes, at lowest order in derivatives, all correlation functions in terms of the speed of sound c{sub s}. In the limit c{sub s} → 1, the ISO(4,1) symmetry reduces to the Galilean symmetry acting on π. On the other hand, we point out that the non-linear realization of SO(4,2), the isometry group of 5D AdS space, does not fix the cubic action in terms of c{sub s}.

  4. Neutron diffraction studies of liquid iso-propanol

    NASA Astrophysics Data System (ADS)

    Zetterström, P.; Dahlborg, U.; Delaplane, R. G.; Howells, W. S.

    1991-07-01

    The structure of deuterated liquid iso-propanol has been studied with neutron diffraction at the LAD diffractometer at the ISIS spallation source. Measurements were performed at temperatures 190, 220, 250 and 275 K. To correct for inelastic effects a model for the dynamic structure factor which obeys detailed balance and included recoil effects was used. The static molecular structure factor SM(Q) exhibits a pre-peak at about 0.75 Å-1. The origin of the pre-peak, which increases in amplitude with temperature, is presently unknown. The structure of the iso-propanol molecule was obtained from the total pair distribution function and from a fit of the intramolecular form factor f1(Q) to the measured SM(Q) at large Q. The obtained values of the bond length and Debye-Waller factors are in good agreement to those obtained from lower alcohols.

  5. High-intensity cyclotron for the IsoDAR experiment

    NASA Astrophysics Data System (ADS)

    Campo, D.; IsoDAR Collaboration

    2015-03-01

    The IsoDAR experiment is the MIT proposal to investigate about several neutrino properties, in order to explain some anomalies experimentally observed. It requires 10mA of proton beam at the energy of 60MeV to produce a high-intensity electron antineutrino flux from the production and the decay of 8Li: it is an ambitious goal for the accelerator design, due also to the fact that the machine has to be placed near a neutrino detector, like KAMLAND or WATCHMAN, located in underground sites. A compact cyclotron able to accelerate H2+ molecule beam up to energy of 60MeV/amu is under study. The critical issues of this machine concern the beam injection due to the effects of space charge, the efficiency of the beam extraction and the technical solutions needed to the machine assembly. Here, the innovative solutions and the preliminary results achieved by the IsoDAR team are discussed.

  6. Gap Analysis Comparing LLNL ISMS and ISO 14001

    SciTech Connect

    Doerr, T B

    2004-08-09

    A gap analysis was conducted comparing the Lawrence Livermore National Laboratory (LLNL) Integrated Safety Management System (ISMS) with the international standard ISO 14001 Environmental Management System and with Department of Energy (DOE) Order 450.1. This analysis was accomplished as part of LLNL's assessment of the impacts of adopting DOE Order 450.1 and comprises a portion of its continuous improvement efforts under ISMS.

  7. Evaluation of environmental aspects significance in ISO 14001.

    PubMed

    Põder, Tõnis

    2006-05-01

    The methodological framework set by standards ISO 14001 and ISO 14004 gives only general principles for environmental aspects assessment, which is regarded as one of the most critical stages of implementing environmental management system. In Estonia, about 100 organizations have been certified to the ISO 14001. Experience obtained from numerous companies has demonstrated that limited transparency and reproducibility of the assessment process serves as a common shortcoming. Despite rather complicated assessment schemes sometimes used, the evaluation procedures have been largely based on subjective judgments because of ill-defined and inadequate assessment criteria. A comparison with some similar studies in other countries indicates a general nature of observed inconsistencies. The diversity of approaches to the aspects' assessment in concept literature and to the related problems has been discussed. The general structure of basic assessment criteria, compatible with environmental impact assessment and environmental risk analysis has also been outlined. Based on this general structure, the article presents a tiered approach to help organize the assessment in a more consistent manner. PMID:16508807

  8. Dopamine agonist: pathological gambling and hypersexuality.

    PubMed

    2008-10-01

    (1) Pathological gambling and increased sexual activity can occur in patients taking dopaminergic drugs. Detailed case reports and small case series mention serious familial and social consequences. The frequency is poorly documented; (2) Most affected patients are being treated for Parkinson's disease, but cases have been reported among patients prescribed a dopamine agonist for restless legs syndrome or pituitary adenoma; (3) Patients treated with this type of drug, and their relatives, should be informed of these risks so that they can watch for changes in behaviour. If such disorders occur, it may be necessary to reduce the dose or to withdraw the drug or replace it with another medication. PMID:19536937

  9. Modulation of Innate Immune Responses via Covalently Linked TLR Agonists

    PubMed Central

    2015-01-01

    We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed in vivo studies using a vaccinia vaccination model. Mice vaccinated with the linked TLR agonists showed an increase in antibody depth and breadth compared to mice vaccinated with the unconjugated mixture. These studies demonstrate how activation of multiple TLRs through chemically and spatially defined organization assists in guiding immune responses, providing the potential to use chemical tools to design and develop more effective vaccines. PMID:26640818

  10. Mechanisms of agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Lin, Hong; Strange, Philip G

    2004-12-01

    In this study, we investigated the biochemical mechanisms of agonist action at the G protein-coupled D2 dopamine receptor expressed in Chinese hamster ovary cells. Stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding by full and partial agonists was determined at different concentrations of [35S]GTPgammaS (0.1 and 10 nM) and in the presence of different concentrations of GDP. At both concentrations of [35S]GTPgammaS, increasing GDP decreased the [35S]GTPgammaS binding observed with maximally stimulating concentrations of agonist, with partial agonists exhibiting greater sensitivity to the effects of GDP than full agonists. The relative efficacy of partial agonists was greater at the lower GDP concentrations. Concentration-response experiments were performed for a range of agonists at the two [35S]GTPgammaS concentrations and with different concentrations of GDP. At 0.1 nM [35S]GTPgammaS, the potency of both full and partial agonists was dependent on the GDP concentration in the assays. At 10 nM [35S]GTPgammaS, the potency of full agonists exhibited a greater dependence on the GDP concentration, whereas the potency of partial agonists was virtually independent of GDP. We concluded that at the lower [35S]GTPgammaS concentration, the rate-determining step in G protein activation is the binding of [35S]GTPgammaS to the G protein. At the higher [35S]GTPgammaS concentration, for full agonists, [35S]GTPgammaS binding remains the slowest step, whereas for partial agonists, another (GDP-independent) step, probably ternary complex breakdown, becomes rate-determining. PMID:15340043

  11. The influence of motivations for seeking ISO 14001 certification: an empirical study of ISO 14001 certified facilities in Hong Kong.

    PubMed

    Fryxell, Gerald E; Szeto, Agnes

    2002-07-01

    This study proposes a model linking firm motivations for seeking ISO 14001 certification to the effectiveness of three major components of an environmental management system (EMS)--environmental policy, the assessment of environmental aspect and impacts, and management review. The relationship of these EMS components with a self-reported measure of environmental performance is also examined. From a sample of 29 ISO 14001 certified facilities in Hong Kong (of 71 total certifications at the time the data was collected), it was found that motivations to enhance firm reputation are positively related to perceptions of the effectiveness of the policy statement. Motivations for reputation enhancement and cost reduction were positively related to perceptions of EMS effectiveness in assessing environmental aspects and impacts. The effectiveness of the methodology for identifying environmental aspects and impacts was also found to be positively related to improved environmental performance. PMID:12357656

  12. Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets.

    PubMed

    Yamazaki, Aiko; Yashiro, Masateru; Mii, Sumiyuki; Aki, Ryoichi; Hamada, Yuko; Arakawa, Nobuko; Kawahara, Katsumasa; Hoffman, Robert M; Amoh, Yasuyuki

    2016-03-01

    Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the follicle. Previous studies have shown that HAP stem cells can differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. HAP stem cells effected nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. The differentiation potential to cardiac muscle cells was greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol. In the present study, we observed that isoproterenol directs HAP stem cells to differentiate to cardiac muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. These results demonstrate that HAP stem cells have great potential to form beating cardiac muscle cells in tissue sheets. PMID:27104748

  13. Computational modeling toward understanding agonist binding on dopamine 3.

    PubMed

    Zhao, Yaxue; Lu, Xuefeng; Yang, Chao-Yie; Huang, Zhimin; Fu, Wei; Hou, Tingjun; Zhang, Jian

    2010-09-27

    The dopamine 3 (D3) receptor is a promising therapeutic target for the treatment of nervous system disorders, such as Parkinson's disease, and current research interests primarily focus on the discovery/design of potent D3 agonists. Herein, a well-designed computational protocol, which combines pharmacophore identification, homology modeling, molecular docking, and molecular dynamics (MD) simulations, was employed to understand the agonist binding on D3 aiming to provide insights into the development of novel potent D3 agonists. We (1) identified the chemical features required in effective D3 agonists by pharmacophore modeling based upon 18 known diverse D3 agonists; (2) constructed the three-dimensional (3D) structure of D3 based on homology modeling and the pharmacophore hypothesis; (3) identified the binding modes of the agonists to D3 by the correlation between the predicted binding free energies and the experimental values; and (4) investigated the induced fit of D3 upon agonist binding through MD simulations. The pharmacophore models of the D3 agonists and the 3D structure of D3 can be used for either ligand- or receptor-based drug design. Furthermore, the MD simulations further give the insight that the long and flexible EL2 acts as a "door" for agonist binding, and the "ionic lock" at the bottom of TM3 and TM6 is essential to transduce the activation signal. PMID:20695484

  14. Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes.

    PubMed

    Agnati, Luigi F; Guidolin, Diego; Cervetto, Chiara; Borroto-Escuela, Dasiel O; Fuxe, Kjell

    2016-01-01

    Intercellular and intracellular communication processes consist of signals and recognition/decoding apparatuses of these signals. In humans, the G protein-coupled receptor (GPCR) family represents the largest family of cell surface receptors. More than 30 years ago, it has been proposed that GPCR could form dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane level and receptor-receptor interactions [RRIs] have been proposed as a new integrative mechanism for chemical signals impinging on cell plasma membranes). The basic phenomena involved in RRIs are allostery and cooperativity of membrane receptors, and the present paper provides basic information concerning their relevance for the integrative functions of RMs. In this context, the possible role of iso-receptor RM is discussed (with a special focus on dopamine receptor subtypes and on some of the RMs they form with other dopamine iso-receptors), and it is proposed that two types of cooperativity, namely, homotropic and heterotropic cooperativity, could allow distinguishing two types of functionally different RMs. From a general point of view, the presence of iso-receptors and their topological organization within RMs allow the use of a reduced number of signals for the intercellular communication processes, since the target cells can recognize and decode the same signal in different ways. This theoretical aspect is further analyzed here by means of an analogy with artificial information systems. Thus, it is suggested that the 'multiplexer' and 'demultiplexer' concepts could, at least in part, model the role of RMs formed by iso-receptors in the information handling by the cell. PMID:26418645

  15. ISO finds a very steamy cloud in interstellar space

    NASA Astrophysics Data System (ADS)

    1998-04-01

    The discovery, which may provide an important clue to the origin of water in the Solar System, is reported in an article in Astrophysical Journal Letters, to be published on 20 April. This Information Note is distributed simultaneously with a Press Release on the same subject from Cornell University, Johns Hopkins University, the Harvard/Smithsonian Center for Astrophysics, and NASA's Ames Research Center. The water vapour is in the Orion Molecular Cloud, a giant interstellar mass composed primarily of hydrogen molecules. The observations were carried out in October 1997 with the Long Wavelength Spectrometer, devised by a British-led team as one of four instruments on board ISO. Looking at long infrared wavelengths, the astronomers saw the characteristic signature of emission by water vapour. "The interstellar gas cloud that we observed is being pummelled by shock waves that compress and heat the gas," says Martin Harwit of Cornell University, an ISO mission scientist and lead author on the article reporting the finding. "These shock waves are the result of the violent early stages of starbirth, in which a young star spews out gas that slams into its surroundings at high speed. The heated water vapour that we observed is the result of that collision." Harwit also suggests that shock waves are a cause of starbirth as well as a result. "In the future," he says, "they may also trigger the formation of additional stars and planets as they compress the gas cloud that we observed, but only if surplus heat can be radiated away. Even though the interstellar gas is composed primarily of hydrogen molecules, water vapour is a particularly efficient radiator at far-infrared wavelengths and plays a critical role in cooling the gas and facilitating the star formation process. Because the Earth's own wet atmosphere is completely opaque at the wavelengths of interest, the observations that we are reporting today are possible only from space with the use of the ISO satellite." A

  16. Strategies for designing synthetic immune agonists.

    PubMed

    Wu, Tom Y-H

    2016-08-01

    Enhancing the immune system is a validated strategy to combat infectious disease, cancer and allergy. Nevertheless, the development of immune adjuvants has been hampered by safety concerns. Agents that can stimulate the immune system often bear structural similarities with pathogen-associated molecular patterns found in bacteria or viruses and are recognized by pattern recognition receptors (PRRs). Activation of these PRRs results in the immediate release of inflammatory cytokines, up-regulation of co-stimulatory molecules, and recruitment of innate immune cells. The distribution and duration of these early inflammatory events are crucial in the development of antigen-specific adaptive immunity in the forms of antibody and/or T cells capable of searching for and destroying the infectious pathogens or cancer cells. However, systemic activation of these PRRs is often poorly tolerated. Hence, different strategies have been employed to modify or deliver immune agonists in an attempt to control the early innate receptor activation through temporal or spatial restriction. These approaches include physicochemical manipulation, covalent conjugation, formulation and conditional activation/deactivation. This review will describe recent examples of discovery and optimization of synthetic immune agonists towards clinical application. PMID:27213842

  17. Proglumide exhibits delta opioid agonist properties.

    PubMed

    Rezvani, A; Stokes, K B; Rhoads, D L; Way, E L

    1987-01-01

    Recently, it was reported that proglumide, a cholecystokinin (CCK) antagonist, potentiates the analgetic effects of morphine and endogenous opioid peptides and reverses morphine tolerance by antagonizing the CCK system in the central nervous system of the rat. In order to provide additional insight into the mode of action of this agent, we assessed the effect of proglumide in the isolated guinea pig ileum and the mouse, rat and rabbit vas deferens. Furthermore, we studied the in vitro binding affinity of this substance to mouse brain synaptosomes. Our results show that proglumide inhibits, dose dependently, the electrically stimulated twitches in the mouse vas deferens and guinea pig ileum, but not in the rat or rabbit vas deferens. The inhibitory action of proglumide on the mouse vas deferens, but not on the guinea pig ileum, is antagonized by naloxone and by the selective delta-antagonist, ICI 174,864, in a competitive fashion. Other CCK antagonists were found to be devoid of such activity on the mouse vas deferens. In vitro binding studies showed that proglumide displaces D-ala-D-[leucine]5-enkephalin (DADLE), a delta agonist, but not ethylketocyclazocine (EKC), a preferentially selective kappa agonist. The effect of proglumide appeared to be elicited presynaptically since it did not alter the norepinephrine-induced contractions of the mouse vas deferens. Our results suggest that proglumide might exert its opiate-like effects by activation of delta-opioid receptors. PMID:3030338

  18. Chimpanzees Extract Social Information from Agonistic Screams

    PubMed Central

    Slocombe, Katie E.; Kaller, Tanja; Call, Josep; Zuberbühler, Klaus

    2010-01-01

    Chimpanzee (Pan troglodytes) agonistic screams are graded vocal signals that are produced in a context-specific manner. Screams given by aggressors and victims can be discriminated based on their acoustic structure but the mechanisms of listener comprehension of these calls are currently unknown. In this study, we show that chimpanzees extract social information from these vocal signals that, combined with their more general social knowledge, enables them to understand the nature of out-of-sight social interactions. In playback experiments, we broadcast congruent and incongruent sequences of agonistic calls and monitored the response of bystanders. Congruent sequences were in accordance with existing social dominance relations; incongruent ones violated them. Subjects looked significantly longer at incongruent sequences, despite them being acoustically less salient (fewer call types from fewer individuals) than congruent ones. We concluded that chimpanzees categorised an apparently simple acoustic signal into victim and aggressor screams and used pragmatics to form inferences about third-party interactions they could not see. PMID:20644722

  19. Europe's space telescope ISO finds water in distant places

    NASA Astrophysics Data System (ADS)

    1997-04-01

    Equally striking is ISO's discovery of water vapour in the outer planets, Saturn, Uranus and Neptune. As those chilly planets cannot release water from within, they probably have a supply of water coming from elsewhere in the Solar System. Since ISO went into orbit at the end of 1995, it has used its unique power of analysing infrared rays coming from the Universe to identify water vapour and water ice near dying stars and newborn stars. It has also measured the water vapour steaming from Comet Hale-Bopp. "Before ISO no instrument was capable of detecting water in so many places," comments ESA's director of science, Roger Bonnet. "To start revealing the cosmic history of the Earth's water is a big success for ESA and for the astronomers who use our unique infrared observatory. And ISO's discovery that water is commonplace in the Galaxy will encourage renewed speculation about life that may exist in the vicinity of other stars." Water amid the stars Primaeval hydrogen atoms make water by joining with oxygen atoms that are manufactured within stars, in nuclear reactions occurring towards the end of a star's life. Oxygen from defunct stars enriches the Galaxy, and abundant hydrogen is available to react with it. Although the existence of water in interstellar space is not surprising, the Earth's moist atmosphere makes life difficult for any astronomer who wishes to spot water vapour in the Universe with ground-based instruments. Observations from aircraft and balloons gave early hints of cosmic water, but thorough investigations had to wait for ISO's unhampered view from space. Three of the satellite's instruments, the Short Wavelength Spectrometer (SWS), the Long Wavelength Spectrometer (LWS) and the photometer ISOPHOT operating in spectroscopic mode, take part in the hunt for water. Last year, for example, users of both SWS and LWS reported water vapour in the vicinity of the aged star, W Hydrae, from which oxygen-rich winds blow into space. The bright infrared

  20. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  1. Physical Chemistry to the Rescue: Differentiating Nicotinic and Cholinergic Agonists

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researches suggest that two agonists can bind to the same binding site of an important transmembrane protein and elicit a biological response through strikingly different binding interactions. Evidence is provided which suggests two possible types of nicotinic acetylcholine receptor agonist binding like acetlycholine (cholinergic) or like nicotine…

  2. ISO/TC 172 'Optics And Optical Instruments'

    NASA Astrophysics Data System (ADS)

    Kittel, Hans F.

    1989-04-01

    In the sixties and seventies, optical items were dealt with in several different Technical Committees of the International Standardization Organization (ISO). TC 10 'Technical drawings' got prepared to day down drawing rules for technical components, TC 22 'Road vehicles' defined terms of physiological optics because of the connection between seeing and driving motor vehicles, TC 59 'Building construction' standardized geodetic instruments, TC 94 'Personal safety - Protective clothing and equipment laid down requirements for sun glasses, and finally Working Group 12 of TC 42 'Photography' was going to work on various optical test methods and requirements for coatings.

  3. ncISO Facilitating Metadata and Scientific Data Discovery

    NASA Astrophysics Data System (ADS)

    Neufeld, D.; Habermann, T.

    2011-12-01

    Increasing the usability and availability climate and oceanographic datasets for environmental research requires improved metadata and tools to rapidly locate and access relevant information for an area of interest. Because of the distributed nature of most environmental geospatial data, a common approach is to use catalog services that support queries on metadata harvested from remote map and data services. A key component to effectively using these catalog services is the availability of high quality metadata associated with the underlying data sets. In this presentation, we examine the use of ncISO, and Geoportal as open source tools that can be used to document and facilitate access to ocean and climate data available from Thematic Realtime Environmental Distributed Data Services (THREDDS) data services. Many atmospheric and oceanographic spatial data sets are stored in the Network Common Data Format (netCDF) and served through the Unidata THREDDS Data Server (TDS). NetCDF and THREDDS are becoming increasingly accepted in both the scientific and geographic research communities as demonstrated by the recent adoption of netCDF as an Open Geospatial Consortium (OGC) standard. One important source for ocean and atmospheric based data sets is NOAA's Unified Access Framework (UAF) which serves over 3000 gridded data sets from across NOAA and NOAA-affiliated partners. Due to the large number of datasets, browsing the data holdings to locate data is impractical. Working with Unidata, we have created a new service for the TDS called "ncISO", which allows automatic generation of ISO 19115-2 metadata from attributes and variables in TDS datasets. The ncISO metadata records can be harvested by catalog services such as ESSI-labs GI-Cat catalog service, and ESRI's Geoportal which supports query through a number of services, including OpenSearch and Catalog Services for the Web (CSW). ESRI's Geoportal Server provides a number of user friendly search capabilities for end users

  4. Comparative study of minutiae selection algorithms for ISO fingerprint templates

    NASA Astrophysics Data System (ADS)

    Vibert, B.; Charrier, C.; Le Bars, J.-M.; Rosenberger, C.

    2015-03-01

    We address the selection of fingerprint minutiae given a fingerprint ISO template. Minutiae selection plays a very important role when a secure element (i.e. a smart-card) is used. Because of the limited capability of computation and memory, the number of minutiae of a stored reference in the secure element is limited. We propose in this paper a comparative study of 6 minutiae selection methods including 2 methods from the literature and 1 like reference (No Selection). Experimental results on 3 fingerprint databases from the Fingerprint Verification Competition show their relative efficiency in terms of performance and computation time.

  5. Relating electrophotographic printing model and ISO13660 standard attributes

    NASA Astrophysics Data System (ADS)

    Barney Smith, Elisa H.

    2010-01-01

    A mathematical model of the electrophotographic printing process has been developed. This model can be used for analysis. From this a print simulation process has been developed to simulate the effects of the model components on toner particle placement. A wide variety of simulated prints are produced from the model's three main inputs, laser spread, charge to toner proportionality factor and toner particle size. While the exact placement of toner particles is a random process, the total effect is not. The effect of each model parameter on the ISO 13660 print quality attributes line width, fill, raggedness and blurriness is described.

  6. Solution structure of oxidized Saccharomyces cerevisiae iso-1-cytochrome c.

    PubMed

    Banci, L; Bertini, I; Bren, K L; Gray, H B; Sompornpisut, P; Turano, P

    1997-07-22

    The solution structure of oxidized Saccharomycescerevisiae Cys102Ser iso-1-cytochromechas been determined using 1361 meaningful NOEs (of 1676 total) after extending the published proton assignment [Gao, Y., et al. (1990) Biochemistry 29, 6994-7003] to 77% of all proton resonances. The NOE patterns indicate that secondary structure elements are maintained upon oxidation in solution with respect to the solid state and solution structures of the reduced species. Constraints derived from the pseudocontact shifts [diamagnetic reference shift values are those of the reduced protein [Baistrocchi, P., et al. (1996) Biochemistry 35, 13788-13796

  7. Communication - An Effective Tool for Implementing ISO 14001/EMS

    SciTech Connect

    Rachel Damewood; Bowen Huntsman

    2004-04-01

    The Idaho National Engineering and Environmental Laboratory (INEEL) received ISO 14001/EMS certification in June 2002. Communication played an effective role in implementing ISO 14001/EMS at the INEEL. This paper describes communication strategies used during the implementation and certification processes. The INEEL achieved Integrated Safety Management System (ISMS) and Voluntary Protection Program (VPP) Star status in 2001. ISMS implemented a formal process to plan and execute work. VPP facilitated worker involvement by establishing geographic units at various facilities with employee points of contact and management champions. The INEEL Environmental Management System (EMS) was developed to integrate the environmental functional area into its ISMS and VPP. Since the core functions of ISMS, VPP, and EMS are interchangeable, they were easy to integrate. Communication is essential to successfully implement an EMS. (According to ISO 14001 requirements, communication interacts with 12 other elements of the requirements.) We developed communication strategies that integrated ISMS, VPP, and EMS. For example, the ISMS, VPP, and EMS Web sites communicated messages to the work force, such as “VPP emphasizes the people side of doing business, ISMS emphasizes the system side of doing business, and EMS emphasizes the systems to protect the environment; but they all define work, identify and analyze hazards, and mitigate the hazards.” As a result of this integration, the work force supported and implemented the EMS. In addition, the INEEL established a cross-functional communication team to assist with implementing the EMS. The team included members from the Training and Communication organizations, VPP office, Pollution Prevention, Employee and Media Relations, a union representative, facility environmental support, and EMS staff. This crossfunctional team used various communication strategies to promote our EMS to all organization levels and successfully implemented EMS

  8. ISO 9000 and/or Systems Engineering Capability Maturity Model?

    NASA Technical Reports Server (NTRS)

    Gholston, Sampson E.

    2002-01-01

    For businesses and organizations to remain competitive today they must have processes and systems in place that will allow them to first identify customer needs and then develop products/processes that will meet or exceed the customers needs and expectations. Customer needs, once identified, are normally stated as requirements. Designers can then develop products/processes that will meet these requirements. Several functions, such as quality management and systems engineering management are used to assist product development teams in the development process. Both functions exist in all organizations and both have a similar objective, which is to ensure that developed processes will meet customer requirements. Are efforts in these organizations being duplicated? Are both functions needed by organizations? What are the similarities and differences between the functions listed above? ISO 9000 is an international standard of goods and services. It sets broad requirements for the assurance of quality and for management's involvement. It requires organizations to document the processes and to follow these documented processes. ISO 9000 gives customers assurance that the suppliers have control of the process for product development. Systems engineering can broadly be defined as a discipline that seeks to ensure that all requirements for a system are satisfied throughout the life of the system by preserving their interrelationship. The key activities of systems engineering include requirements analysis, functional analysis/allocation, design synthesis and verification, and system analysis and control. The systems engineering process, when followed properly, will lead to higher quality products, lower cost products, and shorter development cycles. The System Engineering Capability Maturity Model (SE-CMM) will allow companies to measure their system engineering capability and continuously improve those capabilities. ISO 9000 and SE-CMM seem to have a similar objective, which

  9. Arranging ISO 13606 archetypes into a knowledge base.

    PubMed

    Kopanitsa, Georgy

    2014-01-01

    To enable the efficient reuse of standard based medical data we propose to develop a higher level information model that will complement the archetype model of ISO 13606. This model will make use of the relationships that are specified in UML to connect medical archetypes into a knowledge base within a repository. UML connectors were analyzed for their ability to be applied in the implementation of a higher level model that will establish relationships between archetypes. An information model was developed using XML Schema notation. The model allows linking different archetypes of one repository into a knowledge base. Presently it supports several relationships and will be advanced in future. PMID:25160140

  10. Estrogen receptor beta agonists in neurobehavioral investigations.

    PubMed

    Choleris, Elena; Clipperton, Amy E; Phan, Anna; Kavaliers, Martin

    2008-07-01

    Neurobehavioral investigations into the functions of estrogen receptor (ER)alpha and ERbeta have utilized 'knockout' mice, phytoestrogens and, more recently, ER-specific agonists. Feeding, sexual, aggressive and social behavior, anxiety, depression, drug abuse, pain perception, and learning (and associated synaptic plasticity) are affected by ERalpha and ERbeta in a manner that is dependent upon the specific behavior studied, gender and developmental stage. Overall, ERalpha and ERbeta appear to function together to foster sociosexual behavior while inhibiting behaviors that, if occurring at the time of behavioral estrous, may compete with reproduction (eg, feeding). Recently developed pharmacological tools have limited selectivity and availability to the research community at large, as they are not commercially available. The development of highly selective, commercially available ERbeta-specific antagonists would greatly benefit preclinical and applied research. PMID:18600582

  11. Non-Benzodiazepine Receptor Agonists for Insomnia.

    PubMed

    Becker, Philip M; Somiah, Manya

    2015-03-01

    Because of proven efficacy, reduced side effects, and less concern about addiction, non-benzodiazepine receptor agonists (non-BzRA) have become the most commonly prescribed hypnotic agents to treat onset and maintenance insomnia. First-line treatment is cognitive-behavioral therapy. When pharmacologic treatment is indicated, non-BzRA are first-line agents for the short-term and long-term management of transient and chronic insomnia related to adjustment, psychophysiologic, primary, and secondary causation. In this article, the benefits and risks of non-BzRA are reviewed, and the selection of a hypnotic agent is defined, based on efficacy, pharmacologic profile, and adverse events. PMID:26055674

  12. ISO 14000 information platform. Quarterly report, January 1--March 31, 1998

    SciTech Connect

    1998-09-01

    GETE, through its ISO 14000 Information Platform, globeNet{trademark} (www.iso14000.net), seeks to provide FETC and the US Department of Energy (DOE) with a timely, accurate, and reliable information resource on the issue of environmental management standards. This resource allows FETC to keep track of the latest developments in the ISO 14000 arena, in DOE as well as throughout the federal complex and industry. Utilizing this information, FETC and DOE can make critical decisions on their own use and implementation of the ISO 14000 standards. The information platform also provides FETC with a forum to present information on its activities, such as the DOE ISO 14000 Pilot Projects, and as an information gathering and dissemination resource for its publications. GETE works with an array of national and international contacts and content sources to gather information and provide daily updates on ISO 14000 and related environmental management issues.

  13. [Activity of ISO/TC212, clinical laboratory testing and in vitro diagnostic test systems].

