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Sample records for agonist isoproterenol iso

  1. Nitric oxide inhibits isoproterenol-stimulated adipocyte lipolysis through oxidative inactivation of the beta-agonist.

    PubMed Central

    Klatt, P; Cacho, J; Crespo, M D; Herrera, E; Ramos, P

    2000-01-01

    Nitric oxide has been implicated in the inhibition of catecholamine-stimulated lipolysis in adipose tissue by as yet unknown mechanisms. In the present study, it is shown that the nitric oxide donor, 2,2-diethyl-1-nitroso-oxyhydrazine, antagonized isoproterenol (isoprenaline)-induced lipolysis in rat adipocytes, freshly isolated from white adipose tissue, by decreasing the potency of the beta-agonist without affecting its efficacy. These data suggest that nitric oxide did not act downstream of the beta-adrenoceptor but reduced the effective concentration of isoproterenol. In support of the latter hypothesis, we found that pre-treatment of isoproterenol with nitric oxide abolished the lipolytic activity of the catecholamine. Spectroscopic data and HPLC analysis confirmed that the nitric oxide-mediated inactivation of isoproterenol was in fact because of the modification of the catecholamine through a sequence of oxidation reactions, which apparently involved the generation of an aminochrome. Similarly, aminochrome was found to be the primary product of isoproterenol oxidation by 3-morpholinosydnonimine and peroxynitrite. Finally, it was shown that nitric oxide released from cytokine-stimulated adipocytes attenuated the lipolytic effect of isoproterenol by inactivating the catecholamine. In contrast with very recent findings, which suggest that nitric oxide impairs the beta-adrenergic action of isoproterenol through intracellular mechanisms and not through a chemical reaction between NO and the catecholamine, we showed that nitric oxide was able to attenuate the pharmacological activity of isoproterenol in vitro as well as in a nitric oxide-generating cellular system through oxidation of the beta-agonist. These findings should be taken into account in both the design and interpretation of studies used to investigate the role of nitric oxide as a modulator of isoproterenol-stimulated signal transduction pathways. PMID:11023835

  2. Nitric oxide inhibits isoproterenol-stimulated adipocyte lipolysis through oxidative inactivation of the beta-agonist.

    PubMed

    Klatt, P; Cacho, J; Crespo, M D; Herrera, E; Ramos, P

    2000-10-15

    Nitric oxide has been implicated in the inhibition of catecholamine-stimulated lipolysis in adipose tissue by as yet unknown mechanisms. In the present study, it is shown that the nitric oxide donor, 2,2-diethyl-1-nitroso-oxyhydrazine, antagonized isoproterenol (isoprenaline)-induced lipolysis in rat adipocytes, freshly isolated from white adipose tissue, by decreasing the potency of the beta-agonist without affecting its efficacy. These data suggest that nitric oxide did not act downstream of the beta-adrenoceptor but reduced the effective concentration of isoproterenol. In support of the latter hypothesis, we found that pre-treatment of isoproterenol with nitric oxide abolished the lipolytic activity of the catecholamine. Spectroscopic data and HPLC analysis confirmed that the nitric oxide-mediated inactivation of isoproterenol was in fact because of the modification of the catecholamine through a sequence of oxidation reactions, which apparently involved the generation of an aminochrome. Similarly, aminochrome was found to be the primary product of isoproterenol oxidation by 3-morpholinosydnonimine and peroxynitrite. Finally, it was shown that nitric oxide released from cytokine-stimulated adipocytes attenuated the lipolytic effect of isoproterenol by inactivating the catecholamine. In contrast with very recent findings, which suggest that nitric oxide impairs the beta-adrenergic action of isoproterenol through intracellular mechanisms and not through a chemical reaction between NO and the catecholamine, we showed that nitric oxide was able to attenuate the pharmacological activity of isoproterenol in vitro as well as in a nitric oxide-generating cellular system through oxidation of the beta-agonist. These findings should be taken into account in both the design and interpretation of studies used to investigate the role of nitric oxide as a modulator of isoproterenol-stimulated signal transduction pathways.

  3. Beta-agonists and secretory cell number and intracellular glycoproteins in airway epithelium. The effect of isoproterenol and salbutamol.

    PubMed Central

    Jones, R.; Reid, L.

    1979-01-01

    This study describes the effect of systemic administration of the beta-adrenergic agonists isoproterenol and salbutamol on the secretory cell populations in seven regions of rat airway epithelium (three extrapulmonary and four intrapulmonary) and on the size of salivary glands and heart. Isoproterenol (a nonselective beta-adrenergic agonist) significantly increases secretory cell number in all airway regions except the midtrachea; salbutamol (a selective beta 2 agonist) increases secretory cell number only in proximal and peripheral regions. The absolute number of secretory cells is greatest in the most peripheral region after isoproterenol administration and in the most proximal region after salbutamol, although both drugs produce the greatest relative increase at the periphery. In proximal and, particularly, peripheral regions, the increase by isoproterenol (less than 3- and 14-fold, respectively) is greater than by salbutamol (less than 2- and less than 3-fold, respectively). In all airway regions, both drugs modify intracellular glycoprotein in the secretory cell population; within a given region, modification is much the same. In the most proximal region, the population of cells synthesizing only granules of neutral glycoprotein significantly increases while in other regions increase is in cells synthesizing only granules of acid. A significant shift in glycoprotein synthesis occurs whether or not the secretory cell population is increased, which suggests that existing as well as newly appearing cells modify their product. Isoproterenol significantly increases the size of the parotid and submaxillary glands; salbutamol increases the size of the parotid only. Isoproterenol significantly increases the weight of both ventricles of the heart; salbutamol has no such effect. PMID:36762

  4. The effects of the β-agonist isoproterenol on the down-regulation, functional responsiveness, and trafficking of β2-adrenergic receptors with amino-terminal polymorphisms

    PubMed Central

    Koryakina, Yulia; Jones, Stacie M.; Cornett, Lawrence E.; Seely, Kathryn; Brents, Lisa; Prather, Paul L.; Kofman, Alexander; Kurten, Richard C.

    2014-01-01

    The β2-adrenergic receptor (β2AR) is an important target for respiratory and cardiovascular disease medications. Clinical studies suggest that amino-terminal polymorphisms of the β2AR may act as disease modifiers. We hypothesized that polymorphisms at amino acids 16 and 27 result in differential trafficking and down-regulation of β2AR variants following β-agonist exposure. The functional consequences of the four possible combinations of these polymorphisms in the human β2AR (designated β2AR-RE, -GE, -RQ and -GQ) were studied using site-directed mutagenesis and recombinant expression in HEK 293 cells. Ligand binding assays demonstrated that after 24 h exposure to 1 μM isoproterenol, isoforms with Arg16 (β2AR-RE and β2AR-RQ) underwent increased down-regulation compared to isoforms with Gly16 (β2AR-GE and β2AR-GQ). Consistent with these differences in down-regulation between isoforms, prolonged isoproterenol treatment resulted in diminished cyclic AMP response to subsequent isoproterenol challenge in β2AR-RE relative to β2AR-GE. Confocal microscopy revealed that the receptor isoforms had similar co-localization with the early endosomal marker EEA1 following isoproterenol treatment, suggesting that they had similar patterns of internalization. None of the isoforms exhibited significant co-localization with the recycling endosome marker Rab11 in response to isoproterenol treatment. Furthermore, we found that prolonged isoproterenol treatment led to a higher degree of co-localization of β2AR-RE with the lysosomal marker Lamp1 compared to that of β2AR-GE. Taken together, these results indicate that a mechanism responsible for differential responses of these receptor isoforms to β-agonist involves differences in the efficiency with which agonist-activated receptors are trafficked to lysosomes for degradation, or differences in degradation in the lysosomes. PMID:22938397

  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. 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...

  7. Prolonged pretreatment of mice with cholera toxin, but not isoproterenol, alleviates acute lethal systemic inflammatory response.

    PubMed

    Wang, Jingyang; Guo, Xiangrui; Cao, Junxia; Zhang, Xueying; Zhang, Jiyan; Sun, Dejun; Wang, Qingyang

    2014-11-01

    Isoproterenol, a synthetic non-selective β-adrenergic agonist, is often used during the immediate postoperative period after open heart surgery for its chronotropic and vasodilatory effects. It has been demonstrated that isoproterenol pretreatment followed by immediate LPS administration leads to reduced tumor necrosis factor-α (TNF-α) response in vivo. However, sepsis never happens immediately after the surgery, but rather severe immune dysfunction occurs at least 24h later. It remains elusive what effects isoproterenol might exert to innate immunity during the period. In this scenario, we investigated the effects of 24-h isoproterenol pretreatment on septic shock induced by experimental endotoxemia and bacterial peritonitis, with cholera toxin as another cAMP elevator. Unexpectedly, we found that isoproterenol and cholera toxin exhibited distinct effects in acute lethal systemic inflammatory response. Isoproterenol worsened liver injury without enhancing NK/NKT activity. Meanwhile, cholera toxin but not isoproterenol showed dramatically reduced TNF-α response in LPS induced septic shock. Our data provide a caution for the clinical use of isoproterenol and suggest that isoproterenol has cAMP-independent functions.

  8. Biochemical mechanisms of myocardial adenylate cyclase subsensitivity to isoproterenol in cardiac hypertrophy of spontaneously hypertensive rats

    SciTech Connect

    Cheon, J.W.

    1986-01-01

    The responsiveness of the myocardial adenylate cyclase (AC) system in generating cAMP was studied using isoproterenol (a beta-adrenergic receptor agonist), cholera toxin (a guanosinetriphosphatase inhibitor) and forskolin (a catalytic unit activator) in isolated myocytes of age-matched, 14-17 weeks old Wistar Kyoto normotensive rates (WKYs) and spontaneously hypertensive rats (SHRs). We found a reduction in isoproterenol-stimulated cAMP formation in myocytes of SHRs compared with WKYs. This reduction was not due to changes in isoproterenol-receptor interactions. Scatchard plot analysis of (/sup 3/H)CGP 12177 binding to beta-adrenergic receptors in isolated myocytes of WKYs and SHRs revealed to significant differences in the maximum number of binding sites or dissociation constant. There were no significant differences in Ki and IC/sub 50/ calculated from the competitive displacement of (/sup 3/H)CGP 12177 binding by (-) isoproterenol, suggesting no change in the affinity of the beta-adrenergic receptors for isoproterenol. We found no significant differences in forskolin-stimulated cAMP formation between the two groups. This suggest that the reduction in isoproterenol-stimulated cAMP formation observed in myocytes of SHRs is not due to changes in the ability of catalytic unit to convert ATP to cAMP. Interestingly, cholera toxin-stimulated cAMP formation was increased in myocytes of SHRs. One possible explanation for these observations may be increased guanosinetriphosphatase (GTPase) activation by isoproterenol in myocytes of SHRs. The activation of GTPase by isoproterenol in myocytes of SHRs. The activation of GTPase by isoproterenol was measured as the release of Pi from (..gamma..-/sup 32/P)GTP. There was an increase in isoproterenol-stimulated GTPase activity in myocytes of SHRs compared with WKYs.

  9. 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.

  10. 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...

  11. Tomato lycopene attenuates myocardial infarction induced by isoproterenol: Electrocardiographic, biochemical and anti-apoptotic study

    PubMed Central

    Aman, Upaganlawar; Vaibhav, Patel; Balaraman, R

    2012-01-01

    Objective To assess the protective effects of lycopene on electrocardiographic, hemodynamic, biochemical and apoptotic changes in isoproterenol induced myocardial infarction. Methods Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol (200 mg/kg) for two consecutive days at an interval of 24 h. Rats were treated with lycopene (10 mg/kg/day, p.o.) for a period of 30 days and isoproterenol (ISO) was injected on the 29th and 30th day. At the end of experiment i.e. on the 31st day electrocardiographic, hemodynamic, biochemical and apoptotic changes were monitored from control and experimental groups. Results ISO injected rats showed a significant alteration in electrocardiograph pattern and hemodynamic changes (i.e. systolic, diastolic and mean arterial pressure). It also showed significant increase in C-reactive protein, myeloperoxidase, nitrite levels and Caspase-3 protease activity. In addition, it also exhibited alteration in the levels of electrolytes (Na+, K+ and Ca2+), vitamin E, uric acid and serum protein. Gel electrophoresis of ISO injected rats showed increase in DNA fragmentation. Triphenyl tetrazolium chloride staining of the heart section shows increase area of infarction in ISO injected rats. Pre-co-treatment with lycopene significantly prevented the ISO induced alteration in ECG, haemodynamic, biochemical and apoptotic changes. Conclusions The present result shows that treatment of lycopene in ISO injected rats significantly attenuates induced myocardial infarction. PMID:23569928

  12. Beta/sub 1/-adrenoceptors in rat hepatoma, desensitization by isoproterenol and phorbol-myristate-acetate

    SciTech Connect

    Garcia-Sainz, J.A.; Alcantara, R.; Hernandez-Sotomayor, S.M.T.; Mas-Oliva, J.

    1989-01-01

    The beta-adrenergic responsiveness of hepatocytes obtained from hypothyroid rats and of a transplantable hepatoma cell line (AS-30D) were studied by measuring the accumulation of cyclic AMP. The potency order for agonists in hepatocytes was: isoproterenol > epinephrine >> norepinephrine whereas in the hepatoma cells the potency order was: isoproterenol > norepinephrine /equivalent to/ epinephrine. The effect of isoproterenol was antagonized in hepatocytes by low concentrations of ICI 118551 and only partially by concentrations of atenolol as high as 100 ..mu..M. In hepatome cells the effect of isoproterenol was inhibited by both antagonists with the potency order atenolol > ICI 118551. These data indicate that in hepatocytes the effect is mediated by beta/sub 2/-adrenoceptors whereas in hepatoma cells it is through beta/sub 1/-adrenoceptors. Preincubation of hepatoma cells with isoproterenol or phorbol-myristate-acetate diminished the subsequent beta-adrenergic responsiveness of the cells. Interestingly, when both isoproterenol and phorbol-myristate-acetate were present during the preincubation the beta-adrenergic desensitization observed was bigger than that induced by any of these agents alone.

  13. [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.

  14. Kruppel-like factor 4 protein regulates isoproterenol-induced cardiac hypertrophy by modulating myocardin expression and activity.

    PubMed

    Yoshida, Tadashi; Yamashita, Maho; Horimai, Chihiro; Hayashi, Matsuhiko

    2014-09-19

    Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and vascular injury. Although KLF4 is expressed in the heart in addition to vascular cells, the role of KLF4 in cardiac disease has not been fully determined. The goals of this study were to investigate the role of KLF4 in cardiac hypertrophy and to determine the underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM Klf4 KO) mice were generated by the Cre/LoxP technique. Cardiac hypertrophy was induced by chronic infusion of the β-adrenoreceptor agonist isoproterenol (ISO). Results showed that ISO-induced cardiac hypertrophy was enhanced in CM Klf4 KO mice compared with control mice. Accelerated cardiac hypertrophy in CM Klf4 KO mice was accompanied by the augmented cellular enlargement of cardiomyocytes as well as the exaggerated expression of fetal cardiac genes, including atrial natriuretic factor (Nppa). Additionally, induction of myocardin, a transcriptional cofactor regulating fetal cardiac genes, was enhanced in CM Klf4 KO mice. Interestingly, KLF4 regulated Nppa expression by modulating the expression and activity of myocardin, providing a mechanical basis for accelerated cardiac hypertrophy in CM Klf4 KO mice. Moreover, we showed that KLF4 mediated the antihypertrophic effect of trichostatin A, a histone deacetylase inhibitor, because ISO-induced cardiac hypertrophy in CM Klf4 KO mice was attenuated by olmesartan, an angiotensin II type 1 antagonist, but not by trichostatin A. These results provide novel evidence that KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of myocardin.

  15. Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Tiwari, Roshan; Mohan, Mahalaxmi; Kasture, Sanjay; Maxia, Andrea; Ballero, Mauro

    2009-10-01

    The study aimed to evaluate the protective role of myricetin obtained from Vitis vinifera (Vitaceae) on heart rate, electrocardiographic (ECG) patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphological and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate and ST elevation in ECG, and a significant increase in the levels of cardiac marker enzymes - lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum. Isoproterenol significantly reduced superoxide dismutase (SOD) and catalase (CAT) activity and increased vascular reactivity to various catecholamines. Pretreatment with myricetin (100 mg/kg, p.o. and 300 mg/kg, p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, levels of LDH, CK, AST, SOD, CAT, vascular reactivity changes and ECG patterns. Treatment with myricetin (100 mg/kg and 300 mg/kg) alone did not alter any of the parameters compared with vehicle treated Wistar rats. Myricetin treated animals showed a lesser degree of cellular infiltration in histopathological studies. Thus, myricetin (100 mg/kg and 300 mg/kg) ameliorates the cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

  16. Naloxone potentiates the inotropic effects of isoproterenol in vitro by a nonopiate receptor mechanism.

    PubMed

    Lechner, R B

    1992-11-01

    Naloxone potentiates the effects of adrenergic agonists when administered to hypovolemic dogs, and it has been assumed that this effect is due to naloxone's action at opiate receptors. To help determine the site and mechanism of this interaction, we administered naloxone and its "d" stereo-isomer (which does not bind to opiate receptors) to guinea pig papillary muscles in the presence and absence of pharmacologic (isoproterenol) and physiologic (treppe) inotropic stimulation. In control muscles and in rapidly paced muscles, naloxone was without significant inotropic effect. In the presence of isoproterenol, d- and l-naloxone exerted significant positive inotropic effects that were dose dependent. We conclude that, since both d- and l-naloxone potentiated the inotropic effects of isoproterenol and this was seen in the absence of opioids, naloxone may increase contractility by a nonopiate receptor-mediated mechanism.

  17. The role of beta1 and beta2 adrenoceptors in isoproterenol-induced drinking.

    PubMed

    Kirby, R F; Novak, C M; Thunhorst, R L; Johnson, A K

    1994-09-05

    The present study examined the contribution of beta1 and beta2 adrenoceptor activation to drinking behavior and the stimulation of plasma renin activity produced by the mixed beta adrenoceptor agonist, isoproterenol. The stimulation of drinking by beta adrenoceptor activation could occur via two independent pathways; by either directly stimulating renal beta1 adrenoceptors on the juxtaglomerular cells to release renin or by stimulating vascular beta2 adrenoceptors that would decrease blood pressure and activate afferent neural and humoral mechanisms. Selective pharmacological antagonism of each adrenoceptor type was achieved by administering atenolol (2.5 mg/kg), a beta1 adrenoceptor antagonist, or ICI 118,551 (1 mg/kg), a beta2 adrenoceptor antagonist, before treatment with isoproterenol (25 micrograms/kg). Neither adrenoceptor mechanism alone could account for all of the water intake or stimulation of plasma renin activity due to isoproterenol treatment. Cardiovascular recordings confirmed the selectivity of the antagonists to their respective receptor subtypes, with atenolol blocking the beta1 adrenoceptor-mediated heart rate increases and ICI 118,551 blocking the beta 2 adrenoceptor-mediated depressor response to isoproterenol. The results provide evidence that the stimulation of both beta1 and beta2 adrenoceptors by isoproterenol acts in a synergistic manner to induce drinking and renin-angiotensin system activation.

  18. Chlorogenic acid prevents isoproterenol-induced DNA damage in vascular smooth muscle cells

    PubMed Central

    Wang, Jingshuai; Li, Jiyang; Liu, Jie; Xu, Mengjiao; Tong, Xiaowen; Wang, Jianjun

    2016-01-01

    Numerous clinical therapeutic agents have been identified as DNA damaging. The present study revealed that isoproterenol (Iso) resulted in DNA damage in vascular smooth muscle cells (VSMCs) and increased the levels of intracellular oxygen free radicals. Administration of chlorogenic acid (CGA) inhibited this effect. Pretreatment with CGA abrogated the increase in protein expression levels of γ-H2A histone family member X, phosphorylated ataxia telangiectasia mutated, phosphorylated Rad3-related protein, breast cancer 1 and C-terminal Src homologous kinase induced by Iso. In addition, the increase in levels of intracellular reactive oxygen species (ROS) induced by Iso was inhibited by CGA pretreatment in a dose-dependent manner. The results of the present study suggest that CGA may inhibit Iso-induced VSMC damage via the suppression of ROS generation. Therefore, CGA may be a novel agent for the treatment of vascular diseases. PMID:27634104

  19. Combined Effects of Vincristine and Quercetin in Reducing Isoproterenol-Induced Cardiac Necrosis in Rats.

    PubMed

    Panda, Sunanda; Kar, Anand

    2015-10-01

    Combined effects of vincristine and quercetin in the regulation of isoproterenol (ISO)-induced cardiac necrosis have been evaluated in rats. ISO administration (100 mg/kg, s.c., for two consecutive days) increased the levels of serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), glutamate pyruvate transaminase (SGPT) and cardiac troponin (cTnT) as well as cardiac lipid peroxidation products (malondialdehyde and lipid hydroperoxides). However, it reduced the activities of superoxide dismutase (SOD), catalase and the glutathione peroxidase and the level of reduced glutathione. It also increased the heart rate and ST-segment elevation in ECG. Pretreatment of vincristine (25 μg/kg) or quercetin (10 mg/kg) alone for 2 weeks ameliorated these cardiotoxic effects partially. However, treatment of both vincristine and quercetin for a similar period reduced the serum CK-MB, LDH, SGPT and cTnT levels near to normal levels in ISO-treated rats. Concomitantly, the test drugs improved the status of antioxidants and decreased the cardiac lipid peroxidation products. Combined treatment of both the drugs also restored the pathological electrocardiographic patterns and reduced the area of myocardial necrosis. Histopathology of heart in ISO-administered rats that received both vincristine and quercetin showed nearly normal myocardium with very little inflammatory infiltration. In conclusion, the present finding appears to be the first one, suggesting a better protection of cardiac tissues by combined treatment of vincristine and quercetin in isoproterenol-induced cardiac toxicity.

  20. Cardioprotective effect of vincristine on isoproterenol-induced myocardial necrosis in rats.

    PubMed

    Panda, Sunanda; Kar, Anand; Ramamurthy, Vilayanoor

    2014-01-15

    This study investigated the protective effect of vincristine (VCR) on isoproterenol (ISO)-induced cardiac necrosis (CN) in rats. Animals (n=7 in each group) were pretreated with vincristine (25µg/kg) intraperitoneal (i.p.) daily in 5-day cycles with 2 days pause between cycles using a 5-day-on, 2-day-off schedule for two weeks and then intoxicated with isoproterenol (100mg/kg, s.c., for 2 consecutive days). ISO-induced myocardial damage was indicated by changes in electrocardiographic (ECG) patterns, increased activities of marker enzymes such as creatine kinase-MB, serum glutamate pyruvate transaminase and lactate dehydrogenase and the levels of troponin-T in the serum. The levels of lipid peroxide products, (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (HP)) were increased with a parallel decrease in the activities of antioxidants (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione) in ISO-induced rats. Furthermore, ISO-induced rats showed increase in the activities of membrane bound enzymes such as Ca(2+)-ATPase and Mg(2+)-ATPase with a decreased activity of Na(+)/K(+)-ATPase. Triphenyl tetrazolium chloride (TTC) staining of the heart section showed increased area of necrosis in ISO-induced rats. Pretreatment with VCR (25µg/kg) eliminated all ISO-induced biochemical and histopathological changes, and decreased the myocardial necrosis to a greater extent. Transmission electron microscopic findings on the structure of the heart mitochondria confirmed the protective effects of VCR. Present study provides first scientific report on protective effect of vincristine against ISO-induced cardiac damage in rats.

  1. 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.

  2. 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

  3. Pyruvate attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity.

    PubMed

    Ojha, Shreesh; Goyal, Sameer; Kumari, Santosh; Arya, Dharamvir Singh

    2012-05-01

    Pyruvate, a potent endogenous antioxidant and an important metabolic fuel is essential for the cardiac function and tissue defense mechanism. The present study was evaluated to investigate whether pyruvate attenuates the development of cardiotoxicity in isoproterenol (ISO)-induced myocardial infarction by assessing hemodynamic, biochemical and histopathological parameters. Subcutaneous injection of ISO (85 mg/kg) administered for 2 days at an interval of 24h was used for induction of cardiotoxicity. ISO administration significantly decreased arterial pressure indices, heart rate, contractility {(+)LVdP/dt} and relaxation {(-)LVdP/dt} and increased left ventricular end-diastolic pressure. In addition, a significant reduction in activities of myocardial creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels along with increase in thiobarbituric acid reactive substances were also observed following ISO administration. However, pretreatment with pyruvate (0.25, 0.5 and 1.0 g/kg, p.o.) favorably modulated all most every studied parameters in ISO-induced myocardial injury. Furthermore, protective effect of pyruvate was confirmed by histopathological studies. Rats pretreated only with pyruvate did not produce significant change in hemodynamic, biochemical and histopathological parameters. Pyruvate at 0.50 and 1.0 g/kg doses was found to exert optimal cardioprotective effect against ISO-induced myocardial infarction. The results of our study suggest that pyruvate possessing antioxidant activity has a significant cardioprotective effect against ISO-induced myocardial injury.

  4. Preventive effect of phytic acid on lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Brindha, E; Rajasekapandiyan, M

    2015-02-01

    This study was aimed to evaluate the preventive role of phytic acid on lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for two days showed a significant increase in the activities of lysosomal enzymes (glucuronidase, N-acetyl glucosaminidase, galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with phytic acid (25 and 50 mg/kg) daily for a period of 56 d positively altered activities of lysosomal hydrolases in ISO-induced rats. Thus, phytic acid possesses a cardioprotective effect in ISO-induced MI in rats.

  5. 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

  6. 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.

  7. Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

    PubMed Central

    2011-01-01

    Background Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. Methods Three month old female mdx mice were exposed to the β1 receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining. Results BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers. Conclusions This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice. PMID:21575230

  8. 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

  9. Temperature effect on contractile activity of the Ambystoma dumerilii heart previously treated with isoproterenol.

    PubMed

    Cano-Martínez, A; Vargas-González, A; Guarner-Lans, V

    2007-07-01

    The spontaneous heart rate (HR) and ventricular (V) and atrium (A) tensions (T) were evaluated through isolated organ assays at different temperatures in hearts from Ambystoma dumerilii control and treated with isoproterenol (ISO) [(150 mg/kg i.p. each 24 h, for 3 days)] on days 1, 5, 30 and 90 after ISO. In control hearts, the HR increased and the T decreased when temperature was augmented. One day after ISO the HR (43-24%) and T (50-25%) decreased with respect to control, between 8 and 24 degrees C. Five, 30 and 90 days after ISO, HR showed a gradual recovery with similar effect when the temperature was changed; but the AT increased and VT decreased at temperatures between 8 and 12 degrees C and were only recovered at temperatures above 12 degrees C. Our results indicate that the HR recovers after ISO in A. dumerilii independently of temperature. The recovery of AT and VT is similar to HR at temperatures higher than 12 degrees C and the increases in VT could be compensating the decrease in VT caused by ISO, at temperatures lower than 12 degrees C. The changes in heart contractile activity of A. dumerilii after insult show the thermic plasticity that is observed in ectothermic vertebrates.

  10. 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.

  11. 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.

  12. Differential regulation of the mitogen-activated protein and stress-activated protein kinase cascades by adrenergic agonists in quiescent and regenerating adult rat hepatocytes.

    PubMed Central

    Spector, M S; Auer, K L; Jarvis, W D; Ishac, E J; Gao, B; Kunos, G; Dent, P

    1997-01-01

    To study the mechanisms by which catecholamines regulate hepatocyte proliferation after partial hepatectomy (PHX), hepatocytes were isolated from adult male rats 24 h after sham operation or two-thirds PHX and treated with catecholamines and other agonists. In freshly isolated sham cells, p42 mitogen-activated protein (MAP) kinase activity was stimulated by the alpha1-adrenergic agonist phenylephrine (PHE). Activation of p42 MAP kinase by growth factors was blunted by pretreatment of sham hepatocytes with glucagon but not by that with the beta2-adrenergic agonist isoproterenol (ISO). In PHX cells, the ability of PHE to activate p42 MAP kinase was dramatically reduced, whereas ISO became competent to inhibit p42 MAP kinase activation. PHE treatment of sham but not PHX and ISO treatment of PHX but not sham hepatocytes also activated the stress-activated protein (SAP) kinases p46/54 SAP kinase and p38 SAP kinase. These data demonstrate that an alpha1- to beta2-adrenergic receptor switch occurs upon PHX and results in an increase in SAP kinase versus MAP kinase signaling by catecholamines. In primary cultures of hepatocytes, ISO treatment of PHX but not sham cells inhibited [3H]thymidine incorporation. In contrast, PHE treatment of sham but not PHX cells stimulated [3H]thymidine incorporation, which was reduced by approximately 25 and approximately 95% with specific inhibitors of p42 MAP kinase and p38 SAP kinase function, respectively. Inhibition of the p38 SAP kinase also dramatically reduced basal [3H]thymidine incorporation. These data suggest that p38 SAP kinase plays a permissive role in liver regeneration. Alterations in the abilities of catecholamines to modulate the activities of protein kinase A and the MAP and SAP kinase pathways may represent one physiological mechanism by which these agonists can regulate hepatocyte proliferation after PHX. PMID:9199291

  13. The Syrian Hamster Pineal Gland Responds to Isoproterenol in Vivo at Night

    DTIC Science & Technology

    1987-01-01

    pineal gland transmitter. Proc Nat Acad Sci USA protect against acute stress-induced 70:2411 increase in N-acetyltransferase (EC 2.3.1.5.) activity ...Society Printed in U.S.A. A THE SYRIAN HAMSTER PINEAL GLAND RESPONDS TO ISOPROTERENOL IN VIVO AT NIGHT George M. Vaughan 1 and Russel J. Reiter 2 1US...then kept in light for 2 h, pineal melatonin was equally low 0 • after ISO or vehicle injection. The Syrian hamster pineal gland can respond in vivo

  14. Beta-Adrenergic Receptors and Isoproterenol-stimulated Potassium Transport in Erythrocytes from Normal and Hypothyroid Turkeys

    PubMed Central

    Furukawa, Haruyasu; Loeb, John N.; Bilezikian, John P.