    PubMed

    Kawai, T

    1998-10-01

    ISO is the International Organization for Standardization, which is a worldwide federation of national standards bodies from 130 countries, one from each country. ISO is a non-governmental organization established in 1947. ISO/TC212, Clinical laboratory testing and in vitro diagnostic test systems was newly established in 1995, consisting of 86 P-members and 12 O-members. ISO/TC212 secretariat is the American National Standards Institute, and NCCLS carries out its secretarial activity. On behalf of the Japanese Industrial Standards Committee (JISC), the Japanese Committee for Clinical Laboratory Standards (JCCLS) serves as the secretariat for the ISO/TC212 National Technical Advisory Group. Three working groups are in the process of preparing the Draft International Standards (DIS) among 9 work items. The next plenary session of ISO/TC212 will be held on May 19-21, 1999 in Tokyo, Japan. PMID:9816905

  14. ISO 9001 : 2000 and the Baldrige criteria for performance excellence - a comparison.

    SciTech Connect

    Willette, Gail L.; Richards, Robert Ray

    2004-06-01

    The Sandia National Laboratories Nuclear Weapons Strategic Management Unit (NWSMU) is pursuing performance excellence, by focusing on compliance with the ISO 9001:2000 standard for quality management systems. The NWSMU also intends to achieve ISO Certification and eventually reach levels of performance excellence that are consistent with those of Malcolm Baldrige National Quality Award winners. In that context, this report documents a study undertaken to answer these questions: {sm_bullet} Would achieving ISO 9001:2000 compliance or certification help an organization prepare to achieve Baldrige-level performance excellence? {sm_bullet} Would pursuing Baldrige-based performance excellence help an organization achieve ISO certification? {sm_bullet} What are the areas where the Baldrige and ISO systems are most closely aligned? The study produced answers to those questions, as well as a number of comparisons and contrasts between the ISO standard and the Baldrige criteria.

  15. Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl.

    PubMed

    Maguire, David R; France, Charles P

    2016-08-01

    Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ(9)-THC) enhance some (antinociceptive) but not other (positive reinforcing) effects of mu opioid receptor agonists, suggesting that cannabinoids might be combined with opioids to treat pain without increasing, and possibly decreasing, abuse. The degree to which cannabinoids enhance antinociceptive effects of opioids varies across drugs insofar as Δ(9)-THC and the synthetic cannabinoid receptor agonist CP55940 increase the potency of some mu opioid receptor agonists (e.g., fentanyl) more than others (e.g., nalbuphine). It is not known whether interactions between cannabinoids and opioids vary similarly for other (abuse-related) effects. This study examined whether Δ(9)-THC and CP55940 differentially impact the discriminative stimulus effects of fentanyl and nalbuphine in monkeys (n=4) discriminating 0.01mg/kg of fentanyl (s.c.) from saline. Fentanyl (0.00178-0.0178mg/kg) and nalbuphine (0.01-0.32mg/kg) dose-dependently increased drug-lever responding. Neither Δ(9)-THC (0.032-1.0mg/kg) nor CP55940 (0.0032-0.032mg/kg) enhanced the discriminative stimulus effects of fentanyl or nalbuphine; however, doses of Δ(9)-THC and CP55940 that shifted the nalbuphine dose-effect curve markedly to the right and/or down were less effective or ineffective in shifting the fentanyl dose-effect curve. The mu opioid receptor antagonist naltrexone (0.032mg/kg) attenuated the discriminative stimulus effects of fentanyl and nalbuphine similarly. These data indicate that the discriminative stimulus effects of nalbuphine are more sensitive to attenuation by cannabinoids than those of fentanyl. That the discriminative stimulus effects of some opioids are more susceptible to modification by drugs from other classes has implications for developing maximally effective therapeutic drug mixtures with reduced abuse liability. PMID:27184925

  16. Interim Report on ISO TC 163 Working Group 3. Annual progress report

    SciTech Connect

    Fairey, Philip

    2009-04-02

    This reports cover the initial year efforts of the International Standards Organization (ISO) to develop international standards for rating the energy performance of buildings. The author of this report is a participant in this effort. This report summarizes the activities of the ISO Working Group charged with development of these standards and makes recommendations to the sponsors for future U.S. involvement in this ISO effort.

  17. Development of ISO connection-oriented/correctionless gateways

    NASA Technical Reports Server (NTRS)

    Landweber, Lawrence H.

    1991-01-01

    The project had two goals, establishment of a gateway between French and U.S. academic networks and studies of issues related to the development of ISO connection-oriented/connectionless (CO/CL) gateways. The first component involved installation of a 56K bps line between Princeton Univ. and INRIA in France. The end-points of these lines were connected by Vitalink link level bridges. The Princeton end was then connected to the NSFNET via the John Von Neumann Supercomputer Center. The French end was connected to Transpac, the French X.25 public data network and to the French IP research internet. U.S. users may communicate with users of the French internet by e-mail and may access computational and data resources in France by use of remote login and file transfer. The connection to Transpac enables U.S. users to access the SIMBAD astronomical database outside of Paris. Access to this database from the U.S. can be via TCP/IP or DECNET (via a DECNET to TCP/IP gateway) protocols utilizing a TCP/IP to X.25 gateway developed and operated by INRIA. The second component of the project involved experiments aimed at understanding the issues involved is ISO CO/CL gateways. An experimental gateway was developed at Wisconsin and a preliminary report was prepared. Because of the need to devote most resources to the first component of the project, work in this area did not go beyond development of a prototype gateway.

  18. DROPLET SIZE DISTRIBUTION MEASUREMENTS OF ISO NOZZLES BY SHADOWGRAPHY METHOD.

    PubMed

    De Cock, N; Massinon, M; Salah, S Ouled Taleb; Mercatoris, B C; Lebeau, F

    2015-01-01

    The droplet size distribution of agricultural sprays is a key parameter during the plant protection product applications. Therefore, measurement of the drop size distribution is an important concern for spray users as well as nozzle manufacturers. The present work assessed the capability of a shadowgraphy technique to distinguish correctly the 6 spray class boundaries defined in the ISO draft standard (ISO 25358). The measurement set-up is composed by a high speed camera synchronized with a LED backlighting. The tested spray is positioned between the camera and the light. The droplets appear on the images as shadows on a brighter background. For each acquisition, two frames are recorded within a small time laps (38 μI. The droplet diameter and velocity are retrieved by using advanced image analysis algorithm on each pair of frames. Then, the drop size distribution is obtained by gathering the data retrieved from all the images. The global results showed that the 6 drop size distributions were correctly separated highlighting the ability of the method to measure small as well as large droplets using the same set-up configuration. The spatial analysis showed that the spray scanning should be extended in the minor axis direction in order to catch the whole spray. PMID:27141727

  19. The lean oxidation of iso-octane at elevated pressures

    SciTech Connect

    Chen, J S; Curran, H J; Litzinger, T A

    1998-10-30

    Both spark-ignition and compression-ignition engines burn large molecular-weight blended fuels, a class to which the primary reference fuels (PRF), n-heptane and iso-octane belong. In this study experiments were performed using iso-octane in a high pressure flow reactor at a temperature of 925 K, at 3, 6 and 9 atm pressure and with a fuel/air equivalence ratio of approximately 0.05. Many hydrocarbon and oxygenated hydrocarbon intermediates were identified and quantified as a function of time. These experimental results provide a strin- gent test of the low temperature chemistry portion of a kinetic model as they emphasise the importance of alkyl radical addition to molecular oxygen and internal H-atom isomerization reactions relative to alkyl radical decomposition reactions. A detailed chemical kinetic mechanism is used to simulate these experiments. We provide comparisons of model predictions with experimentally measured species profiles and describe how each species is formed as predicted by the detailed model.

  20. ISO Observations of Starless Bok Globules: Usually No Embedded Stars

    NASA Technical Reports Server (NTRS)

    Clemens, D.; Byrne, A.; Yun, J.; Kane, B.

    1996-01-01

    We have used ISOCAM to search the cores of a sample of small Bok globules previously classified to be mostly starless based on analysis of IRAS data. The ISO observations at 6.75microns (LW2 filter) and 14.5microns (LW3 filter) were sufficiently deep to enable detection of any low-mass hydrogen burning star or young stellar object (YSO) embedded in these globules. Of the 20 Bok globules observed by ISOCAM to date, we have reduced the data for 14. Of these, 13 show no evidence for faint red (S(sub v)(LW3) greater than S(sub v)(LW2)) stars missed by IRAS. One (CB68) does show the first mid-infrared detection of the very cool IRAS source toward this cloud, and may be a Class I or 0 YSO. We conclude, based on these new ISO observations, that Bok globules which have no IRAS sources are in general bona fide starless molecular clouds.

  1. Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

    PubMed Central

    Kim, Keunsoo; Punna, Venkateshwarlu; Karri, Phaneendrasai

    2014-01-01

    Summary IsoGNA, an isomer of glycerol nucleic acid GNA, is a flexible (acyclic) nucleic acid with bases directly attached to its linear backbone. IsoGNA exhibits (limited) base-pairing properties which are unique compared to other known flexible nucleic acids. Herein, we report on the details of the preparation of isoGNA phosphoramidites and an alternative route for the synthesis of the adenine derivative. The synthetic improvements described here enable an easy access to isoGNA and allows for the further exploration of this structural unit in oligonucleotide chemistry thereby spurring investigations of its usefulness and applicability. PMID:25246971

  2. [Accreditation of ISO 15189 in the Department of Laboratory Medicine, Kumamoto University Hospital: successful cases].

    PubMed

    Obayashi, Konen; Teramoto, Koji; Yamamoto, Keiichi; Ikeda, Katsuyoshi; Ando, Yukio

    2009-02-01

    Recently, attention has been focused on international standard organization (ISO) 15189 accreditation, ensuring the quality and competence of medical laboratories in Japan. The Department of Laboratory Medicine, Kumamoto University Hospital also received ISO 15189 accreditation on August 30, 2007. In this paper, we describe our successful experiences before and after ISO 15189 accreditation, and discuss how to apply the qualification more effectively from now on. The key points to use the ISO 15189 tool effectively were summarized as follows: 1. Making sense of the purpose: Successful leadership is one of the most important factors. Our director came up with our slogan, which was called the 4 S's (speed, service, science, and strictness) to apply ISO 15189. 2. Improvement of technical and scientific competence: the development of detailed standard operating procedures(SOPs) aids the improvement of technical and scientific competence. 3. Enrich the contents of the teaching system: after we received ISO 15189 accreditation, the teaching system, not only for medical students but also medical staff and foreign students, was markedly improved to take advantage of the global standard. As it is expensive to run ISO 15189, we must utilize the specified and/or standard health check ups from now on. A laboratory cafe, which we are preparing in our hospital now, may be a new unique trial of how to apply ISO 15189. In conclusion, ISO 15189 may become an effective tool to develop and advance medical laboratories. PMID:19317221

  3. ISO, unique explorer of the invisible cool universe

    NASA Astrophysics Data System (ADS)

    1995-10-01

    As Roger Bonnet, director of ESA's science programme, explains: "The ISO launch will be the culmination of twelve years of intensive effort to build tile mast powerful and precise infrared space telescope to dote, We fully expect astronomers in Europe. and all over the wand, to be rewarded with unprecedented insights into the particularly rich and fertile sources of the universe hidden in the infrared." For the mission looks set to mark a new step forward for astronomy. To date, infrared astronomy has always been hampered by two major difficulties. The first is that infrared radiation is thermal, calorific. This means that any body which is not absolutely cold naturally emits this type of "heat" or "hidden" radiation, Consequently, at the corresponding wavelengths, all telescopes, detectors and the Earth's atmosphere appear to shine spontaneously, Infrared observation is therefore tantamount to attempting to observe the stars in broad daylight using a telescope a million times more luminous than the stars themselves. Moreover, the atmosphere is partly or totally opaque to infrared light. Hence the great attraction of conducting such observations from space, above the Earth's atmospheric layers. using a very low-temperature telescope. The first - and, so far, truly - Satellite actually to have done so is the Infrared Astronomical Satellite (IRAS) - a joint UK/Dutch/US mission - which surveyed and catalogued the sky far ten months in 1983. A corner of the curtain was thus lifted, The scene was set. Now, the task is to observe each character, each object. And here, infrared astronomy is hampered by a second major difficulty: the very detection of light. For while infrared radiation was discovered back in 1800 (in the solar spectrum). infrared-sensitive photoelectric detectors did not materialise until the Second World War, IRAS itself had to make do without the multi-dimensional set-ups that would have allowed it to record true images. It had to build up its images

  4. The cardiovascular effects of peroxisome proliferator-activated receptor agonists.

    PubMed

    Friedland, Sayuri N; Leong, Aaron; Filion, Kristian B; Genest, Jacques; Lega, Iliana C; Mottillo, Salvatore; Poirier, Paul; Reoch, Jennifer; Eisenberg, Mark J

    2012-02-01

    Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiovascular outcomes only in select subgroups: fenofibrate in diabetic patients with metabolic syndrome, gemfibrozil in patients with dyslipidemia, and bezafibrate in patients with diabetes or metabolic syndrome. The cardiovascular safety of the new pan agonist aleglitazar, currently in phase II trials, remains to be determined. The heterogenous effects of peroxisome proliferator-activated receptor agonists to date highlight the importance of postmarketing surveillance. The critical question of why peroxisome proliferator-activated receptor agonists seem to improve cardiovascular risk factors without significantly improving cardiovascular outcomes requires further investigation. PMID:22269613

  5. [PPAR receptors and insulin sensitivity: new agonists in development].

    PubMed

    Pégorier, J-P

    2005-04-01

    Thiazolidinediones (or glitazones) are synthetic PPARgamma (Peroxisome Proliferator-Activated Receptors gamma) ligands with well recognized effects on glucose and lipid metabolism. The clinical use of these PPARgamma agonists in type 2 diabetic patients leads to an improved glycemic control and an inhanced insulin sensitivity, and at least in animal models, to a protective effect on pancreatic beta-cell function. However, they can produce adverse effects, generally mild or moderate, but some of them (mainly peripheral edema and weight gain) may conduct to treatment cessation. Several pharmacological classes are currently in pre-clinical or clinical development, with the objective to retain the beneficial metabolic properties of PPARgamma agonists, either alone or in association with the PPARalpha agonists (fibrates) benefit on lipid profile, but devoid of the side-effects on weight gain and fluid retention. These new pharmacological classes: partial PPARgamma agonists, PPARgamma antagonists, dual PPARalpha/PPARgamma agonists, pan PPARalpha/beta(delta)/gamma agonists, RXR receptor agonists (rexinoids), are presented in this review. Main results from in vitro cell experiments and animal model studies are discussed, as well as the few published short-term studies in type 2 diabetic patients. PMID:15959400

  6. Risk versus benefit considerations for the beta(2)-agonists.

    PubMed

    Kelly, H William

    2006-09-01

    Short-acting beta(2)-agonists are the mainstay of therapy for acute bronchospasm associated with asthma and chronic obstructive pulmonary disease, whereas long-acting beta(2)-agonists are used in maintaining disease control in these respiratory disorders. This review describes and compares the pharmacology of the beta(2)-agonists and explains how these differences translate into differences in efficacy and beta(2)-adrenergic-mediated adverse effects. Questions commonly asked by clinicians regarding the efficacy and safety of short- and long-acting beta(2)-agonists include issues about cardiovascular effects, tolerance to their bronchodilator and bronchoprotective effects, blunting of albuterol response by long-acting beta(2)-agonists, potential masking of worsening asthma control, and the role of long-acting beta(2)-agonists as adjunctive therapy with inhaled corticosteroids in maintaining asthma control. Pharmacogenetics may play a role in determining which patients may be at risk for a reduced response to a beta(2)-agonist. The continued use of racemic albuterol, which contains a mixture of R-albuterol and S-albuterol, has been questioned because of data from preclinical and clinical studies suggesting that S-albuterol causes proinflammatory effects and may increase bronchial hyperreactivity. The preclinical and clinical effects of these two stereoisomers are reviewed. Data describing the efficacy and safety of levalbuterol (R-albuterol) and racemic albuterol are presented. PMID:16945063

  7. β-Adrenergic agonists mediate enhancement of β1-adrenergic receptor N-terminal cleavage and stabilization in vivo and in vitro.

    PubMed

    Hakalahti, Anna E; Khan, Hamayun; Vierimaa, Miia M; Pekkala, Emilia H; Lackman, Jarkko J; Ulvila, Johanna; Kerkelä, Risto; Petäjä-Repo, Ulla E

    2013-01-01

    The β(1)-adrenergic receptor (β(1)AR) is the predominant βAR in the heart and is the main target for β-adrenergic antagonists, widely used in the treatment of cardiovascular diseases. Previously, we have shown that the human (h) β(1)AR is cleaved in its N terminus by a metalloproteinase, both constitutively and in a receptor activation-dependent manner. In this study, we investigated the specific events involved in β(1)AR regulation, focusing on the effects of long-term treatment with β-adrenergic ligands on receptor processing in stably transfected human embryonic kidney 293(i) cells. The key findings were verified using the transiently transfected hβ(1)AR and the endogenously expressed receptor in neonatal rat cardiomyocytes. By using flow cytometry and Western blotting, we demonstrated that isoproterenol, S-propranolol, CGP-12177 [4-[3-[(1,1-dimethylethyl)amino]2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one], pindolol, and timolol, which displayed agonistic properties toward the β(1)AR in either the adenylyl cyclase or the mitogen-activated protein kinase signaling pathways, induced cleavage of the mature cell-surface receptor. In contrast, metoprolol, bisoprolol, and CGP-20712 [1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol], which showed no agonistic activity, had only a marginal or no effect. Importantly, the agonists also stabilized intracellular receptor precursors, possibly via their pharmacological chaperone action, and they stabilized the receptor in vitro. The opposing effects on the two receptor forms thus led to an increase in the amount of cleaved receptor fragments at the plasma membrane. The results underscore the pluridimensionality of β-adrenergic ligands and extend this property from receptor activation and signaling to the regulation of β(1)AR levels. This phenomenon may contribute to the exceptional resistance of β(1)ARs to downregulation and tendency toward

  8. Dopamine agonist withdrawal syndrome: implications for patient care.

    PubMed

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper. PMID:23686524

  9. Supra-physiological efficacy at GPCRs: superstition or super agonists?

    PubMed

    Langmead, Christopher J; Christopoulos, Arthur

    2013-05-01

    The concept of 'super agonism' has been described since the discovery of peptide hormone analogues that yielded greater functional responses than the endogenous agonists, in the early 1980s. It has remained an area of debate as to whether such compounds can really display greater efficacy than an endogenous agonist. However, recent pharmacological data, combined with crystal structures of different GPCR conformations and improved analytical methods for quantifying drug action, are starting to shed light on this phenomenon and indicate that super agonists may be more than superstition. PMID:23441648

  10. Affinity-matured recombinant immunotoxin targeting gangliosides 3′-isoLM1 and 3′,6'-isoLD1 on malignant gliomas

    PubMed Central

    Piao, Hailan; Kuan, Chien-Tsun; Chandramohan, Vidya; Keir, Stephen T; Pegram, Charles N; Bao, Xuhui; Månsson, Jan-Eric; Pastan, Ira H; Bigner, Darell D

    2013-01-01

    About 60 percent of glioblastomas highly express the gangliosides 3′-isoLM1 and 3′,6′-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the gangliosides 3′-isoLM1 and 3′,6′-isoLD1, was constructed with improved affinity and increased cytotoxicity for immunotherapeutic targeting of glioblastoma. We isolated an scFv parental clone from a previously established murine hybridoma, DmAb14, that is specific to both 3′-isoLM1 and 3′,6′-isoLD1. We then performed in vitro affinity maturation by CDR hotspot random mutagenesis. The binding affinity and specificity of affinity-matured DmAb14m-IT were measured by surface-plasmon resonance, flow cytometry, and immunohistochemical analysis. In vitro cytotoxicity of DmAb14m-IT was measured by protein synthesis inhibition and cell death assays in human cell lines expressing gangliosides 3′-isoLM1 and 3′,6′-isoLD1 (D54MG and D336MG) and xenograft-derived cells (D2224MG). As a result, the KD of DmAb14m-IT for gangliosides 3′-isoLM1 and 3′,6′-isoLD1 was 2.6 × 10−9M. Also, DmAb14m-IT showed a significantly higher internalization rate in cells expressing 3′-isoLM1 and 3′,6′-isoLD1. The DmAb14m-IT IC50 was 80 ng/mL (1194 pM) on the D54MG cell line, 5 ng/ml (75 pM) on the D336MG cell line, and 0.5 ng/ml (7.5 pM) on the D2224MG xenograft-derived cells. There was no cytotoxicity on ganglioside-negative HEK293 cells. Immunohistochemical analysis confirmed the specific apparent affinity of DmAb14m-IT with 3′-isoLM1 and 3′,6′-isoLD1. In conclusion, DmAb14m-IT showed specific binding affinity, a significantly high internalization rate, and selective cytotoxicity on glioma cell lines and xenograft-derived cells expressing 3′-isoLM1 and 3′,6′-isoLD1, thereby displaying robust therapeutic potential for testing the antitumor efficacy of DmAb14m-IT at the preclinical level and

  11. Relamorelin: A Novel Gastrocolokinetic Synthetic Ghrelin Agonist

    PubMed Central

    Camilleri, Michael; Acosta, Andres

    2015-01-01

    Synthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM-131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)-1a (also called the ghrelin) receptor with approximately 6-fold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin. In this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a pre-specified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders. PMID:25545036

  12. Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats

    PubMed Central

    Grobe, Connie L.; Beltz, Terry G.; Johnson, Alan Kim

    2011-01-01

    These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), “middle-aged” adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β1- and β2-adrenergic receptors, salbutamol to selectively activate β2-adrenergic receptors, and the combination of isoproterenol and the β2-adrenergic receptor antagonist ICI 118,551 to stimulate only β1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation. PMID:21307363

  13. ISO 9000 for the U. S. nuclear industry Why not

    SciTech Connect

    Wilson, R.B. )

    1993-01-01

    The growing popularity of the recently developed International Standard for Quality, ISO 9000, is challenging the traditional approach to ensuring quality in the nuclear industry and raising new questions as to whether this standard with its likely worldwide acceptance could become a successor to 10CFR50, Appendix B. The experience of a jointly owned British-American engineering consulting firm may be a harbinger of the future. Halcrow Gilbert Associates, Limited (HGA), was established in the fall of 1988 as a joint venture between two of the world's largest consulting engineering firms, Sir William Halcrow Partners, Ltd., of the United Kingdom and Gilbert/Commonwealth, Inc., of the United States. Although it initially concentrated on nonpower infrastructure markets, such as environmental, transportation, and alternative energy systems, it has broadened its focus to include the electric power industry over the past 2 yr and expects to play a major role in the U.K. market for this sector.

  14. Business process mapping techniques for ISO 9001 and 14001 certifications

    SciTech Connect

    Klement, R.E.; Richardson, G.D.

    1997-11-01

    AlliedSignal Federal Manufacturing and Technologies/Kansas City (FM and T/KC) produces nonnuclear components for nuclear weapons. The company has operated the plant for the US Department of Energy (DOE) since 1949. Throughout the history of the plant, procedures have been written to reflect the nuclear weapons industry best practices, and the facility has built a reputation for producing high quality products. The purpose of this presentation is to demonstrate how Total Quality principles were used at FM and T/KC to document processes for ISO 9001 and 14001 certifications. The information presented to the reader will lead to a better understanding of business administration by aligning procedures to key business processes within a business model; converting functional-based procedures to process-based procedures for total integrated resource management; and assigning ownership, validation, and metrics to procedures/processes, adding value to a company`s profitability.

  15. Iso-luminance counterillumination drove bioluminescent shark radiation

    PubMed Central

    Claes, Julien M.; Nilsson, Dan-Eric; Straube, Nicolas; Collin, Shaun P.; Mallefet, Jérôme

    2014-01-01

    Counterilluminating animals use ventral photogenic organs (photophores) to mimic the residual downwelling light and cloak their silhouette from upward-looking predators. To cope with variable conditions of pelagic light environments they typically adjust their luminescence intensity. Here, we found evidence that bioluminescent sharks instead emit a constant light output and move up and down in the water column to remain cryptic at iso-luminance depth. We observed, across 21 globally distributed shark species, a correlation between capture depth and the proportion of a ventral area occupied by photophores. This information further allowed us, using visual modelling, to provide an adaptive explanation for shark photophore pattern diversity: in species facing moderate predation risk from below, counterilluminating photophores were partially co-opted for bioluminescent signalling, leading to complex patterns. In addition to increase our understanding of pelagic ecosystems our study emphasizes the importance of bioluminescence as a speciation driver. PMID:24608897

  16. isoSTED nanoscopy with intrinsic beam alignment.

    PubMed

    Curdt, Franziska; Herr, Simon J; Lutz, Tobias; Schmidt, Roman; Engelhardt, Johann; Sahl, Steffen J; Hell, Stefan W

    2015-11-30

    Despite the need for isotropic optical resolution in a growing number of applications, the majority of super-resolution fluorescence microscopy setups still do not attain an axial resolution comparable to that in the lateral dimensions. Three-dimensional (3D) nanoscopy implementations that employ only a single objective lens typically feature a trade-off between axial and lateral resolution. 4Pi arrangements, in which the sample is illuminated coherently through two opposing lenses, have proven their potential for rendering the resolution isotropic. However, instrument complexity due to a large number of alignment parameters has so far thwarted the dissemination of this approach. Here, we present a 4Pi-STED setup combination, also called isoSTED nanoscope, where the STED and excitation beams are intrinsically co-aligned. A highly robust and convenient 4Pi cavity allows easy handling without the need for readjustments during imaging experiments. PMID:26698722

  17. An ISO and IUE Study of Planetary Nebula NGC 2440

    NASA Technical Reports Server (NTRS)

    Salas, J. Bernard; Pottasch, S. R.; Feibelman, W. A.; Wesselius, P. R.; Oegerle, William R. (Technical Monitor)

    2002-01-01

    The infrared and ultraviolet spectra of planetary nebula NGC 2440 is presented. The observations were made respectively by the Infrared Space Observatory (ISO) and International Ultraviolet Explorer (IUE) These data, in conjunction with published optical observations have been used to derive electron temperature and density. A trend of electron temperature with ionization potential is found. In particular the electron temperature increases from 11000 to 18000 K with increasing IBM. The electron density has a constant value of 4500/cu cm in agreement with previous determination. The chemical abundance has been derived for the following elements; helium, carbon, nitrogen, oxygen, neon, sulfur and argon. The ionization correction factor turns out to be very small (almost unnecessary) for all species except sulfur.

  18. Health risk evaluation of whole-body vibration by ISO 2631-5 and ISO 2631-1 for operators of agricultural tractors and recreational vehicles.

    PubMed

    Park, Min-Soo; Fukuda, Takabumi; Kim, Tae-Gu; Maeda, Setsuo

    2013-01-01

    This paper presents experimental research evaluation of the vibration exposure for the health risk prediction during vehicle operation. The vibration measurements were carried out on a recreational vehicle and two types of agricultural tractors. The vibration levels were measured for different surfaces and vehicle speed conditions. Based on the analysis of the results in the small agricultural tractor operated in the workplace (frameworks), Sed exceeded 0.80 MPa by ISO2631-5:2004, and Av exceeded 0.89 m/s(2) by ISO2631-1:1997. That means that operators driving small agricultural tractors more than 8 h a day have a high probability of adverse health effects. However, the exposure value for the recreational vehicle had Sed < 0.5 MPa by ISO2631-5:2004 and Av < 0.5 m/s(2) by ISO2631-1:1997 on highways and local roads. That means Recreational Vehicle operators driving more than 8 h a day, have a low probability of adverse health effects. Also, for the recreational vehicle, vibration was taken at different speeds (40-60 km/h, 80 km/h, 100-120 km/h). However, the speed change did not appear to affect the vibration dose variation while driving a vehicle on the highway and road. Finally, the health effect index of ISO2631-5:2004 are almost the same as assessment of health effect by ISO2631-1:1997. PMID:23558167

  19. EPA STANDARDS NETWORK FACT SHEET: ISO 14000: INTERNATIONAL ENVIRONMENTAL MANAGEMENT STANDARDS

    EPA Science Inventory

    This flyer provides an overview of the ISO 14000 series of International standards, supplying a brief history, structure of the Technical Committee (TC) 207, structure of the U.S. Technical Advisory Group (TAG) to ISO TC-207, status of the Standards development as of June 1997, w...

  20. A Proposed Interpretation of the ISO 10015 and Implications for HRD Theory and Research

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.; Wang, Bryan

    2007-01-01

    While recent discussions of ISO 10015- Guidelines for Training have done much to promote the need for the standard, no interpretation of the standard has been presented that would guide its actual implementation. This paper proposes an interpretation of the ISO 10015 based on the specifications of the guideline and two other standards related to…

  1. Factors That Relate to the Time to ISO 9000 Registration in Education Institutions

    ERIC Educational Resources Information Center

    Thonhauser, Theresa

    2008-01-01

    The implementation of the ISO 9000 international quality management system in education has become a debated trend. Building on the literature, this study did not attempt to end the debate over ISO 9000 in education but looked at the problem with a new perspective. The purpose of this study was to identify factors that relate to the time required…

  2. An Experimental Study on the Iso-Content-Based Angle Similarity Measure.

    ERIC Educational Resources Information Center

    Zhang, Jin; Rasmussen, Edie M.

    2002-01-01

    Retrieval performance of the iso-content-based angle similarity measure within the angle, distance, conjunction, disjunction, and ellipse retrieval models is compared with retrieval performance of the distance similarity measure and the angle similarity measure. Results show the iso-content-based angle similarity measure achieves satisfactory…

  3. Synthesis and low temperature characterization of iso-oleic ester derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three new iso-oleic ester derivatives (i.e., isopropyl esters (IOA-iPrE), n-butyl esters (IOA-n-BuE), and 2-ethylhexyl esters (IOA-2-EHE)) were synthesized from iso-oleic acid (IOA) using a standard esterification method. These esterified alcohols were chosen because of their bulky and branched-cha...