    1980-01-01

    We have previously reported that in hypothyroid turkeys the number of beta-adrenergic receptors in intact erythrocytes is reduced by ∼50% without any changes in the affinity of the receptor for the agonist, isoproterenol. In view of the physiological action of the catecholamines to stimulate bidirectional ion fluxes in these cells, we have now examined the possibility that the decrease in beta receptor number might be associated with concomitant changes in catecholamine-dependent potassium ion transport. Hypothyroid turkey erythrocytes display decreased sensitivity to isoproterenol-stimulated potassium influx. Half-maximal stimulation of potassium influx occurs at 9.2±1.7 nM in hypothyroid cells as opposed to only 3.8±0.4 nM in normal cells (P < 0.005). A maximal stimulatory concentration of isoproterenol (100 nM) leads to the same increment in ion flux in erythrocytes from hypothyroid and normal turkeys. Analysis of the quantitative relationship between isoproterenol concentration, receptor occupancy, and associated effects upon potassium influx shows that at low levels of isoproterenol, where occupancy is linear with agonist concentration, occupation of a given number of beta receptors leads to a stimulation of potassium transport that is identical in erythrocytes from normal and hypothyroid turkeys. Thus, decreased sensitivity to catecholamine-stimulated potassium transport in hypothyroidism can be attributed to the decrease in receptor number and the resulting two- to threefold higher isoproterenol concentration required for occupancy of the same number of beta receptors. Once a single receptor is occupied, however, the more distal components of the sequence of events mediating the physiological response to beta-adrenergic agonists in the hypothyroid cell function as they do under normal circumstances. It would appear, therefore, that the decrease in sensitivity to isoproterenol-dependent ion flux in the hypothyroid turkey erythrocyte can be accounted for

  15. Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat.

    PubMed

    Mnafgui, Kais; Hajji, Raouf; Derbali, Fatma; Gammoudi, Anis; Khabbabi, Gaddour; Ellefi, Hedi; Allouche, Noureddine; Kadri, Adel; Gharsallah, Neji

    2016-10-01

    This study aimed to evaluate the antithrombotic, anti-inflammatory and anti-cardiac remodeling properties of eugenol in isoproterenol-induced myocardial infarction in rats. Male Wistar rats were randomly divided into four groups, control, iso [100 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI] and pretreated animals with clopidogrel (0.2 mg/kg) and eugenol (50 mg/kg) orally for 7 days and intoxicated with isoproterenol (Iso + Clop) and (Iso + EG) groups. Isoproterenol-induced myocardial infarcted rats showed notable changes in the ECG pattern, increase in heart weight index, deterioration in the hemodynamic function and rise in plasma level of troponin-T, CK-MB and LDH and ALT by 316, 74, 172 and 45 %, respectively, with histological myocardium necrosis and cells inflammatory infiltration. In addition, significant increases in plasma levels of inflammatory biomarkers such as fibrinogen, α1, α2, β1, β2 and γ globulins with decrease level of albumin were observed in infarcted rats as compared to normal ones. Else, the angiotensin-converting enzyme (ACE) activity in plasma, kidney and heart of the isoproterenol-induced rats was significantly increased by 34, 47 and 93 %, respectively, as compared to normal group. However, the administration of eugenol induced a clear improvement in cardiac biomarkers injury, reduced inflammatory mediators proteins, increased heart activities of superoxide dismutase and glutathione peroxidase with reduce in thiobarbituric acid-reactive substances content and inhibition of ventricular remodeling process through inhibition of ACE activity. Overall, eugenol evidences high preventive effects from cardiac remodeling process.

  16. 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

  17. 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

    2015-11-17

    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.

  18. Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.

    PubMed

    Upaganlawar, Aman; Gandhi, Chintan; Balaraman, Ramchandran

    2009-03-01

    The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.

  19. Correlation between oxidative stress and alteration of intracellular calcium handling in isoproterenol-induced myocardial infarction.

    PubMed

    Díaz-Muñoz, Mauricio; Alvarez-Pérez, Marco Antonio; Yáñez, Lucía; Vidrio, Susana; Martínez, Lidia; Rosas, Gisele; Yáñez, Mario; Ramírez, Sotero; de Sánchez, Victoria Chagoya

    2006-09-01

    Myocardial Ca(2+) overload and oxidative stress are well documented effects associated to isoproterenol (ISO)-induced myocardial necrosis, but information correlating these two issues is scarce. Using an ISO-induced myocardial infarction model, 3 stages of myocardial damage were defined: pre-infarction (0-12 h), infarction (12-24 h) and post-infarction (24-96 h). Alterations in Ca(2+) homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca(2+) content, the activity of Ca(2+) handling proteins, and by quantifying TBARs, nitric oxide (NO) and oxidative protein damage (changes in carbonyl and thiol groups). Free radicals generated system, antioxidant enzymes and oxidative stress (GSH/GSSG ratio) were also monitored at different times of ISO-induced cardiotoxicity. The Ca(2+) overload induced by ISO was counterbalanced by a diminution in the ryanodine receptor activity and the Na(+)-Ca(+2) exchanger as well as by the increase in both calcium ATPases activities (vanadate- and thapsigargine-sensitive) and mitochondrial Ca(2+) uptake during pre-infarction and infarction stages. Pro-oxidative reactions and antioxidant defences during the 3 stages of cardiotoxicity were observed, with maximal oxidative stress during the infarction. Significant correlations were found among pro-oxidative reactions with plasmalemma and sarcoplasmic reticulum Ca(2+) ATPases, and ryanodine receptor activities at the onset and development of ISO-induced infarction. These findings could be helpful in the design of antioxidant therapies in this pathology.

  20. 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

  1. Rosiglitazone is a superior bronchodilator compared to chloroquine and β-adrenoceptor agonists in mouse lung slices

    PubMed Central

    2014-01-01

    Background Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor agonist efficacy was limited or impaired in mouse small airways within lung slices. Methods Relaxation to RGZ and CQ was assessed following submaximal methacholine (MCh) pre-contraction, in slices treated overnight with either RGZ, CQ or albuterol (ALB) (to induce β-adrenoceptor desensitization), and in slices treated with caffeine/ryanodine in which contraction is associated with increases in Ca2+ sensitivity in the absence of contractile agonist-induced Ca2+ oscillations. Furthermore, the effects of RGZ, CQ, ALB and isoproterenol (ISO) on the initiation and development of methacholine-induced contraction were also compared. Results RGZ and CQ, but not ALB or ISO, elicited complete relaxation with increasing MCh pre-contraction and maintained their potency and efficacy following β-adrenoceptor desensitization. RGZ, CQ and ALB maintained efficacy following overnight incubation with RGZ or CQ. Relaxation responses to all dilators were generally maintained but delayed after caffeine/ryanodine. Pre-treatment with RGZ, but not CQ, ALB or ISO, reduced MCh potency. Conclusions This study demonstrates the superior effectiveness of RGZ in comparison to CQ and β-adrenoceptor agonists as a dilator of mouse small airways. Further investigation of the mechanisms underlying the relatively greater efficacy of RGZ under these conditions are warranted and should be extended to include studies in human asthmatic airways. PMID:24621080

  2. 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

  3. Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes.

    PubMed

    Ruzsnavszky, Ferenc; Hegyi, Bence; Kistamás, Kornél; Váczi, Krisztina; Horváth, Balázs; Szentandrássy, Norbert; Bányász, Tamás; Nánási, Péter P; Magyar, János

    2014-05-01

    Adrenergic activation of L-type Ca(2+) and various K(+) currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca(2+) and K(+) currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I(Ca), I(Ks), and I(Kr), while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I(Ca) and I(Ks) and moderate stimulation of I(Kr). The ISO-induced plateau shift and I(Ca) increase developed faster than the shortening of APD and stimulation of I(Ks) and I(Kr). Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I(Ca) is turned on faster than the stimulation of I(Ks) and I(Kr) in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.

  4. Crocus sativus L. (saffron) attenuates isoproterenol-induced myocardial injury via preserving cardiac functions and strengthening antioxidant defense system.

    PubMed

    Sachdeva, Jaspreet; Tanwar, Vineeta; Golechha, Mahaveer; Siddiqui, Khalid M; Nag, Tapas C; Ray, Ruma; Kumari, Santosh; Arya, Dharamvir S

    2012-09-01

    Saffron (dried stigmas of Crocus sativus L.), a naturally derived plant product, has long been used as a traditional ancient medicine against various human diseases. The aim of the series of experiments was to systematically determine whether saffron exerts cardioprotection in isoproterenol-induced myocardial damage. Male Wistar rats (150-175 g) were divided into five groups: control, isoproterenol (ISO) and three saffron (200, 400 and 800 mg/kg) treatment groups. Aqueous extract of saffron or vehicle was administered orally to rats for four weeks. On days 28 and 29, the animals in ISO and saffron treatment groups were administered ISO (85 mg/kg, s.c.) at an interval of 24 h. On day 30, after recording hemodynamics and left ventricular functions, animals were sacrificed for biochemical, histopathological and electromicroscopical examinations. Isoproterenol challenged animals showed depressed hemodynamics and left ventricular functions as evident by decreased left ventricular rate of peak positive and negative pressure change and elevated left ventricular end-diastolic pressure. Structural and ultrastructural studies further confirmed the damage which was reconfirmed by increased thiobarbituric acid reactive substances (p<0.001) and decreased creatine kinase-MB and lactate dehydrogenase (p<0.001). In addition, significant reduction in superoxide dismutase and catalase (p<0.001) was observed in ISO group. Our results suggested that saffron at all the doses exerted significant cardioprotective effect by preserving hemodynamics and left ventricular functions, maintaining structural integrity and augmenting antioxidant status. Among the different doses used, saffron at 400mg/kg dose exhibited maximum protective effects which could be due to maintenance of the redox status of the cell reinforcing its role as an antioxidant.

  5. B-type natriuretic peptide and adiponectin releases in rat model of myocardial damage induced by isoproterenol administration

    PubMed Central

    Hasić, Sabaheta; Hadžović-Džuvo, Almira; Jadrić, Radivoj; Kiseljaković, Emina

    2013-01-01

    B-type natriuretic peptide (BNP) and adiponectin play important role in the cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum levels followed by isoproterenol (ISO) administration to rats and explored the relationship between them. Cardiac troponin I (cTnI) blood level was used as biochemical evidence of myocardial damage development. Adult male Wistar rats (average body weight 273.33±21.63 g) were distributed into groups: control group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous single dose 100 mg/kg of rat body weight). ISO group was divided into two groups according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2 hours after ISO administration); ISO II (n=6; 4 hours after ISO administration). Blood for determination of parameters was taken from rat abdominal aorta. BNP, adiponectin and cTnI were determined by ELISA method. Data were statistically analysed by using SPSS version13 computer program. P value less 0.05 was considered statistically significant. Blood BNP and adiponectin were lower at 2 hours after ISO administration in comparison with control group (p=0.004 for BNP and p=0.174 for adiponectin). Four hours after ISO administration, we have noted significant elevation of both parameters compared to ISO I group (p=0.004 for BNP;p=0.02 for adiponectin). Test of correlation have showed significant relation between their blood levels during experimental period (rho=0.577; p=0.01). BNP and adiponectin are not simple indicators of myocardial damage development. They have possible associated and additive effects in cardiovascular homeostasis regulation. PMID:24289757

  6. Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by isoproterenol in male rats.

    PubMed

    Ghanbarzadeh, S; Garjani, A; Ziaee, M; Khorrami, A

    2014-09-01

    Nowadays, cardiovascular diseases and male infertility are two big health problems in industrial countries.The aim of the present study was to investigate the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100 mg/kg) in ISO treated groups. Before ISO administration, pretreatment with Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20 consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant concentration as well as testis, epididymis and seminal vesicle weight were investigated.Increase in the concentration of MDA and decrease in total antioxidant level was observed following ISO administration. Accordingly, the sperm viability as well as testis, epididymis and seminal vesicle weights were decreased. In the case of sex hormones, the testosterone and LH levels were decreased and the concentration of FSH was increased. Pretreatment with L-carnitine and Coenzyme Q10 significantly decreased the MDA level and increased total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and Coenzyme Q10 also improved semen parameters and organs weight which were impaired by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect spermatogenesis in male rats with ISO administration.

  7. 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

  8. Molecular and biochemical evidence on the protective effects of quercetin in isoproterenol-induced acute myocardial injury in rats.

    PubMed

    Kumar, Mukesh; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Kumar, Vikas; Lahkar, Mangala

    2017-01-01

    Cardioprotection represents one of the most important and realistic aspects of preventive therapy today. Quercetin, a naturally occurring dietary flavone, has been studied extensively for its antioxidant properties. The objective of present study is to find out the cardioprotective activity and to explore the underlying mechanisms of quercetin pretreatment (50 mg/kg body weight, orally) for 14 days against isoproterenol (ISO; 100 mg/kg body weight, subcutaneously) induced myocardial infarction in Wistar rats. Cardiac diagnostic markers, oxidative stress, inflammatory cytokines, histopathology along with gene expression analysis of calpain 1 and 2 were carried out in experimental rats. Quercetin pretreatment showed protective effects on heart by significantly attenuating the ISO-induced oxidative stress, inflammation, protecting heart architecture, and by downregulation of the expression of calpain. Overall, these findings revealed the cardio-protective potential of quercetin and its mechanism of action against ISO-induced MI in rats.

  9. 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.

  10. 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

  11. Hydrogen (H2) Inhibits Isoproterenol-Induced Cardiac Hypertrophy via Antioxidative Pathways

    PubMed Central

    Zhang, Yaxing; Xu, Jingting; Long, Zhiyuan; Wang, Chen; Wang, Ling; Sun, Peng; Li, Ping; Wang, Tinghuai

    2016-01-01

    Background and Purpose: Hydrogen (H2) has been shown to have a strong antioxidant effect on preventing oxidative stress-related diseases. The goal of the present study is to determine the pharmacodynamics of H2 in a model of isoproterenol (ISO)-induced cardiac hypertrophy. Methods: Mice (C57BL/6J; 8–10 weeks of age) were randomly assigned to four groups: Control group (n = 10), ISO group (n = 12), ISO plus H2 group (n = 12), and H2 group (n = 12). Mice received H2 (1 ml/100g/day, intraperitoneal injection) for 7 days before ISO (0.5 mg/100g/day, subcutaneous injection) infusion, and then received ISO with or without H2 for another 7 days. Then, cardiac function was evaluated by echocardiography. Cardiac hypertrophy was reflected by heart weight/body weight, gross morphology of hearts, and heart sections stained with hematoxylin and eosin, and relative atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels. Cardiac reactive oxygen species (ROS), 3-nitrotyrosine and p67 (phox) levels were analyzed by dihydroethidium staining, immunohistochemistry and Western blotting, respectively. For in vitro study, H9c2 cardiomyocytes were pretreated with H2-rich medium for 30 min, and then treated with ISO (10 μM) for the indicated time. The medium and ISO were re-changed every 24 h. Cardiomyocyte surface areas, relative ANP and BNP mRNA levels, the expression of 3-nitrotyrosine, and the dissipation of mitochondrial membrane potential (MMP) were examined. Moreover, the expression of extracellular signal-regulated kinase1/2 (ERK1/2), p-ERK1/2, p38, p-p38, c-Jun NH2-terminal kinase (JNK), and p-JNK were measured by Western blotting both in vivo and in vitro. Results: Intraperitoneal injection of H2 prevented cardiac hypertrophy and improved cardiac function in ISO-infused mice. H2-rich medium blocked ISO-mediated cardiomyocytes hypertrophy in vitro. H2 blocked the excessive expression of NADPH oxidase and the accumulation of ROS, attenuated the

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

    PubMed

    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 7 days. 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.

  13. Cardioprotective effect of ethanolic extract of Urtica parviflora Roxb. against isoproterenol induced myocardial infarction in rats

    PubMed Central

    Barman, Nishith Ranjan; Nandy, Subhangkar; Datta, Rana; Kar, Prasanna Kumar

    2013-01-01

    Objective: The objective of this study is to evaluate the effect of ethanolic extract of Urtica parviflora Roxb. in isoproterenol (ISO) induced myocardial infarction (MI) in rats. Materials and Methods: U. parviflora Roxb. (350 mg/kg and 500 mg/kg, p.o) was administered for 15 days in rats. MI was induced with a single dose of ISO (200 mg/kg, s.c.) on the 14th and 15th day. At the end of the experimental period (i.e., on the day 16), serum and heart tissues were collected and total cholesterol (TC), high density lipoprotein, triglyceride and malondialdehyde, superoxide dismutase, catalase (CAT), reduced glutathione (GSH) and body weight were determined. Results: Administration of ISO in control rats showed a significant (P < 0.001) increase serum cholesterol alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and low density lipoprotein (LDL). There was a significant increase (P < 0.01) in the levels of heart tissues as compared with respective control groups. Rats treated with U. parviflora significantly (P < 0.01) decreased ALT, AST, ALP, LDL and TC. Moreover, there was an increased CAT and GSH levels in rat treated with U. parviflora Roxb. as compared with the control group. Conclusion: U. parviflora (350 and 500 mg/kg p.o.) is effective in controlling serum LDL levels and reduced cardiac complication in experimentally induced MI in rats. PMID:24130389

  14. Prohibitin confers cytoprotection against ISO-induced hypertrophy in H9c2 cells via attenuation of oxidative stress and modulation of Akt/Gsk-3β signaling.

    PubMed

    Chowdhury, Debabrata; Kumar, Dinesh; Bhadra, Utpal; Devi, Tangutur Anjana; Bhadra, Manika Pal

    2017-01-01

    Numerous hypertrophic stimuli, including β-adrenergic agonists such as isoproterenol (ISO), result in generation of reactive oxygen species (ROS) and alteration in the mitochondrial membrane potential (Δψ) leading to oxidative stress. This process is well associated with phosphorylation of thymoma viral proto-oncogene Akt (Ser473) and glycogen synthase kinase-3β (Gsk-3β) (Ser9), with resultant inactivation of Gsk-3β. In the present study, we found that the protective defensive role of prohibitin (PHB) against ISO-induced hypertrophic response in rat H9c2 cells is via attenuation of oxidative stress-dependent signaling pathways. The intracellular levels of mitochondrial membrane potential along with cellular ROS levels and mitochondrial superoxide generation were determined. In order to understand the regulation of Akt/Gsk-3β signaling pathway, we carried out immmunoblotting for key proteins of the pathway such as PTEN, PI3K, phosphorylated, and unphosphorylated forms of Akt, Gsk-3β, and immunofluorescence experiments of p-Gsk-3β. Enforced expression of PHB in ISO-treated H9c2 cells suppressed cellular ROS production with mitochondrial superoxide generation and enhanced the mitochondrial membrane potential resulting in suppression of oxidative stress which likely offered potent cellular protection, led to the availability of more healthy cells, and also, significant constitutive activation of Gsk-3β via inactivation of Akt was observed. Knockdown of PHB expression using PHB siRNA in control H9c2 cells reversed these effects. Overall, our results demonstrate that PHB confers cytoprotection against oxidative stress in ISO-induced hypertrophy and this process is associated with modulation of Akt/Gsk-3β signaling mechanisms as evident from our PHB overexpression and knockdown experiments.

  15. Luteolin-7-diglucuronide attenuates isoproterenol-induced myocardial injury and fibrosis in mice

    PubMed Central

    Ning, Bing-bing; Zhang, Yong; Wu, Dan-dan; Cui, Jin-gang; Liu, Li; Wang, Pei-wei; Wang, Wen-jian; Zhu, Wei-liang; Chen, Yu; Zhang, Teng

    2017-01-01

    Myocardial injury and ensuing fibrotic alterations impair normal heart architecture and cause cardiac dysfunction. Oxidative stress has been recognized as a key player in the pathogenesis of cardiac injury and progression of cardiac dysfunction, and promoting fibrosis. In the current study we investigated whether luteolin-7-diglucuronide (L7DG), a naturally occurring antioxidant found in edible plants, could attenuate isoproterenol (ISO)-induced myocardial injury and fibrosis in mice and the underlying mechanisms. Myocardial injury and fibrosis were induced in mice via injection of ISO (5 mg·kg−1·d−1, ip) for 5 or 10 d. Two treatment regimens (pretreatment and posttreatment) were employed to administer L7DG (5–40 mg·kg−1·d−1, ip) into the mice. After the mice were euthanized, morphological examinations of heart sections revealed that both L7DG pretreatment and posttreatment regimens significantly attenuated ISO-induced myocardial injury and fibrosis. But the pretreatment regimen caused better protection against ISO-induced myocardial fibrosis than the posttreatment regimen. Furthermore, L7DG pretreatment blocked ISO-stimulated expression of the genes (Cyba, Cybb, Ncf1, Ncf4 and Rac2) encoding the enzymatic subunits of NADPH oxidase, which was the primary source of oxidant production in mammalian cells. Moreover, L7DG pretreatment significantly suppressed ISO-stimulated expression of collagen genes Col1a1, Col1a2, Col3a1, and Col12a1 and non-collagen extracellular matrix genes fibrillin-1, elastin, collagen triple helix repeat containing 1 and connective tissue growth factor. In addition, L7DG pretreatment almost reversed ISO-altered expression of microRNAs that were crosstalking with TGFβ-mediated fibrosis, including miR-29c-3p, miR-29c-5p, miR-30c-3p, miR-30c-5p and miR-21. The current study demonstrated for the first time that L7DG is pharmacologically effective in protecting the heart against developing ISO-induced injury and fibrosis, justifying

  16. 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 Central

    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

  17. Acute isoproterenol induces anxiety-like behavior in rats and increases plasma content of extracellular vesicles.

    PubMed

    Leo, Giuseppina; Guescini, Michele; Genedani, Susanna; Stocchi, Vilberto; Carone, Chiara; Filaferro, Monica; Sisti, Davide; Marcoli, Manuela; Maura, Guido; Cortelli, Pietro; Guidolin, Diego; Fuxe, Kjell; Agnati, Luigi Francesco

    2015-04-01

    Several clinical observations have demonstrated a link between heart rate and anxiety or panic disorders. In these patients, β-adrenergic receptor function was altered. This prompted us to investigate whether the β-adrenergic receptor agonist isoproterenol, at a dose that stimulates peripheral β-adrenergic system but has no effects at the central nervous system, can induce anxiety-like behavior in rats. Moreover, some possible messengers involved in the peripheral to brain communication were investigated. Our results showed that isoproterenol (5 mg kg(-1) i.p.) increased heart rate, evoked anxiety-like behavior, did not result in motor impairments and increased extracellular vesicle content in the blood. Plasma corticosterone level was unmodified as well as vesicular Hsp70 content. Vesicular miR-208 was also unmodified indicating a source of increased extracellular vesicles different from cardiomyocytes. We can hypothesize that peripheral extracellular vesicles might contribute to the β-adrenergic receptor-evoked anxiety-like behavior, acting as peripheral signals in modulating the mental state.

  18. Effects of Lagenaria sicessaria fruit juice on lipid profile and glycoprotein contents in cardiotoxicity induced by isoproterenol in rats.

    PubMed

    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.

  19. Antilipoperoxidative and antioxidant effects of S-allyl cysteine sulfoxide on isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Sangeetha, T; Quine, S Darlin

    2006-01-01

    Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on lipid peroxidative products and enzymic and nonenzymic antioxidants in isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats were rendered myocardial infarction by ISO (150 mg kg(-1), once a day for two days). The concentrations of thiobarbituric acid reactive substances and lipid hydroperoxides were increased in hearts from ISO-treated rats, whereas the content of enzymic and nonenzymic antioxidants were declined in rats administered ISO. Oral pretreatment with SACS (40 mg kg(-1) and 80 mg kg(-1) daily for a period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative products and significantly (p < 0.05) increased antioxidants in ISO-induced rats. Oral administration of SACS (40 mg kg(-1) and 80 mg kg(-1)) did not show any significant effect in normal rats. Thus, the present study shows that SACS exhibits antilipoperoxidative and antioxidant effects in experimental myocardial infarction.

  20. Protective effect of Lagenaria siceraria (Mol) against membrane-bound enzyme alterations in isoproterenol-induced cardiac damage in rats.

    PubMed

    Vijayakumar, M; Selvi, V; Krishnakumari, S

    2012-01-01

    This study was aimed at evaluating the preventive role of the ethanolic extract of Lagenaria siceraria (Mol) fruit on membrane-bound enzymes, such as sodium potassium-dependent adenosine triphosphatase (Na(+)/K(+) ATPase), calcium-dependent adenosine triphosphatase (Ca(2+) ATPase) and magnesium-dependent adenosine triphosphatase (Mg(2+) ATPase) on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with the ethanolic extract of L. siceraria (Mol) fruit (125, 250 and 500 mg kg(-1) body weight) for a period of 30 days. After the treatment period, ISO (85mg kg(-1) body weight) was subcutaneously injected into rats at 24-h intervals for 2 days. ISO-induced rats showed a significant (p < 0.05) decrease in the activity of Na(+)/K(+) ATPase and an increase in the activities of Ca(2+) and Mg(2+) ATPases in the heart tissues. Pre-treatment with the ethanolic extract of L. siceraria (Mol) fruit for a period of 30 days exhibited a significant (p < 0.05) effect in ISO-induced rats. Thus, our study shows that the ethanolic extract of L. siceraria (Mol) fruit has membrane-stabilising role in ISO-induced MI in rats.

  1. 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.

  2. Mechanism of Taiwan Mingjian Oolong Tea to Inhibit Isoproterenol-Induced Hypertrophy and Apoptosis in Cardiomyoblasts.

    PubMed

    Yeh, Yu-Lan; Tsai, Hsiang-I; Cheng, Shiu-Min; Pai, Peiying; Ho, Tsung-Jung; Chen, Ray-Jade; Lai, Chao-Hung; Huang, Pei-Jane; Padma, V Vijaya; Huang, Chih-Yang

    2016-01-01

    This study investigates the cardio-protective effect of Nos. 1 and 5 extracts from Taiwan Mingjian Oolong Tea on H9c2 cardiomyoblast cells treated with isoproterenol (ISO). Treatment with Nos. 1 and 5 extracts increased cell viability and blocked apoptosis in ISO exposed H9c2 cells. Moreover, Nos. 1 and 5 extracts blocked hypertrophy markers like G[Formula: see text]s, calcineurin, NFATc3, and BNP, thereby increasing cell proliferation markers -PI3K and AKT in a dose dependent manner. In contrast, apoptotic proteins, such as caspase-3 and cytochrome c were decreased in H9c2 cells treated with Nos. 1 and 5 extracts. We confirmed that the protective effect of No. 1 extract was partially mediated through the expression of ERK and p38, however, the No. 5 extract showed a protective effect via the ERK, JNK, and p38 pathways. This evidence provides new insights into the pharmacological role and therapeutic mechanism of Taiwan Mingjian Oolong Tea in heart diseases.

  3. 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.

  4. 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.

  5. 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.

  6. Intraventricular administration of isoproterenol inhibits both heat production and heat loss mechanisms in rats.

    PubMed

    Lin, M T; Chandra, A; Fan, Y C; Sun, R

    1980-07-15

    At an ambient temperature (Ta) of 8 degrees C, intraventricular administration of isoproterenol inhibited metabolic heat production and led to hypothermia in rats. In contrast, at a Ta of 22 degrees C and of 30 degrees C, isoproterenol decreased cutaneous circulation and led to hyperthermia. The data indicate that isoproterenol inhibits both heat production and heat loss mechanisms in rats.

  7. Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

    PubMed Central

    Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

    2016-01-01

    Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

  8. 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

  9. Chlorogenic acid a dietary polyphenol attenuates isoproterenol induced myocardial oxidative stress in rat myocardium: An in vivo study.

    PubMed

    Akila, Palaniyandi; Vennila, Lakshmanan

    2016-12-01

    Intent of the present study has been made to appraise the cardioprotective effect of chlorogenic acid (CGA) on isoproterenol (ISO) induced myocardial infarction (MI) in male albino Wistar rats. ISO-induced myocardial damage was indicated by the elevated levels of marker enzymes such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LHPs) were significantly increased in the plasma and heart tissue. Activities of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the non enzymic antioxidants like vitamin C, vitamin E and reduced glutathione (GSH) were decreased in the erythrocytes, plasma and heart tissue of the ISO-induced rats and myocardium infarct size as observed by staining with triphenyltetrazolium chloride (TTC). Histopathological observation corroborated with the bioochemical parameters. Oral administration of CGA at different doses (10, 20, 40mg/kg BW) for 19days prevented the above changes. The 40mg/kg BW of CGA was more pronounced than other two doses and brought back all the above parameters to near normalcy.

  10. 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

  11. Nutraceutical inherent of Spinacia oleracea Linn. methanolic leaf extract ameliorates isoproterenol induced myocardial necrosis in male albino Wistar rats via mitigating inflammation.

    PubMed

    Vutharadhi, Shivaranjani; Jolapuram, Umamaheswari; Kodidhela, Lakshmi Devi

    2017-01-01

    Cardiovascular diseases (CVDs) remain the principal cause of death in both developed and developing countries. The present study was intended to appraise the nutraceutical inherent of HPLC standardized Spinacia oleracea methanolic leaf extract (SoLE) in isoproterenol (ISO) induced male albino Wistar rats via activation of pro-inflammatory signaling pathway that drives myocardial necrosis. Biochemical analysis of ISO injected rats showed significant alterations in the activities of homocysteine, paraoxonase, lecithin cholesterol acyltransferase, C-reactive protein, myeloperoxidase and caspase-3 which were further confirmed by the histopathological examination. In addition, it also flaunted a significant increase in pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 in ISO administered rats when compared with normal control rats. Pretreatment with SoLE (100, 200, and 300mg/kg bw) along with positive control gallic acid, significantly prevented all the adverse effects in ISO administered rats in a dose dependent manner. These results also reiterated the expected amelioration of myocardial necrosis in ISO induced MI rats conveying anti-atherogenic, anti-apoptotic and anti-inflammatory activities of SoLE.

  12. Protective effect of S-allyl cysteine sulphoxide (alliin) on glycoproteins and hematology in isoproterenol induced myocardial infarction in male Wistar rats.

    PubMed

    Sangeetha, T; Quine, S Darlin

    2008-07-01

    The antihyperlipidemic, antilipoperoxidative and antioxidant effects of S-allyl cysteine sulphoxide (SACS) in myocardial infarcted rats were reported previously. The present study was undertaken to evaluate the preventive role of SACS on some biochemical parameters, glycoproteins and hematology in experimentally induced myocardial infarction in rats. Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol (ISO) (150 mg kg(-1)) at an interval of 24 h for 2 days. ISO-treated rats showed a significant increase in the levels of serum iron, uric acid and blood glucose, Na(+) and Ca(2+) in the heart and a significant decrease in the levels of plasma iron binding capacity, serum total protein, albumin/globulin ratio, heart K(+) and heart glycogen. The levels/concentrations of glycoproteins in serum and the heart were increased in myocardial infarcted rats. Myocardial infarcted rats also showed a significant increase in red blood cells, hemoglobin, packed cell volume, white blood cells, neutrophils, platelet count and fibrinogen level and a significant decrease in erythrocyte sedimentation rate, eosinophils, lymphocytes, bleeding, clotting and prothrombin time. Oral pretreatment with SACS (40 and 80 mg kg(-1)) daily for a period of 35 days showed a positive effect on all the biochemical parameters studied in ISO-induced rats. Thus, the study showed the protective effect of SACS on ISO-induced cardiotoxicity in male Wistar rats.

  13. Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE(2) and 8-iso-PGF(2alpha), in some isolated smooth muscle preparations.

    PubMed

    Sametz, W; Hennerbichler, S; Glaser, S; Wintersteiger, R; Juan, H

    2000-08-01

    We investigated the contracting actions of the isoprostanes (isoPs), 8-iso-prostaglandin (PG) F(2alpha) and 8-iso-PGE(2), in comparison to the effects of the thromboxane (TX) A(2)-mimetic U 46619 and the traditional prostaglandin PGE(2) in the isolated rat aorta, isolated rat gastric fundus and the isolated guinea-pig ileum. U 46619 and 8-iso-PGF(2alpha) caused contractions in the rat aorta and rat gastric fundus in a concentration-dependent manner, whereas these agonists showed no effects in the guinea-pig ileum. However, 8-iso-PGE(2) and PGE(2) caused contractions in all isolated organs used. The prostanoid TP-receptor antagonist SQ 29,548 (10 nM) significantly antagonized vasoconstrictions induced by the agonists used in the rat aorta. SQ 29,548 at a final concentration of 3 microM, but not at lower concentrations, significantly inhibited contractions induced by U 46619, 8-iso-PGF(2alpha) and 8-iso-PGE(2) in the rat fundus. Responses to PGE(2) were unchanged. The prostanoid EP(1)-receptor antagonist SC 51089 (3 microM) significantly inhibited contractions induced by 8-iso-PGE(2) and PGE(2) in the rat fundus and in the guinea-pig ileum. SC 51089 had no effect on responses to any of the agonists tested. Our results show that 8-iso-PGE(2), in contrast to 8-iso-PGF(2alpha), can also cause contractions by activation of the EP(1)-receptors in the rat gastric fundus and the guinea-pig ileum. The findings of the present study do not support the existence of a unique isoP-receptor in the tissues used.

  14. The effect of adrenergic agonists and antagonists on cysteine-proteinase inhibitor (cystatin) in rat saliva.

    PubMed

    Bedi, G S

    1991-01-01

    The effect of a number of adrenergic agonists and antagonists on the induction of rat salivary cystatin was investigated. A highly sensitive and specific radioimmunoassay was used to determine cystatin in rat whole saliva. Treatment for 10 consecutive days with a non-specific beta-adrenergic agonist isoproterenol, or the beta 1-adrenergic agonists dobutamine or methoxyphenamine, resulted in the induction of the salivary cystatin. Induction was also found in rats treated for 10 days with arterenol. Only trace quantities of cystatin could be detected in saliva of rats treated with the beta 2-adrenergic agonists terbutaline or salbutamol. When isoproterenol was injected concomitantly with the mixed beta-antagonist propranolol or the beta 1-adrenergic antagonists metaprolol, proctocol or atenolol the production of cystatin was totally suppressed. However, the beta 2-antagonist, ICI 118551, produced only a partial reduction in salivary cystatin induction elicited by isoproterenol. The findings suggest that the induction of salivary cystatin is regulated, in part, by beta 1-adrenergic receptor stimulation.

  15. Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study.

    PubMed

    Kannan, M Mari; Quine, S Darlin

    2011-05-20

    The present study was designed to evaluate the cardioprotective effects of ellagic acid against isoproterenol induced myocardial infarction in rats by studying electrocardiography, blood pressure, cardiac markers, lipid peroxidation, antioxidant defense system and histological changes. Male Wistar rats were treated orally with ellagic acid (7.5 and 15mg/kg) daily for a period of 10 days. After 10 days of pretreatment, isoproterenol (100mg/kg) was injected subcutaneously to rats at an interval of 24h for 2 days to induce myocardial infarction. Isoproterenol administered rats showed significant changes in the electrocardiogram pattern, arterial pressure, and heart rate. Isoproterenol-induced rats also showed significant (P<0.05) increase in the levels of serum troponin-I, creatine kinase, lactate dehydrogenase, C-reactive protein, plasma homocysteine, heart tissue thiobarbituric acid reactive substances and lipid hydro peroxides. The activities/levels of antioxidant system were decreased in isoproterenol-induced rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol induced rats. The oral pretreatment of ellagic acid restored the pathological electrocardiographic patterns, regulated the arterial blood pressures and heart rate in the isoproterenol induced myocardial infarcted rats. The ellagic acid pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and significantly increased the activities/levels of the antioxidant system in the isoproterenol induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in ellagic acid pretreated isoproterenol induced rats. Our study shows that oral pretreatment of ellagic acid prevents isoproterenol induced oxidative stress in myocardial infarction.

  16. Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

    PubMed Central

    Ghule, Arvindkumar E.; Kulkarni, Chetan P.; Bodhankar, Subhash L.; Pandit, Vijaya A.

    2009-01-01

    Background: Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions. Objective: The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats. Methods: Albino male Wistar rats (250–300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9–18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician. Results: A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly

  17. Recombinant Atrial Natriuretic Peptide Prevents Aberrant Ca2+ Leakage through the Ryanodine Receptor by Suppressing Mitochondrial Reactive Oxygen Species Production Induced by Isoproterenol in Failing Cardiomyocytes

    PubMed Central

    Susa, Takehisa; Nanno, Takuma; Ishiguchi, Hironori; Myoren, Takeki; Nishimura, Shigehiko; Kato, Takayoshi; Hino, Akihiro; Oda, Tetsuro; Okuda, Shinichi; Yamamoto, Takeshi; Yano, Masafumi

    2016-01-01

    Catecholamines induce intracellular reactive oxygen species (ROS), thus enhancing diastolic Ca2+ leakage through the ryanodine receptor during heart failure (HF). However, little is known regarding the effect of atrial natriuretic peptide (ANP) on ROS generation and Ca2+ handling in failing cardiomyocytes. The aim of the present study was to clarify the mechanism by which an exogenous ANP exerts cardioprotective effects during HF. Cardiomyocytes were isolated from the left ventricles of a canine tachycardia-induced HF model and sham-operated vehicle controls. The degree of mitochondrial oxidized DNA was evaluated by double immunohistochemical (IHC) staining using an anti-VDAC antibody for the mitochondria and an anti-8-hydroxy-2′-deoxyguanosine antibody for oxidized DNA. The effect of ANP on ROS was investigated using 2,7-dichlorofluorescin diacetate, diastolic Ca2+ sparks assessed by confocal microscopy using Fluo 4-AM, and the survival rate of myocytes after 48 h. The double IHC study revealed that isoproterenol (ISO) markedly increased oxidized DNA in the mitochondria in HF and that the ISO-induced DNA damage was markedly inhibited by the co-presence of ANP. ROS production and Ca2+ spark frequency (CaSF) were increased in HF compared to normal controls, and were further increased in the presence of ISO. Notably, ANP significantly suppressed both ISO-induced ROS and CaSF without changing sarcoplasmic reticulum Ca2+ content in HF (p<0.01, respectively). The survival rate after 48 h in HF was significantly decreased in the presence of ISO compared with baseline (p<0.01), whereas it was significantly improved by the co-presence of ANP (p<0.01). Together, our results suggest that ANP strongly suppresses ISO-induced mitochondrial ROS generation, which might correct aberrant diastolic Ca2+ sparks, eventually contributing to the improvement of cardiomyocyte survival in HF. PMID:27657534

  18. Thymol attenuates inflammation in isoproterenol induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines.

    PubMed

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

    2015-05-05

    Inflammation plays an important role in the development of myocardial infarction (MI). The current study dealt with the protective effects of thymol on inflammation in isoproterenol (ISO) induced myocardial infarcted rats. Male albino Wistar rats were pre and co-treated with thymol (7.5mg/kg body weight) daily for 7 days. ISO (100mg/kg body weight) was injected subcutaneously into rats at an interval of 24h for two days (6th and 7th day) to induce MI. ISO induced myocardial infarcted rats showed increased levels of serum cardiac troponin-T, high sensitive C-reactive protein (hsCRP), lysosomal thiobarbituric acid reactive substances (TBARS) and elevated ST-segments. Also, the activities of lysosomal enzymes such as β-glucuronidase, β-galactosidase, cathepsin-B and D, the stimulators of inflammatory mediators were increased in the serum and heart of ISO induced myocardial infarcted rats. Furthermore, ISO up regulates the expressions of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) genes in the myocardium of rats analyzed by reverse transcription polymerase chain reaction (RT-PCR). Pre and co-treatment with thymol (7.5mg/kg body weight) near normalized the levels of lysosomal TBARS, activities of serum and heart lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines in the myocardium of ISO induced myocardial infarcted rats. Histopathological and transmission electron microscopic findings were also found in line with biochemical findings. Thus, the results of our study revealed that thymol attenuates inflammation by inhibiting the release of lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines by its potent anti-inflammatory effect.

  19. Early results from ISO

    NASA Astrophysics Data System (ADS)

    1996-01-01

    First findings by Europe's new space telescope ISO (Infrared Space Observatory) will be announced at a press conference to be held at ESA's satellite tracking station in Villafranca, Apartado 50727 - 28080-Madrid, on Wednesday 14 February 1996 Astronomers responsible for ISO's instruments will show results ranging from materials in the planet Saturn, through the birth and death of stars, to the behaviour of colliding galaxies. All instruments are working well and even their preliminary results confirm that ISO is a unique observatory making an unprecedented exploration of the universe by infrared rays. Parallel press conferences will be held at ESA Headquarters in Paris, ESTEC Noordwijk (the Netherlands) and ESOC Darmstadt (Germany) where a live television link will be established with Villafranca and from where the media can participate in the discussion.

  20. Isoproterenol-Induced Myocardial Injury and Diastolic Dysfunction in Mice: Structural and Functional Correlates

    PubMed Central

    Brooks, Wesley W; Conrad, Chester H

    2009-01-01

    The objective of this study was to determine whether a simple, noninvasive method involving administration of isoproterenol could be used to produce myocardial injury and cardiac dysfunction in the mouse heart with a low incidence of mortality. Adult Swiss–Webster mice were injected with isoproterenol (100 mg/kg SC) once daily for 5 d. Myocardial histology and left ventricular (LV) function were assessed 10 to 14 d after the last isoproterenol injection in 14 surviving isoproterenol-treated mice and 15 saline-treated control mice. Left ventricular systolic and diastolic pressures were evaluated in vitro by means of isovolumically contracting, perfused Langendorff preparations. Isoproterenol induced marked endocardial injury, associated with hypertrophy of surviving myocytes, and an increase in myocardial fibrosis (collagen types I and III according to picrosirius red microscopy). The hearts from isoproterenol-treated mice demonstrated decreased LV compliance, as evidenced by an upward shift in the diastolic pressure–volume relationship, with normal LV systolic function. Isoproterenol administration provides a simple, noninvasive means to induce endocardial injury and diastolic dysfunction without significant impairment of systolic function. This model has a low incidence of mortality and may be useful to assess the effects of gene or stem cell therapy on cardiac dysfunction without the potential confounding effects of invasive procedures. PMID:19712573

  1. Basic mechanism leading to stimulation of glycogenolysis by isoproterenol, EGF, elevated extracellular K+ concentrations, or GABA.

    PubMed

    Xu, Junnan; Song, Dan; Bai, Qiufang; Cai, Liping; Hertz, Leif; Peng, Liang

    2014-04-01

    Glycogenolysis, in brain parenchyma an astrocyte-specific process, has changed from being envisaged as an emergency procedure to playing central roles during brain response to whisker stimulation, memory formation, astrocytic K(+) uptake and stimulated release of ATP. It is activated by several transmitters and by even very small increases in extracellular K(+) concentration, and to be critically dependent upon an increase in free cytosolic Ca(2+) concentration ([Ca(2+)]i), whereas cAMP plays only a facilitatory role together with increased [Ca(2+)]i. Detailed knowledge about the signaling pathways eliciting glycogenolysis is therefore of interest and was investigated in the present study in well differentiated cultures of mouse astrocytes. The β-adrenergic agonist isoproterenol stimulated glycogenolysis by a β1-adrenergic effect, which initiated a pathway in which cAMP/protein kinase A activated a Gi/Gs shift, leading to Ca(2+)-activated glycogenolysis. Inhibition of this pathway downstream of cAMP but upstream of the Gi/Gs shift abolished the glycogenolysis. However, inhibitors operating downstream of the Ca(2+)-sensitive step, but preventing transactivation-mediated epidermal growth factor (EGF) receptor stimulation, a later step in the activated pathway, also caused inhibition of glycogenolysis. For this reason the effect of EGF was investigated and it was found to be glycogenolytic. Large increases in extracellular K(+) activated glycogenolysis by a nifedipine-inhibited L-channel opening allowing influx of Ca(2+), known to be glycogenolysis-dependent. Small increases (addition of 5 mM KCl) caused a smaller effect by a similarly glycogenolysis-reliant opening of an IP3 receptor-dependent ouabain signaling pathway. The same pathway could be activated by GABA (also in brain slices) due to its depolarizing effect in astrocytes.

  2. 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.

  3. 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.

  4. ISO successfully launched

    NASA Astrophysics Data System (ADS)

    1995-11-01

    ISO is a high-technology telescope facility designed and built in Europe for use by the scientific community in Europe, Japan and the USA. It will provide astronomers with an unprecedented opportunity - the only one in the next decade - to make scientific observations of a wide variety of weak infrared radiation sources such as cold gases, galaxies and stars dying and being born. ISO represents a leap forward in space technology harnessed for astronomical observation of the universe. ISO is the world's first astronomical observatory in space operating at infrared wavelengths. To observe the weakest heat sources in the universe, its four scientific instruments have to be cooled to extremely low temperatures, using superfluid helium which evaporates slowly at minus 271 or about 2 degrees above absolute zero. The scientific instruments, telescope and liquid helium are all contained in a cryostat, which has been likened to an extraordinarily well insulated thermos flask. It is the first such cryogenically cooled satellite developed in Europe and employs very advanced technologies, notably for the scientific instruments, telescope and attitude control system. ISO will be controlled from the ESA's Space Operations Centre (ESOC) in Darmstadt, Germany, for the first few days, until the final orbit is achieved, and then operational control will be passed to a dedicated ESA operations centre in Villafranca, Spain. The first 21/2 months of operations will be given over to commissioning the satellite and verifying the performance of the scientific instruments. The observation programme is planned to start in early February 1996. ISO's lifetime is expected to be 20 months, by the end of which the helium, steadily evaporating as it cools the cryostat, should be exhausted.

  5. 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.

  6. Testis dysfunction by isoproterenol is mediated by upregulating endothelin receptor A, leptin and protein kinase Cvarepsilon and is attenuated by an endothelin receptor antagonist CPU0213.

    PubMed

    Cheng, Yu-Si; Dai, De-Zai; Dai, Yin

    2010-07-01

    This study has examined whether upregulation of endothelin receptor A, leptin and phosphorylated protein kinase Cvarepsilon contributes to stress-induced testicular damaged and its possible reversal by endothelial (ET) antagonism. Adult male Sprague-Dawley rats were randomly divided into control and isoproterenol (ISO 1mg/kg, subcutaneous (s.c.), 10 days) groups, and intervened with the ET receptor antagonist CPU0213 (20mg/kg, s.c.), on days 6-10. In ISO group, testicular succinate dehydrogenase, lactate dehydrogenase, acid phosphotase, and gamma-glutamyl transpeptidase, and serum testosterone decreased, whereas FSH increased, relative to control. The seminiferous tubules were damaged in association with testicular upregulation of protein abundance of leptin and pPKCvarepsilon, and mRNA and protein expression of leptin receptor (OBRb) and ET(A). CPU0213 was effective in ameliorating these abnormalities. Over-expression of ET(A) and leptin accounting for the testis dysfunction is likely to be mediated by pPKCvarepsilon in the ISO treated rats. The upregulated ET pathway appears to be critical in pathologies of the testis.

  7. Accreditation - ISO/IEC 17025

    NASA Astrophysics Data System (ADS)

    Kaus, Rüdiger

    This chapter gives the background on the accreditation of testing and calibration laboratories according to ISO/IEC 17025 and sets out the requirements of this international standard. ISO 15189 describes similar requirements especially tailored for medical laboratories. Because of these similarities ISO 15189 is not separately mentioned throughout this lecture.

  8. Iso-glucuronides.

    PubMed

    Dickinson, Ronald G

    2011-03-01

    This review on isomers or acyl glucuronides (iso-glucuronides) updates earlier reviews, and attempts to place in context the advances that have been made, especially over the last 15 years. The essential chemistry behind the intramolecular acyl migration and anomerization reactions of acyl glucuronides has been appreciated for 30 years. The great advances in the past 15 years have been in understanding the dynamics and kinetics of these processes in vitro, using highly sophisticated modern technology, e.g. LC-NMR, LC-MS/MS. In this way, earlier assumptions on kinetics and identification of migration isomers and anomers have come under intense review and update. Extensive structure-activity relationships, involving electronic and steric characteristics of an acyl glucuronide and its possible 7 isomers (excluding transient open-chain species) have been delineated. The covalent modification of endogenous proteins and other macromolecules has been further explored, though direct linkage between such modification and toxic sequelae remains elusive. An alternative view of acyl glucuronides and iso-glucuronides as just xenobiotics has perhaps added the dimension that acyl glucuronidation (and attendant formation of iso-glucuronides) does not necessarily mean that glucuronidation of the aglycone has ended metabolic sequences in vivo.

  9. ISO 14000 environmental management standard

    SciTech Connect

    Block, M.R.

    1995-12-01

    National standards organizations around the world are developing an environmental management standard to help organizations address significant environmental aspects of their activities. This standard, designated ISO 14000, will provide guidance for environmental management systems: environmental audits: Environmental performance evaluation: Environmental labeling and life-cycle assessment. The environmental management system specification, the lynch-pin of ISO 14000, will be published as an international standard in early 1996. Audit documents will follow shortly thereafter. Although conformance to ISO 14000 will be voluntary, US multinational companies are likely to discover that failure to participate creates trade barriers in Europe. The Environmental Commission created by NAFTA also is considering whether to make adherence to ISO 14000 a condition of trade. This presentation will provide an understanding of the ISO process to create the standard, key elements of ISO 14000, and implications for US companies. Such an understanding will enable organizations to determine whether adoption of ISO 14000 is strategically sound.

  10. Effects of β-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis.

    PubMed

    van der Drift, S G A; Everts, R R; Houweling, M; van Leengoed, L A M G; Stegeman, J A; Tielens, A G M; Jorritsma, R

    2013-06-01

    An in vitro model was used to investigate effects of β-hydroxybutyrate and isoproterenol (β-adrenergic receptor agonist) on lipolysis in isolated adipocytes from late pregnant and recently calved dairy cows (n=5) and cows with clinical ketosis (n=3). Incubation with 3.0 mmol/L β-hydroxybutyrate reduced lipolysis in isolated adipocytes. This inhibitory effect was lower in the first lactation week (47%±16%) compared with late pregnancy (71%±6.5%). Incubation with 0.3 μmol/L isoproterenol stimulated lipolysis in isolated adipocytes from periparturient dairy cows. Basal lipolysis resulted in non-esterified fatty acid to glycerol ratios in the incubation media of 2.0±0.23 in prepartum samples, 2.1±0.23 in the first lactation week and 2.2±0.09 in cows with clinical ketosis. β-Hydroxybutyrate reduced lipolysis by 45%±9.6% in isolated adipocytes from cows with clinical ketosis, indicating that impaired feedback of β-hydroxybutyrate may not play a role in the disease etiology.

  11. Functional receptor coupling to Gi is a mechanism of agonist-promoted desensitization of the beta2-adrenergic receptor.

    PubMed

    Tepe, N M; Liggett, S B

    2000-01-01

    The beta2-adrenergic receptor (beta2AR) couples to Gs activating adenylyl cyclase (AC) and increasing cAMP. Such signaling undergoes desensitization with continued agonist exposure. Beta2AR also couple to Gi after receptor phosphorylation by the cAMP dependent protein kinase A, but the efficiency of such coupling is not known. Given the PKA dependence of beta2AR-Gi coupling, we explored whether this may be a mechanism of agonist-promoted desensitization. HEK293 cells were transfected to express beta2AR or beta2AR and Gialpha2, and then treated with vehicle or the agonist isoproterenol to evoke agonist-promoted beta2AR desensitization. Membrane AC activities showed that Gialpha2 overexpression decreased basal levels, but the fold-stimulation of the AC over basal by agonist was not altered. However, with treatment of the cells with isoproterenol prior to membrane preparation, a marked decrease in agonist-stimulated AC was observed with the cells overexpressing Gialpha2. In the absence of such overexpression, beta2AR desensitization was 23+/-7%, while with 5-fold Gialpha2 overexpression desensitization was 58+/-5% (p<0.01, n=4). The effect of Gi on desensitization was receptor-specific, in that forskolin responses were not altered by G(i)alpha2 overexpression. Thus, acquired beta2AR coupling to Gi is an important mechanism of agonist-promoted desensitization, and pathologic conditions that increase Gi levels contribute to beta2AR dysfunction.

  12. The role of cytochrome P450 1B1 and its associated mid-chain hydroxyeicosatetraenoic acid metabolites in the development of cardiac hypertrophy induced by isoproterenol.

    PubMed

    Maayah, Zaid H; Althurwi, Hassan N; El-Sherbeni, Ahmed A; Abdelhamid, Ghada; Siraki, Arno G; El-Kadi, Ayman O S

    2017-03-01

    Numerous experimental studies have demonstrated the role of cytochrome P450 1B1 (CYP1B1) and its associated mid-chain hydroxyeicosatetraenoic acids (mid-chain HETEs) metabolite in the pathogenesis of cardiac hypertrophy. However, the ability of isoproterenol (ISO) to induce cardiac hypertrophy through mid-chain HETEs has not been investigated yet. Therefore, we hypothesized that ISO induces cardiac hypertrophy through the induction of CYP1B1 and its associated mid-chain HETE metabolites. To test our hypothesis, Sprague-Dawley rats were treated with ISO (5 mg/kg i.p.) for 12 and 72 h whereas, human ventricular cardiomyocytes RL-14 cells were exposed to 100 μM ISO in the presence and absence of 0.5 μM tetramethoxystilbene (TMS) a selective CYP1B1 inhibitor, or 25 nM CYP1B1-siRNA. Moreover, RL-14 cells were transiently transfected with the CRISPR-CYP1B1 plasmid. Thereafter, real-time PCR, western blot analysis, and liquid chromatography-electrospray ionization mass spectroscopy were used to determine the level of gene expression, protein expression, and mid-chain HETEs, respectively. Our results showed that ISO induced CYP1B1 protein expression and the level of cardiac mid-chain HETEs in vivo at pre-hypertrophic and hypertrophic stage. In vitro, inhibition of CYP1B1 using TMS or CYP1B1-siRNA significantly attenuates ISO-induced hypertrophy. Furthermore, overexpression of CYP1B1 significantly induced cellular hypertrophy and mid-chain HETEs metabolite. Mechanistically, the protective effect of TMS against cardiac hypertrophy was mediated through the modulation of superoxide anion, mitogen-activated protein kinases (MAPKs), and nuclear factor-κB (NF-κB). In conclusion, our study provides the first evidence that CYP1B1 and its associated mid-chain HETE metabolites are directly involved in the ISO-induced cardiac hypertrophy.

  13. 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

  14. 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.

  15. 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.

  16. The pharmacology of epanolol (ICI 141292)--a new beta 1-selective adrenoceptor partial agonist.

    PubMed

    Bilski, A J; Hadfield, S E; Wale, J L

    1988-08-01

    The clinical benefit of beta-adrenoceptor partial agonists is still debated. To clarify the situation, epanolol, ICI 141,292 [N-[-2-(3-o-cyanophenoxy-2-hydroxypropylamino)ethyl]-4- hydroxyphenylactamide], has been developed to assess the role of modest beta-adrenoceptor partial agonist activity in humans. Animal studies have shown that epanolol is a potent beta-adrenoceptor partial agonist with a greater affinity for beta 1- than beta 2-adrenoceptors. In vitro, the PA2 values obtained for espanolol at atrial and tracheal beta-adrenoceptors were 8.42 and 6.33, respectively (isoproterenol as agonist), giving a selectivity ratio of 123. The potency was studied in vivo in the dog, where it was also shown that as an antagonist at the cardiac beta 1-adrenoceptor, it was 18 and 40 times more potent than atenolol and practolol, respectively. Espanolol has less partial agonist activity in the rat than pindolol, but more than practolol. In this species, it is also a classical partial agonist, exhibiting agonist activity at all beta-adrenoceptor blocking doses. This is in contrast to pindolol, which caused predominantly beta-adrenoceptor blockade at low doses and partial agonist activity at higher doses. These differences were confirmed in haemodynamic studies in the dog. In contrast to many other partial agonists, the partition coefficient, log P, of epanolol in octanol and water is low (0.92).

  17. The ISO Michelson

    NASA Astrophysics Data System (ADS)

    Wijnbergen, J. J.; Aalders, J. W. G.; Ploeger, G.; Helmerhorst, Th. J.