  4. IsoWeb: A Bayesian Isotope Mixing Model for Diet Analysis of the Whole Food Web

    PubMed Central

    Kadoya, Taku; Osada, Yutaka; Takimoto, Gaku

    2012-01-01

    Quantitative description of food webs provides fundamental information for the understanding of population, community, and ecosystem dynamics. Recently, stable isotope mixing models have been widely used to quantify dietary proportions of different food resources to a focal consumer. Here we propose a novel mixing model (IsoWeb) that estimates diet proportions of all consumers in a food web based on stable isotope information. IsoWeb requires a topological description of a food web, and stable isotope signatures of all consumers and resources in the web. A merit of IsoWeb is that it takes into account variation in trophic enrichment factors among different consumer-resource links. Sensitivity analysis using realistic hypothetical food webs suggests that IsoWeb is applicable to a wide variety of food webs differing in the number of species, connectance, sample size, and data variability. Sensitivity analysis based on real topological webs showed that IsoWeb can allow for a certain level of topological uncertainty in target food webs, including erroneously assuming false links, omission of existent links and species, and trophic aggregation into trophospecies. Moreover, using an illustrative application to a real food web, we demonstrated that IsoWeb can compare the plausibility of different candidate topologies for a focal web. These results suggest that IsoWeb provides a powerful tool to analyze food-web structure from stable isotope data. We provide R and BUGS codes to aid efficient applications of IsoWeb. PMID:22848427

  5. ISO 9000 and Malcolm Baldrige: In Training and Education. A Practical Application Guide.

    ERIC Educational Resources Information Center

    Russo, C. W. Russ

    This book is addressed to educators and work-place trainers interested in applying the Malcolm Baldrige award criteria and/or the International Organization for Standardization (ISO) 9000 training guidelines for program improvement. An initial section compares and contrasts the ISO standards and the Malcolm Baldrige National Quality Award…

  6. ISO 9001 certification for hospitals in Bulgaria: does it help service?

    PubMed Central

    Stoimenova, Assena; Stoilova, Ani; Petrova, Guenka

    2014-01-01

    The aim of our study is to review the published literature on establishment and implementation of ISO 9001 QMS in European hospitals, to study the availability of International Organization for Standardization (ISO) quality management systems (QMS) in Bulgarian hospitals and to outline the main advantages of ISO implementation in the hospitals in Bulgaria. The information on availability of ISO QMS in the hospitals in Bulgaria was gathered via Bulgarian certification register, the registries of various quality associations, websites of hospitals and certification companies presented in Bulgaria. A total number of 312 hospitals in Bulgaria were screened for the availability of QMS certified against the ISO 9001 requirements. The experience of European hospitals that implemented QMS is positive and the used approaches to improve the processes and the demonstrated effects from ISO implementation are analysed by the researchers. Unlike other European Union member states, the establishment of quality management systems in Bulgaria is not compulsory. However, our study revealed that 14.42% of the hospitals in Bulgaria have implemented and have certified quality systems against the requirements of ISO 9001. Our study confirmed that a quality management system using the ISO 9001 standard is useful for the hospitals as it can help to increase the operational efficiencies, to reduce errors, improve patient safety and produce a more preventive approach instead of a reactive environment. PMID:26019523

  7. IsoFinder: computational prediction of isochores in genome sequences.

    PubMed

    Oliver, José L; Carpena, Pedro; Hackenberg, Michael; Bernaola-Galván, Pedro

    2004-07-01

    Isochores are long genome segments homogeneous in G+C. Here, we describe an algorithm (IsoFinder) running on the web (http://bioinfo2.ugr.es/IsoF/isofinder.html) able to predict isochores at the sequence level. We move a sliding pointer from left to right along the DNA sequence. At each position of the pointer, we compute the mean G+C values to the left and to the right of the pointer. We then determine the position of the pointer for which the difference between left and right mean values (as measured by the t-statistic) reaches its maximum. Next, we determine the statistical significance of this potential cutting point, after filtering out short-scale heterogeneities below 3 kb by applying a coarse-graining technique. Finally, the program checks whether this significance exceeds a probability threshold. If so, the sequence is cut at this point into two subsequences; otherwise, the sequence remains undivided. The procedure continues recursively for each of the two resulting subsequences created by each cut. This leads to the decomposition of a chromosome sequence into long homogeneous genome regions (LHGRs) with well-defined mean G+C contents, each significantly different from the G+C contents of the adjacent LHGRs. Most LHGRs can be identified with Bernardi's isochores, given their correlation with biological features such as gene density, SINE and LINE (short, long interspersed repetitive elements) densities, recombination rate or single nucleotide polymorphism variability. The resulting isochore maps are available at our web site (http://bioinfo2.ugr.es/isochores/), and also at the UCSC Genome Browser (http://genome.cse.ucsc.edu/). PMID:15215396

  8. The ISO View of Palomar-Green Quasars

    NASA Technical Reports Server (NTRS)

    Haas, M.; Klaas, U.; Mueller, S. A. H.; Bertoldi, F.; Camenzind, M.; Chini, R.; Krause, O.; Lemke, D.; Meisenheimer; Richards, P. J.

    2003-01-01

    Mining the ISO data archive we provide the complete ISO view of PG quasars containing 64 infrared spectral energy distributions between 5 and 200 mu m. About half of the sample was supplemented by MAMBO and SCUBA (sub-)millimeter data. Since the PG quasars were selected optically, the high infrared detection rate of more than 80% suggests that every quasar possesses luminous to hyper-luminous dust emission with dust masses comparable to Seyferts and ultra-luminous IR galaxies (ULIRGs). The gas to-dust mass ratio (of those sources where CO measurements are available in the literature) is consistent with the galactic value providing further evidence for the thermal nature of the IR emission of radio quiet quasars. The SEDs represent templates of unprecedented detail and sensitivity. We suggest that the diversity of the SEDs reflects largely the evolution of the dust distribution, and we propose a classification of the SED shapes as well as an evolutionary scheme in which this variety can be understood. During the evolution the surrounding dust redistributes, settling more and more into a torus/disk like configuration, while the SEDs show an initial FIR bump, then an increasing MIR emission and a steeper near- to mid-infrared slope, both of which finally also decrease. Regarding cosmic evolution, our hyper-luminous quasars in the "local" universe at z=l do not show the hyper-luminous (LFIR >? 10(exp 13) L(sub sun)) starburst activity inferred for z=4 quasars detected in several (sub-)millimeter surveys. In view of several caveats this difference should be established further, but it already suggests that in the early dense universe stronger merger events led to more powerful starbursts accompanying the quasar phenomenon, while at later cosmic epochs any coeval starbursts obviously do not reach that high power and are outshone by the AGN. Additional information is included in the original extended abstract.

  9. Selecting agonists from single cells infected with combinatorial antibody libraries.

    PubMed

    Zhang, Hongkai; Yea, Kyungmoo; Xie, Jia; Ruiz, Diana; Wilson, Ian A; Lerner, Richard A

    2013-05-23

    We describe a system for direct selection of antibodies that are receptor agonists. Combinatorial antibody libraries in lentiviruses are used to infect eukaryotic cells that contain a fluorescent reporter system coupled to the receptor for which receptor agonist antibodies are sought. In this embodiment of the method, very large numbers of candidate antibodies expressing lentivirus and eukaryotic reporter cells are packaged together in a format where each is capable of replication, thereby forging a direct link between genotype and phenotype. Following infection, cells that fluoresce are sorted and the integrated genes encoding the agonist antibodies recovered. We validated the system by illustrating its ability to generate rapidly potent antibody agonists that are complete thrombopoietin phenocopies. The system should be generalizable to any pathway where its activation can be linked to production of a selectable phenotype. PMID:23706638

  10. Therapeutic Potential of 5-HT6 Receptor Agonists.

    PubMed

    Karila, Delphine; Freret, Thomas; Bouet, Valentine; Boulouard, Michel; Dallemagne, Patrick; Rochais, Christophe

    2015-10-22

    Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: serotonin) subtype 6 receptor (5-HT6R) has been considered as a valuable target for the development of CNS drugs with limited side effects. After 2 decades of intense research, numerous selective ligands have been developed to target this receptor; this holds potential interest for the treatment of neuropathological disorders. In fact, some agents (mainly antagonists) are currently undergoing clinical trial. More recently, a series of potent and selective agonists have been developed, and preclinical studies have been conducted that suggest the therapeutic interest of 5-HT6R agonists. This review details the medicinal chemistry of these agonists, highlights their activities, and discusses their potential for treating cognitive issues associated with Alzheimer's disease (AD), depression, or obesity. Surprisingly, some studies have shown that both 5-HT6R agonists and antagonists exert similar procognitive activities. This article summarizes the hypotheses that could explain this paradox. PMID:26099069

  11. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    PubMed

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. PMID:20579229

  12. Selective 5-HT2C agonists as potential antidepressants.

    PubMed

    Leysen, D C

    1999-02-01

    The antidepressants currently used need improvement, especially in terms of efficacy, relapse rate and onset of action. In this review the clinical and experimental data which support the rationale for 5-HT2C agonists in the treatment of depression are listed. Next, the results obtained with the non-selective 5-HT2C agonists on the market and in clinical development are described. Finally, the preclinical data on the more selective 5-HT2C agonists are summarized. These recent preclinical results reveal a greater potency and effect size compared to fluoxetine, good tolerability and no evidence of tolerance development. Selective 5-HT2C agonists might become innovative drugs for the treatment of depression, panic, obsessive-compulsive disorder (OCD), some forms of aggression and eating disorders. PMID:16160946

  13. Agonist pharmacology of two Drosophila GABA receptor splice variants.

    PubMed Central

    Hosie, A. M.; Sattelle, D. B.

    1996-01-01

    1. The Drosophila melanogaster gamma-aminobutyric acid (GABA) receptor subunits, RDLac and DRC 17-1-2, form functional homo-oligomeric receptors when heterologously expressed in Xenopus laevis oocytes. The subunits differ in only 17 amino acids, principally in regions of the N-terminal domain which determine agonist pharmacology in vertebrate ionotropic neurotransmitter receptors. A range of conformationally restricted GABA analogues were tested on the two homo-oligomers and their agonists pharmacology compared with that of insect and vertebrate iontropic GABA receptors. 2. The actions of GABA, isoguvacine and isonipecotic acid on RDLac and DRC 17-1-2 homo-oligomers were compared, by use of two-electrode voltage-clamp. All three compounds were full agonists of both receptors, but were 4-6 fold less potent agonists of DRC 17-1-2 homo-oligomers than of RDLac. However, the relative potencies of these agonists on each receptor were very similar. 3. A more complete agonist profile was established for RDLac homo-oligomers. The most potent agonists of these receptors were GABA, muscimol and trans-aminocrotonic acid (TACA), which were approximately equipotent. RDLac homo-oligomers were fully activated by a range of GABA analogues, with the order of potency: GABA > ZAPA ((Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid) > isoguvacine > imidazole-4-acetic acid > or = isonipecotic acid > or = cis-aminocrotonic acid (CACA) > beta-alanine. 3-Aminopropane sulphonic acid (3-APS), a partial agonist of RDLac homo-oligomers, was the weakest agonist tested and 100 fold less potent than GABA. 4. SR95531, an antagonist of vertebrate GABAA receptors, competitively inhibited the GABA responses of RDLac homo-oligomers, which have previously been found to insensitive to bicuculline. However, its potency (IC50 500 microM) was much reduced when compared to GABAA receptors. 5. The agonist pharmacology of Drosophila RDLac homo-oligomers exhibits aspects of the characteristic pharmacology of

  14. ISO, unique explorer of the invisible cool universe

    NASA Astrophysics Data System (ADS)

    1995-10-01

    As Roger Bonnet, director of ESA's science programme, explains: "The ISO launch will be the culmination of twelve years of intensive effort to build tile mast powerful and precise infrared space telescope to dote, We fully expect astronomers in Europe. and all over the wand, to be rewarded with unprecedented insights into the particularly rich and fertile sources of the universe hidden in the infrared." For the mission looks set to mark a new step forward for astronomy. To date, infrared astronomy has always been hampered by two major difficulties. The first is that infrared radiation is thermal, calorific. This means that any body which is not absolutely cold naturally emits this type of "heat" or "hidden" radiation, Consequently, at the corresponding wavelengths, all telescopes, detectors and the Earth's atmosphere appear to shine spontaneously, Infrared observation is therefore tantamount to attempting to observe the stars in broad daylight using a telescope a million times more luminous than the stars themselves. Moreover, the atmosphere is partly or totally opaque to infrared light. Hence the great attraction of conducting such observations from space, above the Earth's atmospheric layers. using a very low-temperature telescope. The first - and, so far, truly - Satellite actually to have done so is the Infrared Astronomical Satellite (IRAS) - a joint UK/Dutch/US mission - which surveyed and catalogued the sky far ten months in 1983. A corner of the curtain was thus lifted, The scene was set. Now, the task is to observe each character, each object. And here, infrared astronomy is hampered by a second major difficulty: the very detection of light. For while infrared radiation was discovered back in 1800 (in the solar spectrum). infrared-sensitive photoelectric detectors did not materialise until the Second World War, IRAS itself had to make do without the multi-dimensional set-ups that would have allowed it to record true images. It had to build up its images

  15. Sleep attacks in patients taking dopamine agonists: review

    PubMed Central

    Homann, Carl Nikolaus; Wenzel, Karoline; Suppan, Klaudia; Ivanic, Gerd; Kriechbaum, Norbert; Crevenna, Richard; Ott, Erwin

    2002-01-01

    Objectives To assess the evidence for the existence and prevalence of sleep attacks in patients taking dopamine agonists for Parkinson's disease, the type of drugs implicated, and strategies for prevention and treatment. Design Review of publications between July 1999 and May 2001 in which sleep attacks or narcoleptic-like attacks were discussed in patients with Parkinson's disease. Results 124 patients with sleep events were found in 20 publications. Overall, 6.6% of patients taking dopamine agonists who attended movement disorder centres had sleep events. Men were over-represented. Sleep events occurred at both high and low doses of the drugs, with different durations of treatment (0-20 years), and with or without preceding signs of tiredness. Sleep attacks are a class effect, having been found in patients taking the following dopamine agonists: levodopa (monotherapy in 8 patients), ergot agonists (apomorphine in 2 patients, bromocriptine in 13, cabergoline in 1, lisuride or piribedil in 23, pergolide in 5,) and non-ergot agonists (pramipexole in 32, ropinirole in 38). Reports suggest two distinct types of events: those of sudden onset without warning and those of slow onset with prodrome drowsiness. Conclusion Insufficient data are available to provide effective guidelines for prevention and treatment of sleep events in patients taking dopamine agonists for Parkinson's disease. Prospective population based studies are needed to provide this information. What is already known on this topicCar crashes in patients with Parkinson's disease have been associated with sleep attacks caused by the dopamine agonists pramipexole and ropiniroleWhether sleep attacks exist, their connection with certain agonists, prevention or treatment, and the justification of legal actions are controversialWhat this study addsSleep attacks as a phenomenon distinct from normal somnolence really do existThey are a class effect of all dopamine drugsEffective prevention and treatment

  16. Identification of M-CSF agonists and antagonists

    DOEpatents

    Pandit, Jayvardhan; Jancarik, Jarmila; Kim, Sung-Hou; Koths, Kirston; Halenbeck, Robert; Fear, Anna Lisa; Taylor, Eric; Yamamoto, Ralph; Bohm, Andrew

    2000-02-15

    The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

  17. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    PubMed

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. PMID:25326839

  18. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    PubMed

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. PMID:25437461

  19. PPAR dual agonists: are they opening Pandora's Box?

    PubMed

    Balakumar, Pitchai; Rose, Madhankumar; Ganti, Subrahmanya S; Krishan, Pawan; Singh, Manjeet

    2007-08-01

    Cardiovascular disorders are the major cause of mortality in patients of diabetes mellitus. Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of three subtypes such as PPARalpha, PPARgamma and PPARdelta/beta. Activation of PPARalpha reduces triglycerides and involves in regulation of energy homeostasis. Activation of PPARgamma causes insulin sensitization and enhances glucose metabolism, whereas activation of PPARdelta enhances fatty acid metabolism. Current therapeutic strategies available for the treatment of diabetes do not inhibit the associated secondary cardiovascular complications. Hence, the development of multimodal drugs which can reduce hyperglycemia and concomitantly inhibit the progression of secondary cardiovascular complications may offer valuable therapeutic option. Several basic and clinical studies have exemplified the beneficial effects of PPARalpha and PPARgamma ligands in preventing the cardiovascular risks. The PPARalpha/gamma dual agonists are developed to increase insulin sensitivity and simultaneously prevent diabetic cardiovascular complications. Such compounds are under clinical trials and proposed for treatment of Type II diabetes with secondary cardiovascular complications. However, PPARalpha/gamma dual agonists such as muraglitazar, tesaglitazar and ragaglitazar have been noted to produce several cardiovascular risks and carcinogenicity, which raised number of questions about the clinical applications of dual agonists in diabetes and its associated complications. The ongoing basic studies have elucidated the cardio protective role of PPARdelta. Therefore, further studies are on the track to develop PPARalpha/delta and PPAR gamma/delta dual agonists and PPARalpha/gamma/delta pan agonists for the treatment of diabetic cardiovascular complications. The present review critically analyzes the protective and detrimental effect of PPAR agonists in

  20. Mechanisms of inverse agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Strange, Philip G

    2005-05-01

    Mechanisms of inverse agonist action at the D2(short) dopamine receptor have been examined. Discrimination of G-protein-coupled and -uncoupled forms of the receptor by inverse agonists was examined in competition ligand-binding studies versus the agonist [3H]NPA at a concentration labelling both G-protein-coupled and -uncoupled receptors. Competition of inverse agonists versus [3H]NPA gave data that were fitted best by a two-binding site model in the absence of GTP but by a one-binding site model in the presence of GTP. K(i) values were derived from the competition data for binding of the inverse agonists to G-protein-uncoupled and -coupled receptors. K(coupled) and K(uncoupled) were statistically different for the set of compounds tested (ANOVA) but the individual values were different in a post hoc test only for (+)-butaclamol. These observations were supported by simulations of these competition experiments according to the extended ternary complex model. Inverse agonist efficacy of the ligands was assessed from their ability to reduce agonist-independent [35S]GTP gamma S binding to varying degrees in concentration-response curves. Inverse agonism by (+)-butaclamol and spiperone occurred at higher potency when GDP was added to assays, whereas the potency of (-)-sulpiride was unaffected. These data show that some inverse agonists ((+)-butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form of the receptor at the expense of the coupled form. For other compounds tested, we were unable to define the mechanism. PMID:15735658

  1. Evaluation of ISO EN 13606 as a result of its implementation in XML

    PubMed Central

    Sun, Shanghua; Hassan, Taher; Kalra, Dipak

    2013-01-01

    The five parts of the ISO EN 13606 standard define a means by which health-care records can be exchanged between computer systems. Starting within the European standardisation process, it has now become internationally ratified in ISO. However, ISO standards do not require that a reference implementation be provided, and in order for ISO EN 13606 to deliver the expected benefits, it must be provided not as a document, but as an operational system that is not vendor specific. This article describes the evolution of an Extensible Markup Language (XML) Schema through three iterations, each of which emphasised one particular approach to delivering an executable equivalent to the printed standard. Developing these operational versions and incorporating feedback from users of these demonstrated where implementation compromises were needed and exposed defects in the standard. These are discussed herein. They may require a future technical revision to ISO EN 13606 to resolve the issues identified. PMID:23995217

  2. Differential effects of AMPK agonists on cell growth and metabolism

    PubMed Central

    Vincent, Emma E.; Coelho, Paula P.; Blagih, Julianna; Griss, Takla; Viollet, Benoit; Jones, Russell G.

    2016-01-01

    As a sensor of cellular energy status, the AMP-activated protein kinase (AMPK) is believed to act in opposition to the metabolic phenotypes favored by proliferating tumor cells. Consequently, compounds known to activate AMPK have been proposed as cancer therapeutics. However, the extent to which the anti-neoplastic properties of these agonists are mediated by AMPK is unclear. Here we examined the AMPK-dependence of six commonly used AMPK agonists (metformin, phenformin, AICAR, 2DG, salicylate and A-769662) and their influence on cellular processes often deregulated in tumor cells. We demonstrate that the majority of these agonists display AMPK-independent effects on cell proliferation and metabolism with only the synthetic activator, A-769662, exerting AMPK-dependent effects on these processes. We find that A-769662 promotes an AMPK-dependent increase in mitochondrial spare respiratory capacity (SRC). Finally, contrary to the view of AMPK activity being tumor suppressive, we find A-769662 confers a selective proliferative advantage to tumor cells growing under nutrient deprivation. Our results indicate that many of the anti-growth properties of these agonists cannot be attributed to AMPK activity in cells, and thus any observed effects using these agonists should be confirmed using AMPK-deficient cells. Ultimately, our data urge caution, not only regarding the type of AMPK agonist proposed for cancer treatment, but also the context in which they are used. PMID:25241895

  3. Blood and urine 8-iso-PGF2α levels in babies of different gestational ages

    PubMed Central

    Li, Sitao; Hao, Hu; Zhou, Ping; Gao, Ping Ming; Xiao, Xin

    2014-01-01

    Objective: We measured cord blood and urine 8-iso-prostaglandin F2α (8-iso-PGF2α) levels in babies of different gestational ages to determine lipid peroxidation status. Methods: Babies at gestational ages of 28-43 weeks were divided into group A (28-32 weeks), group B (33-36 weeks), group C (37-41 weeks), and group D (42-43 weeks). 8-iso-PGF2α in umbilical cord blood (UCB) at birth and urine at 6 hours after birth was and tested by ELISA. Results: UCB and urine 8-iso-PGF2α levels in group C were 130.09 ± 31.73 pg/ml and 27.14 ± 6.73 pg/ml, respectively. UCB 8-iso-PGF2α levels in group A and B were 188.42 ± 59.34 pg/ml and 189.37 ± 68.46 pg/ml, and urine 8-iso-PGF2α were 32.14 ± 7.32 pg/ml and 30.46 ± 8.83 pg/ml, respectively. Blood and urine 8-iso-PGF2α levels in group D (post-term) were 252.01 ± 46.42 pg/ml and 44.00 ± 8.50 pg/ml. For all babies, UCB and urine iso-PGF2α levels were significantly correlated (r = 0.65, P < 0.01). Conclusions: We established blood and urine iso-PGF2α levels in normal full-term babies. Urine 8-iso-PGF2α levels may reflect the extent of lipid peroxidation in babies. In pre-term and post-term babies, there was evidence for increased lipid peroxidation. PMID:25664058

  4. Organizational leadership: A study on the affects of certification to International Organization for Standardization (ISO)

    NASA Astrophysics Data System (ADS)

    Cowart, Jewel S.

    Compliance to requirements of ISO is an important leadership problem for the International Aerospace Quality Group (IAQG) and the Aviation, Space and Defense (AS&D) companies. Furthermore, the IAQG seeks to understand the valuation of ISO/AS9100 requirements (2009), audit practices, management functions, business performance, customer satisfaction, and potential future concepts for the standard to assure quality. Since the release of the AS9100C total certification growth surpassed 1,100,000 organizations in 2010 with ISO 9001 series adoption and implementation governing business operations (ASQ, 2012b; ISO, 2011; Bernardo, Llach, & Marimon, 2011). Historians such as Crosby, Juran, Deming, and others established the foundation for quality assurance. Several researchers explored the issues which complicate overall benefits of ISO certification (Iwaro & Mwasha, 2012; Karthi et al., 2012; Sampaio et al., 2009). This study examined the effects on AS&D industries from ISO compliance to identify the implications (of ever-changing requirements) through an online survey of 15,000 practitioners. The research illuminated how ISO affects AS&D industries with current and future requirements for certification. The data showed that 75% of survey respondents report implementation of the AS9100C requirements still has benefits that outweigh the cost. Findings suggest that AS&D industries perceive significant value in the AS9100C document as part of the overall ISO 9000 series. In general, the comments from the survey can provide insight into the affects of ISO certification. The study concludes by recommending continued research to learn of further impacts from ISO certification within AS&D industries to improve the AS9100 document requirements for quality management systems.

  5. Perception of specific trigeminal chemosensory agonists

    PubMed Central

    Frasnelli, J; Albrecht, J; Bryant, B; Lundström, JN

    2011-01-01

    The intranasal trigeminal system is a third chemical sense in addition to olfaction and gustation. As opposed to smell and taste, we still lack knowledge on the relationship between receptor binding and perception for the trigeminal system. We therefore investigated the sensitivity of the intranasal trigeminal system towards agonists of the trigeminal receptors TRPM8 and TRPA1 by assessing subjects’ ability to identify which nostril has been stimulated in a monorhinal stimulation design. We summed the number of correct identifications resulting in a lateralization score. Stimuli were menthol (activating TRPM8 receptors), eucalyptol (TRPM8), mustard oil (TRPA1) and two mixtures thereof (menthol/eucalyptol and menthol/mustard oil). In addition, we examined the relationship between intensity and lateralization scores and investigated whether intensity evaluation and lateralization scores of the mixtures show additive effects. All stimuli were correctly lateralized significantly above chance. Across subjects the lateralization scores for single compounds activating the same receptor showed a stronger correlation than stimuli activating different receptors. Although single compounds were isointense, the mixture of menthol and eucalyptol (activating only TRPM8) was perceived as weaker and was lateralized less accurately than the mixture of menthol and mustard oil (activating both TRPM8 and TRPA1) suggesting suppression effects in the former mixture. In conclusion, sensitivity of different subpopulations of trigeminal sensory neurons seems to be related, but only to a certain degree. The large coherence in sensitivity between various intranasal trigeminal stimuli suggests that measuring sensitivity to one single trigeminal chemical stimulus may be sufficient to generally assess the trigeminal system’s chemosensitivity. Further, for stimuli activating the same receptor a mixture suppression effect appears to occur similar to that observed in the other chemosensory

  6. Identification of Determinants Required for Agonistic and Inverse Agonistic Ligand Properties at the ADP Receptor P2Y12

    PubMed Central

    Schmidt, Philipp; Ritscher, Lars; Dong, Elizabeth N.; Hermsdorf, Thomas; Cöster, Maxi; Wittkopf, Doreen; Meiler, Jens

    2013-01-01

    The ADP receptor P2Y12 belongs to the superfamily of G protein–coupled receptors (GPCRs), and its activation triggers platelet aggregation. Therefore, potent antagonists, such as clopidogrel, are of high clinical relevance in prophylaxis and treatment of thromboembolic events. P2Y12 displays an elevated basal activity in vitro, and as such, inverse agonists may be therapeutically beneficial compared with antagonists. Only a few inverse agonists of P2Y12 have been described. To expand this limited chemical space and improve understanding of structural determinants of inverse agonist-receptor interaction, this study screened a purine compound library for lead structures using wild-type (WT) human P2Y12 and 28 constitutively active mutants. Results showed that ATP and ATP derivatives are agonists at P2Y12. The potency at P2Y12 was 2-(methylthio)-ADP > 2-(methylthio)-ATP > ADP > ATP. Determinants required for agonistic ligand activity were identified. Molecular docking studies revealed a binding pocket for the ATP derivatives that is bordered by transmembrane helices 3, 5, 6, and 7 in human P2Y12, with Y105, E188, R256, Y259, and K280 playing a particularly important role in ligand interaction. N-Methyl-anthraniloyl modification at the 3′-OH of the 2′-deoxyribose leads to ligands (mant-deoxy-ATP [dATP], mant-deoxy-ADP) with inverse agonist activity. Inverse agonist activity of mant-dATP was found at the WT human P2Y12 and half of the constitutive active P2Y12 mutants. This study showed that, in addition to ADP and ATP, other ATP derivatives are not only ligands of P2Y12 but also agonists. Modification of the ribose within ATP can result in inverse activity of ATP-derived ligands. PMID:23093496

  7. Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats

    PubMed Central

    CHEN, MINCHUN; WANG, MINGMING; YANG, QIONG; WANG, MIN; WANG, ZHIPENG; ZHU, YANRONG; ZHANG, YIKAI; WANG, CHAO; JIA, YANYAN; LI, YUWEN; WEN, AIDONG

    2016-01-01

    Oxidative stress plays an important role in the initiation and development of myocardial injury (MI). The peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is considered to be a potential target for cardioprotection in MI. Acetyl-11-keto-β-boswellic acid (AKBA) is the major organic acid component extracted from Boswellia serrata Roxb. ex Colebr. Hydroxysafflor yellow A (HSYA) is the principal active constituent of Carthamus tinctorius L. In the present study, we aimed to investigate the cardioprotective effects of HSYA and AKBA in combination in vivo and in vitro, as well as the underlying mechanisms responsible for these effects. For this purpose, MI was produced in Sprague-Dawley rats by subcutaneous injection with isoproterenol. To model ischemic-like conditions in vitro, H9C2 cells were subjected to oxygen-glucose deprivation (OGD). The levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity were examined as well as apoptotic cell death. Mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm or MMP) were measured using MitoSOX Red and 5,5′,6,6′-tetraethylbenzimidazolylcarbocya-nine iodide (JC-1) dye. The expression of PGC-1α and Nrf2 was quantified by western blot analysis and immunohistochemistry. HSYA and AKBA prevented myocardial pathological changes, significantly reduced the blood levels of CK-MB and LDH, and decreased apoptotic cell death. They significantly increased the expression of PGC-1α and Nrf2, and the activity of the antioxidant enzyme SOD and also decreased the levels of MDA and ROS. Moreover, the reduction in MMP was partly prevented by HSYA and AKBA. Taken together, these findings elucidate the underlying mechanisms through which HSYA and AKBA protect against MI. Additionally, HSYA and AKBA appear to act synergistically in order to

  8. Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats.

    PubMed

    Chen, Minchun; Wang, Mingming; Yang, Qiong; Wang, Min; Wang, Zhipeng; Zhu, Yanrong; Zhang, Yikai; Wang, Chao; Jia, Yanyan; Li, Yuwen; Wen, Aidong

    2016-06-01

    Oxidative stress plays an important role in the initiation and development of myocardial injury (MI). The peroxisome proliferator-activated receptor gamma coactivator-1α (PGC‑1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is considered to be a potential target for cardioprotection in MI. Acetyl-11-keto-β-boswellic acid (AKBA) is the major organic acid component extracted from Boswellia serrata Roxb. ex Colebr. Hydroxysafflor yellow A (HSYA) is the principal active constituent of Carthamus tinctorius L. In the present study, we aimed to investigate the cardioprotective effects of HSYA and AKBA in combination in vivo and in vitro, as well as the underlying mechanisms responsible for these effects. For this purpose, MI was produced in Sprague-Dawley rats by subcutaneous injection with isoproterenol. To model ischemic-like conditions in vitro, H9C2 cells were subjected to oxygen-glucose deprivation (OGD). The levels of creatine kinase-MB (CK‑MB), lactate dehydrogenase (LDH), malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity were examined as well as apoptotic cell death. Mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm or MMP) were measured using MitoSOX Red and 5,5',6,6'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) dye. The expression of PGC-1α and Nrf2 was quantified by western blot analysis and immunohistochemistry. HSYA and AKBA prevented myocardial pathological changes, significantly reduced the blood levels of CK-MB and LDH, and decreased apoptotic cell death. They significantly increased the expression of PGC-1α and Nrf2, and the activity of the antioxidant enzyme SOD and also decreased the levels of MDA and ROS. Moreover, the reduction in MMP was partly prevented by HSYA and AKBA. Taken together, these findings elucidate the underlying mechanisms through which HSYA and AKBA protect against MI. Additionally, HSYA and AKBA appear to act

  9. ISO sees the pattern in the cosmic wallpaper

    NASA Astrophysics Data System (ADS)

    1998-07-01

    Two dozen distant galaxies that are undergoing a process of intense evolution --either merging to build larger ones or reaching their final shape-- have been detected by a team of French astronomers using the European Space Agency's ISO space telescope. These are the first individual objects known to contribute their energy to the bulk of the Cosmic Infrared Background, a radiation that fills the entire universe like a wallpaper, emitted at the era when galaxies were formed. The new-found distant galaxies are indeed like the 'pattern' in this 'cosmic wallpaper'. This discovery will for the first time enable scientists to test different theories of galaxy formation, and therefore to tackle a key problem of astronomy --the birth process of galaxies which has remained a mystery so far, mainly because current telescopes cannot reach that far back in time, about 12,000 million years ago. This obstacle has been partially overcome by the French team headed by Jean-Loup Puget, at the Institut d'Astrophysique Spatiale in Paris, precisely because they searched for the primeval galaxies by focusing first on the study of the cosmic wallpaper, the 'Cosmic Infrared Background' (see note to editors below). This background glow that fills the whole universe is a by-product of the galaxy formation itself, a relic of the era when the first galaxies were being born. Its existence was predicted three decades ago and it was known to be detectable only at infrared wavelengths, as the dust enshrouding young galaxies causes them to be both opaque in visible light but bright at infrared wavelengths. However, this cosmic wallpaper turned out to be very dim: only two years ago Puget's team detected it after a careful analysis of data from NASA's COBE satellite. Once the 'Cosmic Infrared Background' had been found, the next step was to disentangle it into the sources contributing to it, that is, into the young galaxies in evolution or the 'pattern' in the wallpaper. The two dozen distant

  10. Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

    PubMed Central

    Cheng, Yuanyuan; Zhao, Jia; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

    2015-01-01

    Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

  11. 76 FR 7839 - Notice of Commission and Commission Staff Attendance at ISO/RTO Council and Regional State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... Energy Regulatory Commission Notice of Commission and Commission Staff Attendance at ISO/RTO Council and... of the Commission and Commission staff may attend the following ISO/RTO Council and Regional State..., RTO/ISO Performance Metrics. For more information, contact Sandra Waldstein, Office of...

  12. Purification and characterization of (-)(/sup 125/I)hydroxyphenylisopropyladenosine, an adenosine R-site agonist radioligand and theoretical analysis of mixed stereoisomer radioligand binding

    SciTech Connect

    Linden, J.

    1984-11-01

    (-)-N6-(R-4-Hydroxyphenylisopropyl)adenosine (HPIA) was iodinated with NaI and trace /sup 125/I. Mono- and diiodinated reaction products and the starting material were separated by high pressure liquid chromatography and the structures of the reaction products were verified by NMR. (-)-N6-(R-Phenylisopropyl)adenosine (PIA), IHPIA, and I2HPIA decreased rat atrial contractility with ED50 values of 24, 28, and 33 nM, respectively. The contractile effects of these compounds were competitively blocked by theophylline (KI . 7.9 microM), but were not affected by adenosine deaminase. IHPIA also inhibited (-)isoproterenol-stimulated cyclic AMP accumulation in adipocytes with an ED50 (10 nM) and to an extent (83%) nearly identical to PIA. (/sup 125/I)HPIA prepared using carrier-free /sup 125/I bound to adenosine receptors on membranes from rat cerebral cortex, adipocyte ghosts, and heart ventricles. Binding was inhibited stereospecifically by PIA and by other adenosine analogues and alkylxanthines. The KD of (/sup 125/I)HPIA determined kinetically using brain membranes at 21 degrees was 0.94 nM in good agreement with the equilibrium determination of 1.94 nM. The density of adenosine receptors in brain membranes was found to be 871 fmol/mg of protein. When normalized to protein, the density of receptors in heart membranes and adipocyte ghosts, respectively, was found to be 39- and 2.3-fold less than in brain membranes. It was concluded that (/sup 125/I)HPIA can be rapidly synthesized and purified, binds to adenosine R-sites and is an agonist radioligand resistant to adenosine deaminase. Computer modeling of the equilibrium binding resulting from the use of mixed stereoisomers of a radioligand indicates that the combined use of (-)(/sup 125/I)HPIA and (+)(/sup 125/I)HPIA would result in the generation of nonlinear Scatchard plots.

  13. ISO spectroscopy of disks around Herbig Ae/Be stars

    NASA Astrophysics Data System (ADS)

    Acke, B.; van den Ancker, M. E.

    2004-10-01

    We have investigated the infrared spectra of all 46 Herbig Ae/Be stars for which spectroscopic data are available in the ISO data archive. Our quantitative analysis of these spectra focuses on the emission bands at 3.3, 6.2, ``7.7'', 8.6 and 11.2 micron, linked to polycyclic aromatic hydrocarbons (PAHs), the nanodiamond-related features at 3.4 and 3.5 micron, the amorphous 10 micron silicate band and the crystalline silicate band at 11.3 micron. We have detected PAH emission in 57% of the Herbig stars in our sample. Although for most of these sources the PAH spectra are similar, there are clear examples of differences in the PAH spectra within our sample which can be explained by differences in PAH size, chemistry and/or ionization. Amorphous silicate emission was detected in the spectra of 52% of the sample stars, amorphous silicate absorption in 13%. We have detected crystalline silicate emission in 11 stars (24% of our sample), of which four (9%) also display strong PAH emission. We have classified the sample sources according to the strength of their mid-IR energy distribution. The systems with stronger mid-infared (20-100 μm) excesses relative to their near-infrared (1-5 μm) excess display significantly more PAH emission than those with weaker mid-infrared excesses. There are no pronounced differences in the behaviour of the silicate feature between the two groups. This provides strong observational support for the disk models by \\citet{dullemond01}, in which systems with a flaring disk geometry display a strong mid-infrared excess, whereas those with disks that are strongly shadowed by the puffed-up inner rim of the disk only display modest amounts of mid-infrared emission. Since the silicates are expected to be produced mainly in the warm inner disk regions, no large differences in silicate behaviour are expected between the two groups. In contrast to this, the PAH emission is expected to be produced mainly in the part of the disk atmosphere that is

  14. Sustainable development induction in organizations: a convergence analysis of ISO standards management tools' parameters.

    PubMed

    Merlin, Fabrício Kurman; Pereira, Vera Lúciaduarte do Valle; Pacheco, Waldemar

    2012-01-01

    Organizations are part of an environment in which they are pressured to meet society's demands and acting in a sustainable way. In an attempt to meet such demands, organizations make use of various management tools, among which, ISO standards are used. Although there are evidences of contributions provided by these standards, it is questionable whether its parameters converge for a possible induction for sustainable development in organizations. This work presents a theoretical study, designed on structuralism world view, descriptive and deductive method, which aims to analyze the convergence of management tools' parameters in ISO standards. In order to support the analysis, a generic framework for possible convergence was developed, based on systems approach, linking five ISO standards (ISO 9001, ISO 14001, OHSAS 18001, ISO 31000 and ISO 26000) with sustainable development and positioning them according to organization levels (strategic, tactical and operational). The structure was designed based on Brundtland report concept. The analysis was performed exploring the generic framework for possible convergence based on Nadler and Tushman model. The results found the standards can contribute to a possible sustainable development induction in organizations, as long as they meet certain minimum conditions related to its strategic alignment. PMID:22317134

  15. Anti-nociception mediated by a κ opioid receptor agonist is blocked by a δ receptor agonist

    PubMed Central

    Taylor, A M W; Roberts, K W; Pradhan, A A; Akbari, H A; Walwyn, W; Lutfy, K; Carroll, F I; Cahill, C M; Evans, C J

    2015-01-01

    BACKGROUND AND PURPOSE The opioid receptor family comprises four structurally homologous but functionally distinct sub-groups, the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but not specific, a broad spectrum of behaviours due to activation of different opioid receptors is expected. In this study, we examine whether other opioid receptor systems influenced KOP-mediated antinociception. EXPERIMENTAL APPROACH We used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive effect of systemically administered opioid agonists with varying selectivity at KOP receptors. Pharmacological and genetic approaches were used to analyse the interactions of the other opioid receptors in modulating KOP-mediated antinociception. KEY RESULTS Etorphine, a potent agonist at all four opioid receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine is an efficacious KOP receptor agonist and specific KOP receptor agonists remain analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered KOP-mediated antinociception might be a form of stress-induced analgesia that is blocked by the anxiolytic effects of DOP receptor agonists. In support of this hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg·kg−1), unmasked etorphine (3 mg·kg−1) antinociception in MOP KO mice. Further, in wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg·kg−1) was blocked by pretreatment with the DOP agonist SNC80 (5 mg·kg−1) and diazepam (1 mg·kg−1). CONCLUSIONS AND IMPLICATIONS Systemic DOP receptor agonists blocked systemic KOP antinociception, and these results identify DOP receptor agonists as potential agents for reversing stress-driven addictive and depressive behaviours mediated through KOP receptor activation. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles

  16. Dihydrocodeine/Agonists for Alcohol Dependents

    PubMed Central

    Ulmer, Albrecht; Müller, Markus; Frietsch, Bernhard

    2012-01-01

    Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients. Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC) to 102 heavily alcohol addicted patients, later, also Buprenorphine, Clomethiazole (>6 weeks), Baclofen, and in one case Amphetamine, each on individual indication. This paper focuses on the data with DHC, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-steps scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details. Conclusion: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around 1/4 of the patients already. Many further

  17. Agonists and antagonists for P2 receptors

    PubMed Central

    Jacobson, Kenneth A.; Costanzi, Stefano; Joshi, Bhalchandra V.; Besada, Pedro; Shin, Dae Hong; Ko, Hyojin; Ivanov, Andrei A.; Mamedova, Liaman

    2015-01-01

    Recent work has identified nucleotide agonists selective for P2Y1, P2Y2 and P2Y6 receptors and nucleotide antagonists selective for P2Y1, P2Y12 and P2X1 receptors. Selective non-nucleotide antagonists have been reported for P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, P2X2/3/P2X3 and P2X7 receptors. For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non-nucleotide antagonist A-317491 is selective for P2X2/3/P2X3 receptors. Nucleotide analogues in which the ribose moiety is substituted by a variety of novel ring systems, including conformation-ally locked moieties, have been synthesized as ligands for P2Y receptors. The focus on conformational factors of the ribose-like moiety allows the inclusion of general modifications that lead to enhanced potency and selectivity. At P2Y1,2,4,11 receptors, there is a preference for the North conformation as indicated with (N)-methanocarba analogues. The P2Y1 antagonist MRS2500 inhibited ADP-induced human platelet aggregation with an IC50 of 0.95 nM. MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency (EC50) of 0.4 nM at the P2Y1 receptor, with >10 000-fold selectivity in comparison to P2Y12 and P2Y13 receptors. At P2Y6 receptors there is a dramatic preference for the South conformation. Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three-dimensional structures of P2X receptors have not yet been proposed. PMID:16805423

  18. Sensitive change of iso-branched fatty acid (iso-15:0) in Bacillus pumilus PAMC 23174 in response to environmental changes.

    PubMed

    Yi, Da-Hye; Sathiyanarayanan, Ganesan; Seo, Hyung Min; Kim, Jung-Ho; Bhatia, Shashi Kant; Kim, Yun-Gon; Park, Sung-Hee; Jung, Ji-Young; Lee, Yoo Kyung; Yang, Yung-Hun

    2016-01-01

    In this study, the environmental adaptive metabolic processes were investigated using a psychrotrophic polar bacterium Bacillus pumilus PAMC 23174 in response to various temperatures and nutrients, especially in regard to the synthesis of fatty acids. Fatty acid methyl ester analysis was performed using gas chromatography-mass spectrometry and we found that a sensitive changes in iso-branched fatty acid (iso-15:0) synthesis occurred when adjusting the nutritional ratio of branched chain fatty acids (anteiso/iso) with different temperatures, resulting in a change in the balance of anteiso- and iso-form fatty acids. We also observed that this Arctic bacterium preferred amino acid leucine for the synthesis of fatty acids. The increased and decreased synthesis of iso-form fatty acids in response to different temperatures and leucine preference, changes the fatty acid ratio in bacteria, which further affects the membrane fluidity and it is also directly correlated with survival of bacteria in an extreme environment. Hence, this study suggests that B. pumilus PAMC 23174 is a potential model organism for the analysis of the unique ecological adaptations of polar bacteria in changing and the extreme environments. PMID:26566954

  19. Selective optical detection of n-heptane/iso-octane vapors by polyimide lightguides

    NASA Astrophysics Data System (ADS)

    Podgorsek, R. P.; Franke, H.; Feger, C.

    1995-03-01

    The optical anisotropy of planar polyimide lightguides in an atmosphere of n-heptane / iso-octane is investigated in a transient experiment for pure and several mixed-vapor concentrations. The polymer sensor responds only to n-heptane and not to iso-octane vapors. However, the presence of the latter affects the dynamic behavior of the waveguide anisotropy, which can be fitted by a stretched exponential time dependence. The saturation values of the birefringence are an absolute measure for the n-heptane concentration and are not affected by the presence of the iso-octane vapors.

  20. ISO Guest Observer Data Analysis and LWS Instrument Team Activities

    NASA Technical Reports Server (NTRS)

    Smith, Howard

    2001-01-01

    The following is an interim annual report. Dr. Smith is currently on an extended TDY to the Istituto di Fisica dello Spazio Interplanetario (IFSI) at the Consilio Nazionale delle Richerche (CNR) in Rome, Italy, where he has been working on a related NASA grant in support of analysis of Infrared Space Observatory (ISO) data on star formation in Ultra Luminous Infrared Galaxies and our galaxy. Work emphasizes development of metal mesh grids for use in spacecraft, and the design and fabrication of test elements by the Naval Research Laboratory, Washington D.C. Work has progressed well, but slowly, on that program due to the departure of a key engineer. NASA has been advised of the delay, and granted a no-cost extension, whereby SAO has authorized a delay in the final report from NRL. Nevertheless NRL has continued to make progress. Two papers have been submitted to refereed journals related to this program, and a new design for mesh operating in the 20-40 micron region has been developed. Meetings continue through the summer on these items. A new technical scientist has been made a job offer and hopefully will be on board NRL shortly, although most of the present grant work is already completed. A more complete report, with copies of the submitted papers, designs, and other measures of progress, will be submitted to NASA in September when Dr. Smith returns from his current TDY.

  1. IGS: An IsoGeometric approach for smoothing on surfaces

    NASA Astrophysics Data System (ADS)

    Wilhelm, Matthieu; Dedè, Luca; Sangalli, Laura M.; Wilhelm, Pierre

    2016-04-01

    We propose an Isogeometric approach for smoothing on surfaces, namely estimating a function starting from noisy and discrete measurements. More precisely, we aim at estimating functions lying on a surface represented by NURBS, which are geometrical representations commonly used in industrial applications. The estimation is based on the minimization of a penalized least-square functional. The latter is equivalent to solve a 4th-order Partial Differential Equation (PDE). In this context, we use Isogeometric Analysis (IGA) for the numerical approximation of such surface PDE, leading to an IsoGeometric Smoothing (IGS) method for fitting data spatially distributed on a surface. Indeed, IGA facilitates encapsulating the exact geometrical representation of the surface in the analysis and also allows the use of at least globally $C^1-$continuous NURBS basis functions for which the 4th-order PDE can be solved using the standard Galerkin method. We show the performance of the proposed IGS method by means of numerical simulations and we apply it to the estimation of the pressure coefficient, and associated aerodynamic force on a winglet of the SOAR space shuttle.

  2. Very low force cooling contacts for the ISO cryostat cover

    NASA Astrophysics Data System (ADS)

    Schaellig, R.; Seidel, A.

    1990-03-01

    The infrared Space Observatory (ISO) cryostat cover, which will be ejected from the satellite after a period of 10-15 days in orbit, needs passive cooling of its thermal shields to minimize heat input to the cryostat and to maintain a temperature on the innermost shield of 25 K or less. This passive cooling is provided by spring loaded thermal contacts which are also used for ejection of the cover after release of the clampband device that keeps the cover closed during launch. So as not to disturb the satellite attitude control and to limit the load on the mechanical cover shield supports, the force of a single thermal contact was limited to 25-35 N. An experimental program was conducted to measure the thermal contact conductance of various combinations of two shapes and three materials. Typical measured conductance and heat transfer coefficients for the gold treated copper sphere/flat aluminum plane combination are: 2.54 W/sq cm K and 1.8 mW/K at a contact temperature of 8 K and a force of 25 N, with a pressure of 3.5 x 10 to the 8th Pa.

  3. Operation of the ISO-DALT system: Seventh edition

    SciTech Connect

    Tollaksen, S.L.; Anderson, N.L.; Anderson, N.G.

    1984-05-01

    The ISO-DALT system of two-dimensional electrophoresis was developed as a series of modifications of the original technique of O'Farrell. We have written a series of recipes and more detailed laboratory procedures that incorporate refinements and ''tricks of the trade'' as they have developed during our use of the system. The present collection is the seventh version in this series and represents the state of art as of May 1984. The seventh edition has been prepared to incorporate the changes that we have found helpful, as well as to add a few new sections such as silver staining, transfer gels, ACIDOs, and BASOs. Although these directions are specific for our laboratory, we hope that they will be helpful in other laboratories as well. Although some disagreement still exists, we recommend that gel patterns be oriented with acid isoelectric points (pIs) to the left and high sodium dodecyl sulfate (SDS) molecular weights at the top. This results in a system of pI and molecular weight values that run according to the Cartesian convention and facilitates the use of the charge and molecular weight standards described herein. 67 refs., 14 figs.

  4. [Certification according to ISO 9001--waste of time or necessity?].

    PubMed

    Metz-Schimmerl, S; Schima, W; Herold, C J

    2002-05-01

    Quality management (QM) systems are widely established management tools in the industry and business world today. In the health care sector, the need for quality, the implementation of quality management systems and economic orientation of the hospital management are strongly encouraged. Centers of excellence are created to offer special medical services of the highest possible quality. Furthermore, there is a worldwide tendency to establish standards in clinical medical settings, in teaching profession and medical science. These trends make the implementation of a quality management system in health care system highly desirable. The present manuscript reviews the fundamental principles and concepts and the aims of internationally accepted QM systems. It focuses on the ISO-9000 certificates and the European Foundation of Quality Management (EFQM) model. The advantages and disadvantages are discussed. The resources necessary for installation of a QM system and the different phases of implementation are reported. According to the experience of several groups, QM systems can be reliably used in a radiology department and lead to continuous improvement of the quality of services. PMID:12132126

  5. First results of ISO-SWS observations of Jupiter.

    NASA Astrophysics Data System (ADS)

    Encrenaz, T.; de Graauw, T.; Schaeidt, S.; Lellouch, E.; Feuchtgruber, H.; Beintema, D. A.; Bezard, B.; Drossart, P.; Griffin, M.; Heras, A.; Kessler, M.; Leech, K.; Morris, P.; Roelfsema, P. R.; Roos-Serote, M.; Salama, A.; Vandenbussche, B.; Valentijn, E. A.; Davis, G. R.; Naylor, D. A.

    1996-11-01

    The spectrum of Jupiter has been recorded between 2.75 and 14.5μm with the grating mode of the Short-Wavelength Spectrometer (SWS) of ISO. The resolving power is 1500. The main preliminary results of this observation are (1) at 3μm, the first spectroscopic signature, probably associated with NH_3_ ice, of the Jovian cloud at 0.5 bar and (2) the first detection of a thermal emission at the center of the CH_4_-ν_3_ band at 3.3μm, showing evidence for a high temperature in the upper jovian stratosphere (T=800K at P=0.16 microbar). In addition, the R(2) HD line has been detected for the first time in Jupiter, using the Fabry-Perot (FP) mode of the SWS, with a resolving power of 31000. A preliminary analysis of the HD line indicates a D/H ratio of about 2.2x10^-5^.

  6. ISO 9000 and its effects on the coal industry

    SciTech Connect

    Vardys, R.K.

    1996-12-31

    It is asserted that organizations that do not implement a formal quality program by the year 2000 will not survive. The ISO 9000 quality management standards provide the model for many companies that have determined a quality program is vital not only for their survival, but their growth, in an increasingly competitive business environment. The U.S. coal industry has been hit hard with utility de-regulation and global competition. More emphasis is being placed on bold cost savings measures by utilities and coal producers alike. These measures range from subcontracting analytical work to subcontracting power plant maintenance. Unfortunately, quality management systems are still seen as an expense instead of a cost saving measure and are not being addressed by those who most desperately need quality management systems. What must be understood is that through the implementation of a quality management program, companies can recover costs that were previously accepted as unrecoverable. Prevention costs (documentation, internal auditing, training, management review, etc.) will increase slightly, due to an increased emphasis on a quality management system, but, a net savings is realized through a decrease in failure costs, e.g., waste, scrap, meetings to discuss failures/place blame, worry, re-work, client loss, client doubt, etc.

  7. Honokiol: A non-adipogenic PPARγ agonist from nature☆

    PubMed Central

    Atanasov, Atanas G.; Wang, Jian N.; Gu, Shi P.; Bu, Jing; Kramer, Matthias P.; Baumgartner, Lisa; Fakhrudin, Nanang; Ladurner, Angela; Malainer, Clemens; Vuorinen, Anna; Noha, Stefan M.; Schwaiger, Stefan; Rollinger, Judith M.; Schuster, Daniela; Stuppner, Hermann; Dirsch, Verena M.; Heiss, Elke H.

    2013-01-01

    Background Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators. Methods We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists. Results The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain. Conclusion We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo. General significance This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine. PMID:23811337

  8. Modification of opiate agonist binding by pertussis toxin

    SciTech Connect

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  9. Radiation therapy generates platelet-activating factor agonists

    PubMed Central

    Sahu, Ravi P.; Harrison, Kathleen A.; Weyerbacher, Jonathan; Murphy, Robert C.; Konger, Raymond L.; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph R.; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F.; Travers, Jeffrey B.

    2016-01-01

    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens. PMID:26959112

  10. Radiation therapy generates platelet-activating factor agonists.

    PubMed

    Sahu, Ravi P; Harrison, Kathleen A; Weyerbacher, Jonathan; Murphy, Robert C; Konger, Raymond L; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph R; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F; Travers, Jeffrey B

    2016-04-12

    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens. PMID:26959112

  11. Comparison of chemical permeation data obtained with ASTM and ISO permeation test cells--II. The ISO/DIS standard test procedure.

    PubMed

    Mellström, G A

    1991-04-01

    ASTM and ISO/DIS test cells were used for permeation testing according to the procedure proposed in draft international standard ISO/DIS 6259. Two compounds, toluene and 1,1,1-trichloroethane, were tested with one neoprene glove and one made of a specially prepared Neoprene material. Different open-loop systems, direct-flow measurement and a sampling system with different gas flow rates were compared, and the effects on the test result were evaluated. The initial breakthrough (BTT) times and cumulative breakthrough times (lag-BTT) were significantly influenced only by the measurement systems. Neither cell configuration nor changes in the gas flow rate influenced them to any degree relevant for comparison of the test values on a relative basis in most cases. The permeation rates (PER) and the cumulative amount permeating per cm2 in 60 min showed significant differences between measuring systems, gas flow rates and the ASTM vs the ISO/DIS test procedures. PMID:2042883

  12. Supra-physiological efficacy at GPCRs: superstition or super agonists?

    PubMed Central

    Langmead, Christopher J; Christopoulos, Arthur

    2013-01-01

    The concept of ‘super agonism’ has been described since the discovery of peptide hormone analogues that yielded greater functional responses than the endogenous agonists, in the early 1980s. It has remained an area of debate as to whether such compounds can really display greater efficacy than an endogenous agonist. However, recent pharmacological data, combined with crystal structures of different GPCR conformations and improved analytical methods for quantifying drug action, are starting to shed light on this phenomenon and indicate that super agonists may be more than superstition. Linked Article This article is a commentary on Schrage et al., pp. 357–370 of this issue. To view this paper visit http://dx.doi.org/10.1111/bph.12003 PMID:23441648

  13. Principles of agonist recognition in Cys-loop receptors

    PubMed Central

    Lynagh, Timothy; Pless, Stephan A.

    2014-01-01

    Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine, and GABA. After the term “chemoreceptor” emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands. PMID:24795655

  14. Alpha-2 agonists as pain therapy in horses.

    PubMed

    Valverde, Alexander

    2010-12-01

    Alpha-2 agonists, such as xylazine, clonidine, romifidine, detomidine, medetomidine, and dexmedetomidine, are potent analgesic drugs that also induce physiologic and behavioral changes, such as hypertension, bradycardia, atrioventricular block, excessive sedation and ataxia, all of which can potentially limit their systemic use as analgesics in some clinical cases. The use of medetomidine and dexmetomidine has been introduced for equine anesthesia/analgesia, and although not approved in this species, their increased specificity for alpha-2 receptors may offer some potential advantages over the traditional alpha-2 agonists. Similarly, other routes of administration and benefits of alpha-2 agonists are recognized in the human and laboratory animal literature, which may prove useful in the equine patient if validated in the near future. This review presents this relevant information. PMID:21056297

  15. [Nine-Year Experience after ISO 15189 Acquisition, How Successful was It? Focusing on the Results of Interviews and Questionnaires].

    PubMed

    Fujimoto, Kazumitsu; Asai, Noriaki; Nakajima, Yoshinaga; Inoue, Kaoru

    2015-11-01

    Our laboratory, for the purpose of Quality Management System (QMS) improvement, acquired ISO 15189:2003 accreditation 9 years ago and completed the renewal to ISO 15189:2012 last year. In this study, we reviewed the efficacy of ISO 15189 based on an analysis of laboratory director's and managers' opinions. We could realize QMS improvement through the proactive implementation of preventive and corrective actions, and also the continuous implementation of education and delivery by means of reviewing the interview records of ISO 15189:2012 renewal with the laboratory director. All answers to the questionnaire obtained from managers with regard to the advantages of ISO 15189 acquisition agreed with the purpose of ISO 15189. From these results, we concluded that ISO 15189 acquisition was successful for QMS improvement. [Review]. PMID:26995873

  16. Manufacturing of microcomponents in a research institute under DIN EN ISO 9001

    NASA Astrophysics Data System (ADS)

    Maas, Dieter; Karl, Bernhard; Saile, Volker; Schulz, Joachim

    2000-08-01

    The Institute for Microstructure Technology at Forschungszentrum Karlsruhe has implemented a rigorous quality management system and was certified according to the DIN ISO EN 9001 standard in January 2000.

  17. ISO/GUM UNCERTAINTIES AND CIAAW (UNCERTAINTY TREATMENT FOR RECOMMENDED ATOMIC WEIGHTS AND ISOTOPIC ABUNDANCES)

    SciTech Connect

    HOLDEN,N.E.