    Design work performed in order to prove the feasibility of the instrumentation intended for carriage on the IR space observatory (ISO) is described. The ISO has a 60 cm telescope with a prism at the focus to direct IR light onto one of four instruments. Pointing accuracy is projected to be 10 arcsec and a lifetime of 1.5 yr is planned. A near-IR camera will record data in the 2.5 micron wavelength range, the 2-25 micron band will be covered by two Michelson interferometers with a resolving power of 1:10,000, and a three or four band photometer featuring small detector arrays will be included. Attention has focused on the drive and suspension of the movable mirror, allowing 30 mm movement, and optical step size of 316 mm with 4 mm accuracy, a travel velocity of 125-315 microns/sec, a maximum beam size of 10 mm, and a FOV of 0.5-1 arcmin. An electromagnetic drive was selected, as were the vibration compensator, a double bridge movable base, and the materials.

  18. 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.

  19. 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

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

    PubMed

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

    2013-04-01

    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.

  1. Age, colors and ISO standards

    NASA Astrophysics Data System (ADS)

    van Nes, Floris L.

    2010-01-01

    Age influences all bodily functions, also vision. Therefore, the effects of age on vision should be mirrored in ergonomic requirements laid down in display standards such as ISO 9241-300/307, 'Electronic visual display requirements'. However, this is only true to a limited extent - just as is the case with other standards dealing with ergonomic requirements, because developers of such standards do not possess the necessary specific knowledge. It therefore was an important step by ISO and IEC to publish in 2001 ISO/IEC Guide 71: 'Guidelines for standard developers to address the needs of older persons and persons with disabilities'. This guide was followed by a more specific and detailed Technical Report from ISO, ISO/TR 22411, as well as by 'Guidelines on Accessibility' from CIE. These three guidelines are reviewed. The paper concludes with developments around ISO 9241-300/307 in general, especially future additions on autostereoscopic displays and electronic paper. As to the former, the visual fatigue often accompanying viewing 3D displays needs methods for characterizing and validating such displays, to reduce visual fatigue as much as possible. Standardizing certain properties of electronic paper is an example of the present pro-active way of working of ISO/TC159/SC4/WG2, 'Visual Display Requirements', that developed ISO 9241-300/307.

  2. 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)

  3. 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)

  4. [Effect of isoproterenol on contractility of the heart papillary muscles of a ground squirrel].

    PubMed

    Averin, A S; Zakharova, N M; Ignat'ev, D A; Tarlachkov, S V; Nakipova, O V

    2010-01-01

    The effect of isoproterenol (1 microM) on the force of isometric contractions (0.1-1.0 Hz, 30 +/- 1 degree C, 1.8 mM Ca2+) of papillary muscles of the right ventricle of the heart of the ground squirrel during summer activity (n = 5) and hibernation (activity between hibernation bouts, n = 4; torpor, n = 4; and arousal, n = 5) has been studied. It was shown that isoproterenol increases the force of contraction (positive inotropic effect) in active summer ground squirrels by 20 +/- 3 and 61 +/- 7% at stimulation frequencies of 0.4 and 1.0 Hz, respectively. The isoproterenol-induced increase in the force of contraction in animals during hibernation is brief (within 3 min after the onset of treatment) and this parameter decreases by 30-50% of the control level (negative inotropic effect) at stimulation frequencies from 0.3 and 0.8 Hz. The positive inotropic effect of isoproterenol in active summer ground squirrels is associated with a decrease in the relative value of the potentiating effect of the pause (qualitative indicator of calcium content in the sarcoplasmic reticulum), and the negative inotropic effect, with its increase. It was found that the inotropic effect of isoproterenol in all groups of animals examined (irrespective of its direction) is accompanied by an acceleration of the velocity of the contraction-relaxation cycle. The dependence of the effect of isoproterenol in the heart of hibernating animals on seasonal changes in the calcium homeostasis and the activity of the sympathetic nervous system is discussed.

  5. 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.

  6. Catestatin (chromogranin A344-364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart.

    PubMed

    Mazza, Rosa; Gattuso, Alfonsina; Mannarino, Cinzia; Brar, Bhawanjit K; Barbieri, Sandra Francesca; Tota, Bruno; Mahata, Sushil K

    2008-07-01

    The catecholamine release-inhibitory catestatin [Cts; human chromogranin (Cg) A(352-372), bovine CgA(344-364)] is a vasoreactive and anti-hypertensive peptide derived from CgA. Using the isolated avascular frog heart as a bioassay, in which the interactions between the endocardial endothelium and the subjacent myocardium can be studied without the confounding effects of the vascular endothelium, we tested the direct cardiotropic effects of bovine Cts and its interaction with beta-adrenergic (isoproterenol, ISO) and endothelin-1 (ET-1) signaling. Cts dose-dependently decreased stroke volume and stroke work, with a threshold concentration of 11 nM, approaching the in vivo level of the peptide. Cts reduced contractility by inhibiting phosphorylation of phospholamban (PLN). Furthermore, the Cts effect was abolished by pretreatment with either nitric oxide synthase (N(G)-monomethyl-l-arginine) or guanylate cyclase (ODQ) inhibitors, or an ET(B) receptor (ET(BR)) antagonist (BQ-788). Cts also noncompetitively inhibited the positive inotropic action of ISO. In addition, Cts inhibited the positive inotropic effect of ET-1, mediated by ET(A) receptors, and did not alter the negative inotropic ET-1 influence mediated by ET(BR). Cts action through ET(BR) was further suggested when, in the presence of BQ-788, Cts failed to inhibit the positive inotropism of both ISO and ET-1 stimulation and PLN phosphorylation. We concluded that the cardiotropic actions of Cts, including the beta-adrenergic and ET-1 antagonistic effects, support a novel role of this peptide as an autocrine-paracrine modulator of cardiac function, particularly when the stressed heart becomes a preferential target of both adrenergic and ET-1 stimuli.

  7. ISO Spectroscopy of Titan

    NASA Astrophysics Data System (ADS)

    Coustenis, A.; Salama, A.; Lellouch, E.; Encrenaz, Th.; Schulz, B.; Feuchtgruber, H.; Gautier, D.; Ott, S.; de Graauw, Th.; Kessler, M. F.

    2000-11-01

    In the spectroscopic mode, Titan was observed by ISO in 1997 by SWS/Grating, PHT-S and CAM/CVF. The combination of these data provides Titan's spectrum from 5 to 17 and from 2.5 to 5 μm with resolving powers ranging from 40 (CAM/CVF) to 2000 (SWS). The analysis of the spectra provides information on (a) Titan's atmospheric structure (temperature and composition) and (b) Titan's surface (through the emission observed in the 2.9-micron window). In this paper we concentrate on the 7 to 9 and 2.5 to 5 micron regions. A temperature profile for Titan's disk is inferred from the analysis of the 7.7 μm CH4 band. The CH3D abundance is estimated to be 7.5 (+4.0-3.7) × 10-6, for a D/H ratio of 9.5 (+9.5-1.0) × 10-5. The 2.9 methane ``window'' on Titan is observed in its full shape for the first time. It shows two peaks at 2.7 and 2.8 μm, and an absorption feature at 2.75 μm, which may be the spectral signature of a surface component on Titan.

  8. ISO observations of asteroids

    NASA Astrophysics Data System (ADS)

    Dotto, E.; Barucci, M. A.; Crovisier, J.; Doressoundiram, A.; Encrenaz, Th.; Fulchignoni, M.; Knacke, R.; Lellouch, E.; Morris, P. W.; Müller, T. G.; Owen, T.

    1999-03-01

    Asteroids were observed by ISO with several instruments (PHT-P, PHT-S and SWS). The aim of these observations was to investigate the asteroid physical and compositional properties. Sixteen asteroids have been observed by PHT-P and PHT-S: with PHT-P we obtained the observations at filters 3.6, 10, 11.5, 25, and 60 μm for 10 asteroids and only at filters 3.6 and 10 μm for the other 6 objects. With PHT-S we obtained simultaneously the 2.5-5 and 5.8-11.6 μm spectral ranges. Four of these asteroids have been also observed with SWS between 5.3 and 45 μm. The first analysis of the obtained spectra has shown some features which suggest the presence of oxides (e.g. magnetite, hematite, etc.) among the surface materials of 10 Hygiea and 308 Polyxo, indicating aqueous alteration on the surfaces of these objects.

  9. The effect of thymoquinone, an active component of Nigella sativa, on isoproterenol induced myocardial injury.

    PubMed

    Randhawa, Mohammad Akram; Alghamdi, Mastour Safar; Maulik, Subir Kumar

    2013-11-01

    Myocardial injury constitutes a major cause of morbidity and mortality in humans. Present study aimed to investigate protective role of thymoquinone, which is an active principle of Nigella sativa (N. sativa) seed (Commonly called as black seed), in isoproterenol induced myocardial injury, a classical example of excess catecholamines related coronary insufficiency and stress cardiomyopathy. Thymoquinone, in olive oil, was administered orally (12.5, 25 and 50mg/kg) to three groups of Wistar albino rats for 7 days, while two control groups were given plain olive oil. Thereafter, thymoquinone receiving groups and one control group were injected, subcutaneously, with isoproterenol (125mg/kg) for 2 days. Myocardial injury was assessed by biochemical markers (plasma LDH, TBARS, GR & SOD and myocardial GSH/GSSG ratio) and cardiac histopathology. Plasma LDH, TBARS and GR increased in control groups receiving isoproterenol, while there was a dose related decrease in these markers in thymoquinone treated groups, down to levels in controls given olive oil only. Decrease in plasma SOD and myocardial GSH/GSSG ratio and histological changes produced with isoproternol were also reversed in thymoquinone treated rats. Results of our study revealed that thymoquinone protects the heart from injury induced by isoproterenol.

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

    PubMed Central

    James, D E; Hiken, J; Lawrence, J C

    1989-01-01

    We have examined the acute effects 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 fractions of 32P-labeled fat cells and subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The 32P-labeled IRGT was detected by autoradiography as a species of apparent Mr 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 subcellular 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-32P]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. Images PMID:2554313

  11. Protective effects of sinapic acid on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats.

    PubMed

    Roy, Subhro Jyoti; Stanely Mainzen Prince, Ponnian

    2012-11-01

    In the pathology of myocardial infarction, lysosomal lipid peroxidation and resulting enzyme release play an important role. We evaluated the protective effects of sinapic acid on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats. Male Wistar rats were treated with sinapic acid (12 mg/kg body weight) orally daily for 10 days and isoproterenol (100 mg/kg body weight) was injected twice at an interval of 24 h (9th and 10th day). Then, lysosomal lipid peroxidation, lysosomal enzymes in serum, heart homogenate, lysosomal fraction and myocardial infarct size were measured. Isoproterenol induced myocardial infarcted rats showed a significant increase in serum creatine kinase-MB and lysosomal lipid peroxidation. The activities of β-glucuronidase, β-galactosidase, cathepsin-B and D were significantly increased in serum, heart and the activities of β-glucuronidase and cathepsin-D were significantly decreased in lysosomal fraction of myocardial infarcted rats. Pre-and-co-treatment with sinapic acid normalized all the biochemical parameters and reduced myocardial infarct size in myocardial infarcted rats. In vitro studies confirmed the free radical scavenging effects of sinapic acid. The possible mechanisms for the observed effects are attributed to sinapic acid's free radical scavenging and membrane stabilizing properties. Thus, sinapic acid has protective effects on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats.

  12. 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.

  13. The promise of the ISO

    SciTech Connect

    Santa, D.F. Jr.

    1996-03-01

    Both the electric power industry and the public policy debate about restructuring it have evolved significantly since FERC issued its open access NOPR. One major development is the degree to which the concept of an independent system operator (ISO) has taken hold in the industry. This concept is the central feature in several major utility initiatives across the United States. This article reviews the pros and cons of the ISO concept.

  14. Regulation of isoproterenol-induced salivary gland hyperplasia in young and old mice by substances affecting serotoninergic and dopaminergic systems

    SciTech Connect

    Dontsov, V.I.

    1986-09-01

    This paper studies the effect of substances modulating serotoninergic and dopaminergic structures on induction of hyperplasia of the salivary glands by isoproterenol in young and old mice. /sup 3/H-thymidine was injected into the gland tissue in the experiments. The effect of serotonin and dopamine on isoproterenol-induced proliferation of salivary gland cells and number of activated splenic lymphocytes in old mice is shown. It is found that excitation of serotoninergic structures inhibits, whereas excitation of dopaminergic structures stimulates the response of mice to isoproterenol.

  15. Integrated management system: The integration of ISO 9001, ISO 14001, OHSAS 18001 and ISO 31000

    NASA Astrophysics Data System (ADS)

    Muzaimi, Hafizzudin; Chew, Boon Cheong; Hamid, Syaiful Rizal

    2017-03-01

    The implementation of integrated management system (IMS) for better quality management has become a preference for many organizations. This can be seen as many organizations used the combination of quality ISO 9001, an environment ISO 14001 and occupational health and safety management system OHSAS 18001 as a core for the IMS that largely implemented. Besides, the linked between quality management with risk management system need to be identified as the management system that enhance the effectiveness of IMS. Therefore, the risk management system ISO 31000 also presented as a part of integration. In nowadays competitive environment, the increasing pressure and needs from customer or stakeholders make it compulsory for the organization to propose the new system and standards. This paper presents and discusses about the benefit of integration, the management system components that can be converged and the implementation approach. A series of interview was conducted through in-depth interviews with 8 experts in this field, while data collected were analyzed qualitatively. The results consist of 16 factors of IMS implementation that have been identified and the use of PDCA approach for an effective implementation of IMS. As a conclusion, the paper proposes the integration of four management systems (ISO 9001, ISO 14001, OHSAS 18001 and ISO 31000) and on how the IMS can be used to structure the process of management for quality management towards sustainability practices in the organization.

  16. The β2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis.

    PubMed

    Wills, Lauren P; Trager, Richard E; Beeson, Gyda C; Lindsey, Christopher C; Peterson, Yuri K; Beeson, Craig C; Schnellmann, Rick G

    2012-07-01

    Mitochondrial dysfunction is a common mediator of disease and organ injury. Although recent studies show that inducing mitochondrial biogenesis (MB) stimulates cell repair and regeneration, only a limited number of chemicals are known to induce MB. To examine the impact of the β-adrenoceptor (β-AR) signaling pathway on MB, primary renal proximal tubule cells (RPTC) and adult feline cardiomyocytes were exposed for 24 h to multiple β-AR agonists: isoproterenol (nonselective β-AR agonist), (±)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy] acetic acid sodium hydrate (BRL 37344) (selective β(3)-AR agonist), and formoterol (selective β(2)-AR agonist). The Seahorse Biosciences (North Billerica, MA) extracellular flux analyzer was used to quantify carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled oxygen consumption rate (OCR), a marker of maximal electron transport chain activity. Isoproterenol and BRL 37244 did not alter mitochondrial respiration at any of the concentrations examined. Formoterol exposure resulted in increases in both FCCP-uncoupled OCR and mitochondrial DNA (mtDNA) copy number. The effect of formoterol on OCR in RPTC was inhibited by the β-AR antagonist propranolol and the β(2)-AR inverse agonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol hydrochloride (ICI-118,551). Mice exposed to formoterol for 24 or 72 h exhibited increases in kidney and heart mtDNA copy number, peroxisome proliferator-activated receptor γ coactivator 1α, and multiple genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1β subcomplex subunit 8). Cheminformatic modeling, virtual chemical library screening, and experimental validation identified nisoxetine from the Sigma Library of Pharmacologically Active Compounds and two compounds from the ChemBridge DIVERSet

  17. The effects of 5-bromodeoxyuridine and isoproterenol on the postnatal differentiation of rat submandibular gland.

    PubMed

    Fukushima, M; Barka, T

    1976-10-01

    The effects of 5-bromodeoxyuridine (BrdU) on the postnatal differentiation of rat submandibular gland and on the isoproterenol-induced changes of differentiation were studied. The rats were injected with BrdU for three consecutive days, beginning at two days of age. The total dose of BrdU was 0.9 mg/g body weight. BrdU caused a severe retardation of growth up to 15 days of age. A rapid growth of the animals between 15 and 22 days indicated a recovery from the effect of BrdU. The growth of the submandibular gland was retarded similarly with a corresponding decrease in DNA, RNA and protein content. Incorporation of tritiated thymidine into the submandibular gland was not altered in the BrdU-treated animals at one and three days after the last injection of the analog. At days 15 and 22 the rate of thymidine incorporation was greater in the submandibular gland of BrdU-treated rats as compared to littermate controls. Isoproterenol stimulated thymidine incorporation into the submandibular glands of two-week-old rats. This stimulation was not observed in rats which received BrdU at age 7-9 days, prior to the administration of isoproterenol. Election microscopic observations, including a quantitative analysis of the frequency distribution of the various cell types in the terminal tubules and developing acini, indicated a retardation of acinar cell differentiation in the glands of BrdU-treated rats. In addition, there was an increase in the number and size of the secretory granules in the terminal tubule cells. BrdU treatment, however, caused no obvious pathologic alterations in the submandibular gland. Administration of isoproterenol for five days, beginning at five days of age, caused an apparent acceleration of the differentiation of acinar cells. In the glands of isoproterenol-treated rats the acinar cells were enlarged and were filled with homogeneous secretory granules. Pretreatment with BrdU partially inhibited the effects of isoproterenol on differentiation and

  18. [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.

  19. Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2 pathway.

    PubMed

    Zhou, Ru; Xu, Qingbin; Xu, Yehua; Xiong, Aiqin; Wang, Yang; Ma, Ping

    2016-12-01

    Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2 pathway.

  20. Neuroglobin protects cardiomyocytes against apoptosis and cardiac hypertrophy induced by isoproterenol in rats

    PubMed Central

    Liu, Zhen-Fang; Zhang, Xiao; Qiao, Yan-Xiang; Xu, Wan-Qun; Ma, Cheng-Tai; Gu, Hua-Li; Zhou, Xiu-Mei; Shi, Lei; Cui, Chang-Xing; Xia, Di; Chen, Yu-Guo

    2015-01-01

    Neuroglobin (Ngb) is well known as a physiological role in oxygen homeostasis of neurons and perhaps a protective role against hypoxia and oxidative stress. In this study, we found that Ngb is expressed in rat heart tissues and it is related to isoproterenol induced cardiac hypertrophy. Moreover, overexpression or knock-down of Ngb influences the expression of hypertrophic markers ANP and BNP and the ratio of hypertrophic cells in rat H9c2 myoblasts when isoproterenol treatment. The Annexin V-FITC/PI Staining, Western blot and qPCR analysis showed that the involvement in p53-mediated apoptosis of cardiomyocytes of Ngb is might be the mechanism. This protein could prevent the cells against ROS and POS-induced apoptosis not only in nervous systems but also in cardiomyocytes. From the results, it is concluded that Ngb is a promising protectant in the cardiac hypertrophy, it may be a candidate target to cardiac hypertrophy for clinic treatment. PMID:26131111

  1. Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats.

    PubMed

    Lobo, Reema Orison; Shenoy, Chandrakala K

    2015-07-01

    Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed.

  2. 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.

  3. Serum Biomarkers Reveal Long-term Cardiac Injury in Isoproterenol-treated African Green Monkeys

    PubMed Central

    Liu, Yashu; Parman, Toufan; Schneider, Bridget; Song, Benben; Galande, Amit; Anderson, Dave; Mirsalis, Jon

    2013-01-01

    The assessment of cardiac toxicity is a major challenge in both drug development and clinical trials, and numerous marketed pharmaceuticals have been removed from the market due to unpredicted cardiac effects. Serum troponins are widely-used indicators of cardiac injury; however, they are short-lived, and have not been validated in preclinical animal models. In this study, we have used filter-aided sample preparation (FASP) and tandem mass tag (TMT) labeling to investigate serum protein alterations in isoproterenol-treated African green monkeys. Our results showed that the combination of FASP and TMT labeling provided highly reproducible and efficient sample preparation, which enables us to identify and quantify serum proteins with high confidence. We focused on the proteins that exhibit long-term alteration upon isoproterenol injection and discovered nine proteins exhibiting significant changes at 48 and 72 hr post-dosing. We further chose three proteins, serum amyloid A (SAA), frutose biphosphate aldolase A (FBAA), and fetuin A, for validation using enzyme-linked immunosorbent assay (ELISA). The serum concentration of SAA showed a ~50 fold increase, while concentration of FBAA and fetuin A exhibited a significant decrease accompanying isoproterenol-induced cardiotoxicity. This work provides valuable insights for multi-marker evaluation of long-term cardiac injury. PMID:23473367

  4. 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

  5. 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…

  6. Analysis of full and partial agonists binding to beta2-adrenergic receptor suggests a role of transmembrane helix V in agonist-specific conformational changes.

    PubMed

    Katritch, Vsevolod; Reynolds, Kimberly A; Cherezov, Vadim; Hanson, Michael A; Roth, Christopher B; Yeager, Mark; Abagyan, Ruben

    2009-01-01

    The 2.4 A crystal structure of the beta(2)-adrenergic receptor (beta(2)AR) in complex with the high-affinity inverse agonist (-)-carazolol provides a detailed structural framework for the analysis of ligand recognition by adrenergic receptors. Insights into agonist binding and the corresponding conformational changes triggering G-protein coupled receptor (GPCR) activation mechanism are of special interest. Here we show that while the carazolol pocket captured in the beta(2)AR crystal structure accommodates (-)-isoproterenol and other agonists without steric clashes, a finite movement of the flexible extracellular part of TM-V helix (TM-Ve) obtained by receptor optimization in the presence of docked ligand can further improve the calculated binding affinities for agonist compounds. Tilting of TM-Ve towards the receptor axis provides a more complete description of polar receptor-ligand interactions for full and partial agonists, by enabling optimal engagement of agonists with two experimentally identified anchor sites, formed by Asp113/Asn312 and Ser203/Ser204/Ser207 side chains. Further, receptor models incorporating a flexible TM-V backbone allow reliable prediction of binding affinities for a set of diverse ligands, suggesting potential utility of this approach to design of effective and subtype-specific agonists for adrenergic receptors. Systematic differences in capacity of partial, full and inverse agonists to induce TM-V helix tilt in the beta(2)AR model suggest potential role of TM-V as a conformational "rheostat" involved in the whole spectrum of beta(2)AR responses to small molecule signals.

  7. 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

  8. DNA duplex stability of the thio-iso-guanine•methyl-iso-Cytosine base pair.

    PubMed

    Lee, Dongkye; Switzer, Christopher

    2015-01-01

    We report the synthesis, incorporation into oligonucleotides, and base-pairing properties of the 2-thio-variant of iso-guanine. Iso-guanine is the purine component of a nonstandard base pair with 5-methyl-iso-cytosine. The 2-thio-iso-guanine • 5-methyl-iso-cytosine base pair is found to have similar stability to an adenine • thymine pair.

  9. 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.

  10. ISO: highlights of recent results

    NASA Astrophysics Data System (ADS)

    Metcalfe, L.; Salama, A.

    ESA's Infrared Space Observatory (ISO) mission, operating in the wavelength range from 2.5 to 240 microns, made over 26000 scientific observations during its 2.5 year operational lifetime. ISO's results broke new ground on all scales. New asteroid counts and improved asteroid thermophysical models augmented important advances in Solar System chemistry to comprise a striking body of results addressing our planetary system. In turn, parallels between the chemical composition of Solar System dust and dust around other stars revealed by the comparison of stellar spectra with cometary spectra, together with results on the incidence and stability of stellar disks, recall the birth of our Solar System and point to fundamental similarities with other star systems. Numerous important facts concerning the chemistry of the ISM have unfolded, such as the ubiquity of water and of the probably-organic carriers of the Unidentified Infrared Bands (UIBs). The large systematic body of data on galactic stars has permitted fascinating advances in the characterisation of important aspects of stellar evolution. Investigations of nearby normal galaxies complement template specimens of interacting galaxies. These in turn exemplify galaxy evolutionary processes in the early Universe associated with a huge burst of dust-obscured star formation at redshifts of just below one. This global surge of star formation has vital implications for the interpretation and explanation of major components of the Extragalactic Background Light (EBL) and for charting the global history of star formation and the relative importance of sources which derive their energy from accretion processes. Representative examples of key aspects of ISO's recent scientific output will be presented, once again affirming ISO's place at the forefront of successful space-borne astronomy missions.

  11. 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...

  12. Dietary palm olein oil augments cardiac antioxidant enzymes and protects against isoproterenol-induced myocardial necrosis in rats.

    PubMed

    Narang, D; Sood, S; Thomas, M; Dinda, A K; Maulik, S K

    2005-11-01

    Wistar rats, 150-200 g, of either sex, were fed daily with commercial rat diet supplemented with palm olein oil in two doses (5% v/w (n = 16) and 10% v/w (n = 16) of diet) for 30 days. Control rats (n = 16) were fed with normal diet. On the 29(th) and 30(th) days, 8 rats from each group were administred isoproterenol (85 mg/kg, s.c., 24-h interval). On the 31(st) day, all rats were sacrificed and myocardial tissues were studied for thiobarbituric acid reactive substances (TBARS), antioxidant enzymes and light microscopic changes, along with the ferric-reducing ability of plasma (FRAP). A significant rise in myocardial superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity and FRAP level were observed in rats fed with palm olein oil. Isoproterenol caused an increase in myocardial oxidative stress in control rats, as evidenced by an increase in myocardial TBARS level, reduction in FRAP and myocardial SOD, catalase and GPx activity, along with focal necrosis of cardiac muscle fibres on light microscopy. The rise in myocardial TBARS and depletion of SOD and catalase activity following isoproterenol administration were prevented in palm-olein-oil-supplemented diet-fed rats at both doses. Isoproterenol-induced myocardial light-microscopic changes were also prevented in the treated groups. The results suggest that dietary palm olein oil caused augmentation of myocardial antioxidant enzymes and protected against isoproterenol-induced myocardial necrosis and associated oxidative stress.

  13. 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.

  14. CRM 1-mediated degradation and agonist-induced down-regulation of beta-adrenergic receptor mRNAs.

    PubMed

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

    2006-10-01

    The beta1-adrenergic receptor (beta1-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 beta1-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 beta1-ARs in the brain, results in significant decreases in beta1-AR mRNA stability, while treatment with leptomycin B, an inhibitor of the nuclear export receptor CRM 1, results in significant increases in beta1-AR mRNA stability and nuclear retention. UV-crosslinking/immunoprecipitation and glycerol gradient fractionation analyses indicate that the beta1-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 beta1-AR mRNA levels. Our results suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation and agonist-mediated down-regulation of the beta1-AR mRNAs.

  15. DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States

    PubMed Central

    Chen, Haodong; Orozco, Luz; Wang, Jessica; Rau, Christoph D.; Rubbi, Liudmilla; Ren, Shuxun; Wang, Yibin; Pellegrini, Matteo; Lusis, Aldons J.; Vondriska, Thomas M.

    2016-01-01

    Rationale Only a small portion of the known heritability of cardiovascular diseases such as heart failure can be explained based on single gene mutations. Chromatin structure and regulation provide a substrate through which genetic differences in non-coding regions may impact cellular function and response to disease, but the mechanisms are unknown. Objective We conducted genome-wide measurements of DNA methylation in different strains of mice that are susceptible and resistant to isoproterenol-induced dysfunction to test the hypothesis that this epigenetic mark may play a causal role in the development of heart failure. Methods and Results BALB/cJ and BUB/BnJ mice, determined to be susceptible and resistant to isoproterenol-induced heart failure respectively, were administered the drug for 3 weeks via osmotic minipump. Reduced representational bisulfite sequencing was then used to compare the differences between the cardiac DNA methylome in the basal state between strains and then following isoproterenol treatment. Single base resolution DNA methylation measurements were obtained and revealed a bimodal distribution of methylation in the heart, enriched in lone intergenic CpGs and depleted from CpG islands around genes. Isoproterenol induced global decreases in methylation in both strains; however, the basal methylation pattern between strains shows striking differences that may be predictive of disease progression prior to environmental stress. The global correlation between promoter methylation and gene expression (as measured by microarray) was modest and revealed itself only with focused analyses of transcription start site and gene body regions (in contrast to when gene methylation was examined in toto). Modules of co-methylated genes displayed correlation with other protein-based epigenetic marks supporting the hypothesis that chromatin modifications act in a combinatorial manner to specify transcriptional phenotypes in the heart. Conclusions This study

  16. 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.

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

    PubMed

    Upaganlawar, A; Balaraman, R

    2011-10-01

    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 29(th) and 30(th) 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.

  18. [Melatonin receptor agonist].

    PubMed

    Uchiyama, Makoto

    2015-06-01

    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  19. Desensitization of the insulin receptor by antireceptor antibodies in vivo is blocked by treatment of mice with beta-adrenergic agonists.

    PubMed

    Elias, D; Rapoport, M; Cohen, I R; Shechter, Y

    1988-06-01

    In previous studies we reported that immunization of mice with ungulate insulins induced the development of antiinsulin antibodies, which include an idiotype that appeared to recognize the part of the insulin molecule recognized by the hormone receptor. The antiinsulin antibodies of this idiotype were replaced spontaneously by antiidiotypic antibodies. The antiidiotypic antibodies, which persisted for about 14 d, mimicked insulin and functioned as antibodies to the insulin receptor. They induced down regulation, desensitization and refractoriness of the insulin receptor and disturbances in glucose homeostasis in vivo (Shechter, Y., D. Elias, R. Maron, and I.R. Cohen., 1984; Elias, D., R. Maron, I.R. Cohen, and Y. Shechter. 1984, J. Biol. Chem. 259: 6411-6419). We now report that effects of the antiidiotypic antibodies on the insulin receptor effector system can be modified pharmacologically. Administration of the beta-adrenergic agonist isoproterenol during the period of insulin resistance (days 26-40 after primary immunization), largely restored fat cell responsiveness to insulin, and eliminated the appearance of fasting hyperglycemia. This restoration appeared to be caused by inhibition of both insulin receptor desensitization and refractoriness. In contrast, down regulation of insulin receptors was not reversed by isoproterenol treatment in vivo. The effects of treatment with isoproterenol persisted for 2-4 d after termination of treatment. The beta-antagonist, propranolol and more so, the beta 1a-antagonist metoprolol, specifically blocked the effect of isoproterenol at a molar ratio of 3-10:1. Oral administration of the cAMP phosphodiesterase inhibitor, aminophylline, was also effective in inhibiting the development of desensitization in fat cells. These results indicate that treatment with beta 1-adrenergic agonists in vivo, or other agents that elevate cellular cAMP levels, can inhibit the development of the "postbinding" defects induced by insulin

  20. 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

  1. Myoglobin-deficient mice activate a distinct cardiac gene expression program in response to isoproterenol-induced hypertrophy.

    PubMed

    Molojavyi, Andrei; Lindecke, Antje; Raupach, Annika; Moellendorf, Sarah; Köhrer, Karl; Gödecke, Axel

    2010-04-01

    Myoglobin knockout mice (myo-/-) adapt to the loss of myoglobin by the activation of a variety of compensatory mechanisms acting on the structural and functional level. To analyze to what extent myo-/- mice would tolerate cardiac stress we used the model of chronic isoproterenol application to induce cardiac hypertrophy in myo-/- mice and wild-type (WT) controls. After 14 days of isoproterenol infusion cardiac hypertrophy in WT and myo-/- mice reached a similar level. WT mice developed lung edema and left ventricular dilatation suggesting the development of heart failure. In contrast, myo-/- mice displayed conserved cardiac function and no signs of left ventricular dilatation. Analysis of the cardiac gene expression profiles using 40K mouse oligonucleotide arrays showed that isoproterenol affected the expression of 180 genes in WT but only 92 genes of myo-/- hearts. Only 40 of these genes were regulated in WT as well as in myo-/- hearts. In WT hearts a pronounced induction of genes of the extracellular matrix occurred suggesting a higher level of cardiac remodeling. myo-/- hearts showed altered transcription of genes involved in carbon metabolism, inhibition of apoptosis and muscular repair. Interestingly, a subset of genes that was altered in myo-/- mice already under basal conditions was differentially expressed in WT hearts under isoproterenol treatment. In summary, our data show a high capacity of myoglobin-deficient mice to adapt to catecholamine induced cardiac stress which is associated with activation of a distinct cardiac gene expression program.

  2. 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)

  3. Protective Effect of Adansonia digitata against Isoproterenol-Induced Myocardial Injury in Rats.

    PubMed

    Ghoneim, Mona A M; Hassan, Amal I; Mahmoud, Manal G; Asker, Mohsen S

    2016-01-01

    The baobab fruit (Adansonia digitata) was analyzed for proximate composition, amino acids, and minerals. The fruit pulp was found to be a good source of carbohydrates, proteins, phenols, and substantial quantities of K, Ca, and Mg. Amino acid analyses revealed high glutamic and aspartic acid, but the sulfur amino acids were the most limited. The present study was designed to investigate the role of Adansonia digitata (Baobab fruit pulp) against isoproterenol induced myocardial oxidative stress in experimental rats by demonstrating the changes in tissue cardiac markers, some antioxidant enzymes, interleukin-1 β (IL-1 β), monocyte chemoattractant protein-1(MCP-1), myeloperoxidase (MPO), Collagen-1, galectin-3, and serum corticosterone. The activities of enzymatic antioxidant glutathione peroxidase (GPX) and non-enzymatic antioxidant reduced glutathione (GSH) in the heart tissue; additionally, histopathological examination of the heart was estimated. Male albino rats were randomly divided into four groups of ten animals each. Group I served as normal control animal. Group II animals received isoproterenol (ISP) (85 mg/kg body weight intraperitonealy (i.p.) to develop myocardial injury. Group III were myocardial oxidative animals treated with Baobab fruit pulp (200 µg/rats/day) for 4 weeks. Group IV received Baobab fruit pulp only. The data suggested an isoproterenol increase in levels of cardiac marker enzymes [creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)], IL-1ß, MCP-1, MPO, Collagen, and galectin-3, with concomitant decrease in the activities GPX and GSH in heart tissue as well as corticosterone in serum. Baobab fruit pulp brings all the parameters to near normal level in ISP-induced myocardial infarction in rats. Histopathological examination of heart tissue of ISP-administered model rat showed infiltration of inflammatory cells and congestion in the blood vessels. However, treatment with Baobab fruit pulp (200

  4. 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)

  5. 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…

  6. Lesions of the commissural subnucleus of the nucleus of the solitary tract increase isoproterenol-induced water intake.

    PubMed

    Blanch, G T; Freiria-Oliveira, A H; Colombari, E; Menani, J V; Colombari, D S A

    2007-08-01

    The nucleus of the solitary tract (NTS) is the primary site of the cardiovascular afferent information about arterial blood pressure and volume. The NTS projects to areas in the central nervous system involved in cardiovascular regulation and hydroelectrolyte balance, such as the anteroventral third ventricle region and the lateral parabrachial nucleus. The aim of the present study was to investigate the effects of electrolytic lesion of the commissural NTS on water and 0.3 M NaCl intake and the cardiovascular responses to subcutaneous injection of isoproterenol. Male Holtzman rats weighing 280 to 320 g were submitted to sham lesion or electrolytic lesion of the commissural NTS (N = 6-15/group). The sham-lesioned rats had the electrode placed along the same coordinates, except that no current was passed. Water intake induced by subcutaneous isoproterenol (30 microg/kg body weight) significantly increased in chronic (15 days) commissural NTS-lesioned rats (to 2.4 +/- 0.2 vs sham: 1.9 +/- 0.2 mL 100 g body weight-1 60 min-1). Isoproterenol did not induce any sodium intake in sham or in commissural NTS-lesioned rats. The isoproterenol-induced hypotension (sham: -27 +/- 4 vs commissural NTS-lesioned rats: -22 +/- 4 mmHg/20 min) and tachycardia (sham: 168 +/- 10 vs commissural NTS: 144 +/- 24 bpm/20 min) were not different between groups. The present results suggest that the commissural NTS is part of an inhibitory neural pathway involved in the control of water intake induced by subcutaneous isoproterenol, and that the overdrinking observed in lesioned rats is not the result of a cardiovascular imbalance in these animals.

  7. Department of Defense Quality Management Systems and ISO 9000:2000

    DTIC Science & Technology

    2002-03-01

    ISO /TS 16949 :1999, Quality systems - Automotive suppliers - Particular requirements for the application of ISO 9001 :1994...9000:1994 Family, [After Ref. 3]. ..................................70 Table 4. ISO 9001 :2000 to ISO 9001 :1994, [From Ref. 55...certification" means certification against ISO 9001 , ISO 9002 or ISO 9003 (1994 version) or ISO 9001 and 9004 (2000 version). The generic term " ISO

  8. Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum- and glucocorticoid-regulated kinase type 1.

    PubMed

    Martín-Fernández, Beatriz; de las Heras, Natalia; Miana, María; Ballesteros, Sandra; Valero-Muñoz, María; Vassallo, Dalton; Davel, Ana Paula; Rossoni, Luciana Venturini; Cachofeiro, Victoria; Lahera, Vicente

    2012-06-01

    Persistent β-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg(-1) day(-1)) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg(-1) day(-1)). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor β, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor α, interleukin 1β, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.

  9. The effects of posture and isoproterenol on the velocity of left ventricular contraction in man

    PubMed Central

    Paley, H. W.; McDonald, Ian G.; Blumenthal, Joseph; Mailhot, James; Modin, Gunnard W.

    1971-01-01

    A study was performed in five normal men in whom left ventricular volume was measured by thermodilution in the supine and 60° head-up postures, in the control state, and then during steady-state response to isoproterenol. The mean rate of circumferential shortening of the left ventricle was calculated for each of the postures in both inotropic states and was found to remain constant in the control state at 12.5 ±0.6 cm/sec in the supine posture and 13.3 ±0.5 cm/sec in the tilted posture. Similarly, mean rate of circumferential shortening remained constant in response to the positive inotropic effect of isoproterenol at 20.9 ±0.5 cm/sec in the supine position and 20.7 ±0.5 cm/sec in the tilted posture. It is concluded that the constancy of mean rate of circumferential shortening over the relatively broad physiologic range of left ventricular end-diastolic volume and mean force of ejection during a given state of myocardial contractility represents the coupled reciprocal influences of ventricular wall tension and myocardial fiber length on the velocity of ventricular wall shortening. Unlike stroke work, stroke power, and mean rate of left ventricular ejection, which are volume-dependent parameters of myocardial performance, the mean rate of circumferential shortening appears to be a reasonable index of left ventricular contractility, which in steady-state conditions is independent of left ventricular end-diastolic volume and mean ventricular wall force of ejection. In this study, changes in mean rate of circumferential shortening associated with changes of heart rate were small and variable. PMID:4938131

  10. Marked increases in mucociliary clearance produced by synergistic secretory agonists or inhibition of the epithelial sodium channel

    PubMed Central

    Joo, Nam Soo; Jeong, Jin Hyeok; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca2+-activated chloride channels mediate anion/fluid secretion. MCCV was increased by the cAMP-elevating agonists, forskolin or isoproterenol (10 μM) and by the Ca2+-elevating agonist, carbachol (0.3 μM). The CFTR-selective inhibitor, CFTRinh-172, modestly reduced MCCV-increases induced by forskolin or isoproterenol but not increases induced by carbachol. The ENaC inhibitor benzamil increased basal MCCV as well as MCCV increases produced by forskolin or carbachol. MCC velocity was most dramatically accelerated by the synergistic combination of forskolin and carbachol, which produced near-maximal clearance rates regardless of prior treatment with CFTR or ENaC inhibitors. In CF airways, where CFTR-mediated secretion (and possibly synergistic MCC) is lost, ENaC inhibition via exogenous agents may provide therapeutic benefit, as has long been proposed. PMID:27830759

  11. Melatonin agonists and insomnia.

    PubMed

    Ferguson, Sally A; Rajaratnam, Shantha M W; Dawson, Drew

    2010-02-01

    The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here - ramelteon, tasimelteon and agomelatine - all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the agonists requires a good understanding of their phase-dependent properties. Long-term effects of melatonin should be evaluated in large-scale, independent randomized controlled trials.

  12. 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. PMID:27713285

  13. 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.

  14. 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.

  15. 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 ...

  16. The practical application of ISO 22301.

    PubMed

    Zawada, Brian

    2014-01-01

    As well as providing a brief background of ISO 22301, this paper describes three practical uses of the standard, as well as ways to use the content to solve common challenges that business continuity professionals face every day.

  17. Implement an ISO 14001 environmental management system

    SciTech Connect

    Schiffman, R.I.; Delaney, B.T.; Fleming, S.; Hamilton, E.

    1997-11-01

    The ISO 14001 Environmental Management System (EMS) standard brings environmental concerns into the mainstream of business operations by providing a framework for balancing and integrating environmental and economic interests. ISO 14001 requires that an organization develop an environmental management program that describes all of its environmental objectives and targets and how each will be achieved. The program must include a specific plan that details the actions required to meet each objective and target, the person(s) responsible for meeting each objective, and a time scale for when each target will be attained. Objectives and targets can be prioritized within the program, but all objectives must be included. This article outlines the benefits of developing an EMS, explains the ISO 14001 EMS standard, and provides detailed step-by-step guidance on what to do to become ISO 14001 certified.

  18. 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

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

    PubMed

    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 100μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study (0.5mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48h. 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 70kD 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.

  20. Cardioprotective effect of Sida rhomboidea. Roxb extract against isoproterenol induced myocardial necrosis in rats.

    PubMed

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Ansarullah; Karn, Sanjay S; Shah, Jigar D; Patel, Dipak K; Salunke, Sunita P; Padate, Geeta S; Devkar, Ranjitsinh V; Ramachandran, A V

    2011-05-01

    The present study investigates cardioprotective effect of Sida rhomboidea. Roxb (SR) extract on heart weight, plasma lipid profile, plasma marker enzymes, lipid peroxidation, endogenous enzymatic and non-enzymatic antioxidants and membrane bound ATPases against isoproterenol (IP) induced myocardial necrosis (MN) in rats. Rats treated with IP (85 mg/kg, s.c.) recorded significant (p<0.05) increment in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation (LPO) and activity levels of Ca(+2) ATPase whereas there was significant (p<0.05) decrease in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na(+)-K(+) ATPase and Mg(+2) ATPase. Pre-treatment with SR extract (400 mg/kg per day, p.o.) for 30 consecutive days followed by IP injections on days 29th and 30th, showed significant (p<0.05) decrease in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation, Ca(+2) ATPase and significant increase in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na(+)-K(+) ATPase and Mg(+2) ATPase compared to IP treated group. Hence, this study is the first scientific report on cardioprotective effect of SR against IP induced MN in rats.

  1. TA-2005, a novel, long-acting, and selective beta 2-adrenoceptor agonist: characterization of its in vivo bronchodilating action in guinea pigs and cats in comparison with other beta 2-agonists.

    PubMed

    Kikkawa, H; Kanno, K; Ikezawa, K

    1994-08-01

    Relaxant effects of the beta 2-selective adrenoceptor agonist TA-2005 on bronchoconstriction in the anesthetized guinea pig and cat were evaluated in comparison with other known beta 2-adrenoceptor agonists. The ED50 values of intravenously administered TA-2005, procaterol, formoterol, isoproterenol, salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00 micrograms/kg, respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039, 0.042, 0.13, and 0.52 micrograms/kg, respectively, in the same increasing order. When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0 micrograms/kg, i.v., respectively, while those of TA-2005, procaterol, formoterol, and salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0 micrograms/kg. When TA-2005 was administered by inhalation to guinea pigs or by the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect comparable or superior to the effects of salmeterol and formoterol. These data indicate that, among the known beta 2-adrenoceptor agonists examined, TA-2005 exerts the most potent bronchodilating effects with a long duration of action in vivo, and its potency ratios to the other reference drugs were greater in antigen- than spasmogen-induced bronchoconstriction models.

  2. 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…

  3. Molecular actions of two synthetic brassinosteroids, iso-carbaBL and 6-deoxoBL, which cause altered physiological activities between Arabidopsis and rice

    PubMed Central

    Fujioka, Shozo; Ito, Shinsaku; Kigawa, Takanori; Shimada, Yukihisa; Matsuoka, Makoto; Yoshida, Shigeo; Kinoshita, Toshinori; Asami, Tadao; Seto, Hideharu; Nakano, Takeshi

    2017-01-01

    Brassinosteroid (BR) is an important plant hormone that is perceived by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor. BRI1 is conserved among dicot and monocot species; however, the molecular mechanism underlying BR perception in monocots is not fully understood. We synthesised two BRs, iso-carbabrassinolide (iso-carbaBL) and 6-deoxoBL, which have different BR activities in Arabidopsis thaliana (Arabidopsis) and rice. Our bioassay indicated that iso-carbaBL has relatively strong BR activity in Arabidopsis, but is inactive in rice and competitively inhibits BR activity. The bioactivity of 6-deoxoBL was similar to that of BL in Arabidopsis, but was much lower in rice. Binding experiments using recombinant Arabidopsis and rice BRI1 protein fragments suggested that iso-carbaBL and 6-deoxoBL bind to both receptors. These results showed that iso-carbaBL and 6-deoxoBL act as an antagonist and agonist, respectively, of BRs in rice. A docking simulation analysis suggested that iso-carbaBL fits deeper in the binding pocket to block the binding of active BR to rice BRI1. The simulated binding energy of 6-deoxoBL with rice BRI1 is much lower than that with Arabidopsis BRI1. The possible structural characteristics of rice BRI1 were determined based on the difference in the BR activities of iso-carbaBL and 6-deoxoBL in Arabidopsis and rice. PMID:28369122

  4. Molecular actions of two synthetic brassinosteroids, iso-carbaBL and 6-deoxoBL, which cause altered physiological activities between Arabidopsis and rice.

    PubMed

    Nakamura, Ayako; Tochio, Naoya; Fujioka, Shozo; Ito, Shinsaku; Kigawa, Takanori; Shimada, Yukihisa; Matsuoka, Makoto; Yoshida, Shigeo; Kinoshita, Toshinori; Asami, Tadao; Seto, Hideharu; Nakano, Takeshi

    2017-01-01

    Brassinosteroid (BR) is an important plant hormone that is perceived by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor. BRI1 is conserved among dicot and monocot species; however, the molecular mechanism underlying BR perception in monocots is not fully understood. We synthesised two BRs, iso-carbabrassinolide (iso-carbaBL) and 6-deoxoBL, which have different BR activities in Arabidopsis thaliana (Arabidopsis) and rice. Our bioassay indicated that iso-carbaBL has relatively strong BR activity in Arabidopsis, but is inactive in rice and competitively inhibits BR activity. The bioactivity of 6-deoxoBL was similar to that of BL in Arabidopsis, but was much lower in rice. Binding experiments using recombinant Arabidopsis and rice BRI1 protein fragments suggested that iso-carbaBL and 6-deoxoBL bind to both receptors. These results showed that iso-carbaBL and 6-deoxoBL act as an antagonist and agonist, respectively, of BRs in rice. A docking simulation analysis suggested that iso-carbaBL fits deeper in the binding pocket to block the binding of active BR to rice BRI1. The simulated binding energy of 6-deoxoBL with rice BRI1 is much lower than that with Arabidopsis BRI1. The possible structural characteristics of rice BRI1 were determined based on the difference in the BR activities of iso-carbaBL and 6-deoxoBL in Arabidopsis and rice.

  5. ISO-PLM test evaluation with THERMOPT

    NASA Astrophysics Data System (ADS)

    Sander, Martin

    1991-12-01

    In 1990 the STM (Structural/Thermal Model) of the ISO PLM (Infrared Space Observatory PayLoad Module) underwent testing in laboratory and thermal vacuum environment, with both tests ending in steady state conditions. Work performed in the PLM thermal model in order to correlate its results to the test data measured is reported. The (newly developed) optimizer program THERMOPT was used to help the adjusting. The program and its interface to the ESA Thermal Analysis Network (ESATAN) model of ISO are described and the findings after a set of 39 optimizer runs are given. Having used a reduced ESATAN model for this part of work the correlation results were introduced into the big ISO thermal model and the new lifetime was assessed to a value of approximately 664 days, well beyond the 548 days required.

  6. 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.

  7. Protective effect of Emblica officinalis (amla) on isoproterenol-induced cardiotoxicity in rats.

    PubMed

    Ojha, Shreesh; Golechha, Mahaveer; Kumari, Santosh; Arya, Dharamvir Singh

    2012-06-01

    Emblica officinalis, commonly known as amla, is an important medicinal plant reputed for its dietary and therapeutic uses. The aim of the present study was to investigate the protective role of E. officinalis against isoproterenol (ISP)-induced cardiotoxicity in rats and elucidate the possible mechanism involved. Rats were administered E. officinalis (100, 250 and 500 mg/kg, p.o.) or vehicle (normal saline) for 30 days, with concurrent subcutaneous injections of ISP (85 mg/kg, at 24 h interval) on 29th and 30th day. ISP-induced cardiac dysfunction as evidenced by decreased mean arterial pressure, heart rate, contractility (+LVdP/dt) and relaxation (-LVdP/dt) along with increased left ventricular end diastolic pressure. ISP significantly (p < 0.05) decreased antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase and myocyte-injury-specific marker enzymes, creatine phosphokinase-MB and lactate dehydrogenase in heart. A significant (p < 0.05) depletion of reduced glutathione and increase in thiobarbituric acid reactive substances along with histopathological alteration has further indicated the oxidative damage of myocardium. However, pretreatment with E. officinalis exhibited restoration of hemodynamic and left ventricular function along with significant preservation of antioxidants, myocytes-injury-specific marker enzymes and significant inhibition of lipid peroxidation. Furthermore, histopathological salvage of myocardium reconfirmed the protective effects of E. officinalis. Results of the present study demonstrate cardioprotective potential of E. officinalis attributed to its potent antioxidant and free radical scavenging activity as evidenced by favorable improvement in hemodynamic, contractile function and tissue antioxidant status.

  8. [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.

  9. 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.

  10. ISO 14000: Where to from here?

    SciTech Connect

    Martin, R.; Sleeman, S.

    1997-05-01

    Achieving acceptable environmental performance by a firm requires a commitment to a systemic approach to environmental management. The leading drivers today in this effort are represented by emergent environmental management systems (EMS) standards such as ISO 14000. While ISO 14000 represents the current trend in environmental management, it is only the beginning of a more fully realized management approach to environmental concerns. The concept of Strategic Environmental Management (SEM) incorporates EMS elements, but also extends to capture additional leading edge accounting indices such as full costs accounting, activity-based costing, and other methods of identifying and effectively managing the costs to the company of their environmental aspects. ISO 14000 is an evolving series of generic standards developed to provide business management with the structure for managing varied environmental concerns and impacts. The standards include a broad range of environmental concerns and impacts. The standards include a broad range of environmental disciplines, including a basic management system, auditing, performance evaluation, product labeling, and life-cycle assessment. The paper discusses the ISO 14001 certification process, what gets certified, and the self-audit versus third-party audit.

  11. The Technical Communicator and ISO 9000.

    ERIC Educational Resources Information Center

    Weiss, Edmond H.

    1993-01-01

    Describes the complexities of ISO 9000, a set of generic quality standards to which any commercial firm wishing to do business with a member firm of the European Economic Community will have to comply. Describes opportunities for professional technical communicators in providing the required product documentation. (SR)

  12. 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.

  13. 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.

  14. 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

  15. Agonist-activated ion channels

    PubMed Central

    Colquhoun, David

    2006-01-01

    This paper looks at ion channels as an example of the pharmacologist's stock in trade, the action of an agonist on a receptor to produce a response. Looked at in this way, ion channels have been helpful because they are still the only system which is simple enough for quantitative investigation of transduction mechanisms. A short history is given of attempts to elucidate what happens between the time when agonist first binds, and the time when the channel opens. PMID:16402101

  16. Involvement of tyrosine residues located in the carboxyl tail of the human beta 2-adrenergic receptor in agonist-induced down-regulation of the receptor.

    PubMed Central

    Valiquette, M; Bonin, H; Hnatowich, M; Caron, M G; Lefkowitz, R J; Bouvier, M

    1990-01-01

    Chronic exposure of various cell types to adrenergic agonists leads to a decrease in cell surface beta 2-adrenergic receptor (beta 2AR) number. Sequestration of the receptor away from the cell surface as well as a down-regulation of the total number of cellular receptors are believed to contribute to this agonist-mediated regulation of receptor number. However, the molecular mechanisms underlying these phenomena are not well characterized. Recently, tyrosine residues located in the cytoplasmic tails of several membrane receptors, such as the low density lipoprotein and mannose-6-phosphate receptors, have been suggested as playing an important role in the agonist-induced internalization of these receptors. Accordingly, we assessed the potential role of two tyrosine residues in the carboxyl tail of the human beta 2AR in agonist-induced sequestration and down-regulation of the receptor. Tyr-350 and Tyr-354 of the human beta 2AR were replaced with alanine residues by site-directed mutagenesis and both wild-type and mutant beta 2AR were stably expressed in transformed Chinese hamster fibroblasts. The mutation dramatically decreased the ability of the beta 2AR to undergo isoproterenol-induced down-regulation. However, the substitution of Tyr-350 and Tyr-354 did not affect agonist-induced sequestration of the receptor. These results suggest that tyrosine residues in the cytoplasmic tail of human beta 2AR are crucial determinants involved in its down-regulation. PMID:2164220

  17. COMPARISON METHODOLOGIES FOR CALIBRATION OF Hp(10) PERSONAL DOSEMETERS USING ISO 4037 AND ISO 29661 STANDARDS.

    PubMed

    Cardoso, J; Santos, L; Carvalhal, G; Oliveira, C

    2016-09-01

    The calibration of electronic personal dosemeters at the Portuguese ionizing radiation metrology laboratory uses the standard IEC 61526 for calibration methodology. This standard describes the irradiation geometry for testing and indicates that the standard ISO 4037-1, 2, 3 and 4 should be used. The ISO 4037 establishes that the reference point of test is a point in the radiation monitor, known or established, and the calibration phantom should be placed on its back in order to simulate the trunk body. Recently, ISO published another standard, the ISO 29661, that changes the reference point from the radiation monitor to the front face of the calibration phantom. The aim of this work is to present the result of the comparison of these two methodologies on personal dosemeters from five different manufacturers. The work shows differences in the Hp(10) response up to 4% resulting from the two different reference point concepts.

  18. 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…

  19. 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.

  20. 40 CFR 721.10554 - Iso-tridecanol (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Iso-tridecanol (generic). 721.10554... Substances § 721.10554 Iso-tridecanol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as iso-tridecanol (PMN P-06-153) is subject...

  1. 40 CFR 721.10554 - Iso-tridecanol (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Iso-tridecanol (generic). 721.10554... Substances § 721.10554 Iso-tridecanol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as iso-tridecanol (PMN P-06-153) is subject...

  2. 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

  3. 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

  4. Atorvastatin reduces the myocardial content of coenzyme Q10 in isoproterenol-induced heart failure in rats.

    PubMed

    Andalib, S; Shayanfar, A; Khorrami, A; Maleki-Dijazi, N; Garjani, A

    2014-05-01

    The present study was aimed to study the effects of different doses of atorvastatin on Co Q10 content in the myocardium tissue in rats. A subcutaneous injection of isoproterenol (5 mg/kg/day) for 10 days was used for the induction of heart failure. Rats were randomly assigned to control, treatment with atorvastatin (5, 10, 20 mg/kg/day) and treatment with atorvastatin plus coenzyme Q10 (10 mg/kg/day). Coenzyme Q10 content of myocardium was measured using HPLC method with UV detector after hemodynamic parameters measurements. The malondialdehyde (MDA) content of the myocardium was evaluated in order to determine coenzyme Q10 antioxidative effect. A high dose of atorvastatin (20 mg/kg/day) was significantly reduced the myocardium content of coenzyme Q10 as compared with isoproterenol treated group (p<0.001). Compared with atorvastatin alone treated animals, co-administration of coenzyme Q10 with atorvastatin was improved the level of coenzyme Q10 in the myocardium (p<0.05, p<0.001). Increasing the dose of atorvastatin also led to increase in MDA content of the myocardium (p<0.01). Serum lipid profile showed no changes in atorvastatin treated groups. The results of this study demonstrate that high doses of atorvastatin reduce coenzyme Q10 content of the myocardium and increase lipid peroxidation in myocardium which is reversed by coenzyme Q10 co-administration.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

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

    PubMed

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

    2016-05-03

    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.

  13. (3H)-isoproterenol binding to subcellular fractions of mouse parotid: relationship to cyclic nucleotide formation and the stimulation of DNA synthesis.

    PubMed

    Durham, J P; Galanti, N

    1976-12-01

    (3H) Isoproterenol binding to subcellular fractions of mouse parotid: Relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (Unión the (3H) Isoproterenol a fracciones subcelulares de parótida de ratón y su relacón con la formacón de nucleótidos cíclicos y la estimulación de la síntesis de DNA). Arch. Biol. Med. Exper. 10: 105-114, 1976. Tritiated isoproterenol binds to all subcellular fractions of mouse parotid but 70% of the binding is to the nuclear fraction. Binding to other mouse tissues was less than to the parotid. The patterns of binding did not correlate with the distribution of adenylate cyclase, guanylate cyclase or catechol-O-methyl transferase among the fractions or tissues nor with the extent of response in stimulation of DNA synthesis among the tissues. Inhibition of (3H) Isoproterenol binding to parotid fractions by catecholamine analogs was studied. There was no correlation between their ability to inhibit binding and the ability of the analogs themselves to raise cyclic AMP levels or stimulate DNA synthesis.

  14. A graded approach to ISO 9000 implementation for records managers

    SciTech Connect

    Pasterczyk, C.E.

    1994-08-01

    ISO 9000 is a series of quality system standards developed by Technical Committee 176 of the International Standards Organization. The series includes three standards, ISO 9001 `Quality systems--Model for quality assurance in design/development, production, installation and serving,` ISO 9002 `Quality systems--Model for quality assurance in production and installation,` ISO 9003 `Quality systems--Model for quality assurance in final inspection and test,` and two guidelines, ISO 9000 `Quality management and quality assurance standards` and ISO 9004 `Quality management and quality system elements--Guidelines.` In companies with quality programs already in place, the structure of the ISO series lends itself to augmenting those policies, procedures, and instructions where problems exist or where the risks of failure are greater. The objectives of this paper are to provide a basic familiarity to ISO 9000 and quality assurance concepts; provide a higher level of familiarity to the records management and document control portions of the ISO 9000 series; and to discuss a graded approach to meeting the intent of ISO 9000.