    2007-07-23

    The International Organization for Standardization (ISO) has published a Guide to the expression of Uncertainty in Measurement (GUM). The IUPAC Commission on Isotopic Abundance and Atomic Weight (CIAAW) began attaching uncertainty limits to their recommended values about forty years ago. CIAAW's method for determining and assigning uncertainties has evolved over time. We trace this evolution to their present method and their effort to incorporate the basic ISO/GUM procedures into evaluations of these uncertainties. We discuss some dilemma the CIAAW faces in their present method and whether it is consistent with the application of the ISO/GUM rules. We discuss the attempt to incorporate variations in measured isotope ratios, due to natural fractionation, into the ISO/GUM system. We make some observations about the inconsistent treatment in the incorporation of natural variations into recommended data and uncertainties. A recommendation for expressing atomic weight values using a tabulated range of values for various chemical elements is discussed.

  18. Avoiding ISO-lation: What international standards mean for U.S. industry

    SciTech Connect

    Crognale, G.; Walter-Slepicka, M.

    1996-03-01

    US companies are awash in an effort to promote and self-proclaim conformance to ISO 9000, the series of quality standards established by the International Organization for Standardization (Geneva, Switzerland). One only needs to drive along any roadway to note another banner proclaiming a company`s conformance or certification, or pick up a magazine or newspaper to read that a company is ISO 9001-certified. Quality standards are not quite the same as environmental standards, however. As a result, some companies may be receiving mixed signals with how ISO 9000 compares to the proposed ISO 14000 standards series for environmental management systems. This article clarifies some of these perceptions, and describes in greater detail what the environmental standards are, what they mean for industry and what they can do for companies that implement them.

  19. A flow reactor study of the oxidation of n-octane and iso-octane

    SciTech Connect

    Dryer, F.L.; Brezinsky, K.

    1986-01-01

    An experimental study has been conducted in a flow reactor on the oxidation of n-octane and iso-octane at 1080 K, one atmosphere pressure and equivalence ratio equal to one. It was found that (despite similar ratios of initial fuel decay) the conversion of the reaction intermediates to CO and CO/sub 2/ is much slower during the oxidation of iso-octane than n-octane. Iso-octane produced primarily iso-butylene and propylene as intermediate hydrocarbons whereas n-octane oxidation resulted primarily in the formation of ethylene. Both the nature of the intermediates formed from each fuel and the relative rates of oxidation of the intermediates were shown to be related to the number of primary, secondary and tertiary H atoms present in the initial fuel. The basic chemistry revealed by the flow reactor experiments is suggestive of new insights into the chemical phenomena pertinent to knock in spark ignition engines.

  20. [The application of ISO 9000 quality control system in the medical equipment management].

    PubMed

    Ma, Qiao-yun

    2006-05-01

    This paper expounds the importance of the application of ISO 9000 quality control system in hospitals, introduces the program files and the relavant software established for its application, and gives its effective results. PMID:16929782

  1. Agonist treatment in opioid use: advances and controversy.

    PubMed

    Viswanath, Biju; Chand, Prabhat; Benegal, Vivek; Murthy, Pratima

    2012-06-01

    Opioid dependence is a chronic relapsing condition which requires comprehensive care; pharmacological agents form the mainstay of its long term treatment. The two most popular approaches are the harm reduction method using agonists and the complete abstinence method using antagonists. Currently, particularly from the harm minimization perspective and the low feasibility of an abstinence based approach, there is an increasing trend toward agonist treatment. The use of buprenorphine has gained popularity in view of its safety profile and the availability of the buprenorphine-naloxone combination has made it popular as a take-home treatment. This review outlines the pharmacological advances and controversies in this area. PMID:22813654

  2. Insect Nicotinic Receptor Agonists as Flea Adulticides in Small Animals

    PubMed Central

    Vo, Dai Tan; Hsu, Walter H.; Martin, Richard J.

    2013-01-01

    Fleas are significant ectoparasites of small animals. They can be a severe irritant to animals and serve as a vector for a number of infectious diseases. In this article, we discuss the pharmacological characteristics of four insect nicotinic acetylcholine receptor (nAChR) agonists used as fleacides in dogs and cats, which include three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) and spinosad. Insect nAChR agonists are one of the most important new classes of insecticides, which are used to control sucking insects both on plants and on companion animals. These new compounds provide a new approach for practitioners to safely and effectively eliminate fleas. PMID:20646191

  3. Piperidine derivatives as nonprostanoid IP receptor agonists 2.

    PubMed

    Hayashi, Ryoji; Ito, Hiroaki; Ishigaki, Takeshi; Morita, Yasuhiro; Miyamoto, Mitsuko; Isogaya, Masafumi

    2016-06-15

    We searched for a strong and selective nonprostanoid IP agonist bearing piperidine and benzanilide moieties. Through optimization of substituents on the benzanilide moiety, the crucial part of the agonist, 43 (2-((1-(2-(N-(4-tolyl)benzo[d][1,3]dioxole-5-carboxamido)ethyl)piperidin-4-yl)oxy)acetic acid monohydrate monohydrochloride) was discovered and exhibited strong platelet aggregation inhibition (IC50=21nM) and 100-fold selectivity for IP receptor over other PG receptors. The systemic exposure level and bioavailability after oral administration of 43 were also good in dog. PMID:27133594

  4. 21 CFR 184.1165 - n-Butane and iso-butane.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false n-Butane and iso-butane. 184.1165 Section 184.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Listing of Specific Substances Affirmed as GRAS § 184.1165 n-Butane and iso-butane. (a) n-Butane and...

  5. 21 CFR 184.1165 - n-Butane and iso-butane.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true n-Butane and iso-butane. 184.1165 Section 184.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Listing of Specific Substances Affirmed as GRAS § 184.1165 n-Butane and iso-butane. (a) n-Butane and...

  6. 21 CFR 184.1165 - n-Butane and iso-butane.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false n-Butane and iso-butane. 184.1165 Section 184.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1165 n-Butane and iso-butane....

  7. 21 CFR 184.1165 - n-Butane and iso-butane.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false n-Butane and iso-butane. 184.1165 Section 184.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Listing of Specific Substances Affirmed as GRAS § 184.1165 n-Butane and iso-butane. (a) n-Butane and...

  8. Post-accelerator issues at the IsoSpin Laboratory

    SciTech Connect

    Chattopadhyay, S.; Nitschke, J.M.

    1994-05-01

    The workshop on ``Post-Accelerator Issues at the Isospin Laboratory`` was held at the Lawrence Berkeley Laboratory from October 27--29, 1993. It was sponsored by the Center for Beam Physics in the Accelerator and Fusion Research Division and the ISL Studies Group in the Nuclear Science Division. About forty scientists from around the world participated vigorously in this two and a half day workshop, (c.f. Agenda, Appendix D). Following various invited review talks from leading practitioners in the field on the first day, the workshop focussed around two working groups: (1) the Ion Source and Separators working group and (2) the Radio Frequency Quadrupoles and Linacs working group. The workshop closed with the two working groups summarizing and outlining the tasks for the future. This report documents the proceedings of the workshop and includes the invited review talks, the two summary talks from the working groups and individual contributions from the participants. It is a complete assemblage of state-of-the-art thinking on ion sources, low-{beta}, low(q/A) accelerating structures, e.g. linacs and RFQS, isobar separators, phase-space matching, cyclotrons, etc., as relevant to radioactive beam facilities and the IsoSpin Laboratory. We regret to say that while the fascinating topic of superconducting low-velocity accelerator structure was covered by Dr. K. Shepard during the workshop, we can only reproduce the copies of the transparencies of his talk in the Appendix, since no written manuscript was available at the time of publication of this report. The individual report have been catologed separately elsewhere.

  9. [CII] emission across M31 seen by Herschel and ISO

    NASA Astrophysics Data System (ADS)

    Kapala, Maria Julia; Groves, Brent; Sandstrom, Karin; Survey of Lines in M31 (SLIM)

    2015-01-01

    The [CII] 158 micron line is typically the brightest far-IR emission line from star-forming (SF) galaxies. As such, this line is a potentially useful tracer of star formation. To calibrate such applications, we must understand the relative contributions of different ISM phases to the [CII] emission. Using high physical resolution observations of the [CII] 158 micron line from Herschel PACS in five 3'x3' field in M31 and optical IFU spectra from PPaK and ancillary IR data, we are able to spatially separate out the ISM phases. Additionally, to study the full radial profile of heating and cooling of the ISM in Andromeda, we include [CII] observations from ISO in the bulge. We find that SF regions in M31 do not exhibit a "[CII] line deficit" on 50 pc scales, even in regions where the dust is very warm. Using the optical line emission, we determine the fraction of [CII] emission spatially associated with SF regions. Our method implies a high fraction ~20-90% of [CII] emission is coming from diffuse regions. These diffuse regions appear to dominated by the UV interstellar radiation field which arises from B stars and possible photon leakage from the SF regions. Due to the presence of this large diffuse fraction, we find on ~50pc scales that the relation between [CII] and SFR is sub-linear in most of the fields. However, when averaged over ~700pc scales it becomes steeper and is in agreement with other extragalactic studies on similar scales. Interestingly, even with this correlation of SFR & [CII], we find that [CII]/TIR decreases with radius by a factor of ~3 from 16 to 7 kpc, with a slight increase in the bulge. We discuss metallicity, stellar radiation fields and emission from diffuse ionized phase as possible explanations for these trends.

  10. Pyrrolo- and Pyridomorphinans: Non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists

    PubMed Central

    Kumar, V.; Clark, M.J.; Traynor, J.R.; Lewis, J.W.; Husbands, S.M.

    2014-01-01

    Opioid ligands have found use in a number of therapeutic areas, including for the treatment of pain and opiate addiction (using agonists) and alcohol addiction (using antagonists such as naltrexone and nalmefene). The reaction of imines, derived from the opioid ligands oxymorphone and naltrexone, with Michael acceptors leads to pyridomorphinans with structures similar to known pyrrolo- and indolomorphinans. One of the synthesized compounds, 5e, derived from oxymorphone had substantial agonist activity at delta opioid receptors but not at mu and/or kappa opioid receptors and in that sense profiled as a selective delta opioid receptor agonist. The pyridomorphinans derived from naltrexone and naloxone were all found to be non-selective potent antagonists and as such could have utility as treatments for alcohol abuse. PMID:24973818

  11. Pyrrolo- and pyridomorphinans: non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists.

    PubMed

    Kumar, V; Clark, M J; Traynor, J R; Lewis, J W; Husbands, S M

    2014-08-01

    Opioid ligands have found use in a number of therapeutic areas, including for the treatment of pain and opiate addiction (using agonists) and alcohol addiction (using antagonists such as naltrexone and nalmefene). The reaction of imines, derived from the opioid ligands oxymorphone and naltrexone, with Michael acceptors leads to pyridomorphinans with structures similar to known pyrrolo- and indolomorphinans. One of the synthesized compounds, 5e, derived from oxymorphone had substantial agonist activity at delta opioid receptors but not at mu and/or kappa opioid receptors and in that sense profiled as a selective delta opioid receptor agonist. The pyridomorphinans derived from naltrexone and naloxone were all found to be non-selective potent antagonists and as such could have utility as treatments for alcohol abuse. PMID:24973818

  12. Molecular mechanisms behind the antimicrobial activity of hop iso-α-acids in Lactobacillus brevis.

    PubMed

    Schurr, Benjamin C; Hahne, Hannes; Kuster, Bernhard; Behr, Jürgen; Vogel, Rudi F

    2015-04-01

    The main bittering component in beer, hop iso-α-acids, have been characterised as weak acids, which act as ionophores impairing microbial cells' function under acidic conditions as present in beer. Besides medium pH, divalent cations play a central role regarding the efficacy of the antimicrobial effect. The iso-α-acids' non-bitter derivatives humulinic acids can be found in isomerised hop extracts and can be generated during hop storage. Therefore, they have been under investigation concerning their influence on beer sensory properties. This study sketches the molecular mechanism behind iso-α-acids' antimicrobial activity in Lactobacillus (L.) brevis regarding their ionophore activity versus the dependence of the inhibitory potential on manganese binding, and suggests humulinic acids as novel tasteless food preservatives. We designed and synthesised chemically modified iso-α-acids to enhance the basic understanding of the molecular mechanism of antimicrobial iso-α-acids. It could be observed that a manganese-binding dependent transmembrane redox reaction (oxidative stress) plays a crucial role in inhibition. Privation of an acidic hydroxyl group neither erased ionophore activity, nor did it entirely abolish antimicrobial activity. Humulinic acids proved to be highly inhibitory, even outperforming iso-α-acids. PMID:25475328

  13. Comparison of ISO Standard and TKR Patient Axial Force Profiles during the Stance Phase of Gait

    PubMed Central

    Lundberg, Hannah J.; Ngai, Valentina; Wimmer, Markus A.

    2012-01-01

    Preclinical endurance testing of total knee replacements (TKRs) is performed using International Organization for Standardization (ISO) load and motion protocols. The standards are based on data from normal subjects and may not sufficiently mimic in vivo implant conditions. In this study, a mathematical model was used to calculate the axial force profile of 30 TKR patients with two current implant types, 22 with NexGen and eight with Miller-Galante II Cruciate-Retaining TKRs, and statistically compare the axial force specified by the ISO standard to the TKR patients. Significant differences were found between the axial forces of both groups of TKR patients and the ISO standard at local maxima and minima points in the first half of stance. The force impulse (area under the axial force curve, representing cumulative loading) was smaller for the ISO standard than the TKR patients, but only for those with NexGen implants. Waveform analysis using the coefficient of multiple correlation showed that the ISO and TKR patient axial force profiles were similar. The combined effect of ISO standard compressive load and motion differences from TKR patients could explain some of the differences between the wear scars on retrieved tibial components and those tested in total joint simulators. PMID:22558837

  14. ISO terminological analysis of the VIM3 concepts 'quantity' and 'kind-of-quantity'

    NASA Astrophysics Data System (ADS)

    Dybkaer, René

    2010-06-01

    The recent third edition of the International Vocabulary of Metrology—Basic and General Concepts and Associated Terms (VIM3) (JCGM 200:2008 (Sèvres: BIPM); also ISO/IEC Guide 99:2007 3rd edn (Geneva: ISO)) has undergone important changes, not least by adhering to ISO International Standards on terminology work (ISO 704:2000 Terminology Work—Principles and Methods; ISO 1087-1:2000 Terminology Work—Vocabulary—Part 1: Theory and Application; ISO 10241:1992 International Terminology Standards—Preparation and Layout). A recent critique (Mari 2009 Metrologia 46 L11-L15)—based on Object-Oriented Analysis—centres on the meaning and relation of the two first and fundamental concepts 'quantity'Single quotation marks ('...') or bold type indicate a concept when necessary, double quotation marks ("...") a term or quotation. and the new entry 'kind-of-quantity'. This makes it timely to analyse the two concepts, their relation and their respective role in forming the generic hierarchical concept system of VIM3 from 'property' to individual quantities. It is suggested that 'kind-of-quantity' acts as a division criterionSynonyms are "criterion of subdivision", "type of characteristic(s)", see the annexe..

  15. Does the selection of ISO 14001 registrars matter? Registrar reputation and environmental policy statements in China.

    PubMed

    Fryxell, Gerald E; Chung, Shan Shan; Lo, Carlos W H

    2004-05-01

    This study investigates the relationship between characteristics of environmental policy statements and the reputations of ISO 14001 registrars who had performed certification audits of firms operating in mainland China. Three characteristics of environmental policy statements were examined: (1) The conformance of the policy to strict interpretations of the international standard; (2) The policy statement's adherence to the good practice guidelines specified in ISO 14004; and, (3) Self-reported evaluations of the policy statement's effectiveness as implemented. Data from 106 facilities in Beijing, Shanghai and Guangzhou reveal that registrar quality has a relatively weak, positive relationship with conformance to both ISO 14001 standards and to ISO 14004 guidelines, but no relationship was observed with the self-reported data. Additional findings are that the use of foreign registrars is significantly associated with the adoption of ISO 14004 guidelines and that conformance with ISO 14001 standards is somewhat higher for international joint ventures and foreign-owned firms than for state-owned enterprises. PMID:15084359

  16. ISO 14001 as an environmental capacity building tool--variations among nations.

    PubMed

    Kerret, Dorit

    2008-04-15

    As a contribution to the long, ongoing debate regarding the effects of ISO 14001 on improving environmental performance of industrial facilities, this article focuses on ISO 14001 as an external environmental capacity (EC) building tool. It presents findings from a study of the effects of ISO 14001 within Israeli industry conducted through questionnaires and in-depth interviews at all certified Israeli facilities. A comparative analysis of the Israeli findings with results reported from the US and Japan found that there were differences in implementation of ISO 14001 in regard to building external actors' EC. Janicke's "environmental capacity building," Gunningham, Kagan, and Thornton's"license to operate," and Potosky and Prakash's "club's goods" were applied to explain these differences. The argument offered claims that differences in the motivations of facilities to influence their ISO 14001 club's license to operate depends on society's initial EC. This suggests operation of a vicious cycle: whenever the effect of ISO 14001 is most required, it is the smallest. Recommendations for improvement are offered in the domain of the standard's specification. PMID:18497122

  17. Causal Analysis of ISO/TS16949 Efforts in Automotive Industry

    NASA Astrophysics Data System (ADS)

    Zakuan, Norhayati; Ariff, Mohd Shoki Md; Norfian Alifiah, Mohd; Mohd Yusof, Shari; Zameri Mat Saman, Muhamad

    2014-06-01

    The principal aim of this study is to determine the impact of ISO/TS16949 efforts on total quality management (TQM) and the ISO/TS16949 efforts relationship in Malaysian automotive industry. A survey method was employed to collect data using English version for Malaysian respondents. Exploratory factor analysis and reliability analysis empirically verified and validated the underlying items of TQM, ISO/TS16949 and organizational performance. Structural equation modeling was employed to test the proposed model. Data analysis revealed that TQM implementations have a strong and positive impact on organizational performance through direct relationship as well as through a mediating role of ISO/TS16949 efforts. From the research findings, it is viable to recommend that ISO/TS16949 should be incorporated with philosophy and methods of TQM to achieve better performance. This study proved to be valuable to academic researchers as well as automotive practitioners. It systematically analyzes the mediating effect of ISO/TS16949 efforts on TQM and organizational performance relationship.

  18. [ISO 15189 accreditation in clinical microbiology laboratory: general concepts and the status in our laboratory].

    PubMed

    Akyar, Işin

    2009-10-01

    One important trend in the laboratory profession and quality management is the global convergence of laboratory operations. The goal of an accredited medical laboratory is to continue "offering useful laboratory service for diagnosis and treatment of the patients and also aid to the health of the nation". An accredited clinical laboratory is managed by a quality control system, it is competent technically and the laboratory service meets the needs of all its patients and physicians by taking the responsibility of all the medical tests and therapies. For this purpose, ISO 15189 international standard has been prepared by 2003. ISO 15189 standard is originated from the arrangement of ISO 17025 and ISO 9001:2000 standards. Many countries such as England, Germany, France, Canada and Australia have preferred ISO 15189 as their own laboratory accreditation programme, meeting all the requirements of their medical laboratories. The accreditation performance of a clinical microbiology laboratory is mainly based on five essential points; preanalytical, analytical, postanalytical, quality control programmes (internal, external, interlaboratory) and audits (internal, external). In this review article, general concepts on ISO 15189 accreditation standards for the clinical microbiology laboratories have been summarized and the status of a private laboratory (Acibadem LabMed, Istanbul) in Turkey has been discussed. PMID:20084925

  19. Investigation of dominant modes of monsoon ISO in the northwest and eastern Himalayan region

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sandipan; Ballav, Srabanti; Soni, Sandeep; Kumar, Kireet; Kumar De, Utpal

    2016-08-01

    This study investigates the altitudinal variation of dominant modes of summer monsoon intra-seasonal oscillation (ISO) over the Northwest (NWH) and Eastern Himalayan (EH) region using (i) spatially scattered 133 number of station rainfall observations and (ii) latitudinal transect-wise (LT) rainfall variation, obtained from an observed interpolated gridded rainfall data for the period 1995-2004. The altitudinal variation of dominant modes of monsoon ISO were investigated by exploring the strong and weak phases of the principal components of 10-90 days bandpass rainfall data of June to September with respect to location specific station height. Investigation of frequency of days for light and moderate rainfall along with the occurrence of total seasonal rainy days has revealed existence of a rainfall maximum around 2100 m height for the NWH region. Similarly, the total seasonal rainy days of EH region was found to have maxima between 1100 and 1400 m height. Analyses of the spatially scattered station rainfall observation for the NWH region showed that the strong periods of ISO modes exist around 747.9 (±131.7) m and 2227.2 (±100.2) m heights. Over the EH region, the dominant modes of the monsoon ISO were found to be centred around 1200 m. Significant alterations of strong and weak phases of monsoon ISO as a response to altitudinal variation in the mountain surface were observed when latitudinal transect-wise variation of monsoon ISO modes were investigated.

  20. Meridional Propagation of the MJO/ISO and Prediction of Off-equatorial Monsoon Variability

    NASA Technical Reports Server (NTRS)

    Wu, Man Li C.; Schubert, S.; Suarez, M.; Pegion, P.; Waliser, D.

    2003-01-01

    This study was examine the links between tropical heating, the Madden Julian Oscillation (MJO)/Intraseasonal Oscillation (ISO), and the off-equatorial monsoon development. We examine both observations and idealized "MJO heating" experiments employing the NASA Seasonal-Interannual Prediction Project (NSIPP) atmospheric general circulation model (AGCM). In the simulations, the model is forced by climatological SST and an idealized eastward propagating heating profile that is meant 'to mimic the canonical heating associated with the MJO in the Indian Ocean and western Pacific. The observational analysis highlights the strong link between the Indian summer monsoon and the tropical ISO/MJO activity and heating. Here we focus on the potential for skillful predictions of the monsoon on sub-seasonal time scales associated with the meridional propagation of the ISO/MJO. In particular, we show that the variability of the Indian summer monsoon lags behind the variability of tropical ISO/MJO heating by about 15 days when the tropical heating is around 60E and 90E. This feature of the ISO/MJO is reproduced in the AGCM experiments with the idealized eastward propagating MJO-like heating, suggesting that models with realistic ISO/MJO variability should provide useful skill of monsoon breaks and surges on sub-seasonal time scales.

  1. Definition of a CDI metadata profile and its ISO 19139 based encoding

    NASA Astrophysics Data System (ADS)

    Boldrini, Enrico; de Korte, Arjen; Santoro, Mattia; Schaap, Dick M. A.; Nativi, Stefano; Manzella, Giuseppe

    2010-05-01

    The Common Data Index (CDI) is the middleware service adopted by SeaDataNet for discovery and query. The primary goal of the EU funded project SeaDataNet is to develop a system which provides transparent access to marine data sets and data products from 36 countries in and around Europe. The European context of SeaDataNet requires that the developed system complies with European Directive INSPIRE. In order to assure the required conformity a GI-cat based solution is proposed. GI-cat is a broker service able to mediate from different metadata sources and publish them through a consistent and unified interface. In this case GI-cat is used as a front end to the SeaDataNet portal publishing the original data, based on CDI v.1 XML schema, through an ISO 19139 application profile catalog interface (OGC CSW AP ISO). The choice of ISO 19139 is supported and driven by INSPIRE Implementing Rules, that have been used as a reference through the whole development process. A mapping from the CDI data model to the ISO 19139 was hence to be implemented in GI-cat and a first draft quickly developed, as both CDI v.1 and ISO 19139 happen to be XML implementations based on the same abstract data model (standard ISO 19115 - metadata about geographic information). This first draft mapping pointed out the CDI metadata model differences with respect to ISO 19115, as it was not possible to accommodate all the information contained in CDI v.1 into ISO 19139. Moreover some modifications were needed in order to reach INSPIRE compliance. The consequent work consisted in the definition of the CDI metadata model as a profile of ISO 19115. This included checking of all the metadata elements present in CDI and their cardinality. A comparison was made with respect to ISO 19115 and possible extensions were individuated. ISO 19139 was then chosen as a natural XML implementation of this new CDI metadata profile. The mapping and the profile definition processes were iteratively refined leading up to a

  2. Synthetic RORγt Agonists Enhance Protective Immunity.

    PubMed

    Chang, Mi Ra; Dharmarajan, Venkatasubramanian; Doebelin, Christelle; Garcia-Ordonez, Ruben D; Novick, Scott J; Kuruvilla, Dana S; Kamenecka, Theodore M; Griffin, Patrick R

    2016-04-15

    The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer). Enhanced immunity and blockage of immune checkpoints has transformed cancer treatment; thus such a molecule would provide a unique approach for the treatment of cancer. PMID:26785144

  3. Amphetamine- type reinforcement by dopaminergic agonists in the rat.

    PubMed

    Yokel, R A; Wise, R A

    1978-07-19

    Intravenous self-administration of d-amphetamine (0.25 mg/kg/injection) decreased in a dose-related fashion after injections of the dopaminergic agonists apomorphine and piribedil. The dopaminergic agonists appear to suppress amphetamine intake in the same way as do 'free' amphetamine injections, by extending drug satiation in a given interresponse period. Clonidine, an alpha noradrenergic agonist, did not have similar effects. Apomorphine and piribedil did not increase 14C-amphetamine levels in rat brains, nor did they retard disappearance of 14C-amphetamine; thus their amphetamine-like effects are not due to alterations of amphetamine metabolism. Rats responding for amphetamine continued to respond for apomorphine or peribedil when the latter drugs were substituted for the former. Rats experienced in amphetamine self-administration readily initiated and maintained responding for apomorphine and piribedil. The dopaminergic blocker (+)-butaclamol disrupted responding for apomorphine and piribedil, although it produced no marked increase in responding for the dopaminergic agonists, as it does for amphetamine. These data add to the evidence that actions in the dopaminergic synapse account for amphetamine's reinforcing properties. PMID:98800

  4. Alkaloid delta agonist BW373U86 increases hypoxic tolerance.

    PubMed

    Bofetiado, D M; Mayfield, K P; D'Alecy, L G

    1996-06-01

    Activation of delta opioid receptors increases survival time during acute, lethal hypoxia in mice. delta Agonists therefore present a promising avenue for therapeutic application to reduce the morbidity and mortality associated with clinical hypoxia in settings such as drowning, head injury apnea, and complicated childbirths. However, most delta agonists now available are peptides, and may have limited clinical utility. In the present study, we evaluate the neuroprotective ability of an alkaloid delta agonist, BW373U86. Alkaloid compounds, due to increased stability and increased systemic distribution, may be more favorable for clinical use. We found that BW373U86, like the peptide delta agonist, DPDPE ([D-Pen2, D-Pen5]-enkephalin), increases survival time of mice during lethal hypoxia. The mechanism of neuroprotection induced by delta receptor activation appears to involve decreasing body temperature. Further, using selective opioid receptor antagonists, it appears that BW373U86 exerts these neuroprotective effects by acting at delta-opioid receptors. PMID:8638797

  5. The Agonistic Approach: Reframing Resistance in Qualitative Research

    ERIC Educational Resources Information Center

    Vitus, Kathrine

    2008-01-01

    The agonistic approach--aimed at embracing opposing perspectives as part of a qualitative research process and acknowledging that process as fundamentally political--sheds light on both the construction of and the resistance to research identities. This approach involves reflexively embedding interview situations into the ethnographic context as a…

  6. [Alpha-2 adrenoreceptor agonists in anaesthesia and intensive care medicine].

    PubMed

    Mavropoulos, G; Minguet, G; Brichant, J F

    2014-02-01

    Alpha-2 adrenoreceptor agonists have long been used in the treatment of arterial hypertension. However, in that indication they have progressively been replaced by antihypertensive drugs with a more interesting therapeutic profile. Nonetheless, pharmacological activation of alpha-2 adrenoreceptors leads to a variety of clinical effects that are of major interest for anaesthesia and intensive care practice. Indeed, the sedative and analgesic properties of alpha-2 adrenoreceptor agonists allow a reduction of hypnotic and opioid needs during general anaesthesia. In addition, they induce a down-regulation of the level of consciousness comparable to that of natural slow-wave sleep during post-anaesthesia and intensive care unit stay. These drugs may also prevent some deleterious effects of the sympathetic discharge in response to surgical stress. Furthermore, alpha-2 adrenoreceptor agonists are potent adjuncts for locoregional anaesthesia. In this article, we will summarize the most frequent applications of alpha-2 adrenoreceptor agonists in anaesthesia and intensive care medicine. We will focus on the clinical data available for the two most representative molecules of this pharmacological class: clonidine and dexmedetomidine. PMID:24683831

  7. The emerging therapeutic roles of κ-opioid agonists.

    PubMed

    Jones, Mark R; Kaye, Alan D; Kaye, Aaron J; Urman, Richard D

    2016-01-01

    The current practice of μ-opioid receptor agonists such as morphine as the primary means of acute and chronic pain relief has several dangerous consequences that limit their effectiveness, including respiratory depression, gastrointestinal motility inhibition, addiction, tolerance, and abuse. Several other opioid receptors, notably the μ-opioid (KOP) receptor, have long been known to play a role in pain relief. Recent discoveries and advancements in laboratory techniques have allowed significant developments of KOP agonists as potential novel therapies for pain relief and other pathological processes. These drugs exhibit none of the classic opioid adverse effects and have displayed pronounced analgesia in several different scenarios. New formulations since 2014 have unveiled increased oral bioavailability, exceptional peripheral versus central selectivity, and a positive safety profile. Continued refinements of established μ-opioid agonist formulations have virtually eliminated the centrally mediated side effects of dysphoria and sedation that limited the applicability of previous KOP agonists. Further research is required to better elucidate the potential of these compounds in pain management, as well as in the mediation or modulation of other complex pathophysiological processes as therapeutic agents. PMID:27194194

  8. Aerobic biodegradation of iso-butanol and ethanol and their relative effects on BTEX biodegradation in aquifer materials.

    PubMed

    Schaefer, Charles E; Yang, Xiaomin; Pelz, Oliver; Tsao, David T; Streger, Sheryl H; Steffan, Robert J

    2010-11-01

    The aerobic biodegradability of iso-butanol, a new biofuel, and its impact on benzene, toluene, ethylbenzene and xylenes (BTEX) degradation was investigated in aerobic microcosms consisting of groundwater and sediment from a California site with a history of gasoline contamination. To the best of our knowledge this is the first study directly examining the effects of iso-butanol on BTEX degradation. Microcosms that received either low (68 μM) or high (3400 μM) concentrations of iso-butanol showed complete biodegradation of iso-butanol within 7 and 23 d, respectively, of incubation at 15°C under aerobic conditions. A maximum utilization rate coefficient of 2.3±0.1×10⁻⁷ μmol cell⁻¹ h⁻¹ and a half saturation constant of 610±54 μM were regressed from the iso-butanol data. Iso-butanol biodegradation resulted in transient formation of the degradation intermediate products iso-butylaldehyde and iso-butyric acid, and both compounds were subsequently degraded within the timeframe of the experiments. Ethanol was biodegraded more slowly than iso-butanol. Ethanol also exhibited greater adverse impacts on BTEX biodegradation than iso-butanol. Results of the study suggest that iso-butanol added to fuels will be readily biodegraded in the environment under aerobic conditions without the accumulation of major intermediate products (iso-butylaldehyde and iso-butyric acid), and that it will pose less impacts on BTEX biodegradation than ethanol. PMID:20875664

  9. Physician perceptions of GLP-1 receptor agonists in the UK.

    PubMed

    Matza, Louis S; Curtis, Sarah E; Jordan, Jessica B; Adetunji, Omolara; Martin, Sherry A; Boye, Kristina S

    2016-05-01

    Objectives Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetes for almost a decade, and new treatments in this class have recently been introduced. The purpose of this study was to examine perceptions of GLP-1 receptor agonists among physicians who treat patients with type 2 diabetes in the UK. Methods A total of 670 physicians (226 diabetes specialists; 444 general practice [GP] physicians) completed a survey in 2014. Results Almost all physicians had prescribed GLP-1 receptor agonists (95.4% total sample; 99.1% specialists; 93.5% GP), most frequently to patients whose glucose levels are not adequately controlled with oral medications (85.9% of physicians) and obese/overweight patients (83.7%). Physicians' most common reasons for prescribing a GLP-1 receptor agonist were: associated with weight loss (65.8%), good efficacy (55.7%), less hypoglycemia risk than insulin (55.2%), not associated with weight gain (34.5%), and better efficacy than oral medications (32.7%). Factors that most commonly cause hesitation when prescribing this class were: not considered first line therapy according to guidelines (56.9%), injectable administration (44.6%), cost (36.7%), gastrointestinal side effects (33.4%), and risk of pancreatitis (26.7%). Almost all specialists (99.1%) believed they had sufficient knowledge to prescribe a GLP-1 receptor agonist, compared with 76.1% of GPs. Conclusions Results highlight the widespread use of GLP-1 receptor agonists for treatment of type 2 diabetes in the UK. However, almost a quarter of GPs reported that they do not have enough knowledge to prescribe GLP-1s, suggesting a need for increased dissemination of information to targeted groups of physicians. Study limitations were that the generalizability of the clinician sample is unknown; survey questions required clinicians to select answers from multiple response options rather than generating the responses themselves; and responses to this survey conducted

  10. Activation of endplate nicotinic acetylcholine receptors by agonists.

    PubMed

    Auerbach, Anthony

    2015-10-15

    The interaction of a small molecule made in one cell with a large receptor made in another is the signature event of cell signaling. Understanding the structure and energy changes associated with agonist activation is important for engineering drugs, receptors and synapses. The nicotinic acetylcholine receptor (AChR) is a ∼300kD ion channel that binds the neurotransmitter acetylcholine (ACh) and other cholinergic agonists to elicit electrical responses in the central and peripheral nervous systems. This mini-review is in two sections. First, general concepts of skeletal muscle AChR operation are discussed in terms of energy landscapes for conformational change. Second, adult vs. fetal AChRs are compared with regard to interaction energies between ACh and agonist-site side chains, measured by single-channel electrophysiology and molecular dynamics simulations. The five aromatic residues that form the core of each agonist binding site can be divided into two working groups, a triad (led by αY190) that behaves similarly at all sites and a coupled pair (led by γW55) that has a large influence on affinity only in fetal AChRs. Each endplate AChR has 5 homologous subunits, two of α(1) and one each of β, δ, and either γ (fetal) or ϵ (adult). These nicotinic AChRs have only 2 functional agonist binding sites located in the extracellular domain, at αδ and either αγ or αϵ subunit interfaces. The receptor undergoes a reversible, global isomerization between structures called C and O. The C shape does not conduct ions and has a relatively low affinity for ACh, whereas O conducts cations and has a higher affinity. When both agonist sites are empty (filled only with water) the probability of taking on the O conformation (PO) is low, <10(-6). When ACh molecules occupy the agonist sites the C→O opening rate constant and C↔O gating equilibrium constant increase dramatically. Following a pulse of ACh at the nerve-muscle synapse, the endplate current rises rapidly

  11. Spectroscopic and computational studies of matrix-isolated iso-CHBr{sub 3}: Structure, properties, and photochemistry of iso-bromoform

    SciTech Connect

    George, Lisa; Kalume, Aimable; Wagner, James; Reid, Scott A.; Esselman, Brian J.; McMahon, Robert J.

    2011-09-28

    Iso-polyhalomethanes are known reactive intermediates that play a pivotal role in the photochemistry of halomethanes in condensed phases. In this work, iso-bromoform (iso-CHBr{sub 3}) and its deuterated isotopomer were characterized by matrix isolation infrared and UV/visible spectroscopy, supported by ab initio and density functional theory calculations, to further probe the structure, spectroscopy, and photochemistry of this important intermediate. Selected wavelength laser irradiation of CHBr{sub 3} isolated in Ar or Ne matrices at {approx}5 K yielded iso-CHBr{sub 3}; the observed infrared and UV/visible absorptions are in excellent agreement with computational predictions, and the energies of various stationary points on the CHBr{sub 3} potential energy surface were characterized computationally using high-level methods in combination with correlation consistent basis sets. These calculations show that, while the corresponding minima lie {approx}200 kJ/mol above the global CHBr{sub 3} minimum, the isomer is bound by some 60 kJ/mol in the gas phase with respect to the CHBr{sub 2}+ Br asymptote. The photochemistry of iso-CHBr{sub 3} was investigated by selected wavelength laser irradiation into the intense S{sub 0}{yields} S{sub 3} transition, which resulted in back photoisomerization to CHBr{sub 3}. Intrinsic reaction coordinate calculations confirmed the existence of a first-order saddle point connecting the two isomers, which lies energetically below the threshold of the radical channel. Subsequently, natural bond orbital analysis and natural resonance theory were used to characterize the important resonance structures of the isomer and related stationary points, which demonstrate that the isomerization transition state represents a crossover from dominantly covalent to dominantly ionic bonding. In condensed phases, the ion-pair dominated isomerization transition state structure is preferentially stabilized, so that the barrier to isomerization is lowered.

  12. Discovery of Tertiary Amine and Indole Derivatives as Potent RORγt Inverse Agonists.

    PubMed

    Yang, Ting; Liu, Qian; Cheng, Yaobang; Cai, Wei; Ma, Yingli; Yang, Liuqing; Wu, Qianqian; Orband-Miller, Lisa A; Zhou, Ling; Xiang, Zhijun; Huxdorf, Melanie; Zhang, Wei; Zhang, Jing; Xiang, Jia-Ning; Leung, Stewart; Qiu, Yang; Zhong, Zhong; Elliott, John D; Lin, Xichen; Wang, Yonghui

    2014-01-01

    A novel series of tertiary amines as retinoid-related orphan receptor gamma-t (RORγt) inverse agonists was discovered through agonist/inverse agonist conversion. The level of RORγt inhibition can be enhanced by modulating the conformational disruption of H12 in RORγt LBD. Linker exploration and rational design led to the discovery of more potent indole-based RORγt inverse agonists. PMID:24900774

  13. Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists.

    PubMed

    Gilmore, John L; Sheppeck, James E; Wang, Jim; Dhar, T G Murali; Cavallaro, Cullen; Doweyko, Arthur M; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Nadler, Steven G; Dodd, John H; Somerville, John E; Barrish, Joel C

    2013-10-01

    SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors. PMID:23916594

  14. Sex differences in opioid antinociception: kappa and 'mixed action' agonists.

    PubMed

    Craft, R M; Bernal, S A

    2001-08-01

    A number of investigators have shown that male animals are more sensitive than females to the antinociceptive effects of mu-opioid agonists. The present study was conducted to examine sex differences in opioid antinociception in the rat using agonists known to differ in selectivity for and efficacy at kappa- versus mu-receptors. Dose- and time-effect curves were obtained for s.c. U69593, U50488, ethylketazocine, (-)-bremazocine, (-)-pentazocine, butorphanol and nalbuphine on the 50 or 54 degrees C hotplate and warm water tail withdrawal assays; spontaneous locomotor activity was measured 32-52 min post-injection in the same rats. On the hotplate assay, only butorphanol (54 degrees C) and nalbuphine (50 degrees C) were significantly more potent in males than females. On the tail withdrawal assay, all agonists were significantly more potent or efficacious in males than females at one or both temperatures. In contrast, no agonist was consistently more potent in one sex or the other in decreasing locomotor activity. Estrous stage in female rats only slightly influenced opioid effects, accounting for an average of 2.6% of the variance in females' antinociceptive and locomotor responses to drug (50 degrees C experiment). These results suggest that (1) sex differences in antinociceptive effects of opioids are not mu-receptor-dependent, as they may occur with opioids known to have significant kappa-receptor-mediated activity; (2) the mechanisms underlying sex differences in kappa-opioid antinociception may be primarily spinal rather than supraspinal; (3) sex differences in antinociceptive effects of opioid agonists are not secondary to sex differences in their sedative effects. PMID:11418226

  15. Analyzing the impact of ISO on digital imager defects with an automatic defect trace algorithm

    NASA Astrophysics Data System (ADS)

    Leung, Jenny; Chapman, Glenn H.; Choi, Yong H.; Thomas, Rohit; Koren, Israel; Koren, Zahava

    2010-01-01

    Reliability of image sensors is limited by the continuous development of in-field defects. Laboratory calibration on 21 DSLRs has revealed hot pixels as the main defect type found in all tested cameras, with 78% of the identified defects having a time-independent offset. The expanded ISO range that exists in new cameras enables natural light photography. However, the gain applied to all pixels also enhances the appearance of defects. Analysis of defects at varying ISO levels shows that compared to the number of defects at ISO 400, the number of defects at ISO 1600 is 2-3 times higher. Amplifying the defect parameters helps differentiate faults from noise, thus detecting larger defect sets and causes some hot pixels to become saturated. The distribution of defect parameters at various ISO levels shows that the gain applied to faults with moderate defect magnitude caused 2-10% of the defects to saturate at short exposure times (0.03-0.5s). With our expanded defect collection, spatial analysis confirmed the uniform distribution of defects, indicating a random defect source. In our extended study, the temporal growth of defects is analyzed using our defecttracing algorithm. We introduce an improved defect model which incorporates the ISO gain, allowing the detection of defects even in short exposure images at high ISO and thus providing a wider selection of historical images and more accurate defect tracing. Larger area sensors show more hot pixels, while hot pixel rates strongly grow as the pixel size decreases to 2.2 microns.

  16. Multivariate Statistical Analysis of Cigarette Design Feature Influence on ISO TNCO Yields.

    PubMed

    Agnew-Heard, Kimberly A; Lancaster, Vicki A; Bravo, Roberto; Watson, Clifford; Walters, Matthew J; Holman, Matthew R

    2016-06-20

    The aim of this study is to explore how differences in cigarette physical design parameters influence tar, nicotine, and carbon monoxide (TNCO) yields in mainstream smoke (MSS) using the International Organization of Standardization (ISO) smoking regimen. Standardized smoking methods were used to evaluate 50 U.S. domestic brand cigarettes and a reference cigarette representing a range of TNCO yields in MSS collected from linear smoking machines using a nonintense smoking regimen. Multivariate statistical methods were used to form clusters of cigarettes based on their ISO TNCO yields and then to explore the relationship between the ISO generated TNCO yields and the nine cigarette physical design parameters between and within each cluster simultaneously. The ISO generated TNCO yields in MSS are 1.1-17.0 mg tar/cigarette, 0.1-2.2 mg nicotine/cigarette, and 1.6-17.3 mg CO/cigarette. Cluster analysis divided the 51 cigarettes into five discrete clusters based on their ISO TNCO yields. No one physical parameter dominated across all clusters. Predicting ISO machine generated TNCO yields based on these nine physical design parameters is complex due to the correlation among and between the nine physical design parameters and TNCO yields. From these analyses, it is estimated that approximately 20% of the variability in the ISO generated TNCO yields comes from other parameters (e.g., filter material, filter type, inclusion of expanded or reconstituted tobacco, and tobacco blend composition, along with differences in tobacco leaf origin and stalk positions and added ingredients). A future article will examine the influence of these physical design parameters on TNCO yields under a Canadian Intense (CI) smoking regimen. Together, these papers will provide a more robust picture of the design features that contribute to TNCO exposure across the range of real world smoking patterns. PMID:27222918

  17. The Effect of ISO 9001 and the EFQM Model on Improving Hospital Performance: A Systematic Review

    PubMed Central

    Yousefinezhadi, Taraneh; Mohamadi, Efat; Safari Palangi, Hossein; Akbari Sari, Ali

    2015-01-01

    Context: This study aimed to explore the effect of the International Organization for Standardization (ISO) ISO 9001 standard and the European foundation for quality management (EFQM) model on improving hospital performance. Evidence Acquisition: PubMed, Embase and the Cochrane Library databases were searched. In addition, Elsevier and Springer were searched as main publishers in the field of health sciences. We included empirical studies with any design that had used ISO 9001 or the EFQM model to improve the quality of healthcare. Data were collected and tabulated into a data extraction sheet that was specifically designed for this study. The collected data included authors’ names, country, year of publication, intervention, improvement aims, setting, length of program, study design, and outcomes. Results: Seven out of the 121 studies that were retrieved met the inclusion criteria. Three studies assessed the EFQM model and four studies assessed the ISO 9001 standard. Use of the EFQM model increased the degree of patient satisfaction and the number of hospital admissions and reduced the average length of stay, the delay on the surgical waiting list, and the number of emergency re-admissions. ISO 9001 also increased the degree of patient satisfaction and patient safety, increased cost-effectiveness, improved the hospital admissions process, and reduced the percentage of unscheduled returns to the hospital. Conclusions: Generally, there is a lack of robust and high quality empirical evidence regarding the effects of ISO 9001 and the EFQM model on the quality care provided by and the performance of hospitals. However, the limited evidence shows that ISO 9001 and the EFQM model might improve hospital performance. PMID:26756012

  18. Evaluation of PC-ISO for customized, 3D Printed, gynecologic 192-Ir HDR brachytherapy applicators.

    PubMed

    Cunha, J Adam M; Mellis, Katherine; Sethi, Rajni; Siauw, Timmy; Sudhyadhom, Atchar; Garg, Animesh; Goldberg, Ken; Hsu, I-Chow; Pouliot, Jean

    2015-01-01

    The purpose of this study was to evaluate the radiation attenuation properties of PC-ISO, a commercially available, biocompatible, sterilizable 3D printing material, and its suitability for customized, single-use gynecologic (GYN) brachytherapy applicators that have the potential for accurate guiding of seeds through linear and curved internal channels. A custom radiochromic film dosimetry apparatus was 3D-printed in PC-ISO with a single catheter channel and a slit to hold a film segment. The apparatus was designed specifically to test geometry pertinent for use of this material in a clinical setting. A brachytherapy dose plan was computed to deliver a cylindrical dose distribution to the film. The dose plan used an 192Ir source and was normalized to 1500 cGy at 1 cm from the channel. The material was evaluated by comparing the film exposure to an identical test done in water. The Hounsfield unit (HU) distributions were computed from a CT scan of the apparatus and compared to the HU distribution of water and the HU distribution of a commercial GYN cylinder applicator. The dose depth curve of PC-ISO as measured by the radiochromic film was within 1% of water between 1 cm and 6 cm from the channel. The mean HU was -10 for PC-ISO and -1 for water. As expected, the honeycombed structure of the PC-ISO 3D printing process created a moderate spread of HU values, but the mean was comparable to water. PC-ISO is sufficiently water-equivalent to be compatible with our HDR brachytherapy planning system and clinical workflow and, therefore, it is suitable for creating custom GYN brachytherapy applicators. Our current clinical practice includes the use of custom GYN applicators made of commercially available PC-ISO when doing so can improve the patient's treatment.  PMID:25679174

  19. Pressure-dependent kinetics of initial reactions in iso-octane pyrolysis.

    PubMed

    Ning, HongBo; Gong, ChunMing; Li, ZeRong; Li, XiangYuan

    2015-05-01

    This study focuses on the studies of the main pressure-dependent reaction types of iso-octane (iso-C8H18) pyrolysis, including initial C-C bond fission of iso-octane, isomerization, and β-scission reactions of the alkyl radicals produced by the C-C bond fission of iso-octane. For the C-C bond fission of iso-octane, the minimum energy potentials are calculated at the CASPT2(2e,2o)/6-31+G(d,p)//CAS(2e,2o)/6-31+G(d,p) level of theory. For the isomerization and the β-scission reactions of the alkyl radicals, the optimization of the geometries and the vibrational frequencies of the reactants, transition states, and products are performed at the B3LYP/CBSB7 level, and their single point energies are calculated by using the composite CBS-QB3 method. Variable reaction coordinate transition state theory (VRC-TST) is used for the high-pressure limit rate constant calculation and Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME) is used to calculate the pressure-dependent rate constants of these channels with pressure varying from 0.01-100 atm. The rate constants obtained in this work are in good agreement with those available from literatures. We have updated the rate constants and thermodynamic parameters for species involved in these reactions into a current chemical kinetic mechanism and also have improved the concentration profiles of main products such as C3H6 and C4H6 in the shock tube pyrolysis of iso-octane. The results of this study provide insight into the pyrolysis of iso-octane and will be helpful in the future development of branched paraffin kinetic mechanisms. PMID:25868004

  20. Synthesis and SAR of potent LXR agonists containing an indole pharmacophore

    SciTech Connect

    Washburn, David G.; Hoang, Tram H.; Campobasso, Nino; Smallwood, Angela; Parks, Derek J.; Webb, Christine L.; Frank, Kelly A.; Nord, Melanie; Duraiswami, Chaya; Evans, Christopher; Jaye, Michael; Thompson, Scott K.

    2009-03-27

    A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXR{alpha} will be disclosed.

  1. Glucagon-Like Peptide-1 Receptor Agonists: Beta-Cell Protection or Exhaustion?

    PubMed

    van Raalte, Daniël H; Verchere, C Bruce

    2016-07-01

    Glucagon-like peptide (GLP)-1 receptor agonists enhance insulin secretion and may improve pancreatic islet cell function. However, GLP-1 receptor (GLP-1R) agonist treatment may have more complex, and sometimes deleterious, effects on beta cells. We discuss the concepts of beta cell protection versus exhaustion for different GLP-1R agonists based on recent data. PMID:27160799

  2. Biodegradation of C7 and C8 iso-alkanes under methanogenic conditions.

    PubMed

    Abu Laban, Nidal; Dao, Anh; Semple, Kathleen; Foght, Julia

    2015-12-01

    Iso-alkanes comprise a substantial proportion of petroleum and refined products that impact the environment, but their fate is cryptic under methanogenic conditions. We investigated methanogenic biodegradation of C7 and C8 iso-alkanes found in naphtha, specifically 2-methylhexane, 3-methylhexane, 2-methylheptane, 4-methylheptane and 3-ethylhexane. These were incubated as a mixture or individually with enrichment cultures derived from oil sands tailings ponds that generate methane from naphtha components; substrate depletion and methane production were monitored for up to 663 days. 3-Methylhexane and 4-methylheptane were degraded both singly and in the mixture, whereas 2-methylhexane and 2-methylheptane resisted degradation as single substrates but were depleted in the iso-alkane mixture, suggesting co-metabolism. 3-Ethylhexane was degraded neither singly nor with co-substrates. Putative metabolites consistent with succinylated C7 and C8 were detected, suggesting activation by addition of iso-alkanes to fumarate and corresponding to detection of alkylsuccinate synthase-like genes. 454 pyrotag sequencing, cloning and terminal restriction fragment length polymorphism of 16S rRNA genes revealed predominance of a novel member of the family Peptococcaceae (order Clostridiales) and Archaea affiliated with Methanoregula and Methanosaeta. We report here isomer-specific metabolism of C7 -C8 iso-alkanes under methanogenic conditions and propose their activation by a novel Peptococcaceae via addition to fumarate. PMID:25331365

  3. KSC Center Director Bridges addresses the audience at an ISO 9001 certification ceremony

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Center Director Roy Bridges speaks to KSC employees at the ISO certification ceremony held at the Training Auditorium. Bridges was presented an ISO 9001 certificate and plaque awarded to KSC by Det Norske Veritas (DNV), Inc., an international ISO certification organization. ISO 9001 comprises the most detailed, comprehensive set of standard requirements for quality programs established by the International Standards Organization. The presentation followed a successful independent audit by DNV of the KSC Management System in May of this year. The third-party auditors examined about 20 elements of KSC's system, including management responsibility, design control, documentation, test and inspection, and corrective action procedures. DNV found that KSC met or exceeded the stringent quality standards in all areas. KSC will use this certification as a tool to improve an already world- class team. All NASA centers are required by NASA Administrator Daniel S. Goldin to be ISO 9001 registered by September 1999. NASA is the first federal agency to seek the quality certification. Next to Bridges is Heidi Hollingsworth, with the Center for Independent Living, who uses American Sign Language for any hearing-impaired employees in the audience.

  4. Specification of Energy Assessment Methodologies to Satisfy ISO 50001 Energy Management Standard

    NASA Astrophysics Data System (ADS)

    Kanneganti, Harish

    Energy management has become more crucial for industrial sector as a way to lower their cost of production and in reducing their carbon footprint. Environmental regulations also force the industrial sector to increase the efficiency of their energy usage. Hence industrial sector started relying on energy management consultancies for improvements in energy efficiency. With the development of ISO 50001 standard, the entire energy management took a new dimension involving top level management and getting their commitment on energy efficiency. One of the key requirements of ISO 50001 is to demonstrate continual improvement in their (industry) energy efficiency. The major aim of this work is to develop an energy assessment methodology and reporting format to tailor the needs of ISO 50001. The developed methodology integrates the energy reduction aspect of an energy assessment with the requirements of sections 4.4.3 (Energy Review) to 4.4.6 (Objectives, Targets and Action Plans) in ISO 50001 and thus helping the facilities in easy implementation of ISO 50001.

  5. Assessing analytical methods to monitor isoAsp formation in monoclonal antibodies

    PubMed Central

    Eakin, Catherine M.; Miller, Amanda; Kerr, Jennifer; Kung, James; Wallace, Alison

    2014-01-01

    A ubiquitous post-translational modification observed in proteins is isomerization of aspartic acid to isoaspartic acid (isoAsp). This non-enzymatic post-translational modification occurs spontaneously in proteins and plays a role in aging, autoimmune response, cancer, neurodegeneration, and other diseases. Formation of isoAsp is also a significant issue for recombinant monoclonal antibody based protein therapeutics particularly when isomerization occurs in a complementarity-determining region due to potential impact to the clinical efficacy. Here, we present and compare three analytical methods to monitor and/or quantify isoAsp formation in a monoclonal antibody. The methods include two peptide map based technologies with quantitation from either UV integration or total ion peak areas, as well as an alternative approach using IdeS digestion to generate Fc/2 and Fab’2 regions, followed by hydrophobic interaction chromatography (HIC) to separate the population of Fab’2 containing an isoAsp. The level of isoAsp detected by the peptide map and the digested-HIC methods presented here show similar trends although sample throughput varies by method. PMID:24808864

  6. The Autoignition of iso-Cetane: Shock Tube Experiments and Kinetic Modeling

    SciTech Connect

    Oehlschlaeger, M A; Steinberg, J; Westbrook, C K; Pitz, W J

    2009-02-25

    Iso-cetane (2,2,4,4,6,8,8-heptamethylnonane, C{sub 16}H{sub 34}) is a highly branched alkane reference compound for determining cetane ratings. It is also a candidate branched alkane representative in surrogate mixtures for diesel and jet fuels. Here new experiments and kinetic modeling results are presented for the autoignition of iso-cetane at elevated temperatures and pressures relevant to combustion in internal combustion engines. Ignition delay time measurements were made in reflected shock experiments in a heated shock tube for {Phi} = 0.5 and 1.0 iso-cetane/air mixtures at temperatures ranging from 953 to 1347 K and pressures from 8 to 47 atm. Ignition delay times were measured using electronically excited OH emission, monitored through the shock tube end wall, and piezoelectric pressure transducer measurements, made at side wall locations. A new kinetic mechanism for the description of the oxidation of iso-cetane is presented that is developed based on a previous mechanism for iso-octane. Computed results from the mechanism are found in good agreement with the experimental measurements. To our knowledge, the ignition time measurements and detailed kinetic mechanism for isocetane presented here are the first of their kind.

  7. KSC Center Director Bridges accepts an ISO 9001 certification plaque from DNV

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Center Director Roy Bridges (right) displays the 2000th ISO Certificate Plaque he was given by Dalton Lyon (left) of Det Norske Veritas (DNV), Inc., an international ISO certification organization, at a ceremony at KSC. The plaque is a representation of the ISO 9001 certification awarded to KSC by DNV. ISO 9001 comprises the most detailed, comprehensive set of standard requirements for quality programs established by the International Standards Organization. The presentation followed a successful independent audit by DNV of the KSC Management System in May of this year. The third-party auditors examined about 20 elements of KSC's system, including management responsibility, design control, documentation, test and inspection, and corrective action procedures. DNV found that KSC met or exceeded the stringent quality standards in all areas. KSC will use this certification as a tool to improve an already world- class team. All NASA centers are required by NASA Administrator Daniel S. Goldin to be ISO 9001 registered by September 1999. NASA is the first federal agency to seek the quality certification.

  8. KSC Center Director Bridges accepts an ISO 9001 certificate from DNV

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Center Director Roy Bridges displays the ISO 9001 certificate he was awarded by Det Norske Veritas (DNV), Inc., an international ISO certification organization, at a ceremony at KSC. Dalton Lyon of DNV made the presentation, which included a 2000th ISO Certificate Plaque. ISO 9001 comprises the most detailed, comprehensive set of standard requirements for quality programs established by the International Standards Organization. The presentation followed a successful independent audit by DNV of the KSC Management System in May of this year. The third-party auditors examined about 20 elements of KSC's system, including management responsibility, design control, documentation, test and inspection, and corrective action procedures. DNV found that KSC met or exceeded the stringent quality standards in all areas. KSC will use this certification as a tool to improve an already world-class team. All NASA centers are required by NASA Administrator Daniel S. Goldin to be ISO 9001 registered by September 1999. NASA is the first federal agency to seek the quality certification.