  15. Dopamine agonist therapy in hyperprolactinemia.

    PubMed

    Webster, J

    1999-12-01

    Introduction of the dopamine agonist bromocriptine heralded a major advance in the management of hyperprolactinemic disorders. Although its side effects of nausea, dizziness and headache and its short elimination half-life are limiting factors, its efficacy established it as a reference compound against the activity of which several dopamine agonists, like pergolide, lysuride, metergoline, terguride and dihydroergocristine, fell by the wayside. More recently, two new agents, cabergoline and quinagolide, have been introduced and appear to offer considerable advantages over bromocriptine. Cabergoline, an ergoline D2 agonist, has a long plasma half-life that enables once- or twice-weekly administration. Quinagolide, in contrast, is a nonergot D2 agonist with an elimination half-life intermediate between those of bromocriptine and cabergoline, allowing the drug to be administered once daily. Comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (prolactin suppression, restoration of gonadal function) and in tolerability. In similar studies, quinagolide appeared to have similar efficacy and superior tolerability to that of bromocriptine. Results of a small crossover study indicate that cabergoline is better tolerated, with a trend toward activity superior to that of quinagolide. In hyperprolactinemic men and in women not seeking to become pregnant, cabergoline may be regarded as the treatment of choice.

  16. 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…

  17. 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

  18. 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.

  19. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

    PubMed

    Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

    2007-05-01

    We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

  20. Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

    PubMed

    Sommer, Rebecca J; Hume, Adam J; Ciak, Jessica M; Vannostrand, John J; Friggens, Megan; Walker, Mary K

    2005-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.

  1. The ISO View of Star Forming Galaxies

    NASA Astrophysics Data System (ADS)

    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 100K

  2. 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.

  3. Matching the Spectrometers on board ISO

    NASA Astrophysics Data System (ADS)

    Burgdorf, M.; Feuchtgruber, H.; Salama, A.; García-Lario, P.; Müller, T.; Lord, S.

    We report on the findings of the Spectral Matching Working Group, the main aim of which was to investigate discontinuities between SWS and LWS in complete ISO spectra from 2 - 200 μm. In order to check in a quantitative way the agreement between the two spectrometers, a software tool was developed which automatically selected observations made with SWS and LWS on the same coordinates and which calculated the ratio of the fluxes in the overlap region from the browser products. In this way all observations suitable for this cross-calibration exercise could be selected, provided that they were performed with standard Astronomical Observing Templates and covered the wavelength range that SWS and LWS have in common. 95% of those targets which were neither extended nor variable showed an agreement better than 20% between the two spectrometers. Several problems with the data from the instruments, like saturation effects, detector transients and discontinuities between the sub-spectra from different detectors, affect both spectrometers in a similar way and require special processing steps. We show, for some solar system objects, to which extent the spectra taken with ISO from the mid- to the far-infrared agree with theoretical models. Furthermore, we discuss for the example of Neptune how the combined information from both spectrometers can be used to put new constraints on models of objects that are possible calibration standards for future missions.

  4. 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.

  5. 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.

  6. Use ISO-14000 as a compliance and productivity tool

    SciTech Connect

    Shah, G.C.

    1997-08-01

    Many HPI companies ponder whether or not to invest the time and resources in attaining ISO-14000 accreditation. Similar to ISO-9000, ISO-14000 is a verification process that assures that the operating company is continuously working to achieve its environmental goals and policies. The standards broadly define that organizations should develop an environmental management system (EMS) as the infrastructure to customize procedures and guidelines. From a strategic competition viewpoint, many organizations are focusing on issues such as: quick response (to customer needs), customer relationships, core competence, and continuous improvement, in addition to conventional indicators including: cost control and technology. ISO-14001 EMS could help organizations address these issues.

  7. Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy

    PubMed Central

    Errami, Mounir; Tassa, Amina T; Galindo, Cristi L; Skinner, Michael A.; Hill, Joseph A; Garner, Harold R

    2010-01-01

    β-adrenergic signaling is involved in the development of cardiac hypertrophy (CH), justifying the use of β-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the β-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ), an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO)-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB) (P=0.07). When carbamazepine was given in combination with the antibiotic doxycycline (DOX), which inhibits matrix metalloproteinases (MMPs), therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze -pine as a β-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB) were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a β-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA) as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional β-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as additional

  8. Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy.

    PubMed

    Errami, Mounir; Tassa, Amina T; Galindo, Cristi L; Skinner, Michael A; Hill, Joseph A; Garner, Harold R

    2010-06-23

    β-adrenergic signaling is involved in the development of cardiac hypertrophy (CH), justifying the use of β-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the β-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ), an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO)-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB) (P=0.07). When carbamazepine was given in combination with the antibiotic doxycycline (DOX), which inhibits matrix metalloproteinases (MMPs), therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze -pine as a β-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB) were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a β-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA) as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional β-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as additional

  9. Novel diazabicycloalkane delta opioid agonists.

    PubMed

    Loriga, Giovanni; Lazzari, Paolo; Manca, Ilaria; Ruiu, Stefania; Falzoi, Matteo; Murineddu, Gabriele; Bottazzi, Mirko Emilio Heiner; Pinna, Giovanni; Pinna, Gérard Aimè

    2015-09-01

    Here we report the investigation of diazabicycloalkane cores as potential new scaffolds for the development of novel analogues of the previously reported diazatricyclodecane selective delta (δ) opioid agonists, as conformationally constrained homologues of the reference δ agonist (+)-4-[(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80). In particular, we have simplified the diazatricyclodecane motif of δ opioid agonist prototype 1a with bridged bicyclic cores. 3,6-diazabicyclo[3.1.1]heptane, 3,8-diazabicyclo[3.2.1]octane, 3,9-diazabicyclo[3.3.1]nonane, 3,9-diazabicyclo[4.2.1]nonane, and 3,10-diazabicyclo[4.3.1]decane were adopted as core motifs of the novel derivatives. The compounds were synthesized and biologically assayed as racemic (3-5) or diastereoisomeric (6,7) mixtures. All the novel compounds 3-7 showed δ agonism behaviour and remarkable affinity to δ receptors. Amongst the novel derivatives, 3,8-diazabicyclo[3.2.1]octane based compound 4 evidenced improved δ affinity and selectivity relative to SNC80.

  10. 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.

  11. 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.

  12. ISO proves that intergalactic space is dusty

    NASA Astrophysics Data System (ADS)

    1997-11-01

    In the past, astronomers have considered intergalactic space to be extremely clean. Except in the vast concentrations of stars, gas and dust that make up the galaxies themselves, the Universe was supposed to be filled only by very thin traces of invisible gas. ISO's detection of dust means that the Universe is less transparent than astronomers have assumed. Their cosmic window-pane is slightly dirty and large-scale inferences based on the brightnesses of distant galaxies and quasars may be affected. Emissions from the intergalactic dust were picked up by the photometer ISOPHOT. A team of German, British, Spanish and Danish astronomers contributed this versatile set of detectors to ISO. The leader of the ISOPHOT team is Dietrich Lemke of the Max-Planck Institut fr Astronomie (MPIA) in Heidelberg, Germany. "ISOPHOT in ISO is the only instrument in existence capable of making this detection" Lemke says. "The intergalactic dust is so cold that we need a very cold telescope to detect it. The strongest emissions from the dust are at a wavelength of 0.1-0.2 millimetre, which cannot be well observed from the Earth. ISO provides telescope in space cooled by superfluid helium to within 2 degrees of absolute zero. ISOPHOT is the instrument on ISO that measures infrared intensities at the longest wavelengths, up to 0.2 millimetre." ISOPHOT's advantages made finding the intergalactic dust possible, but not easy. The observations pushed instrumental sensitivity to the limit, and emissions from cold dust clouds in the Milky Way Galaxy confused the picture. The signal of intergalactic dust emerged clearly only after extensive data analysis. Cold dust in a hot cluster Our home Galaxy, the Milky Way, belongs to a very small group of galaxies. Intergalactic dust may very well be present nearby, but it is likely to be sparse and scattered. A team of astronomers, from MPIA Heidelberg and Helsinki Observatory, hoped that the intergalactic dust might be easier to recognise in a large

  13. Effects of structural modifications of N-CPM-normorphine derivatives on agonist and antagonist activities in isolated organs.

    PubMed

    Riba, P; Tóth, Z; Hosztafi, S; Friedmann, T; Fürst, S

    2003-01-01

    The agonistic and antagonistic properties of N-cyclopropylmethyl (N-CPM) morphine derivatives were observed in mouse vas deferens (MVD), longitudinal muscle of guinea pig ileum (GPI) and rabbit vas deferens (LVD). In MVD the K(e) values of the titled compounds (N-CPM-morphine, N-CPM-isomorphine, N-CPM-dihydromorphine, N-CPM-dihydroisomorpPhine, N-CPM-dihydromorphone and naltrexone) were measured for mu-, kappa- and delta-receptors using normorphine, ethylketocyclazocine (EKC) and D-Pen2-D-Pen5-enkephaline (DPDPE) as selective agonists on the receptors, respectively. For mu-receptors of MVD the tested compounds showed similar affinity. For kappa-receptors the non-iso-6-OH derivatives possessed much less affinity than the iso-derivatives. Similar difference could be observed for delta-receptors. The agonistic activities of these compounds in MVD were observed to be between 0-20% of the inhibition of muscle contractions. In GPI the compounds except naltrexone possessed strong agonistic activities effectively antagonized by nor-binaltorphimine (nor-BNI) (K(e) of nor-BNI was 0.23 nM) suggesting that they were strong kappa-receptor agonists. We investigated these agents in LVD too, which contains kappa-receptors, but they did not produce any agonist potencies. It raises the possibility that the kappa-receptor subtypes of LVD and MVD are different from the kappa-receptor subtype of GPI or the vasa deferentia contain much fewer kappa-receptors than GPI and the intrinsic activities of these compounds are too small to reach the 50% inhibition of the contractions.

  14. 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

  15. 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.

  16. Regulation of membrane cholecystokinin-2 receptor by agonists enables classification of partial agonists as biased agonists.

    PubMed

    Magnan, Rémi; Masri, Bernard; Escrieut, Chantal; Foucaud, Magali; Cordelier, Pierre; Fourmy, Daniel

    2011-02-25

    Given the importance of G-protein-coupled receptors as pharmacological targets in medicine, efforts directed at understanding the molecular mechanism by which pharmacological compounds regulate their presence at the cell surface is of paramount importance. In this context, using confocal microscopy and bioluminescence resonance energy transfer, we have investigated internalization and intracellular trafficking of the cholecystokinin-2 receptor (CCK2R) in response to both natural and synthetic ligands with different pharmacological features. We found that CCK and gastrin, which are full agonists on CCK2R-induced inositol phosphate production, rapidly and abundantly stimulate internalization. Internalized CCK2R did not rapidly recycle to plasma membrane but instead was directed to late endosomes/lysosomes. CCK2R endocytosis involves clathrin-coated pits and dynamin and high affinity and prolonged binding of β-arrestin1 or -2. Partial agonists and antagonists on CCK2R-induced inositol phosphate formation and ERK1/2 phosphorylation did not stimulate CCK2R internalization or β-arrestin recruitment to the CCK2R but blocked full agonist-induced internalization and β-arrestin recruitment. The extreme C-terminal region of the CCK2R (and more precisely phosphorylatable residues Ser(437)-Xaa(438)-Thr(439)-Thr(440)-Xaa(441)-Ser(442)-Thr(443)) were critical for β-arrestin recruitment. However, this region and β-arrestins were dispensable for CCK2R internalization. In conclusion, this study allowed us to classify the human CCK2R as a member of class B G-protein-coupled receptors with regard to its endocytosis features and identified biased agonists of the CCK2R. These new important insights will allow us to investigate the role of internalized CCK2R·β-arrestin complexes in cancers expressing this receptor and to develop new diagnosis and therapeutic strategies targeting this receptor.

  17. 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.

  18. 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.

  19. 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 -...

  20. Lessons learned with ISO 14001 at DOE sites

    SciTech Connect

    Wilkinson, C. H., LLNL

    1998-03-01

    ISO 14001 is the international standard for environmental management systems (EMS). The standard applies the `plan, do, check, act` management system model to assure that the environmental impacts of operations are fully considered in planning and facility operations. ISO 14001 has grown in popularity in both the public and the private sector and has seen increasing utility within the U.S. Department of Energy (DOE). While there is no final DOE policy or requirement for ISO 14001 EMS implementation, ISO 14001 commands an active presence at many DOE sites. In general, the impetus for ISO 14001 in the DOE complex has been either an initiative by site management contractors to improve performance, or an actual requirement in the new management contracts for the sites. Several DOE sites now are committed to implement EMS`s in conformance with ISO 14001: Brookhaven National Laboratory (BNL), Hanford, Idaho National Engineering and Environmental Laboratory (INEEL), Kansas City Plant, Nevada Test Site, Savannah River Site (SRS), Waste Isolation Pilot Project (WIPP), West Valley. Several other DOE sites are expected to proceed in the near future with an EMS consistent with ISO 14001. However, not all sites are proceeding with an ISO 14001 EMS based on individual site business considerations. This paper describes the status of EMS implementation at these sites and identifies lessons learned that may be of use to other DOE sites.

  1. High standards: ISO 9000 comes to health care.

    PubMed

    Moore, L M

    1999-02-01

    ISO 9000, an international quality system, is catching on in health care. Providers see it as a much less expensive alternative or as a complement to the JCAHO. And because ISO has been used for years in manufacturing, it has one big advantage over JCAHO: employers know it and trust it.

  2. ISO 9000:2000 revisions and their implications.

    PubMed

    Sim, P

    2000-05-01

    The planned revision of the ISO 9000 series of standards means that all medical device companies will have to revise their quality systems to align them with the new ISO 9000:2000 standards. This overview outlines the changes and the factors companies need to consider, and highlights future standards activity.

  3. 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…

  4. 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…

  5. 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…

  6. Denopamine, a beta(1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs.

    PubMed

    Sakuma, T; Tuchihara, C; Ishigaki, M; Osanai, K; Nambu, Y; Toga, H; Takahashi, K; Ohya, N; Kurihara, T; Matthay, M A

    2001-01-01

    The effect of denopamine, a selective beta(1)-adrenergic agonist, on alveolar fluid clearance was determined in both ex vivo rat and guinea pig lungs. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue-labeled albumin over 1 h at 37 degrees C. Denopamine (10(-6) to 10(-3) M) increased alveolar fluid clearance in a dose-dependent manner in ex vivo rat lungs. Denopamine also stimulated alveolar fluid clearance in guinea pig lungs. Atenolol, a selective beta(1)-adrenergic antagonist, and amiloride, a sodium channel inhibitor, inhibited denopamine-stimulated alveolar fluid clearance. The potency of denopamine was similar to that of similar doses of isoproterenol or terbutaline. Short-term hypoxia (100% nitrogen for 1-2 h) did not alter the stimulatory effect of denopamine. Denopamine (10(-4), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate levels in cultured rat alveolar type II cells. In summary, denopamine, a selective beta(1)-adrenergic agonist, stimulates alveolar fluid clearance in both ex vivo rat and guinea pig lungs.

  7. 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.

  8. 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.

  9. Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a water-soluble forskolin derivative, compared with those of isoproterenol, dopamine and dobutamine.

    PubMed

    Yoneyama, Masahiko; Sugiyama, Atsushi; Satoh, Yoshioki; Takahara, Akira; Nakamura, Yuji; Hashimoto, Keitaro

    2002-12-01

    Colforsin daropate is a recently developed water-soluble derivative of forskolin that directly stimulates adenylate cyclase, unlike the catecholamines. The chronotropic, inotropic and coronary vasodilator actions of colforsin daropate were compared with those of isoproterenol, dopamine and dobutamine, using canine isolated, blood-perfused heart preparations. The stimulating effect of each drug on adenylate cyclase activity was also assessed. Colforsin daropate, as well as each of the catecholamines, exerted positive chronotropic, inotropic and coronary vasodilator actions. The order of selectivity for the cardiovascular variables of colforsin daropate was coronary vasodilation > positive inotropy > positive chronotropy; whereas that of isoproterenol, dopamine and dobutamine was positive inotropy > coronary vasodilation > positive chronotropy. Thus, a marked characteristic of colforsin daropate is its potent coronary vasodilator action. On the other hand, each drug significantly increased the adenylate cyclase activity in a dose-related manner: colforsin daropate > isoproterenol > dopamine = dobutamine. These results suggest that colforsin daropate may be preferable in the treatment of severe heart failure where the coronary blood flow is reduced and beta-adrenoceptor-dependent signal transduction pathway is down-regulated.

  10. Regulation of signal transducer and activator of transcription 3 and apoptotic pathways by betaine attenuates isoproterenol-induced acute myocardial injury in rats.

    PubMed

    Zheng, P; Liu, J; Mai, S; Yuan, Y; Wang, Y; Dai, G

    2015-05-01

    The present study was designed to investigate the cardioprotective effects of betaine on acute myocardial ischemia induced experimentally in rats focusing on regulation of signal transducer and activator of transcription 3 (STAT3) and apoptotic pathways as the potential mechanism underlying the drug effect. Male Sprague Dawley rats were treated with betaine (100, 200, and 400 mg/kg) orally for 40 days. Acute myocardial ischemic injury was induced in rats by subcutaneous injection of isoproterenol (85 mg/kg), for two consecutive days. Serum cardiac marker enzyme, histopathological variables and expression of protein levels were analyzed. Oral administration of betaine (200 and 400 mg/kg) significantly reduced the level of cardiac marker enzyme in the serum and prevented left ventricular remodeling. Western blot analysis showed that isoproterenol-induced phosphorylation of STAT3 was maintained or further enhanced by betaine treatment in myocardium. Furthermore, betaine (200 and 400 mg/kg) treatment increased the ventricular expression of Bcl-2 and reduced the level of Bax, therefore causing a significant increase in the ratio of Bcl-2/Bax. The protective role of betaine on myocardial damage was further confirmed by histopathological examination. In summary, our results showed that betaine pretreatment attenuated isoproterenol-induced acute myocardial ischemia via the regulation of STAT3 and apoptotic pathways.

  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. The stability of iso-α-acids and reduced iso-α-acids in stored blood specimens.

    PubMed

    Rodda, Luke N; Gerostamoulos, Dimitri; Drummer, Olaf H

    2014-06-01

    The long-term stability of the iso-α-acids, and three structurally similar but chemically altered iso-α-acids (known as 'reduced iso-α-acids' and consisting of the rho-, tetrahydro- and hexahydro-iso-α-acid groups) were investigated in whole blood. Pools of blank blood spiked with the four beer-specific ingredient congener groups at two different concentration levels were stored at 20°C, 4°C and -20°C; and extracted in duplicate in weeks 1, 3, 5 and 8, using a previously published method. A loss of 15% of the initial concentration was considered to indicate possible instability and losses greater than 30% demonstrated significant losses. The individual analytes within the four iso-α-acid groups were also measured to determine which iso-α-acids were subject to greater degradation and were responsible for the overall group instability. All four iso-α-acid groups showed significant losses after 8 weeks of storage under room temperature conditions in particularly the natural iso-α-acid group where major losses were observed (96% and 85% losses for low and high concentrations, respectively). Some degradation in all iso-α-acid groups were seen at 4°C samples predominantly due to the 'n' analogs of the groups showing an increased instability in blood. The -20°C storage conditions resulted in minimal changes in concentrations of all analytes. Higher than frozen storage temperatures can result in substantial changes on the stability of the iso-α-acid type groups in blood. The aim of this study was to highlight the stabilities of the IAA analytes in order to assist in the interpretation of IAA in stored blood specimens.

  13. 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

  14. Sodium acetate decreases phosphorylation of hormone sensitive lipase in isoproterenol-stimulated 3T3-L1 mature adipocytes.

    PubMed

    Aberdein, Nicola; Schweizer, Michael; Ball, Derek

    2014-04-01

    Lipolysis, the process of hydrolysis of stored triacylglycerol into glycerol and non-esterified fatty acids (NEFA), is reported to be reduced by short chain fatty acids (SCFA) but the mechanism of this inhibition is poorly understood. The aim of this study was to measure the phosphorylation at serine residue 563 of hormone sensitive lipase with and without exposure to sodium acetate. Using the 3T3-L1 cell line, we identified that stimulating the cells with isoproterenol increased phosphorylated hormone sensitive lipase (pHSL) expression by 60% compared with the basal state. In the presence of the SCFA acetate in stimulated cells, pHSL decreased by 15% compared with stimulated cells alone. These results were mirrored by the NEFA release from stimulated cells that had significantly decreased in the presence of sodium acetate after 60 min (from 0.53 µmol mg(-1) protein to 0.41 µmol mg(-1) protein, respectively, P = 0.004); and 180 min (1.73 µmol mg(-1) protein to 1.13 µmol mg(-1) protein, P = 0.020); however, treatment had no effect on glycerol release (P = 0.109). In conclusion, exposure to 4 mM acetate reduced the level of phosphorylation of HSL(SER563) in mature 3T3-L1 adipocytes and led to a significant reduction in NEFA release, although glycerol release was not affected.

  15. 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

  16. The co-operative action of hyaluronidase and urokinase on the isoproterenol-induced myocardial infarction in rats.

    PubMed

    Borrelli, F; Antonetti, F; Martelli, F; Caprino, L

    1986-04-15

    The effects of the intravenous administration of hyaluronidase (HY; 2,500 IU/kg) and urokinase (UK; 20,000 and 40,000 IU/kg), alone or in combination, on the isoproterenol (ISP) induced myocardial infarction (MI) in rats, were studied. The severity of infarction was determined by measuring the levels of serum enzymes (CPK, GOT, LDH) and by evaluating the extent of the injured areas and the incidence of mortality. Plasma thromboxane B2 (TXB2) levels were also determined. All the treatments reduced the infarction area and the enzyme levels (increased by ISP) to a varying degree. However, a definite potentiating activity was obtained when HY was combined with the highest dose of UK. This combination was also capable of reducing the mortality rate. Finally, both HY and UK or the combined preparation brought the plasma TXB2 levels back to normal. These findings suggest the possibility of complementary activities of HY and UK in the treatment of experimental MI.

  17. ISO-SWS Spectroscopy of NGC 1068

    NASA Astrophysics Data System (ADS)

    Lutz, D.; Sturm, E.; Genzel, R.; Moorwood, A. F. M.; Alexander, T.; Netzer, H.; Sternberg, A.

    2000-06-01

    We present Infrared Space Observatory-Short Wave Spectrometer (ISO-SWS) spectroscopy of NGC 1068 for the complete wavelength range 2.4-45 μm at resolving power ~1500. Selected subranges have been observed at higher sensitivity and full resolving power ~2000. We detect a total of 36 emission lines and derive upper limits for 13 additional transitions. Most of the observed transitions are fine-structure and recombination lines originating in the narrow-line region (NLR) and the inner part of the extended emission-line region. We compare the line profiles of optical lines and reddening-insensitive infrared lines to constrain the dynamical structure and extinction properties of the NLR. The most likely explanation of the considerable differences found is a combination of two effects: (1) The spatial structure of the NGC 1068 NLR is a combination of a highly ionized outflow cone and lower excitation extended emission. (2) Parts of the NLR, mainly in the receding part at velocities above systemic, are subject to extinction that is significantly suppressing optical emission from these clouds. Line asymmetries and net blueshifts remain, however, even for infrared fine-structure lines suffering very little obscuration. This may be either due to an intrinsic asymmetry of the NLR, as perhaps also suggested by the asymmetric radio continuum emission or due to a very high column density obscuring component which is hiding part of the NLR even from infrared view. We present detections and limits for 11 rotational and rovibrational emission lines of molecular hydrogen (H2). They arise in a dense molecular medium at temperatures of a few hundred kelvins that is most likely closely related to the warm and dense components seen in the near-infrared H2 rovibrational transitions, and in millimeter-wave tracers (CO, HCN) of molecular gas. Any emission of the putative parsec-scale molecular torus is likely overwhelmed by this larger scale emission. In companion papers we use the SWS

  18. Dopamine receptor agonists, partial agonists and psychostimulant addiction.

    PubMed

    Pulvirenti, L; Koob, G F

    1994-10-01

    Despite the epidemic growth of psychostimulant addiction over the past years, few pharmacological means of intervention are available to date for clinical treatment. This is of importance since the withdrawal syndrome that follows abstinence from drugs such as cocaine and the amphetamines is characterized, among other symptoms, by intense craving for the abused drug, and this is considered a critical factor leading into relapse of drug use. In this article, Luigi Pulvirenti and George Koob focus on the modulatory role shown by drugs acting at the dopamine receptor on the various phases of psychostimulant dependence in preclinical models and in human studies, and suggest that a class of compounds with partial agonist properties at the dopamine receptor may have therapeutic potential.

  19. ISO 9000 series standards: what healthcare facilities need to know.

    PubMed

    1995-03-01

    With the recent trend toward implementing or improving quality systems and the increasing frequency with which vendors looking to secure a place in the world market have cited the International Organization for Standardization's (ISO) 9000 Series quality system standards, healthcare facilities have been expressing increased interest in learning about these standards, especially ISO 9001, 9002, and 9003. In this article, we briefly discuss the ISO 9000 Series standards--what they are and what they mean--so that healthcare facilities can properly assess the significance of vendors' statements citing compliance with one or more of these standards.

  20. Improving (NEPA) the National Environmental Policy Act through ISO 14001

    SciTech Connect

    Wilkinson, C H

    1999-02-25

    Federal application of ISO 14001 and / or the EPA Code of Environmental Management Principles (CEMP) could substantially improve the mitigation and monitoring aspects of the NEPA process. In addition, application of those management systems could also enhance fulfillment of Section 101 goals of NEPA. An ISO 14001 Environmental Management System would provide for a plan to continually address and improve environmental aspects and impacts. The strong feedback and improvement loops in both CEMP and ISO 14001 would help strengthen this weakness of NEPA by providing a mechanism to foster excellent environmental action, not just more dusty paperwork.

  1. Experience of 2 dental clinics registered to ISO 9002.

    PubMed

    Casas, Michael J; Kenny, David J; Johnston, Douglas H

    2003-04-01

    This paper describes the 3-year experience of managing 2 hospital-based dental clinics registered to ISO 9002:1994; it also examines the revision of previous quality management standards in 2 separate institutions to prepare for registration under the new ISO 9001:2000 standard. Daily equipment and process checks, combined with internal audits, were the backbone of the quality system at both locations. Corrective and protective actions had been underused, because of the partial duplication produced by 2 different institutionally mandated risk management and incident reporting systems. ISO 9002 registration provided both dental clinics with responsive quality systems, emphasizing patient satisfaction and providing measurable continuous quality improvement.

  2. The historical impact of ISO 9000 on Lebanese firms.

    PubMed

    Mezher, Toufic; Ajam, Maher; Shehab, Mohamad

    2004-01-01

    The objective of this paper is to assess the impact of the new ISO 9001:2000 standard on the Quality Management Systems (QMS) of Lebanese firms that were already certified under ISO 9000:1994. To get an accurate feedback of stakeholders in a firm, three different questionnaires were developed and distributed to management, employees, and customers respectively. Empirical results indicate that ISO 9001:2000 has improved the QMS performance of Lebanese firms over that of the 1994 edition. Nevertheless, results showed that the new standard still has some weaknesses when it comes to improving suppliers' relationships and empowering employees.

  3. 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.

  4. 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

  5. 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...

  6. Small molecule fluoride toxicity agonists.

    PubMed

    Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

    2015-04-23

    Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride.

  7. Small Molecule Fluoride Toxicity Agonists

    PubMed Central

    Nelson1, James W.; Plummer, Mark S.; Blount, Kenneth F.; Ames, Tyler D.; Breaker, Ronald R.

    2015-01-01

    SUMMARY Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch-reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. PMID:25910244

  8. [Accreditation of clinical laboratories based on ISO standards].

    PubMed

    Kawai, Tadashi

    2004-11-01

    International Organization for Standardization (ISO) have published two international standards (IS) to be used for accreditation of clinical laboratories; ISO/IEC 17025:1999 and ISO 15189:2003. Any laboratory accreditation body must satisfy the requirements stated in ISO/IEC Guide 58. In order to maintain the quality of the laboratory accreditation bodies worldwide, the International Laboratory Accreditation Cooperation (ILAC) has established the mutual recognition arrangement (MRA). In Japan, the International Accreditation Japan (IAJapan) and the Japan Accreditation Board for Conformity Assessment (JAB) are the members of the ILAC/MRA group. In 2003, the Japanese Committee for Clinical Laboratory Standards (JCCLS) and the JAB have established the Development Committee of Clinical Laboratory Accreditation Program (CLAP), in order to establish the CLAP, probably starting in 2005.