  9. Coordination of Retail Demand Response with Midwest ISO Markets

    SciTech Connect

    Bharvirkar, Ranjit; Bharvirkar, Ranjit; Goldman, Charles; Heffner, Grayson; Sedano, Richard

    2008-05-27

    The Organization of Midwest ISO States (OMS) launched the Midwest Demand Resource Initiative (MWDRI) in 2007 to identify barriers to deploying demand response (DR) resources in the Midwest Independent System Operator (MISO) region and develop policies to overcome them. The MWDRI stakeholders decided that a useful initial activity would be to develop more detailed information on existing retail DR programs and dynamic pricing tariffs, program rules, and utility operating practices. This additional detail could then be used to assess any"seams issues" affecting coordination and integration of retail DR resources with MISO's wholesale markets. Working with state regulatory agencies, we conducted a detailed survey of existing DR programs, dynamic pricing tariffs, and their features in MISO states. Utilities were asked to provide information on advance notice requirements to customers, operational triggers used to call events (e.g. system emergencies, market conditions, local emergencies), use of these DR resources to meet planning reserves requirements, DR resource availability (e.g., seasonal, annual), participant incentive structures, and monitoring and verification (M&V) protocols. This report describes the results of this comprehensive survey and discusses policy implications for integrating legacy retail DR programs and dynamic pricing tariffs into organized wholesale markets. Survey responses from 37 MISO members and 4 non-members provided information on 141 DR programs and dynamic pricing tariffs with a peak load reduction potential of 4,727 MW of retail DR resource. Major findings of this study area:- About 72percent of available DR is from interruptible rate tariffs offered to large commercial and industrial customers, while direct load control (DLC) programs account for ~;;18percent. Almost 90percent of the DR resources included in this survey are provided by investor-owned utilities. - Approximately, 90percent of the DR resources are available with less than

  10. Ligand Binding Ensembles Determine Graded Agonist Efficacies at a G Protein-coupled Receptor.

    PubMed

    Bock, Andreas; Bermudez, Marcel; Krebs, Fabian; Matera, Carlo; Chirinda, Brian; Sydow, Dominique; Dallanoce, Clelia; Holzgrabe, Ulrike; De Amici, Marco; Lohse, Martin J; Wolber, Gerhard; Mohr, Klaus

    2016-07-29

    G protein-coupled receptors constitute the largest family of membrane receptors and modulate almost every physiological process in humans. Binding of agonists to G protein-coupled receptors induces a shift from inactive to active receptor conformations. Biophysical studies of the dynamic equilibrium of receptors suggest that a portion of receptors can remain in inactive states even in the presence of saturating concentrations of agonist and G protein mimetic. However, the molecular details of agonist-bound inactive receptors are poorly understood. Here we use the model of bitopic orthosteric/allosteric (i.e. dualsteric) agonists for muscarinic M2 receptors to demonstrate the existence and function of such inactive agonist·receptor complexes on a molecular level. Using all-atom molecular dynamics simulations, dynophores (i.e. a combination of static three-dimensional pharmacophores and molecular dynamics-based conformational sampling), ligand design, and receptor mutagenesis, we show that inactive agonist·receptor complexes can result from agonist binding to the allosteric vestibule alone, whereas the dualsteric binding mode produces active receptors. Each agonist forms a distinct ligand binding ensemble, and different agonist efficacies depend on the fraction of purely allosteric (i.e. inactive) versus dualsteric (i.e. active) binding modes. We propose that this concept may explain why agonist·receptor complexes can be inactive and that adopting multiple binding modes may be generalized also to small agonists where binding modes will be only subtly different and confined to only one binding site. PMID:27298318

  11. A Potent and Site-Selective Agonist of TRPA1.

    PubMed

    Takaya, Junichiro; Mio, Kazuhiro; Shiraishi, Takuya; Kurokawa, Tatsuki; Otsuka, Shinya; Mori, Yasuo; Uesugi, Motonari

    2015-12-23

    TRPA1 is a member of the transient receptor potential (TRP) cation channel family that is expressed primarily on sensory neurons. This chemosensor is activated through covalent modification of multiple cysteine residues with a wide range of reactive compounds including allyl isothiocyanate (AITC), a spicy component of wasabi. The present study reports on potent and selective agonists of TRPA1, discovered through screening 1657 electrophilic molecules. In an effort to validate the mode of action of hit molecules, we noted a new TRPA1-selective agonist, JT010 (molecule 1), which opens the TRPA1 channel by covalently and site-selectively binding to Cys621 (EC50 = 0.65 nM). The results suggest that a single modification of Cys621 is sufficient to open the TRPA1 channel. The TRPA1-selective probe described herein might be useful for further mechanistic studies of TRPA1 activation. PMID:26630251

  12. β2-adrenoceptor agonists in the regulation of mitochondrial biogenesis

    PubMed Central

    Peterson, Yuri K.; Cameron, Robert B.; Wills, Lauren P.; Trager, Richard E.; Lindsey, Chris C.; Beeson, Craig C.; Schnellmann, Rick G.

    2014-01-01

    The stimulation of mitochondrial biogenesis (MB) via cell surface G-protein coupled receptors is a promising strategy for cell repair and regeneration. Here we report the specificity and chemical rationale of a panel of β2-adrenoceptor agonists with regards to MB. Using primary cultures of renal cells, a diverse panel of β2-adrenoceptor agonists elicited three distinct phenotypes: full MB, partial MB, and non-MB. Full MB compounds had efficacy in the low nanomolar range and represent two chemical scaffolds containing three distinct chemical clusters. Interestingly, the MB phenotype did not correlate with reported receptor affinity or chemical similarity. Chemical clusters were then subjected to pharmacophore modeling creating two models with unique and distinct features, consisting of five conserved amongst full MB compounds were identified. The two discrete pharmacophore models were coalesced into a consensus pharmacophore with four unique features elucidating the spatial and chemical characteristics required to stimulate MB. PMID:23954364

  13. Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping

    PubMed Central

    Augustsson, Per; Karlsen, Jonas T.; Su, Hao-Wei; Bruus, Henrik; Voldman, Joel

    2016-01-01

    Mechanical phenotyping of single cells is an emerging tool for cell classification, enabling assessment of effective parameters relating to cells' interior molecular content and structure. Here, we present iso-acoustic focusing, an equilibrium method to analyze the effective acoustic impedance of single cells in continuous flow. While flowing through a microchannel, cells migrate sideways, influenced by an acoustic field, into streams of increasing acoustic impedance, until reaching their cell-type specific point of zero acoustic contrast. We establish an experimental procedure and provide theoretical justifications and models for iso-acoustic focusing. We describe a method for providing a suitable acoustic contrast gradient in a cell-friendly medium, and use acoustic forces to maintain that gradient in the presence of destabilizing forces. Applying this method we demonstrate iso-acoustic focusing of cell lines and leukocytes, showing that acoustic properties provide phenotypic information independent of size. PMID:27180912

  14. Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping.

    PubMed

    Augustsson, Per; Karlsen, Jonas T; Su, Hao-Wei; Bruus, Henrik; Voldman, Joel

    2016-01-01

    Mechanical phenotyping of single cells is an emerging tool for cell classification, enabling assessment of effective parameters relating to cells' interior molecular content and structure. Here, we present iso-acoustic focusing, an equilibrium method to analyze the effective acoustic impedance of single cells in continuous flow. While flowing through a microchannel, cells migrate sideways, influenced by an acoustic field, into streams of increasing acoustic impedance, until reaching their cell-type specific point of zero acoustic contrast. We establish an experimental procedure and provide theoretical justifications and models for iso-acoustic focusing. We describe a method for providing a suitable acoustic contrast gradient in a cell-friendly medium, and use acoustic forces to maintain that gradient in the presence of destabilizing forces. Applying this method we demonstrate iso-acoustic focusing of cell lines and leukocytes, showing that acoustic properties provide phenotypic information independent of size. PMID:27180912

  15. Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping

    NASA Astrophysics Data System (ADS)

    Augustsson, Per; Karlsen, Jonas T.; Su, Hao-Wei; Bruus, Henrik; Voldman, Joel

    2016-05-01

    Mechanical phenotyping of single cells is an emerging tool for cell classification, enabling assessment of effective parameters relating to cells' interior molecular content and structure. Here, we present iso-acoustic focusing, an equilibrium method to analyze the effective acoustic impedance of single cells in continuous flow. While flowing through a microchannel, cells migrate sideways, influenced by an acoustic field, into streams of increasing acoustic impedance, until reaching their cell-type specific point of zero acoustic contrast. We establish an experimental procedure and provide theoretical justifications and models for iso-acoustic focusing. We describe a method for providing a suitable acoustic contrast gradient in a cell-friendly medium, and use acoustic forces to maintain that gradient in the presence of destabilizing forces. Applying this method we demonstrate iso-acoustic focusing of cell lines and leukocytes, showing that acoustic properties provide phenotypic information independent of size.

  16. A Consolidated Block Grant Proposal to Carry Out the Analysis of Data from the ISO Satellite

    NASA Technical Reports Server (NTRS)

    Allen, Ron

    2000-01-01

    This block grant covers the activities of three research groups at STScI: search for cold molecular hydrogen in the galaxy; dust characterization in circumstellar shells around evolved massive stars; and the relationship between dust absorption and emission in galaxies. We proposed to group the efforts and resources available to several approved ISO projects in order to more efficiently deal with the data reduction and analysis. We give a brief description of primary objectives and scope of each project, along with the final status of the project as of the expiration date of the grant. Owing to many delays on the part of the ISO Project, the calibrated data was received very late, which resulted in significant delays in deriving the results. In addition, for one of the components of this project, the ISO data was finally determined to be of too low a quality to be useful.

  17. Infrared Space Observatory (ISO) Key Project: the Birth and Death of Planets

    NASA Technical Reports Server (NTRS)

    Stencel, Robert E.; Creech-Eakman, Michelle; Fajardo-Acosta, Sergio; Backman, Dana

    1999-01-01

    This program was designed to continue to analyze observations of stars thought to be forming protoplanets, using the European Space Agency's Infrared Space Observatory, ISO, as one of NASA Key Projects with ISO. A particular class of Infrared Astronomy Satellite (IRAS) discovered stars, known after the prototype, Vega, are principal targets for these observations aimed at examining the evidence for processes involved in forming, or failing to form, planetary systems around other stars. In addition, this program continued to provide partial support for related science in the WIRE, SOFIA and Space Infrared Telescope Facility (SIRTF) projects, plus approved ISO supplementary time observations under programs MCREE1 29 and VEGADMAP. Their goals include time dependent changes in SWS spectra of Long Period Variable stars and PHOT P32 mapping experiments of recognized protoplanetary disk candidate stars.

  18. A Consolidated Block Grant Proposal to Carry Out the Analysis of Data from the ISO Satellite

    NASA Astrophysics Data System (ADS)

    Allen, Ron

    2000-08-01

    This block grant covers the activities of three research groups at STScI: search for cold molecular hydrogen in the galaxy; dust characterization in circumstellar shells around evolved massive stars; and the relationship between dust absorption and emission in galaxies. We proposed to group the efforts and resources available to several approved ISO projects in order to more efficiently deal with the data reduction and analysis. We give a brief description of primary objectives and scope of each project, along with the final status of the project as of the expiration date of the grant. Owing to many delays on the part of the ISO Project, the calibrated data was received very late, which resulted in significant delays in deriving the results. In addition, for one of the components of this project, the ISO data was finally determined to be of too low a quality to be useful.

  19. Initial cold ground tests of the Infrared Space Observatory (ISO) satellite payload

    NASA Astrophysics Data System (ADS)

    Lemke, Dietrich; Anderegg, M.; Cesarsky, Catherine J.; Clegg, Peter E.; Emery, Roger J.; de Graauw, Thijs; Katterloher, Reinhard O.; Kessler, Martin F.; Schaap, H.; Swinyard, Bruce M.; Tilgner, Clemens N.; Vigroux, Laurent G.; Wolf, Juergen

    1994-09-01

    The European Space Agency's ISO satellite is a liquid helium cooled space observatory for infrared astronomy. It will be launched for an 18 month mission in 1995 by the Ariane 4 rocket. The payload module contains a 60 cm telescope and 4 focal plane instruments covering the wavelength range 2.4 to 240 micrometers . During the first cold tests early in 1994, ISO's 2300 1 tank was partially filled with superfluid helium. The main purpose of this test was to check all the functions of the instruments and their compatibility in ISO's cryovacuum environment. In addition the straylight level caused by thermal emission of the cryostat's interior was measured by the focal plane instruments.

  20. A Human Platelet Calcium Calculator Trained by Pairwise Agonist Scanning

    PubMed Central

    Lee, Mei Yan; Diamond, Scott L.

    2015-01-01

    Since platelet intracellular calcium mobilization [Ca(t)]i controls granule release, cyclooxygenase-1 and integrin activation, and phosphatidylserine exposure, blood clotting simulations require prediction of platelet [Ca(t)]i in response to combinatorial agonists. Pairwise Agonist Scanning (PAS) deployed all single and pairwise combinations of six agonists (ADP, convulxin, thrombin, U46619, iloprost and GSNO used at 0.1, 1, and 10xEC50; 154 conditions including a null condition) to stimulate platelet P2Y1/P2Y12 GPVI, PAR1/PAR4, TP, IP receptors, and guanylate cyclase, respectively, in Factor Xa-inhibited (250 nM apixaban), diluted platelet rich plasma that had been loaded with the calcium dye Fluo-4 NW. PAS of 10 healthy donors provided [Ca(t)]i data for training 10 neural networks (NN, 2-layer/12-nodes) per donor. Trinary stimulations were then conducted at all 0.1x and 1xEC50 doses (160 conditions) as was a sampling of 45 higher ordered combinations (four to six agonists). The NN-ensemble average was a calcium calculator that accurately predicted [Ca (t)]i beyond the single and binary training set for trinary stimulations (R = 0.924). The 160 trinary synergy scores, a normalized metric of signaling crosstalk, were also well predicted (R = 0.850) as were the calcium dynamics (R = 0.871) and high-dimensional synergy scores (R = 0.695) for the 45 higher ordered conditions. The calculator even predicted sequential addition experiments (n = 54 conditions, R = 0.921). NN-ensemble is a fast calcium calculator, ideal for multiscale clotting simulations that include spatiotemporal concentrations of ADP, collagen, thrombin, thromboxane, prostacyclin, and nitric oxide. PMID:25723389

  1. Octopaminergic agonists for the cockroach neuronal octopamine receptor

    PubMed Central

    Hirashima, Akinori; Morimoto, Masako; Kuwano, Eiichi; Eto, Morifusa

    2003-01-01

    The compounds 1-(2,6-diethylphenyl)imidazolidine-2-thione and 2-(2,6-diethylphenyl)imidazolidine showed the almost same activity as octopamine in stimulating adenylate cyclase of cockroach thoracic nervous system among 70 octopamine agonists, suggesting that only these compounds are full octopamine agonists and other compounds are partial octopamine agonists. The quantitative structure-activity relationship of a set of 22 octopamine agonists against receptor 2 in cockroach nervous tissue, was analyzed using receptor surface modeling. Three-dimensional energetics descriptors were calculated from receptor surface model/ligand interaction and these three-dimensional descriptors were used in quantitative structure-activity relationship analysis. A receptor surface model was generated using some subset of the most active structures and the results provided useful information in the characterization and differentiation of octopaminergic receptor. Abbreviation: AEA arylethanolamine AII 2-(arylimino)imidazolidine AIO 2-(arylimino)oxazolidine AIT 2-(arylimino)thiazolidine APAT 2-(α-phenylethylamino)-2-thiazoline BPAT 2-(β-phenylethylamino)-2-thiazoline CAO 2-(3-chlorobenzylamino)-2-oxazoline DCAO 2-(3,5-dichlorobenzylamino)-2-oxazoline DET5 2-(2,6-diethylphenylimino)-5-methylthiazolidine DET6 2-(2,6-diethylphenylimino)thiazine EGTA ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid GFA genetic function approximation G/PLS genetic partial least squares IND 2-aminomethyl-2-indanol LAH lithium aluminum hydride MCSG maximum common subgroup MCT6 2-(2-methyl-4-chlorophenylimino)thiazine OA octopamine PLS partial least squares QSAR quantitative structure-activity relationship SBAT 2-(substituted benzylamino)-2-thiazoline SD the sum of squared deviations of the dependent variable values from their mean SPIT 3-(substituted phenyl)imidazolidine-2-thione THI 2-amino-1-(2-thiazoyl)ethanol TMS tetramethyl silane PMID:15841226

  2. A human platelet calcium calculator trained by pairwise agonist scanning.

    PubMed

    Lee, Mei Yan; Diamond, Scott L

    2015-02-01

    Since platelet intracellular calcium mobilization [Ca(t)]i controls granule release, cyclooxygenase-1 and integrin activation, and phosphatidylserine exposure, blood clotting simulations require prediction of platelet [Ca(t)]i in response to combinatorial agonists. Pairwise Agonist Scanning (PAS) deployed all single and pairwise combinations of six agonists (ADP, convulxin, thrombin, U46619, iloprost and GSNO used at 0.1, 1, and 10xEC50; 154 conditions including a null condition) to stimulate platelet P2Y1/P2Y12 GPVI, PAR1/PAR4, TP, IP receptors, and guanylate cyclase, respectively, in Factor Xa-inhibited (250 nM apixaban), diluted platelet rich plasma that had been loaded with the calcium dye Fluo-4 NW. PAS of 10 healthy donors provided [Ca(t)]i data for training 10 neural networks (NN, 2-layer/12-nodes) per donor. Trinary stimulations were then conducted at all 0.1x and 1xEC50 doses (160 conditions) as was a sampling of 45 higher ordered combinations (four to six agonists). The NN-ensemble average was a calcium calculator that accurately predicted [Ca (t)]i beyond the single and binary training set for trinary stimulations (R = 0.924). The 160 trinary synergy scores, a normalized metric of signaling crosstalk, were also well predicted (R = 0.850) as were the calcium dynamics (R = 0.871) and high-dimensional synergy scores (R = 0.695) for the 45 higher ordered conditions. The calculator even predicted sequential addition experiments (n = 54 conditions, R = 0.921). NN-ensemble is a fast calcium calculator, ideal for multiscale clotting simulations that include spatiotemporal concentrations of ADP, collagen, thrombin, thromboxane, prostacyclin, and nitric oxide. PMID:25723389

  3. Improving the developability profile of pyrrolidine progesterone receptor partial agonists

    SciTech Connect

    Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.; Frazee, James S.; Stoy, Patrick; Johnson, Latisha; Lu, Qing; Hammond, Marlys; Barton, Linda S.; Patterson, Jaclyn R.; Azzarano, Leonard M.; Nagilla, Rakesh; Madauss, Kevin P.; Williams, Shawn P.; Stewart, Eugene L.; Duraiswami, Chaya; Grygielko, Eugene T.; Xu, Xiaoping; Laping, Nicholas J.; Bray, Jeffrey D.; Thompson, Scott K.

    2010-09-17

    The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

  4. Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline.

    PubMed

    Haenisch, Britta; Walstab, Jutta; Herberhold, Stephan; Bootz, Friedrich; Tschaikin, Marion; Ramseger, René; Bönisch, Heinz

    2010-12-01

    Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting α-adrenoceptor agonists during a common cold. However, it is largely unknown which of the six α-adrenoceptor subtypes are actually present in human nasal mucosa, which are activated by the two alpha-adrenoceptor agonists and to what extent. Therefore, mRNA expression in human nasal mucosa of the six α-adrenoceptor subtypes was studied. Furthermore, the affinity and potency of the imidazolines oxymetazoline and xylometazoline at these α-adrenoceptor subtypes were examined in transfected HEK293 cells. The rank order of mRNA levels of α-adrenoceptor subtypes in human nasal mucosa was: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) > α(1B) . Oxymetazoline and xylometazoline exhibited in radioligand competition studies higher affinities than the catecholamines adrenaline and noradrenaline at most α-adrenoceptor subtypes. Compared to xylometazoline, oxymetazoline exhibited a significantly higher affinity at α(1A) - but a lower affinity at α(2B) -adrenoceptors. In functional studies in which adrenoceptor-mediated Ca(2+) signals were measured, both, oxymetazoline and xylometazoline behaved at α(2B) -adrenoceptors as full agonists but oxymetazoline was significantly more potent than xylometazoline. Furthermore, oxymetazoline was also a partial agonist at α(1A) -adrenoceptors; however, its potency was relatively low and it was much lower than its affinity. The higher potency at α(2B) -adrenoceptors, i.e. at receptors highly expressed at the mRNA level in human nasal mucosa, could eventually explain why in nasal decongestants oxymetazoline can be used in lower concentrations than xylometazoline. PMID:20030735

  5. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    PubMed Central

    Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452

  6. Synthesis of fluorinated agonist of sphingosine-1-phosphate receptor 1.

    PubMed

    Aliouane, Lucie; Chao, Sovy; Brizuela, Leyre; Pfund, Emmanuel; Cuvillier, Olivier; Jean, Ludovic; Renard, Pierre-Yves; Lequeux, Thierry

    2014-09-01

    The bioactive metabolite sphingosine-1-phosphate (S1P), a product of sphingosine kinases (SphKs), mediates diverse biological processes such as cell differentiation, proliferation, survival and angiogenesis. A fluorinated analogue of S1P receptor agonist has been synthesized by utilizing a ring opening reaction of oxacycles by a lithiated difluoromethylphosphonate anion as the key reaction. In vitro activity of this S1P analogue is also reported. PMID:25047939

  7. Newspapers and newspaper ink contain agonists for the ah receptor.

    PubMed

    Bohonowych, Jessica E S; Zhao, Bin; Timme-Laragy, Alicia; Jung, Dawoon; Di Giulio, Richard T; Denison, Michael S

    2008-04-01

    Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the AhR signaling pathway. AhR agonist activity was observed for dimethyl sulfoxide (DMSO), ethanol, and water extracts of printed newspaper, unprinted virgin paper, and black printing ink, where activation of luciferase reporter gene expression was transient, suggesting that the AhR active chemical(s) was metabolically labile. DMSO and ethanol extracts also stimulated AhR transformation and DNA binding, and also competed with [(3)H]TCDD for binding to the AhR. In addition, DMSO extracts of printed newspaper induced cytochrome P450 1A associated 7-ethoxyresorufin-O-deethylase activity in zebrafish embryos in vivo. Although the responsible bioactive chemical(s) remain to be identified, our results demonstrate that newspapers and printing ink contain relatively potent metabolically labile agonists of the AhR. Given the large amount of recycling and reprocessing of newspapers throughout the world, release of these easily extractable AhR agonists into the environment should be examined and their potential effects on aquatic organisms assessed. PMID:18203687

  8. Comparative advantage: the impact of ISO 14001 environmental certification on exports.

    PubMed

    Bellesi, Florencia; Lehrer, David; Tal, Alon

    2005-04-01

    Relative to the enormous acceptance of the ISO 9000 quality standard, the ISO 14001 environmental management certification has been met with only moderate enthusiasm among industrial facilities. The literature on corporate motivation for ISO 14001 participation is relatively modest considering the enormous number of publications reviewing other aspects of its adoption and implementation. It would seem that the present "marketing" package supporting ISO environmental commitments does not seem to offer sufficiently persuasive incentives for increased sales, either domestically or internationally. While researchers assume that a higher export rate of companies is positively associated with higher ISO participation rates, there have been very few empirical studies that support this inference, and conclusions have not been based on data taken from importing countries orfrom a systematic evaluation of expressed corporate preference for products sold by ISO 14001 certified companies. The present study reports the results of a survey to firms in six countries that are Israel's leading trade partners, importing chemicals, textiles, and produce. The survey results confirm that while the international market still considers price and quality as the paramount factors in selection of suppliers, environmental management systems (EMS) are an important feature that is frequently taken into consideration. EMS certification appears to signify a supplier who is managing the business well and exhibiting ethical responsibility. The European market proved to be more environmentally conscious than those in other industrialized parts of the world. EMS offer a particularly valuable advantage for producers wishing to reach European markets. As policy-makers seek to expand the voluntary adoption of EMS, a clear advantage for exporters should be highlighted among national industries. PMID:15871222

  9. Selection and Implementation of the ISO9001 Standard to Support Biobanking Research Infrastructure Development.

    PubMed

    Davis, Emma; Hampson, Katie; Bray, Christopher; Dixon, Kate; Ollier, William; Yuille, Martin

    2012-04-01

    The UK DNA Banking Network (UDBN) undertakes biobanking for genetic epidemiology research projects. A task assigned to it is the addition of scientific value to the resources under its management. This task is implemented by enabling appropriate access to the resources. We reasoned that access requires not only a fair access policy but also a quality policy implemented via a Quality Management System (QMS). UDBN decided to achieve consistency in sample management by identifying and implementing a suitable QMS with external certification. UDBN selected ISO9001 as a QMS. It was soon recognized that the QMS needed to encompass not only UDBN but also the academic department in which UDBN sits. An external certification body was selected and a post was dedicated to the role of QMS-Management Representative. Specialized software was acquired. A Quality Manual, individual training files and Standard Operating Procedures (SOPs) were prepared. QMS training was provided. These actions led to the approval of the ISO9001:2000 standard. This is the first report of an academic genetic epidemiology research laboratory receiving approval of the ISO9001 standard to validate the consistency of its operations. ISO9001 was selected because of its greater breadth of scope compared with other QMSs. We found that while laboratory protocols are transferable between labs, QMS SOPs are not transferable. This has consequences for efforts to ensure consistency across a biobank network: joint adoption of one multiparty QMS is probably required. We found that it was not possible to implement a QMS for biobanking in isolation: its host university department needed to be included. We have found that ISO9001 helps enable longitudinal accrual of data on the use of biobanking methods. Thus ISO9001 is not only a management tool to improve access to a biobanking research infrastructure but also a research tool for research infrastructure development. PMID:24844905

  10. Performance of two updated blood glucose monitoring systems: an evaluation following ISO 15197:2013.

    PubMed

    Pleus, Stefan; Baumstark, Annette; Rittmeyer, Delia; Jendrike, Nina; Haug, Cornelia; Freckmann, Guido

    2016-05-01

    Objective For patients with diabetes, regular self-monitoring of blood glucose (SMBG) is essential to ensure adequate glycemic control. Therefore, accurate and reliable blood glucose measurements with SMBG systems are necessary. The international standard ISO 15197 describes requirements for SMBG systems, such as limits within which 95% of glucose results have to fall to reach acceptable system accuracy. The 2013 version of this standard sets higher demands, especially regarding system accuracy, than the currently still valid edition. ISO 15197 can be applied by manufacturers to receive a CE mark for their system. Research design and methods This study was an accuracy evaluation following ISO 15197:2013 section 6.3 of two recently updated SMBG systems (Contour * and Contour TS; Bayer Consumer Care AG, Basel, Switzerland) with an improved algorithm to investigate whether the systems fulfill the requirements of the new standard. For this purpose, capillary blood samples of approximately 100 participants were measured with three test strip lots of both systems and deviations from glucose values obtained with a hexokinase-based comparison method (Cobas Integra † 400 plus; Roche Instrument Center, Rotkreuz, Switzerland) were determined. Percentages of values within the acceptance criteria of ISO 15197:2013 were calculated. This study was registered at clinicaltrials.gov (NCT02358408). Main outcome Both updated systems fulfilled the system accuracy requirements of ISO 15197:2013 as 98.5% to 100% of the results were within the stipulated limits. Furthermore, all results were within the clinically non-critical zones A and B of the consensus error grid for type 1 diabetes. Conclusions The technical improvement of the systems ensured compliance with ISO 15197 in the hands of healthcare professionals even in its more stringent 2013 version. Alternative presentation of system accuracy results in radar plots provides additional information with certain advantages. In addition

  11. Covalent agonists for studying G protein-coupled receptor activation

    PubMed Central

    Weichert, Dietmar; Kruse, Andrew C.; Manglik, Aashish; Hiller, Christine; Zhang, Cheng; Hübner, Harald; Kobilka, Brian K.; Gmeiner, Peter

    2014-01-01

    Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the formation of stable and conformationally homogeneous ligand-receptor complexes. Native hormones, neurotransmitters, and synthetic agonists that bind with low affinity are ineffective at stabilizing an active state for crystallogenesis. To promote structural studies on the pharmacologically highly relevant class of aminergic GPCRs, we here present the development of covalently binding molecular tools activating Gs-, Gi-, and Gq-coupled receptors. The covalent agonists are derived from the monoamine neurotransmitters noradrenaline, dopamine, serotonin, and histamine, and they were accessed using a general and versatile synthetic strategy. We demonstrate that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalent ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. A crystal structure of the β2-adrenoreceptor in complex with a covalent noradrenaline analog and a conformationally selective antibody (nanobody) verified that these agonists can be used to facilitate crystallogenesis. PMID:25006259

  12. Molecular impact of juvenile hormone agonists on neonatal Daphnia magna.

    PubMed

    Toyota, Kenji; Kato, Yasuhiko; Miyakawa, Hitoshi; Yatsu, Ryohei; Mizutani, Takeshi; Ogino, Yukiko; Miyagawa, Shinichi; Watanabe, Hajime; Nishide, Hiroyo; Uchiyama, Ikuo; Tatarazako, Norihisa; Iguchi, Taisen

    2014-05-01

    Daphnia magna has been used extensively to evaluate organism- and population-level responses to pollutants in acute toxicity and reproductive toxicity tests. We have previously reported that exposure to juvenile hormone (JH) agonists results in a reduction of reproductive function and production of male offspring in a cyclic parthenogenesis, D. magna. Recent advances in molecular techniques have provided tools to understand better the responses to pollutants in aquatic organisms, including D. magna. DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to JH agonists: methoprene (125, 250 and 500 ppb), fenoxycarb (0.5, 1 and 2 ppb) and epofenonane (50, 100 and 200 ppb). Exposure to these JH analogs resulted in chemical-specific patterns of gene expression. The heat map analyses based on hierarchical clustering revealed a similar pattern between treatments with a high dose of methoprene and with epofenonane. In contrast, treatment with low to middle doses of methoprene resulted in similar profiles to fenoxycarb treatments. Hemoglobin and JH epoxide hydrolase genes were clustered as JH-responsive genes. These data suggest that fenoxycarb has high activity as a JH agonist, methoprene shows high toxicity and epofenonane works through a different mechanism compared with other JH analogs, agreeing with data of previously reported toxicity tests. In conclusion, D. magna DNA microarray is useful for the classification of JH analogs and identification of JH-responsive genes. PMID:24038158

  13. Biased signaling: potential agonist and antagonist of PAR2.

    PubMed

    Kakarala, Kavita Kumari; Jamil, Kaiser

    2016-06-01

    Protease activated receptor 2 (PAR2) has emerged as one of the promising therapeutic targets to inhibit rapidly metastasizing breast cancer cells. However, its elusive molecular mechanism of activation and signaling has made it a difficult target for drug development. In this study, in silico methods were used to unfold PAR2 molecular mechanism of signaling based on the concept of GPCR receptor plasticity. Although, there are no conclusive evidences of the presence of specific endogenous ligands for PAR2, the efficacy of synthetic agonist and antagonist in PAR2 signaling has opened up the possibilities of ligand-mediated signaling. Furthermore, it has been proved that ligands specific for one GPCR can induce signaling in GPCRs belonging to other subfamilies. Therefore, the aim of this study was to identify potential agonists and antagonists from the GPCR ligand library (GLL), which may induce biased signaling in PAR2 using the concept of existence of multiple ligand-stabilized receptor conformations. The results of our in silico study suggest that PAR2 may show biased signaling mainly with agonists of serotonin type 1, β-adrenergic type 1,3 and antagonists of substance K (NK1), serotonin type 2, dopamine type 4, and thromboxane receptors. Further, this study also throws light on the putative ligand-specific conformations of PAR2. Thus, the results of this study provide structural insights to putative conformations of PAR2 and also gives initial clues to medicinal chemists for rational drug design targeting this challenging receptor. PMID:26295578

  14. Emerging strategies for exploiting cannabinoid receptor agonists as medicines.

    PubMed

    Pertwee, Roger G

    2009-02-01

    Medicines that activate cannabinoid CB(1) and CB(2) receptor are already in the clinic. These are Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol) and Sativex (Delta(9)-tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol can also be prescribed to stimulate appetite, while Sativex is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB(2) receptors; or (v) 'multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. PMID:19226257

  15. Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists.