  9. 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.

  10. ISO Lensing Studies: background galaxies and foreground cluster properties

    NASA Astrophysics Data System (ADS)

    Perez-Martinez, Ricardo

    2003-02-01

    A number of ISO programmes, totaling over 100 hours of observation time, made use of the gravitational lensing phenomenon to extend the sensitivity of ISO observations. Substantial results derived from those programmes have been published, or are in the peer review process, addressing the MIR properties of the background lensed galaxy population. These results, which have important implications for galaxy evolution, and which resolve a large fraction of the 15 and 7 μm infrared-background light, will be briefly summarised. But the data has much further potential. Little has been published to date concerning the implications of the ISO lensing data for the foreground clusters themselves, nor addressing the overlap between the observed ISO sources and lensed populations seen at X-Ray and Sub-mm wavelengths. We report briefly on an ongoing programme to systematically reassess the set of ISO observations of lensing galaxy clusters and to describe and compare the IR properties of the clusters themselves. The overlap between ISO source lists and recently published lists of X-Ray and Sub-mm sources in the same fields is under study.

  11. 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

  12. Surviving the Transition from FGDC to ISO Metadata Standards

    NASA Astrophysics Data System (ADS)

    Fox, C. G.; Milan, A.; Sylvester, D.; Habermann, T.; Kozimor, J.; Froehlich, D.

    2008-12-01

    The NOAA Metadata Manager and Repository (NMMR) has served a well established group of data managers at NOAA's National Data Centers for over a decade. It provides a web interface for managing FGDC compliant metadata and publishing that metadata to several large data discovery systems (GeoSpatial One-Stop, NASA's Global Change Master Directory, the Comprehensive Large-Array data Stewardship System, and FirstGov). The Data Center's are now faced with migration of these metadata to new International Metadata Standards (ISO 19115, 19115-2, "). We would like to accomplish this migration while minimizing disruption to the current users and supporting significant new capabilities of the ISO standards. Our current approach involves relational ISO views on top of the existing XML database to convert FGDC content into ISO without changing the data manager interface. These views are the foundation for ISO- compliant XML metadata access via REST-like web services. Additionally, new database tables provide information required by ISO that is not included in the FGDC standard. This approach allows us to support the new standard without disrupting the current system.

  13. Effect of Piper betle on cardiac function, marker enzymes, and oxidative stress in isoproterenol-induced cardiotoxicity in rats.

    PubMed

    Arya, Dharamvir Singh; Arora, Sachin; Malik, Salma; Nepal, Saroj; Kumari, Santosh; Ojha, Shreesh

    2010-11-01

    The present study was designed to investigate the cardioprotective potential of Piper betle (P. betle) against isoproterenol (ISP)-induced myocardial infarction in rats. Rats were randomly divided into eight groups viz. control, ISP, P. betle (75, 150, and 300 mg/kg) and P. betle (75, 150, and 300 mg/kg) + ISP treated group. P. betle leaf extract (75, 150, or 300 mg/kg) or saline was orally administered for 30 days. ISP (85 mg/kg, s.c.) was administered at an interval of 24 h on the 28(th) and 29(th) day and on day 30 the functional and biochemical parameters were measured. ISP administration showed a significant decrease in systolic, diastolic, mean arterial pressure (SAP, DAP, MAP), heart rate (HR), contractility (+LVdP/dt), and relaxation (-LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP). ISP also caused significant decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and myocyte injury marker enzymes; creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; thiobarbituric acid reacting species (TBARS) in heart. Pre-treatment with P. betle favorably modulated hemodynamic (SAP, DAP, and MAP) and ventricular function parameters (-LVdP/dt and LVEDP). P. betle pre-treatment also restored SOD, CAT, GSH, and GPx, reduced the leakage of CK-MB isoenzyme and LDH along with decreased lipid peroxidation in the heart. Taken together, the biochemical and functional parameters indicate that P. betle 150 and 300 mg/kg has a significant cardioprotective effect against ISP-induced myocardial infarction. Results of the present study suggest the cardioprotective potential of P. betle.

  14. 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.

  15. 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.

  16. 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...

  17. Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptors.

    PubMed

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

    2004-05-01

    This study investigated, for the D2 dopamine receptor, the relation between the ability of agonists and inverse agonists to stabilise different states of the receptor and their relative efficacies. Ki values for agonists were determined in competition versus the binding of the antagonist [3H]spiperone. Competition data were fitted best by a two-binding site model (with the exception of bromocriptine, for which a one-binding site model provided the best fit) and agonist affinities for the higher (Kh) (G protein-coupled) and lower affinity (Kl) (G protein-uncoupled) sites determined. Ki values for agonists were also determined in competition versus the binding of the agonist [3H]N-propylnorapomorphine (NPA) to provide a second estimate of Kh. Maximal agonist effects (Emax) and their potencies (EC50) were determined from concentration-response curves for agonist stimulation of guanosine-5'-O-(3-[32S]thiotriphosphate) ([35S]GTPgammaS) binding. The ability of agonists to stabilise the G protein-coupled state of the receptor (Kl/Kh determined from ligand-binding assays) did not correlate with either of two measures of relative efficacy (relative Emax, Kl/EC50) of agonists determined in [35S]GTPgammaS-binding assays, when the data for all of the compounds tested were analysed. For a subset of compounds, however, there was a relation between Kl/Kh and Emax. Competition-binding data versus [3H]spiperone and [3H]NPA for a range of inverse agonists were fitted best by a one-binding site model. Ki values for the inverse agonists tested were slightly lower in competition versus [3H]NPA compared to [3H]spiperone. These data do not provide support for the idea that inverse agonists act by binding preferentially to the ground state of the receptor.

  18. 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)

  19. Comparing four softwares based on ISO 9241 part 10.

    PubMed

    Safdari, Reza; Dargahi, Hussein; Shahmoradi, Leila; Farzaneh Nejad, Ahmadreza

    2012-10-01

    Evaluation of Iran's HIS (hospital Information System) ergonomic quality using IsoMetric 9241 part 10 and compared results of that evaluation with results of ergonomic quality evaluation other softwares which evaluated by IsoMetric 9241 part 10. This research study was conducted in two stages. In the first stage, the researchers evaluated the HIS of 13 hospitals in Iran using ISO 9241 part 10, and in the second stage, they compared the evaluation results with the following softwares: a) IS-H*med (evaluated by Hamborg et al. 2004) b) SAP-HR (evaluated by Gruber 2000) c) Microsoft Word for Windows, Version 2 (evaluated by Gediga et al. 1999). For first stage used usability questionnaire called IsoMetrics which is based on the international standard ISO 9241 Part 10. This questionnaire is including 75 items based on the seven principles. Data analyzed using SPSS and Excel. The comparison between HIS and IS-H*med reveal that the former is significantly more usable than the latter in terms of all IsoMetrics sales. The HIS also proved to be significantly more applicable than SAP-HR in terms of such IsoMetrics scales as "suitability for task," "suitability for learning", "Error tolerance" and "learning ability". However, HIS was found to be significantly less usable than Microsoft Word. The results of the study show that compared with the mentioned three softwares, Iran's hospital information system enjoys an average ergonomic quality. Therefore, it is recommended that the users' comments and expectations be considered more when information systems are designed and developed.

  20. ISO completes its observations of the Universe by infrared light

    NASA Astrophysics Data System (ADS)

    1998-04-01

    At 07:00 on 8 April 1998, engineers at ESA's ground station at Villafranca near Madrid reported that ISO's telescope was beginning to warm up, above its nominal operating temperature close to absolute zero. This was the sign that ISO had exhausted the superfluid helium used to achieve the very low temperatures necessary for infrared astronomy. Observations ceased at 23h07 when the temperature of the instruments had risen above -269°C. At that time, ISO was observing the galaxy NGC 1808 with the camera (ISOCAM) for Prof. J. Hough (UK). The astronomers then handed ISO over to the engineering team for check-outs and decommissioning. The spacecraft will be switched off in about 28 days' time. Infrared rays come from cool places in the sky, and ISO would have been dazzled by its own heat unless its optical system were extremely cold. At its launch in November 1995, ISO carried a supply of 2000 litres of superfluid helium, which boils at -271 degrees C. Slow venting of the helium into space maintained the low temperature of the optical system. How did ISO achieve its extended life? Three months came from a prudent safety margin in the engineering calculations of the rate of loss of helium. Two months were the result of favourable circumstances in the launch campaign at Kourou in French Guiana. During a technical check of the Ariane 44P launcher, ISO's engineers seized the chance to recharge the helium, and the quick launch that followed meant that the outer parts of the cryogenic system of the spacecraft had little time to warm up in Kourou's tropical climate. Finally, the daily loss of helium turned out to be 17 less than expected, at the lower end of a range of possibilities considered by the engineers. That gave ISO an estimated five months of additional life. The date for the helium to run out remained somewhat uncertain, and astronomers and engineers have been alert to the possibility of its exhaustion for the past few weeks. The huge bonus to astronomers, from ISO

  1. 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

  2. [Safety of beta-agonists in asthma].

    PubMed

    Oscanoa, Teodoro J

    2014-01-01

    Beta 2 agonist bronchodilators (β2A) are very important part in the pharmacotherapy of bronchial asthma, a disease that progresses in the world in an epidemic way. The β2A are prescribed to millions of people around the world, therefore the safety aspects is of public interest. Short-Acting β2 Agonists (SABAs), such as albuterol inhaler, according to current evidence, confirming its safety when used as a quick-relief or rescue medication. The long-acting β2 agonists (LABAs) The long-acting bronchodilators β2A (Long acting β2 Agonists or LABAs) are used associated with inhaled corticosteroids as controller drugs for asthma exacerbationsaccess, for safety reasons LABAs are not recommended for use as monotherapy.

  3. A look back at achieving ISO 14001 certification

    SciTech Connect

    Heyob, K.; Heigel, G.

    1999-07-01

    In 1996, Honda of America Mfg., Inc. (Honda) set a goal of achieving ISO 14001 certification for all major US manufacturing plants by the end of 1998. This paper is a reality-based look at what implementation of ISO 14001 really entailed and, after implementation, the benefits and problems that Honda has experienced. Honda will describe the implementation experience from start to finish, including development of the implementation strategy, problems encountered along the way, implementation tips learned during the process, and what would be done differently the second time. Honda initially developed an implementation plan, estimated resource requirements and assigned plant-wide implementation teams. A core team of project leaders was trained to lead the implementation and general training was provided for all project team members. Honda evaluated the gaps between Honda's existing TQM-based environmental management systems and the requirements of ISO 14001 and developed a strategy to fill the gaps using TQM principles. The paper will describe how Honda addressed each element of the ISO 14001 standard and integrated them within existing business and environmental management practices. The paper will also look-back at the implementation process and identify problems that Honda experienced and what could be done differently to save time and resources. Finally, Honda will describe any problems encountered with maintaining the ISO 14001 certified environmental management system and the benefits that have come from certification.

  4. 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.

  5. PPAR Agonists and Cardiovascular Disease in Diabetes

    PubMed Central

    Calkin, Anna C.; Thomas, Merlin C.

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARα agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARγ agonists, and more recently dual PPARα/γ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARγ receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease. PMID:18288280

  6. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

  7. The release of soluble VAP-1/SSAO by 3T3-L1 adipocytes is stimulated by isoproterenol and low concentrations of TNFalpha.

    PubMed

    García-Vicente, S; Abella, A; Viguerie, N; Ros-Baró, A; Camps, M; Testar, X; Palacín, M; Zorzano, A; Marti, L

    2005-06-01

    Plasma level of the protein VAP-1/SSAO (Vascular Adhesion Protein-1/Semicarbazide-Sensitive Amine Oxidase) is increased in diabetes and/or obesity and may be related to vascular complications associated to these pathologies. The aim of this work was to complete a preceding study where we described the role played by some hormones or metabolites, implicated in diabetes and/or obesity, in the regulation of the release of VAP-1/SSAO by 3T3-L1 adipocytes. Here we focused on the previously observed effect produced by TNFalpha in the release of VAP-1/SSAO and studied the effect of a beta-adrenergic compound, isoproterenol. Both compounds stimulated the release of VAP-1/SSAO to the culture medium but had a different effect on the VAP-1/SSAO membrane form. While TNFalpha produced a decrease on VAP-1/SSAO membrane form content, isoproterenol did not modify it. We thus observed two different ways of regulation of the release of VAP-1/SSAO by 3T3-L1 adipocytes by metabolites implicated in diabetes and adipose tissue physiopathology. Our work permits a better understanding of this increased plasma VAP-1/SSAO levels observed in diabetes.

  8. [ISO 9000: guidelines for a total quality system in health].

    PubMed

    Pasini, E; Opasich, C; Scherillo, M

    1998-04-01

    The Italian National Health System has recently been revised and reorganized. In the new scenario, the quality of the service being provided is considered extremely important. The international ISO 9000 standard has made it possible to implement a total-quality management system that can be documented and certified independently by a third party. Several hospitals in Italy and abroad have implemented a total-quality system according to ISO 9000 standards in order to provide a service that can satisfy the expectations of the patients in a controlled and efficient way. This article describes ISO 9000, proposes its application to ensure quality in the structures and organizations involved in the national health system and reports several examples of how the standard has been implemented in hospitals.

  9. 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.

  10. ISO environmental testing and reliability standards for optics

    NASA Astrophysics Data System (ADS)

    Parks, Robert E.

    1993-12-01

    In this paper, we give a little background into the work of ISO/TC172/SC1/WG1, the ISO subcommittee that is writing standards for the environmental testing of optics and optical instruments. By environmental test standards, we mean standards that outline what sort of climatic variations and conditions of use optical instruments must survive and still operate within given performance specifications. The scope of the standards this subcommittee is writing is then described followed by a thorough description of the general content of the 2 standards that are nearing completion. Finally, we discuss the applicability of these standards and how they may affect optics and optical systems that are intended for sale in international markets. We also discuss briefly the relationship of these ISO standards to MIL-STD-810E, Environmental Test Methods and Engineering Guidelines, the U.S. Military standard.

  11. ISO and CEN documents on quality in medical laboratories.

    PubMed

    Kenny, D

    2001-07-20

    The forthcoming international standard ISO 15189 "Quality management in the medical laboratory" is a document of great importance for the development of quality systems and accreditation for medical/clinical laboratories. For the first time, there will be an internationally recognized standard designed specifically for the accreditation of medical laboratories. The document takes into account the special requirements imposed by the medical environment and by the essential contribution of the medical laboratory service to patient care. It recognizes that medical laboratories must provide not only testing of patient samples, but also advisory, interpretative and educational services. A further document, still in draft form (ISO/DIS 15190), deals with safety management for medical laboratories. ISO 15189 (and probably 15190 also) are expected be adopted by CEN as a European Standard (EN).

  12. 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.

  13. 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.

  14. ISO 14000: Review and guidelines for the photovoltaic industry

    SciTech Connect

    DePhillips, M.P.

    1997-08-01

    The International Organization for Standardization (ISO) has released and is in the process of ratifying a new set of environmental management system standards, ISO 14000. These voluntary international standards will have a significant impact on how companies throughout the international community manage their environmental programs. Initially this impact will result in increased international trade opportunities due to the anticipated customer requirement for suppliers to demonstrate certification. Other potential impacts will benefit both companies engaged in international commerce and companies with a domestic focus. These would include installing a cohesive system to manage environmental matters, participation within a new regulatory paradigm, and adhering to a potentially new set of legal standards. The wide range of potential environmental, commercial, legal and regulatory benefits offered by ISO 14000 offer most companies significant reason to explore the possibilities of implementing an environmental management system. Organizations will be able to anticipate and meet growing environmental expectations and to ensure ongoing compliance with national and international requirements as well as satisfy the growing demands of customers, stakeholders and the interested public. As an emerging industry with significant international ties, the photovoltaic (PV) community will be effected from these standards if they do become globally adopted. In fact some major players in the PV industry have recently received certification to ISO 9000. This again demonstrates a trend within the industry to move toward a uniform system approach to management. This paper will expose interested parties within the PV industry to the details of ISO 14000 and will assist decision makers assess the various possibilities for implementation certification of ISO 14000 for an individual facility.

  15. Simultaneous determination of beta2-agonists in human urine by fast-gas chromatography/mass spectrometry: method validation and clinical application.

    PubMed

    Di Corcia, Daniele; Morra, Veronica; Pazzi, Marco; Vincenti, Marco

    2010-04-01

    A fast screening protocol was developed and validated for the simultaneous determination of 15 beta(2)-agonists in human urine (bambuterol, cimbuterol, clenbuterol, fenoterol, formoterol, isoproterenol, mapenterol, metaproterenol, procaterol, ractopamine, ritodrine, salbutamol, salmeterol, terbutaline, tulobuterol). The overall sample processing includes deconjugation with enzyme hydrolysis, liquid-liquid extraction, followed by derivatization of the extract and detection of beta(2)-agonists trimethylsilyl-derivatives by fast-gas chromatography/electron impact-mass spectrometry (fast-GC/EI-MS). Sample extraction and derivatization were optimized with the purpose of improving recoveries and reaction yields for a variety of analytes with different structures simultaneously, while keeping the procedure simple and reliable. Validation parameters were determined for each analyte under investigation, including selectivity, linearity, intra- and inter-assay precision, extraction recoveries and signal to noise ratio (S/N) at the lowest calibration level. Fast-GC/MS sequences, based on the use of short columns, high carrier-gas velocity and fast temperature ramping, allow considerable reduction of the analysis time (7 min), while maintaining adequate chromatographic resolution. The overall GC cycle time was less than 9 min, allowing a processing rate of 6 samples/h. High MS-sampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. The method was successfully tested on real samples arising from clinical treatments. Copyright (c) 2009 John Wiley & Sons, Ltd.

  16. Agonist-independent effects of muscarinic antagonists on Ca2+ and K+ currents in frog and rat cardiac cells.

    PubMed

    Hanf, R; Li, Y; Szabo, G; Fischmeister, R

    1993-02-01

    1. The whole-cell patch clamp and intracellular perfusion techniques were used for studying the effects of atropine and other muscarinic acetylcholine receptor (mAChR) antagonists on the L-type calcium currents (ICa) in frog and rat ventricular myocytes, and on the mAChR-activated K+ current (IK(ACh)) in frog atrial myocytes. 2. In frog ventricular myocytes, atropine (0.1 nM to 1 microM) reversed the inhibitory effect of acetylcholine (ACh, 1 nM) on ICa previously stimulated by isoprenaline (Iso, 2 microM), a beta-adrenergic agonist. However, in the concomitant presence of Iso, ACh and atropine, ICa was > 50% larger than in Iso alone. 3. The effects of atropine were then examined in the absence of mAChR agonists. After a preliminary stimulation of ICa with Iso (0.1 or 2 microM), atropine induced a dose-dependent stimulation of ICa. EC50 (i.e. the concentration of atropine at which the response was 50% of the maximum) and Emax (i.e. maximal stimulation of ICa expressed as percentage increase in ICa with respect to the level in Iso alone) were respectively 0.6 nM and 35%. The stimulatory effect of atropine on ICa was not voltage dependent. 4. Atropine (1 microM) had no effect on frog ICa (i) under basal conditions, (ii) upon stimulation of ICa by the dihydropyridine agonist (-)-Bay K 8644 (1 microM), or (iii) when ICa had been previously stimulated by intracellular perfusion with cyclic AMP (3 microM). However, atropine increased ICa after a stimulation by forskolin (0.3 microM). Therefore, an increased adenylyl cyclase activity was required for atropine to produce its stimulatory effect on ICa. 5. The order of potency of mAChR antagonists to reverse the inhibitory effect of ACh on Iso elevated ICa in frog ventricle was atropine > AF-DX 116 > pirenzepine. In the absence of ACh, mAChR antagonists produced their stimulatory effect on Iso elevated ICa with the same order of potency. 6. Intracellular substitution of Gpp(NH)p (5'-guanylylimidiphosphate) for GTP (420 micro

  17. IsoSel: Protein Isoform Selector for phylogenetic reconstructions

    PubMed Central

    Philippon, Héloïse; Souvane, Alexia; Brochier-Armanet, Céline

    2017-01-01

    The reliability of molecular phylogenies is strongly dependent on the quality of the assembled datasets. In the case of eukaryotes, the selection of only one protein isoform per genomic locus is mandatory to avoid biases linked to redundancy. Here, we present IsoSel, a tool devoted to the selection of alternative isoforms in the context of phylogenetic reconstruction. It provides a better alternative to the widely used approach consisting in the selection of the longest isoforms and it performs better than Guidance, its only available counterpart. IsoSel is publicly available at http://doua.prabi.fr/software/isosel. PMID:28323858

  18. 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}

  19. The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor.

    PubMed

    Warne, Tony; Moukhametzianov, Rouslan; Baker, Jillian G; Nehmé, Rony; Edwards, Patricia C; Leslie, Andrew G W; Schertler, Gebhard F X; Tate, Christopher G

    2011-01-13

    β-adrenergic receptors (βARs) are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins upon binding catecholamine agonist ligands such as adrenaline and noradrenaline. Synthetic ligands have been developed that either activate or inhibit βARs for the treatment of asthma, hypertension or cardiac dysfunction. These ligands are classified as either full agonists, partial agonists or antagonists, depending on whether the cellular response is similar to that of the native ligand, reduced or inhibited, respectively. However, the structural basis for these different ligand efficacies is unknown. Here we present four crystal structures of the thermostabilized turkey (Meleagris gallopavo) β(1)-adrenergic receptor (β(1)AR-m23) bound to the full agonists carmoterol and isoprenaline and the partial agonists salbutamol and dobutamine. In each case, agonist binding induces a 1 Å contraction of the catecholamine-binding pocket relative to the antagonist bound receptor. Full agonists can form hydrogen bonds with two conserved serine residues in transmembrane helix 5 (Ser(5.42) and Ser(5.46)), but partial agonists only interact with Ser(5.42) (superscripts refer to Ballesteros-Weinstein numbering). The structures provide an understanding of the pharmacological differences between different ligand classes, illuminating how GPCRs function and providing a solid foundation for the structure-based design of novel ligands with predictable efficacies.

  20. Mechanism of glucocorticoid protection of airway smooth muscle from proasthmatic effects of long-acting β2-adrenoceptor agonist exposure

    PubMed Central

    Nino, Gustavo; Hu, Aihua.; Grunstein, Judith S.; Grunstein, Michael M.

    2010-01-01

    Background Chronic use of long-acting β2-adrenergic receptor (β2AR) agonists (LABAs), resulting in β2AR desensitization, has been associated with increased asthma morbidity. When LABAs are used in combination with inhaled glucocorticoids (GCs), however, asthma control is improved, raising the question: Do GCs inhibit the proasthmatic mechanism that mediates altered contractility in LABA-exposed airway smooth muscle (ASM)? Objective This study aimed to identify the potential protective role and mechanism of action of GCs in mitigating the effects of prolonged LABA exposure on ASM constrictor and relaxation responsiveness. Methods Cultured human ASM (HASM) cells and isolated rabbit ASM tissues were examined for induced changes in agonist-mediated cAMP accumulation, constrictor and relaxation responsiveness, and expression of specific GC-regulated molecules following 24h exposure to the LABA, salmeterol, in the absence and presence of dexamethasone (DEX). Results Salmeterol-exposed ASM exhibited impaired cAMP and relaxation responses to isoproterenol and increased acetylcholine-induced contractility. These pro-asthmatic effects of prolonged LABA exposure were attributed to upregulated phosphodiesterase 4 (PDE4) activity, and ablated by pretreatment with DEX. Further studies demonstrated that: 1) DEX suppressed activation of the mitogen-activated protein kinase (MAPK), ERK1/2, which upregulates PDE4 expression in salmeterol-exposed ASM; and 2) the inhibitory actions of DEX on salmeterol-induced ERK1/2 activation and resultant PDE4-mediated changes in ASM responsiveness were prevented by gene silencing or pharmacological inhibition of DEX-induced expression of MAPK phosphatase-1 (MKP-1), an endogenous deactivator of ERK1/2 signaling. Conclusion GCs prevent the adverse proasthmatic effects of prolonged LABA exposure on airway responsiveness due to GC-induced upregulation of MKP-1, which inhibits proasthmatic ERK1/2 signaling in the LABA-exposed ASM. PMID:20392484

  1. 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

  2. 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.

  3. ISO 9001:2000--setting the standard for quality management.

    PubMed

    Edelstein, M E

    2001-04-01

    How will you approach the next quality management initiative? This article offers an introduction to the ISO 9001:2000 quality management system standards that can be applied to the HIM industry and how these standards can improve your department's policies and procedures.

  4. 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.

  5. ISO 9000: a guide to world-class quality standards.

    PubMed

    Tambolas, S F

    1996-02-01

    World standards for determining companies' commitment to continuous quality improvement (CQI) have been established. These standards are collectively known as ISO-9000. Prudent buyers of goods and services for health care organizations that are also committed to CQI should understand these standards and use them to facilitate supplier certification.

  6. 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)

  7. 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)

  8. 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.

  9. 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…

  10. 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.

  11. 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.…

  12. 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…

  13. 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.

  14. US companies gear up for ISO 14001 certification

    SciTech Connect

    Donaldson, J.

    1996-05-01

    Expecting the first international environmental management systems (EMS) standard to be in print and official by mid-summer, several U.S. companies are moving ahead with early certification plans. In fact, SGS-Thomson Microelectronics has claimed the first facility certification in the U.S. to the draft international standard (DIS) version developed and approved by the International Organization for Standardization (ISO). This certification refers to the EMS specification standard identified as ISO 14001, which provides for the basic tenets of an environmental management system. Austria, Switzerland, and Turkey adopted an early committee-draft (CD) version of 14001. The Japanese Ministry of International Trade and Industry (MITI) is asking companies to prepare new environmental-management plans that conform with 14001 by the end of 1996. Some Japan observers speculate that MITI is using the 14001 process to spur Japanese companies into raising environmental performance levels. Already, 30 companies are DIS 14001 certified. The U.S. firms that have been taking a wait-and-see approach may want to reevaluate their positions, suggests Joseph Cascio, chairman of the U.S. Technical Advisory Group (TAG) developing the U.S. position on the EMS standards. {open_quotes}The benefits may far outweight the risks,{close_quotes} Cascio says. {open_quotes}While it is true that there is not a product-quality driver in ISO 14001 as in ISO 9000, there are other drivers having to do with reliable management of environmental obligations, reduced risk, potential regulatory relief, and satisfying customer demand for responsible environmental behavior. ISO 14000 has to do with demonstrating intention and responsibility through conscious, organized, institutional commitment to an environmental mode of doing business.{close_quotes}

  15. Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study.

    PubMed

    Chagoya de Sánchez, V; Hernández-Muñoz, R; López-Barrera, F; Yañez, L; Vidrio, S; Suárez, J; Cota-Garza, M D; Aranda-Fraustro, A; Cruz, D

    1997-12-01

    Acute myocardial infarction is the second cause of mortality in most countries, therefore, it is important to know the evolution and sequence of the physiological and biochemical changes involved in this pathology. This study attempts to integrate these changes and to correlate them in a long-term model (96 h) of isoproterenol-induced myocardial cell damage in the rat. We achieved an infarct-like damage in the apex region of the left ventricle, occurring 12-24 h after isoproterenol administration. The lesion was defined by histological criteria, continuous telemetric ECG recordings, and the increase in serum marker enzymes, specific for myocardial damage. A distinction is made among preinfarction, infarction, and postinfarction. Three minutes after drug administration, there was a 60% increase in heart rate and a lowering of blood pressure, resulting possibly in a functional ischemia. Ultrastructural changes and mitochondrial swelling were evident from the first hour of treatment, but functional alterations in isolated mitochondria, such as decreases in oxygen consumption, respiratory quotient, ATP synthesis, and membrane potential, were noticed only 6 h after drug administration and lasted until 72 h later. Mitochondrial proteins decreased after 3 h of treatment, reaching almost a 50% diminution, which was maintained during the whole study. An energy imbalance, reflected by a decrease in energy charge and in the creatine phosphate/creatine ratio, was observed after 30 min of treatment; however, ATP and total adenine nucleotides diminished clearly only after 3 h of treatment. All these alterations reached a maximum at the onset of infarction and were accompanied by damage to the myocardial function, drastically decreasing left ventricular pressure and shortening the atrioventricular interval. During postinfarction, a partial recovery of energy charge, creatine phosphate/creatine ratio, membrane potential, and myocardial function occurred, but not of mitochondrial

  16. [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.

  17. Site-directed mutagenesis of human beta-adrenergic receptors: substitution of aspartic acid-130 by asparagine produces a receptor with high-affinity agonist binding that is uncoupled from adenylate cyclase.