    PubMed

    Lin, Hsiang-Ru; Chou, Tsung-Hsien; Huang, Din-Wen; Chen, Ih-Sheng

    2014-09-01

    Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a variety of health benefits. The origin of their possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and for hyperglycemia. We studied whether cryptochinones A-D, which are structurally similar to known FXR ligands, may act at this target. Indeed, in mammalian one-hybrid and transient transfection reporter assays, cryptochinones A-D transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through molecular modeling docking studies we evaluated their ability to bind to the FXR ligand binding pocket. Our results indicate that cryptochinones A-D can behave as FXR agonists. PMID:25127166

  16. Dopamine-deficient mice are hypersensitive to dopamine receptor agonists.

    PubMed

    Kim, D S; Szczypka, M S; Palmiter, R D

    2000-06-15

    Dopamine-deficient (DA-/-) mice were created by targeted inactivation of the tyrosine hydroxylase gene in dopaminergic neurons. The locomotor activity response of these mutants to dopamine D1 or D2 receptor agonists and l-3,4-dihydroxyphenylalanine (l-DOPA) was 3- to 13-fold greater than the response elicited from wild-type mice. The enhanced sensitivity of DA-/- mice to agonists was independent of changes in steady-state levels of dopamine receptors and the presynaptic dopamine transporter as measured by ligand binding. The acute behavioral response of DA-/- mice to a dopamine D1 receptor agonist was correlated with c-fos induction in the striatum, a brain nucleus that receives dense dopaminergic input. Chronic replacement of dopamine to DA-/- mice by repeated l-DOPA administration over 4 d relieved the hypersensitivity of DA-/- mutants in terms of induction of both locomotion and striatal c-fos expression. The results suggest that the chronic presence of dopaminergic neurotransmission is required to dampen the intracellular signaling response of striatal neurons. PMID:10844009

  17. Potent Adjuvanticity of a Pure TLR7-Agonistic Imidazoquinoline Dendrimer

    PubMed Central

    Shukla, Nikunj M.; Salunke, Deepak B.; Balakrishna, Rajalakshmi; Mutz, Cole A.; Malladi, Subbalakshmi S.; David, Sunil A.

    2012-01-01

    Engagement of toll-like receptors (TLRs) serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. We synthesized a dendrimeric molecule bearing six units of a potent TLR7/TLR8 dual-agonistic imidazoquinoline to explore if multimerization of TLR7/8 would result in altered activity profiles. A complete loss of TLR8-stimulatory activity with selective retention of the TLR7-agonistic activity was observed in the dendrimer. This was reflected by a complete absence of TLR8-driven proinflammatory cytokine and interferon (IFN)-γ induction in human PBMCs, with preservation of TLR7-driven IFN-α induction. The dendrimer was found to be superior to the imidazoquinoline monomer in inducing high titers of high-affinity antibodies to bovine α-lactalbumin. Additionally, epitope mapping experiments showed that the dendrimer induced immunoreactivity to more contiguous peptide epitopes along the amino acid sequence of the model antigen. PMID:22952720

  18. Emerging strategies for exploiting cannabinoid receptor agonists as medicines

    PubMed Central

    Pertwee, Roger G

    2009-01-01

    Medicines that activate cannabinoid CB1 and CB2 receptor are already in the clinic. These are Cesamet® (nabilone), Marinol® (dronabinol; Δ9-tetrahydrocannabinol) and Sativex® (Δ9-tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol® can also be prescribed to stimulate appetite, while Sativex® is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB2 receptors; or (v) ‘multi-targeting’. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. PMID:19226257

  19. Highly selective agonists for substance P receptor subtypes.

    PubMed Central

    Wormser, U; Laufer, R; Hart, Y; Chorev, M; Gilon, C; Selinger, Z

    1986-01-01

    The existence of a third tachykinin receptor (SP-N) in the mammalian nervous system was demonstrated by development of highly selective agonists. Systematic N-methylation of individual peptide bonds in the C-terminal hexapeptide of substance P gave rise to agonists which specifically act on different receptor subtypes. The most selective analog of this series, succinyl-[Asp6,Me-Phe8]SP6-11, elicits half-maximal contraction of the guinea pig ileum through the neuronal SP-N receptor at a concentration of 0.5 nM. At least 60,000-fold higher concentrations of this peptide are required to stimulate the other two tachykinin receptors (SP-P and SP-E). The action of selective SP-N agonists in the guinea pig ileum is antagonized by opioid peptides, suggesting a functional counteraction between opiate and SP-N receptors. These results indicate that the tachykinin receptors are distinct entities which may mediate different physiological functions. PMID:2431898

  20. Suppression of atherosclerosis by synthetic REV-ERB agonist

    SciTech Connect

    Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  1. Development of specific dopamine D-1 agonists and antagonists

    SciTech Connect

    Sakolchai, S.

    1987-01-01

    To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo(a,d)cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo(1,2)cyclohepta(3,4,5d,e)isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC{sub 50} of compound 11 for displacement of {sup 3}H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of {sup 3}H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor.

  2. Direct injection into the IsoDAR Cyclotron using a RFQ

    NASA Astrophysics Data System (ADS)

    Axani, Spencer; IsoDAR Collaboration

    2015-04-01

    Beginning in the 1970s, the use of Radio Frequency Quadrupoles (RFQs) has been pervasive in linear accelerators in order to accelerate, bunch, and separate ion species. Current research suggests this may be an ideal way to inject a low energy H2+ beam axially into a cyclotron. The IsoDAR (Isotope Decay At Rest) experiment aims to implement this injection system in order to achieve higher Low Energy Beam Transport (LEBT) efficiencies and ultimately construct a novel compact neutrino factory to test the hypothesis of sterile neutrinos. This talk will focus on the research and development needed to implement a RFQ into the IsoDAR experiment.

  3. Pdf modeling for premixed turbulent combustion based on the properties of iso-concentration surfaces

    NASA Technical Reports Server (NTRS)

    Vervisch, L.; Kollmann, W.; Bray, K. N. C.; Mantel, T.

    1994-01-01

    In premixed turbulent flames the presence of intense mixing zones located in front of and behind the flame surface leads to a requirement to study the behavior of iso-concentration surfaces defined for all values of the progress variable (equal to unity in burnt gases and to zero in fresh mixtures). To support this study, some theoretical and mathematical tools devoted to level surfaces are first developed. Then a database of direct numerical simulations of turbulent premixed flames is generated and used to investigate the internal structure of the flame brush, and a new pdf model based on the properties of iso-surfaces is proposed.

  4. [Quality assurance in student training. Prerequisites for DIN EN ISO 9001:2000 in teaching].

    PubMed

    Ochsner, W; Kaiser, C; Schirmer, U

    2007-07-01

    Standards of quality assurance according to DIN EN ISO 9001:2000 have been implemented in many university hospital departments, but often teaching activities are not included. This work presents a method that allows, after having defined the various teaching activities as sub-processes of one single core process, to include the manifold teaching activities of university hospital departments into the certification process. The stepwise description of the prerequisites for including teaching activities into ISO 9001 certification is illustrated by a concrete implementation example. PMID:17297598

  5. Corporate environmental policy statements in mainland China: to what extent do they conform to ISO 14000 documentation?

    PubMed

    Chung, Shan Shan; Fryxell, Gerald E; Lo, Carlos W H

    2005-04-01

    For decades, industry has been the main source of pollution in China. Determined to make changes, the mainland Chinese authorities have decided to promote mechanisms that incorporate environmental concerns into the internal management of enterprises. This is manifested in the rapid adoption of the ISO14000 standards, including a significant increase in ISO14001 registrations in China. Thus, this study examined the environmental policy statements of 106 certified facilities in mainland China against a strict interpretation of the mandatory requirements of the ISO 14001:1996 standard and the nonmandatory ISO14004 requirements in order to shed some light on the implementation of environmental management systems in an emerging economic giant. It was decided to analyze the environmental policy statement because such a statement is a core element in the ISO system of environmental management of each facility and there are relatively clear and specific requirements on what an environmental policy statement shall include. An analysis of the contents of the environmental policy statements shows that conformance to the relevant requirements of both the mandatory ISO14001 standard and the nonmandatory ISO14004 standard is far from impressive and that the facilities in our sample seldom went beyond the minimum requirements. By using ISO14001 and ISO14004 conformance scores as the dependent variables, we found that conformity to ISO14001 and overall conformance to ISO14000 series can be explained to some extent by the degree of top management commitment, the experience with informal environmental management systems, and the form of ownership of the facilities. PMID:15902447

  6. 2-Triazole-Substituted Adenosines: A New Class of Selective A3 Adenosine Receptor Agonists, Partial Agonists, and Antagonists

    PubMed Central

    Cosyn, Liesbet; Palaniappan, Krishnan K.; Kim, Soo-Kyung; Duong, Heng T.; Gao, Zhan-Guo; Jacobson, Kenneth A.; Van Calenbergh, Serge

    2016-01-01

    “Click chemistry” was explored to synthesize two series of 2-(1,2,3-triazolyl)adenosine derivatives (1–14). Binding affinity at the human A1, A2A, and A3ARs (adenosine receptors) and relative efficacy at the A3AR were determined. Some triazol-1-yl analogues showed A3AR affinity in the low nanomolar range, a high ratio of A3/A2A selectivity, and a moderate-to-high A3/A1 ratio. The 1,2,3-triazol-4-yl regiomers typically showed decreased A3AR affinity. Sterically demanding groups at the adenine C2 position tended to reduce relative A3AR efficacy. Thus, several 5′-OH derivatives appeared to be selective A3AR antagonists, i.e., 10, with 260-fold binding selectivity in comparison to the A1AR and displaying a characteristic docking mode in an A3AR model. The corresponding 5′-ethyluronamide analogues generally showed increased A3AR affinity and behaved as full agonists, i.e., 17, with 910-fold A3/A1 selectivity. Thus, N6-substituted 2-(1,2,3-triazolyl)-adenosine analogues constitute a novel class of highly potent and selective nucleoside-based A3AR antagonists, partial agonists, and agonists. PMID:17149867

  7. Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR.

    PubMed

    Huang, Wendong; Zhang, Jun; Wei, Ping; Schrader, William T; Moore, David D

    2004-10-01

    The constitutive androstane receptor (CAR, NR1I3) is a key regulator of xenobiotic and endobiotic metabolism. The ligand-binding domains of murine (m) and human (h) CAR are divergent relative to other nuclear hormone receptors, resulting in species-specific differences in xenobiotic responses. Here we identify the widely used antiemetic meclizine (Antivert; Bonine) as both an agonist ligand for mCAR and an inverse agonist for hCAR. Meclizine increases mCAR transactivation in a dose-dependent manner. Like the mCAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, meclizine stimulates binding of steroid receptor coactivator 1 to the murine receptor in vitro. Meclizine administration to mice increases expression of CAR target genes in a CAR-dependent manner. In contrast, meclizine suppresses hCAR transactivation and inhibits the phenobarbital-induced expression of the CAR target genes, cytochrome p450 monooxygenase (CYP)2B10, CYP3A11, and CYP1A2, in primary hepatocytes derived from mice expressing hCAR, but not mCAR. The inhibitory effect of meclizine also suppresses acetaminophen-induced liver toxicity in humanized CAR mice. These results demonstrate that a single compound can induce opposite xenobiotic responses via orthologous receptors in rodents and humans. PMID:15272053

  8. Flexible scope for ISO 15189 accreditation: a guidance prepared by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO).

    PubMed

    Thelen, Marc H M; Vanstapel, Florent J L A; Kroupis, Christos; Vukasovic, Ines; Boursier, Guilaime; Barrett, Edward; Bernabeu Andreu, Francisco; Brguljan, Pika Meško; Brugnoni, Duilio; Lohmander, Maria; Sprongl, Ludek; Vodnik, Tatjana; Ghita, Irina; Vaubourdolle, Michel; Huisman, Willem

    2015-07-01

    The recent revision of ISO15189 has further strengthened its position as the standard for accreditation for medical laboratories. Both for laboratories and their customers it is important that the scope of such accreditation is clear. Therefore the European co-operation for accreditation (EA) demands that the national bodies responsible for accreditation describe the scope of every laboratory accreditation in a way that leaves no room for doubt about the range of competence of the particular laboratories. According to EA recommendations scopes may be fixed, mentioning every single test that is part of the accreditation, or flexible, mentioning all combinations of medical field, examination type and materials for which the laboratory is competent. Up to now national accreditation bodies perpetuate use of fixed scopes, partly by inertia, partly out of fear that a too flexible scope may lead to over-valuation of the competence of laboratories, most countries only use fixed scopes. The EA however promotes use of flexible scopes, since this allows for more readily innovation, which contributes to quality in laboratory medicine. In this position paper, the Working Group Accreditation and ISO/CEN Standards belonging to the Quality and Regulation Committee of the EFLM recommends using an approach that has led to successful introduction of the flexible scope for ISO15189 accreditation as intended in EA-4/17 in The Netherlands. The approach is risk-based, discipline and competence-based, and focuses on defining a uniform terminology transferable across the borders of scientific disciplines, laboratories and countries. PMID:26055950

  9. Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?

    NASA Technical Reports Server (NTRS)

    Pawelczyk, James A.; Levine, Benjamin D.

    2002-01-01

    Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this "dependent hypertension" would be associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x 100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb volume-1 x min-1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1; P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions (P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.

  10. 75 FR 18828 - PSEG Power Connecticut LLC, Complainant v. ISO New England Inc., Respondent; Notice of Complaint

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission PSEG Power Connecticut LLC, Complainant v. ISO New England Inc., Respondent... (Complainant) filed a formal complaint against ISO New England Inc. (Respondent) challenging the justness...

  11. 40 CFR 721.1825 - Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative. 721.1825 Section 721.1825 Protection of Environment ENVIRONMENTAL..., polyalkylenepolyol and poly-iso-cyanato derivative. (a) Chemical substance and significant new uses subject...

  12. 40 CFR 721.1825 - Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bisphenol A, epichloro-hy-drin, polyalkylenepolyol and poly-iso-cyanato derivative. 721.1825 Section 721.1825 Protection of Environment ENVIRONMENTAL..., polyalkylenepolyol and poly-iso-cyanato derivative. (a) Chemical substance and significant new uses subject...

  13. 78 FR 1851 - New England States Committee on Electricity v. ISO New England Inc.; Notice of Complaint

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission New England States Committee on Electricity v. ISO New England Inc.; Notice... States Committee on Electricity (Complainant) filed a formal complaint against ISO New England...

  14. 77 FR 16036 - Guidance for Industry, Third Parties and Food and Drug Administration Staff; Medical Device ISO...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ...--Requirements for regulatory purposes,'' (ISO 13485:2003) audit report provides FDA a degree of assurance of... Submission Program'' was published for comment in the Federal Register of May 20, 2010 (75 FR 28257... Administration Staff; Medical Device ISO 13485:2003 Voluntary Audit Report Submission Pilot Program;...

  15. Application of ISO 9000 Standards to Education and Training. Interpretation and Guidelines in a European Perspective. CEDEFOP Document.

    ERIC Educational Resources Information Center

    Van den Berghe, Wouter

    This report brings together European experience on the interpretation and implementation of ISO 9000 in education and training (ET) environments. Chapter 1 discusses the importance of quality concepts in ET and summarizes key concepts of total quality management (TQM) and its relevance for ET. Chapter 2 introduces the ISO 9000 standards. It…

  16. ISO 16840-2:2007 load deflection and hysteresis measurements for a sample of wheelchair seating cushions.

    PubMed

    Hollington, James; Hillman, Susan J; Torres-Sánchez, Carmen; Boeckx, Jens; Crossan, Neil

    2014-04-01

    Load deflection and hysteresis measurements were made on 37 wheelchair seating cushions according to ISO 16840-2:2007. Load deflection plots for all 37 cushions are reported and fundamental aspects of graph interpretation discussed. ISO hysteresis data are also reported and interpretation discussed. PMID:24230981

  17. Involvement of Vacuolar Sequestration and Active Transport in Tolerance of Saccharomyces cerevisiae to Hop Iso-α-Acids▿ † ¶

    PubMed Central

    Hazelwood, Lucie A.; Walsh, Michael C.; Pronk, Jack T.; Daran, Jean-Marc

    2010-01-01

    The hop plant, Humulus lupulus L., has an exceptionally high content of secondary metabolites, the hop α-acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso-α-acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso-α-acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso-α-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the S. cerevisiae haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-α-acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-α-acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso-α-acids and alteration of cell wall structure and, to a lesser extent, active export of iso-α-acids across the plasma membrane. Furthermore, iso-α-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators. PMID:19915041

  18. Different serotonin receptor agonists have distinct effects on sound-evoked responses in inferior colliculus.

    PubMed

    Hurley, Laura M

    2006-11-01

    The neuromodulator serotonin has a complex set of effects on the auditory responses of neurons within the inferior colliculus (IC), a midbrain auditory nucleus that integrates a wide range of inputs from auditory and nonauditory sources. To determine whether activation of different types of serotonin receptors is a source of the variability in serotonergic effects, four selective agonists of serotonin receptors in the serotonin (5-HT) 1 and 5-HT2 families were iontophoretically applied to IC neurons, which were monitored for changes in their responses to auditory stimuli. Different agonists had different effects on neural responses. The 5-HT1A agonist had mixed facilitatory and depressive effects, whereas 5-HT1B and 5-HT2C agonists were both largely facilitatory. Different agonists changed threshold and frequency tuning in ways that reflected their effects on spike count. When pairs of agonists were applied sequentially to the same neurons, selective agonists sometimes affected neurons in ways that were similar to serotonin, but not to other selective agonists tested. Different agonists also differentially affected groups of neurons classified by the shapes of their frequency-tuning curves, with serotonin and the 5-HT1 receptors affecting proportionally more non-V-type neurons relative to the other agonists tested. In all, evidence suggests that the diversity of serotonin receptor subtypes in the IC is likely to account for at least some of the variability of the effects of serotonin and that receptor subtypes fulfill specialized roles in auditory processing. PMID:16870843

  19. The Relationship between ISO 9000 Participation and Educational Outcomes of Schools

    ERIC Educational Resources Information Center

    Bae, Sang Hoon

    2007-01-01

    Purpose: The study seeks to examine the relationship between the implementation of the ISO 9000 quality management system and educational outcomes of schools, measured by student achievement on the state-mandated tests and school attendance rates--graduation rates, in the case of high schools. Design/methodology/approach: The study was conducted…

  20. 16 CFR Figure 2 to Part 1203 - ISO Headform-Basic, Reference, and Median Planes

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false ISO Headform-Basic, Reference, and Median Planes 2 Figure 2 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 2 Figure 2 to Part...

  1. 16 CFR Figure 2 to Part 1203 - ISO Headform-Basic, Reference, and Median Planes

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false ISO Headform-Basic, Reference, and Median Planes 2 Figure 2 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 2 Figure 2 to Part...

  2. 16 CFR Figure 2 to Part 1203 - ISO Headform-Basic, Reference, and Median Planes

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false ISO Headform-Basic, Reference, and Median Planes 2 Figure 2 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 2 Figure 2 to Part...

  3. Quality Assurance in Engineering Education: Comparison of Accreditation Schemes and ISO 9001.

    ERIC Educational Resources Information Center

    Karapetrovic, Stanislav; Rajamani, Divakar; Willborn, Walter

    1998-01-01

    Outlines quality assurance schemes for distance-education technologies that are based on the ISO 9000 family of international quality-assurance standards. Argues that engineering faculties can establish such systems on the basis of and integrated with accreditation schemes. Contains 34 references. (DDR)

  4. Modelling the impact of ISO 14001 on environmental performance: a comparative approach.

    PubMed

    Boiral, Olivier; Henri, Jean-François

    2012-05-30

    Studies analyzing the effects of ISO 14001 certification and determinants of environmental performance tend to be based on a traditional and instrumental model of efficiency. Using structural equation modelling developed through a survey of 303 organizations, this paper compares the validity of this instrumental model with two alternatives models: the legitimacy-based model and the hybrid model. The findings question the efficiency of ISO 14001 and show that the traditional model does not explain the environmental performance of the surveyed organizations. Study results show that the legitimacy-based model, which questions the efficiency of ISO 14001 certification, is more pertinent in explaining the environmental performance but leads to a rather critical view of management practices. The development of a hybrid model based on the principal hypotheses of the legitimacy-based model, but integrating certain managerial and operational practices distinct from ISO 14001 certification, results in a less critical and more pertinent view of the determinants of environmental performance. Study results suggest that this hybrid model provides the best data fit. PMID:22326757

  5. Meta-audit of laboratory ISO accreditation inspections: measuring the old emperor's clothes.

    PubMed

    Wilson, Ian G; Smye, Michael; Wallace, Ian J C

    2016-02-01

    Accreditation to ISO/IEC 17025 is required for EC official food control and veterinary laboratories by Regulation (EC) No. 882/2004. Measurements in hospital laboratories and clinics are increasingly accredited to ISO/IEC 15189. Both of these management standards arose from command and control military standards for factory inspection during World War II. They rely on auditing of compliance and have not been validated internally as assessment bodies require of those they accredit. Neither have they been validated to criteria outside their own ideology such as the Cochrane principles of evidence-based medicine which might establish whether any benefit exceeds their cost. We undertook a retrospective meta-audit over 14 years of internal and external laboratory audits that checked compliance with ISO 17025 in a public health laboratory. Most noncompliances arose solely from clauses in the standard and would not affect users. No effect was likely from 91% of these. Fewer than 1% of noncompliances were likely to have consequences for the validity of results or quality of service. The ISO system of compliance auditing has the performance characteristics of a poor screening test. It adds substantially to costs and generates more noise (false positives) than informative signal. Ethical use of resources indicates that management standards should not be used unless proven to deliver the efficacy, effectiveness, and value required of modern healthcare interventions. PMID:26620076

  6. 21 CFR 184.1165 - n-Butane and iso-butane.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false n-Butane and iso-butane. 184.1165 Section 184.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS...

  7. The transformation of Lebanese firms from ISO 9000 certified to TQM.

    PubMed

    Mezher, T

    2000-01-01

    Over the past decade, the most effective method of implementing a quality system has been ISO 9000 certification. Lebanese companies have recently followed the same path of adopting and improving their status in quality systems. The overwhelming belief is that ISO 9000 is, by itself, not enough. It is a first stepping-stone in the road to business excellence, but ISO 9000 does not guarantee an improvement in the product or service being offered. All indications are that Total Quality Management (TQM) is the method for improving quality as a whole. This improvement is, of course, entirely reliant on the proper implementation and understanding of the scope and underlying objectives. The relatively new adoption of TQM as an effective tool in the struggle to achieve substantial improvements in quality is made clear in the results of a survey that are presented in this article. Recommendations as how to make the transition between ISO 9000 and TQM are made, and a discussion is provided of the need for organizational change, both internal and external, within companies in the Lebanese market. The aim of this work is to present a clear representation of what is actually occurring within the Lebanese domestic market with regards to the understanding the TQM philosophy. PMID:11710307

  8. 16 CFR Figure 2 to Part 1203 - ISO Headform-Basic, Reference, and Median Planes

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false ISO Headform-Basic, Reference, and Median Planes 2 Figure 2 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT... Headform-Basic, Reference, and Median Planes ER10MR98.002...

  9. 16 CFR Figure 2 to Part 1203 - ISO Headform-Basic, Reference, and Median Planes

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false ISO Headform-Basic, Reference, and Median Planes 2 Figure 2 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT... Headform-Basic, Reference, and Median Planes ER10MR98.002...

  10. Commitment to Quality Education Services through ISO 9000: A Case Study of Romania

    ERIC Educational Resources Information Center

    Paunescu, Carmen; Fok, Wing

    2005-01-01

    The paper discusses a model of quality management system for higher education. One of the main objectives of this paper is to highlight the challenges facing the school during implementation of the ISO 9001 standard and the benefits of successfully implementing such a quality system can bring to higher education. Based on the experience of a…

  11. ISO and US Standards for Thermal Cutting and Joint Preparation (U)

    SciTech Connect

    Kautz, D.; Hochanadel, P.

    2012-07-02

    The summary of this presentation is: (1) There is a lot of shared space between AWS and ISO documents; (2) Several areas use the same specifications and standards, especially true in process materials; and (3) Equipment is one area with very little overlap.

  12. Gas amplification factor in Kr + ISO-pentane filled proportional counters

    NASA Astrophysics Data System (ADS)

    Kowalski, T. Z.

    1983-11-01

    The gas amplification factor, A, has been measured for krypton/iso-pentane mixtures (over the range 1 < A < 5 × 104) to verify the validity of the formulae of Rose and Korff, Curran and Craggs, Diethorn, Williams and Sara, Khristov and Zastawny. Only the expressions of Zastawny and Diethorn can be fitted over a limited range of A.

  13. Implementation of ISO 10110 optics drawing standards for the National Ignition Facility

    SciTech Connect

    English, R.E. Jr.; Aikens, D.M.; Whistler, W.T.

    1995-07-07

    LLNL plans to specify optical components for the National Ignition Facility according to ISO 10110, the new international standard for preparation of optics drawings. The standards have been approved by the international optics community and represent a fairly comprehensive language for describing optical components. We will describe our plan for implementation and experience to date in doing so.

  14. Rapidly calculated density functional theory (DFT) relaxed Iso-potential Phi Si Maps: Beta-cellobiose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New cellobiose Phi-H/Si-H maps are rapidly generated using a mixed basis set DFT method, found to achieve a high level of confidence while reducing computer resources dramatically. Relaxed iso-potential maps are made for different conformational states of cellobiose, showing how glycosidic bond dihe...

  15. 78 FR 32384 - New England Power Generators Association v. ISO New England Inc.; Notice of Complaint

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission New England Power Generators Association v. ISO New England Inc.; Notice of... Federal Power Act (FPA), 16 U.S.C. 824(e), the New England Power Generators Association...

  16. 77 FR 71585 - Brookfield Energy Marketing LP v. ISO New England Inc.; Notice of Complaint

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-03

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Brookfield Energy Marketing LP v. ISO New England Inc.; Notice of... of the Federal Power Act, 16 U.S.C. 824(e) and 825(e), Brookfield Energy Marketing LP...

  17. A study of compliance with environmental regulations of ISO 14001 certified companies in Korea.

    PubMed

    Kwon, Dong-Myung; Seo, Min-Seok; Seo, Yong-Chil

    2002-08-01

    This article investigates the impact of ISO 14001 certification on the compliance with environmental regulations by Korean companies. The impact of ISO 14001 certification on the industry was studied through a questionnaire survey and the compliance of environmental regulations were investigated using government-released data. The motivation for an environment management system was a result of the current international situation and the need to maintain fair competition. ISO 14001 certification has been recognized as an essential strategy for industrial competition and to improve company/product recognition. The certified and non-certified companies' environmental regulation violation (ERV) rates were 3.5% and 11.6%, respectively, in 1997. In 1998, the ERV rate had an eight-time difference with 1.0% and 8.5% for certified and non-certified companies, respectively. Annual regulation violation rates were reduced from 3.5% in 1997 to 1.0% in 1998 with certified companies and from 11.6% in 1997 to 8.5% in 1998 with their non-certified counterparts, respectively. ISO 14001 certified companies showed more improvement than non-certified companies in regards to environmental performance. PMID:12369399

  18. Putting ISO 9000 Standards and Baldrige Quality Criteria To Work Now in Public Education.

    ERIC Educational Resources Information Center

    Clark, Don

    1999-01-01

    The National Association for Industry-Education Cooperation (NAIEC) creates an approach for school system improvement that combines the necessary standards for achieving mileposts of the Baldrige Quality Criteria and the International Organization of Standardization (ISO) 9000 Standards for Education. Together, the Baldrige Criteria and ISO…

  19. Using TQM and ISO 9000 Principles in Assuring Education Service Quality.

    ERIC Educational Resources Information Center

    Kabashkin, Igor; Michnev, Boris; Utchin, Georgy

    1998-01-01

    Describes Riga Aviation University's movement from a controlled professional-education program to a system of contract relations with students as education service customers. Discusses a study of students' demands, requirements, and issues and the development of a quality assurance system based on Total Quality Management and ISO 9000 standards.…

  20. Using Performance Analysis for Training in an Organization Implementing ISO-9000 Manufacturing Practices: A Case Study.

    ERIC Educational Resources Information Center

    Kunneman, Dale E.; Sleezer, Catherine M.

    2000-01-01

    This case study examines the application of the Performance Analysis for Training (PAT) Model in an organization that was implementing ISO-9000 (International Standards Organization) processes for manufacturing practices. Discusses the interaction of organization characteristics, decision maker characteristics, and analyst characteristics to…