    PubMed Central

    Fraser, C M; Chung, F Z; Wang, C D; Venter, J C

    1988-01-01

    By using oligonucleotide-directed mutagenesis, we have produced a point mutation (guanine to adenine) at nucleotide 388 of the gene for human beta-adrenergic receptor (beta AR) that results in a substitution of asparagine for the highly conserved aspartic acid at position 130 in the putative third transmembrane domain of the human beta AR ([Asn130]beta AR). We have examined the functional significance of this mutation in B-82 cells continuously expressing the mutant [Asn130]beta AR. The mutant [Asn130]beta AR displayed normal antagonist binding but unusually high-affinity agonist binding (5- to 10-fold higher than wild-type beta AR), consistent with a single class of high-affinity binding sites. The mutant beta AR displayed guanine nucleotide-sensitive changes in agonist affinity (3- to 5-fold shift) implying an interaction between the beta AR and the stimulatory guanine nucleotide-binding regulatory protein; however, the ability of guanine nucleotides to alter agonist affinity was attenuated. Addition of saturating concentrations of isoproterenol to cell cultures expressing mutant [Asn130]-beta ARs had no effect on intracellular levels of cAMP, indicating that the mutant beta AR is unable to affect stimulation of adenylate cyclase. These results indicate that substitution of the aspartic acid with asparagine at residue 130 of the human beta AR dissociates the well-characterized guanine nucleotide effects on agonist affinity from those on activation of the stimulatory guanine nucleotide-binding regulatory protein and adenylate cyclase and suggests the existence of two distinct counterions for the amine portion of catecholamines that are associated with high- and low-affinity agonist binding states of beta AR. Images PMID:2840663

  18. Muscimol as an ionotropic GABA receptor agonist.

    PubMed

    Johnston, Graham A R

    2014-10-01

    Muscimol, a psychoactive isoxazole from Amanita muscaria and related mushrooms, has proved to be a remarkably selective agonist at ionotropic receptors for the inhibitory neurotransmitter GABA. This historic overview highlights the discovery and development of muscimol and related compounds as a GABA agonist by Danish and Australian neurochemists. Muscimol is widely used as a ligand to probe GABA receptors and was the lead compound in the development of a range of GABAergic agents including nipecotic acid, tiagabine, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, (Gaboxadol(®)) and 4-PIOL.

  19. 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

  20. Spectroscopic and computational studies of matrix-isolated iso-CHBr3: structure, properties, and photochemistry of iso-bromoform.

    PubMed

    George, Lisa; Kalume, Aimable; Esselman, Brian J; Wagner, James; McMahon, Robert J; Reid, Scott A

    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(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(3) isolated in Ar or Ne matrices at ~5 K yielded iso-CHBr(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(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 ~200 kJ/mol above the global CHBr(3) minimum, the isomer is bound by some 60 kJ/mol in the gas phase with respect to the CHBr(2) + Br asymptote. The photochemistry of iso-CHBr(3) was investigated by selected wavelength laser irradiation into the intense S(0) → S(3) transition, which resulted in back photoisomerization to CHBr(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.

  1. 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.

  2. ISO 9001: 2008 Quality Assurance Assessment of Defense Acquisition University Processes

    DTIC Science & Technology

    2012-09-27

    ISO 9001 :2008 Quality Management System Requirements. The...overall objective was to perform a quality review, using ISO 9001 :2008 Quality Management System assessment techniques, of Defense Acquisition...57 Introduction Objectives Our overall objective was to perform a quality review, using ISO 9001 :2008 Quality Management

  3. 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

    ... Energy Regulatory Commission New England Power Generators Association Inc., Complainant v. ISO New England Inc., Respondent; ISO New England Inc. and New England Power Pool; Notice of Complaint March 24... Generators Association Inc. (Complainant) filed a formal complaint against ISO New England Inc....

  4. 76 FR 4104 - Notice of Commission Staff Attendance at Midwest ISO Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-24

    ... Energy Regulatory Commission Notice of Commission Staff Attendance at Midwest ISO Meetings January 13... Commission staff may attend the following Midwest ISO-related meetings during the 2011 year: Advisory.... Paul, MN) September 14 October 19 November 16 December 6 Midwest ISO Informational Forum (3 p.m.-5...

  5. 75 FR 5779 - Notice Providing Agenda for Technical Conference on RTO/ISO Responsiveness

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... Energy Regulatory Commission Notice Providing Agenda for Technical Conference on RTO/ISO Responsiveness.... ER09-1050-000, ER09- 1192-000. ISO New England, Inc. and New England Docket No. ER09-1051-000. Power... , (202) 502-8048. Kimberly D. Bose, Secretary. Agenda--Technical Conference on RTO/ISO...

  6. 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

  7. Basal responses of the L-type Ca2+ and hyperpolarization-activated currents to autonomic agonists in the rabbit sino-atrial node.

    PubMed Central

    Zaza, A; Robinson, R B; DiFrancesco, D

    1996-01-01

    1. The dose dependence of the cholinergic agonist acetylcholine (ACh) and the beta-adrenergic agonist isoprenaline (Iso) were determined for the hyperpolarization-activated current (If) and the L-type Ca2+ current (ICa,L) in single cells isolated from the rabbit sino-atrial (SA) node. 2. ACh inhibited If by a negative shift of its activation curve with a maximal effect of -9.9 mV; half-maximal effect was produced by 0.019 microM ACh. High ACh concentrations were required to inhibit ICa,L only partially (31% inhibition at 300 microM). 3. In contrast, If and ICa,L responded to Iso over a similar dose range, with concentrations for half-maximal enhancement of 0.0136 and 0.0070 microM, respectively. 4. The effects on spontaneous activity of ACh (range 0.001-0.03 microM) and Iso (range 0.001-1 microM) were investigated. ACh decreased the slope of diastolic depolarization at concentrations similar to those inhibiting If (> 50% at 0.03 microM). Iso enhanced diastolic depolarization at concentrations similar to those affecting both If and ICa,L (half-maximal effect at 0.027 microM). 5. In a ramp-clamp protocol simulating diastolic depolarization, the threshold for activation of inward nifedipine-sensitive current was -41.22 +/- 0.68 mV. Although enhancing ICa,L, Iso did not affect this threshold. 6. Half-maximal ACh concentrations for inhibition of automaticity and If are similar and are lower than the threshold concentrations for modulation of ICa,L; this argues against a role of ICa,L in direct muscarinic modulation of pacemaking. In contrast, modulation of If, ICa,L and automaticity occur at similar Iso concentrations. The difference between maximum diastolic potential (-61.95 +/- 0.93 mV) and the threshold for Iso-stimulated ICa,L (-39.54 +/- 1.03 mV) suggests that this current plays a role only at later stages of diastolic depolarization. PMID:8866859

  8. Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: are AMPK and TLRs connected?

    PubMed

    Soraya, Hamid; Farajnia, Safar; Khani, Sajjad; Rameshrad, Maryam; Khorrami, Arash; Banani, Armita; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2012-12-01

    AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI). Besides, the innate immune response through TLRs is activated during MI. In the present study, the effects of short-term treatment with metformin on TLRs activity and its relation with AMPK in isoproterenol-induced MI were assessed in rats. To induce MI, a subcutaneous injection of isoproterenol was given to Wistar rats for two consecutive days. Metformin (25, 50, and 100mg/kg) was orally administered to rats twice daily for two days. Interstitial fibrosis was dose-dependently attenuated in the treated groups in comparison to the MI group (score: 1.25 ± 0.28 with 100 mg/kg metformin versus 3.5 ± 0.28; P<0.001). Further, metformin reduced TLR-dependent inflammatory cytokines as indexed by reduced myocardial levels of TNFα (maximum 68%; P<0.001) and IL6 (maximum 84%; P<0.001) as well as by reduced myocardial MPO activity (25%; P<0.01). It was found that the level of phosphorylated AMPK was significantly upregulated by 165% (P<0.001) when treated with 100 mg/kg of metformin, but not with 25 and 50mg/kg. This was associated with a remarkable suppression of TLR4 expression and reduction of protein level of TLRs adapter protein, MyD88 (P<0.01) in the infarcted myocardium. These results suggest that AMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart, which may indicate a link between AMPK and TLRs.

  9. Corepressors of agonist-bound nuclear receptors

    SciTech Connect

    Gurevich, Igor; Aneskievich, Brian J.

    2007-09-15

    Nuclear receptors (NRs) rely on coregulator proteins to modulate transcription of target genes. NR coregulators can be broadly subdivided into coactivators which potentiate transcription and corepressors which silence gene expression. The prevailing view of coregulator action holds that in the absence of agonist the receptor interacts with a corepressor via the corepressor nuclear receptor (CoRNR, 'corner') box motifs within the corepressor. Upon agonist binding, a conformational change in the receptor causes the shedding of corepressor and the binding of a coactivator which interacts with the receptor via NR boxes within the coregulator. This view was challenged with the discovery of RIP140 which acts as a NR corepressor in the presence of agonist and utilizes NR boxes. Since then a number of other corepressors of agonist-bound NRs have been discovered. Among them are LCoR, PRAME, REA, MTA1, NSD1, and COPR1 Although they exhibit a great diversity of structure, mechanism of repression and pathophysiological function, these corepressors frequently have one or more NR boxes and often recruit histone deacetylases to exert their repressive effects. This review highlights these more recently discovered corepressors and addresses their potential functions in transcription regulation, disease pharmacologic responses and xenobiotic metabolism.

  10. 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

  11. Serotonergic agonists behave as partial agonists at the dopamine D2 receptor.

    PubMed

    Rinken, A; Ferré, S; Terasmaa, A; Owman, C; Fuxe, K

    1999-02-25

    RAT dopamine D2short receptors expressed in CHO cells were characterized by activation of [35S]GTPgammaS binding. There were no significant differences between the maximal effects seen in activation of [35S]GTPgammaS binding caused by dopaminergic agonists, but the effects of 5-HT, 8OH-DPAT and 5-methoxytryptamine amounted to 47 +/- 7%, 43 +/- 5% and 70 +/- 7% of the dopamine effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited activations of both types of ligands with equal potency (pA2 = 8.9 +/- 0.1), indicating that only one type of receptor is involved. In competition with [3H]raclopride binding, dopaminergic agonists showed 53 +/- 2% of the binding sites in the GTP-dependent high-affinity state, whereas 5-HT showed only 20 +/- 3%. Taken together, the results indicate that serotonergic agonists behave as typical partial agonists for D2 receptors with potential antiparkinsonian activity.

  12. ISO standards on test methods for water radioactivity monitoring.

    PubMed

    Calmet, D; Ameon, R; Bombard, A; Forte, M; Fournier, M; Herranz, M; Jerome, S; Kwakman, P; Llaurado, M; Tokonami, S

    2013-11-01

    Water is vital to humans and each of us needs at least 1.5L of safe water a day to drink. Beginning as long ago as 1958 the World Health Organization (WHO) has published guidelines to help ensure water is safe to drink. Focused from the start on monitoring radionuclides in water, and continually cooperating with WHO, the International Standardization Organization (ISO) has been publishing standards on radioactivity test methods since 1978. As reliable, comparable and 'fit for purpose' results are an essential requirement for any public health decision based on radioactivity measurements, international standards of tested and validated radionuclide test methods are an important tool for production of such measurements. This paper presents the ISO standards already published that could be used as normative references by testing laboratories in charge of radioactivity monitoring of drinking water as well as those currently under drafting and the prospect of standardized fast test methods in response to a nuclear accident.

  13. 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}.

  14. 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?'

  15. 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.

  16. Testing the generalizability of the ISO model for nursing diagnoses.

    PubMed

    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.

  17. 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.

  18. Synthesis and Applications of iso-Hajos–Parrish Ketones**

    PubMed Central

    Eagan, James M.; Hori, Masahiro; Wu, Jianbin; Kanyiva, Kyalo Stephen; Snyder, Scott A.

    2015-01-01

    Although numerous natural products possess ring systems and functionality for which “iso-Hajos–Parrish” ketones would be of value, such building blocks have not been exploited to the same degree as the more typical Hajos–Parrish hydrindane. Herein we outline an efficient three-step synthesis of such materials fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. We then show how one iso-Hajos–Parrish ketone can be converted into two distinct natural product analogs as well as one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos–Parrish ketone. PMID:25974879

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

    NASA Astrophysics Data System (ADS)

    Creminelli, Paolo; Emami, Razieh; Simonović, Marko; Trevisan, Gabriele

    2013-07-01

    In DBI inflation the cubic action is a particular linear combination of the two, otherwise independent, cubic operators dot pi3 and dot pi(∂iπ)2. We show that in the Effective Field Theory (EFT) of inflation this is a consequence of an approximate 5D Poincar&apose 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 cs. In the limit cs → 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 cs.

  20. 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.

  1. ISO 9000 quality standards: a model for blood banking?

    PubMed

    Nevalainen, D E; Lloyd, H L

    1995-06-01

    The recent American Association of Blood Banks publications Quality Program and Quality Systems in the Blood Bank and Laboratory Environment, the FDA's draft guidelines, and recent changes in the GMP regulations all discuss the benefits of implementing quality systems in blood center and/or manufacturing operations. While the medical device GMPs in the United States have been rewritten to accommodate a quality system approach similar to ISO 9000, the Center for Biologics Evaluation and Research of the FDA is also beginning to make moves toward adopting "quality systems audits" as an inspection process rather than using the historical approach of record reviews. The approach is one of prevention of errors rather than detection after the fact (Tourault MA, oral communication, November 1994). The ISO 9000 series of standards is a quality system that has worldwide scope and can be applied in any industry or service. The use of such international standards in blood banking should raise the level of quality within an organization, among organizations on a regional level, within a country, and among nations on a worldwide basis. Whether an organization wishes to become registered to a voluntary standard or not, the use of such standards to become ISO 9000-compliant would be a move in the right direction and would be a positive sign to the regulatory authorities and the public that blood banking is making a visible effort to implement world-class quality systems in its operations. Implementation of quality system standards such as the ISO 9000 series will provide an organized approach for blood banks and blood bank testing operations. With the continued trend toward consolidation and mergers, resulting in larger operational units with more complexity, quality systems will become even more important as the industry moves into the future.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. JCAHO accreditation and ISO 9000 certification: an update.

    PubMed

    1998-10-01

    With hospital security now considered by the JCAHO as part of the hospital's total environment of care, security directors must be prepared to answer questions about areas where multidisciplinary solutions are sought. At the same time, it may pay to become familiar with ISO 9000 certification, quality standards that may in the future complement JCAHO accreditation. In this report, we'll provide detailed information that may stand you in good stead in the years ahead.

  3. Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM ...

    EPA Pesticide Factsheets

    this file contains the raw data on the effects of in utero administration of di-iso-butyl phthalate on maternal weight gain during dosing and the numbers of fetuses and fetal resorptions. The data have all been previously published, as described on the file metadata sheet. Raw data file from our published studies on DIBP specifically requested (6/14/2016) by NCEA scientists for analysis and inclusion in their assessment of this chemical.

  4. ISO standards for pathology - a step too far?

    PubMed

    Burnett, David

    2015-11-01

    The International Standard, ISO 15189 which specifies requirements for quality and competence in medical laboratories was written by medical laboratory professionals. Since its first publication in 2003, it has raised awareness of the importance of medical laboratories with governments throughout the world and provided a tool with which laboratories may develop their quality management systems and assess their own competence. This paper examines the use of the Standard in the context of self-assessment, accreditation and regulation of medical laboratories.

  5. 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.

  6. [ISO 9001 conformity in research, teaching and rehabilitation].

    PubMed

    Howorka, K; Kletschka, G; Pumprla, J; Thoma, H

    1998-01-01

    Quality assurance, in particular in the areas of development and production of medical devices, is one of the tasks of biomedical engineering. The interdisciplinary working group "Functional Rehabilitation and Group Education, Vienna" is committed to the development and implementation of group education models on three levels: (1) direct education/instruction of patients with chronic diseases, (2) university research and teaching, and (3) development of technical aids for rehabilitation and the means for disseminating group education models in rehabilitation and therapy. Major aims were, by generating conformity with ISO 9001 standards, to achieve greater transparency and process optimization with very small resources in university (teaching, research, technical aids) and extra-university (rehabilitation) areas. A secondary aim was the establishment of interdisciplinary (clinical and biomedical) cooperation at university level. In all main areas (research, teaching and group education/instruction), ISO 9001-conformity was achieved by our activities on three methodological levels: (1) description and analysis of processes, (2) use of ISO 9001 standards for evaluating internal processes, and (3) optimization measures. The following article contains relevant elements of the quality manual and quality assurance system, and offers a typical example of innovative cooperation between medicine and medical engineering.

  7. ISO Far-Infrared Spectroscopic Observations of Jupiter

    NASA Astrophysics Data System (ADS)

    Burgdorf, M. J.; Encrenaz, Th.; Feuchtgruber, H.; Davis, G. R.; Fouchet, Th.; Gautier, D.; Lellouch, E.; Orton, G. S.; Sidher, S. D.

    2001-07-01

    We present the far-infrared spectrum of Jupiter that was measured with the Short and Long Wavelength Spectrometers (SWS and LWS) aboard the Infrared Space Observatory (ISO). The region between 38 and 44 microns was observed in grating mode, where the SWS provides a spectral resolution of about 1300. For longer waves up to 197 microns the LWS-FP (Fabry-Perot) was used to achieve a resolution of several thousand. The observations were made between 23 and 26 May 1997 during ISO's revolutions 554, 556 and 557. The Jovian spectrum in the far-infrared is compared to an atmospheric radiative transfer model using expected values for the vertical profiles of the atmospheric constituents. Rotational transitions of ammonia and phosphine are responsible for the absorption features observed: Strong ammonia absorption manifolds are obvious against the background continuum slope, appearing at 39, 42, 46, 51, 56, 63, 72, 84, 100 and 125 microns in both the data and the model. Also PH3 features are present at the expected wavelengths of 113 and 141 microns in both the data and the model. This is the first time that most of these far-infrared features have been detected. The ISO observations are therefore of interest for the preparation of the planned submillimeter studies of the atmospheres of the Jovian planets with FIRST.

  8. 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.

  9. 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

  10. A practical synthesis of long-chain iso-fatty acids (iso-C12-C19) and related natural products.

    PubMed

    Richardson, Mark B; Williams, Spencer J

    2013-01-01

    A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12-C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12-C14) or the C15 and C16 lactones pentadecanolide (for iso-C15-C17) and hexadecanolide (for iso-C18-C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13-C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

  11. 78 FR 67357 - New England Power Generators Association, Inc. v. ISO New England Inc.; Notice of Complaint

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... Energy Regulatory Commission New England Power Generators Association, Inc. v. ISO New England Inc... Association, Inc. (NEPGA or Complainant) filed a complaint against ISO New England, Inc. (ISO-NE or Respondent). NEPGA alleges that the provisions of the ISO-NE Tariff that set capacity prices during...

  12. Agonistic and reproductive interactions in Betta splendens.

    PubMed

    Bronstein, P M

    1984-12-01

    Reproductive and agonistic behaviors in Siamese fighting fish were investigated in eight experiments, and some consequences and determinants of these sequences were isolated. First, fights and the formation of dominance-subordinancy relations were studied. Second, it was determined that large body size as well as males' prior residency in a tank produced an agonistic advantage; the magnitude of this advantage was positively related to the duration of residency. Third, the prior-residency effect in Bettas was determined by males' familiarity with visual and/or tactile cues in their home tanks. Fourth, dominant males had greater access to living space and were more likely to display at a mirror, build nests, and approach females than were subordinates. Finally, it was discovered that chemical cues associated with presumedly inert plastic tank dividers influence Bettas' social behavior.

  13. Agonists block currents through acetylcholine receptor channels.

    PubMed Central

    Sine, S M; Steinbach, J H

    1984-01-01

    We have examined the effects of high concentrations of cholinergic agonists on currents through single acetylcholine receptor (AChR) channels on clonal BC3H1 cells. We find that raised concentrations of acetylcholine (ACh; above 300 microM) or carbamylcholine (Carb; above 1,000 microM) produce a voltage- and concentration-dependent reduction in the mean single-channel current. Raised concentrations of suberyldicholine (Sub; above 3 microM) produce a voltage- and concentration-dependent increase in the number of brief duration low-conductance interruptions of open-channel currents. These observations can be quantitatively described by a model in which agonist molecules enter and transiently occlude the ion-channel of the AChR. PMID:6478036

  14. Ropinirole, a non-ergoline dopamine agonist.

    PubMed

    Jost, Wolfgang H; Angersbach, Dieter

    2005-01-01

    Dopamine agonists have become indispensable in the treatment of Parkinson's disease. In every-day practice, however, the decision to select the best compound for an individual patient is rendered difficult because of the large number of substances available on the market. This review article provides a closer look at the experimental and clinical studies with ropinirole published so far. Ropinirole is a non-ergoline dopamine agonist which has been proven to be effective in both, monotherapy and combination therapy of idiopathic Parkinson's disease. In addition to ameliorating bradykinesia, rigor, and tremor, ropinirole facilitates the daily life and improves depressive moods of patients with Parkinson's disease. The long-term complications of levodopa are avoided, and problems commonly associated with levodopa treatment are reduced. Ropinirole appears to have a neuroprotective effect. In addition to Parkinson's disease, ropinirole has also been used successfully in the treatment of restless legs syndrome.

  15. The identification of orally bioavailable thrombopoietin agonists.

    PubMed

    Munchhof, Michael J; Antipas, Amy S; Blumberg, Laura C; Brissette, William H; Brown, Matthew F; Casavant, Jeffrey M; Doty, Jonathan L; Driscoll, James; Harris, Thomas M; Wolf-Gouveia, Lilli A; Jones, Christopher S; Li, Qifang; Linde, Robert G; Lira, Paul D; Marfat, Anthony; McElroy, Eric; Mitton-Fry, Mark; McCurdy, Sandra P; Reiter, Lawrence A; Ripp, Sharon L; Shavnya, Andrei; Thomasco, Lisa M; Trevena, Kristen A

    2009-03-01

    Recently, we disclosed a series of potent pyrimidine benzamide-based thrombopoietin receptor agonists. Unfortunately, the structural features required for the desired activity conferred physicochemical properties that were not favorable for the development of an oral agent. The physical properties of the series were improved by replacing the aminopyrimidinyl group with a piperidine-4-carboxylic acid moiety. The resulting compounds possessed favorable in vivo pharmacokinetic properties, including good bioavailability.

  16. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

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

    2016-02-08

    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.

  17. Isolation of anteiso-C17, iso-C17, iso-C16, and iso-C15 bacillomycin D from Bacillus amyloliquefaciens SD-32 and their antifungal activities against plant pathogens.

    PubMed

    Tanaka, Keijitsu; Ishihara, Atsushi; Nakajima, Hiromitsu

    2014-02-19

    Two new cyclic lipopeptides (3 and 4) were isolated from the culture filtrate of Bacillus amyloliquefaciens strain SD-32, together with two known metabolites, iso-C15 and iso-C16 bacillomycin D (1 and 2). Spectroscopic and chemical analyses identified the structures of the new compounds 3 and 4 as anteiso-C17 bacillomycin D, cyclic (l-Asn-d-Tyr-d-Asn-l-Pro-l-Glu-d-Ser-l-Thr-3-amino-14-methylhexadecanoic acid) and iso-C17 bacillomycin D, cyclic (l-Asn-d-Tyr-d-Asn-l-Pro-l-Glu-d-Ser-l-Thr-3-amino-15-methylhexadecanoic acid), respectively. The absolute configuration of C-3 in the β-amino fatty acid was determined to be R on the basis of the CD spectrum of its dinitrophenyl-p-methoxyaniline derivative. The activities of compounds 1-4 were evaluated against 13 plant pathogens: the activities of anteiso- and iso-C17 bacillomycin D (3 and 4) were almost the same and stronger than those of iso-C15 and iso-C16 bacillomycin D (1 and 2); iso-C15 bacillomycin D (1) was weakest. Compounds 2-4 inhibited the growth of all fungi tested; however, Pythium aphanidermatum was not inhibited at all by any of the compounds. Furthermore, compounds 1-4 at concentrations of 80, 40, 30, and 30 μM, respectively, inhibited completely the Botrytis cinerea infection in cucumber leaf.

  18. Implementation of ISO guide 25 in a medical dosimetry secondary standards calibration laboratory

    SciTech Connect

    DeWerd, L.A.

    1995-12-31

    Currently, there is a great deal of discussion among industry and government agencies about ISO 9000 accreditation. U.S. manufacturers with ISO 9000 accreditation are regarded more favorably by European countries. The principles behind the ISO 9000 accreditation are based on the Total Quality Management (TQM) principles that are being implemented in many U.S. industries. This paper will deal only with the calibration issue. There is a difference in the areas covered by ISO 9000 and ISO Guide 25 documents. ISO 9000, in particular ISO 9001 - ISO 9003, cover the {open_quotes}calibration{close_quotes} of inspection, measuring and test equipment. This equipment is basically used for {open_quotes}factory calibrations{close_quotes} to determine that equipment is performing within manufacturer specifications. ISO Guide 25 is specifically for {open_quotes}calibration and testing laboratories,{close_quotes} generally laboratories that have painstaking procedures to reduce uncertainties and establish high accuracy of the transfer of calibration. The experience of the University of Wisconsin Accredited Dosimetry Calibration Laboratory in conforming to ISO Guide 25 will be outlined. The entire laboratory staff must become familiar with the process and an individual with direct authority must become the one to maintain the quality of equipment and calibrations in the role of {open_quotes}quality-assurance manager.{close_quotes}

  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. ISO 14000: Potential impediments to implementation in the United States

    SciTech Connect

    Neet, J.O. Jr.; Fletcher, J.P.

    1997-12-31

    The past few years have seen a movement away from the command and control style of enforcing environmental policy towards corporate performance and self regulation by way of voluntary environmental audits. The EPA`s Voluntary Environmental Self-Policing and Self-Disclosure Interim Policy Statement issued on December 22, 1995, and the adoption of the ISO 14001 standard embody this principle. With respect to its self-policing policy, the EPA, in return for voluntary disclosure of internal self audits, offers reduced penalties for any regulatory violations identified by such audits. It is proposed that similar inducements be offered to those organizations which adopt the ISO 14001 standard. Although many organizations are happy to see the decline in form of the command and control method of enforcing environmental policy, its replacement brings with it a different assortment of legal problems. The voluntary disclosure of environmental audits and performances could result in the confidentiality status attaching to those papers being lost and an organization finding itself on the receiving end of either a civil or criminal action in relation to information it voluntarily disclosed. A further cause for concern is that the new international standard could be used by the courts to define a new standard of care where a failure to comply could result in a finding of negligence. This paper explores the movement away from the command and control method to enforce federal environmental policy prior to the publishing of ISO 14001 to that of voluntary compliance. The paper reviews new legal issues organizations now face as a consequence and explores ways of protecting information voluntarily disclosed under a self audit. Finally, the paper contrasts the shift in enforcement policy in the United States to the European culture of enforcing environmental policy through performance standards and uniform technology-based controls.

  1. 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.

  2. 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

  3. 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.

  4. New guideline represents 'processed-oriented' approach for ISO 9000.

    PubMed

    2001-02-01

    Hospitals that have been tracking the development of ISO 9000 in the health care industry should pay close attention to a new guideline about to emerge. According to Laura Preole, health care services manager of SGS International Certification Services based in Rutherford, NJ, the new guideline is the latest step in an effort to establish a more 'process-oriented' method of looking at the health care environment from the moment a patient walks into a facility to the moment he or she is discharged.

  5. Implementation of ISO 9000 to the food industry: an overview.

    PubMed

    Efstratiadis, M M; Karirti, A C; Arvanitoyannis, I S

    2000-11-01

    Since the early 1980s, manufacturing industries worldwide have seen a revolution in the way they operate. Consumers have become more and more demanding and the key to company/firm survival is the recognition of customers' satisfaction. In a way, companies have been forced to enhance the quality of their processes and their products. Some of them chose to establish internal quality systems whereas others have opted for employing a general quality system standard, such as the BS 5750 or the ISO 9000 series. In Greece, a great part of the companies (about 80%) employ quality system standards, among which the highest percentage (80%) belong to food manufacturing industries.

  6. Application of ISO/IEC 15504 in Very Small Enterprises

    NASA Astrophysics Data System (ADS)

    Mas, Antonia; Amengual, Esperança; Mesquida, Antoni Lluís

    This paper presents the experience of application of the ISO/IEC 15504 standard in eight software companies. Firstly, the objectives, the participants and the work plan are exposed. Secondly, the implementation of the project activities and its results are summarized. And finally, the cost of the implementation is detailed. The project which has allowed this improvement effort in these organizations has been named "QuaSAR II" and represents the continuance of the "QuaSAR" project, a software process improvement initiative started in 2002 in the Balearic Islands.

  7. Local control network and internetwork ISO-OSI reference model

    SciTech Connect

    Damsker, D.

    1983-05-01

    The paper describes a new local control network architecture. The new control network is totally distributed and redundantly hardware and software structured, based on a bus configuration and on CSMA/CD media access control. The architecture of the control structure and of the data communications structure for both Local Network and Internetwork is discussed in comparison with ISO-OSI and Local Area Network IEEE Standard 802 (Draft) Reference Models. A previous paper dealt with the physical implementation of this concept. The present paper is more software structure oriented.

  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. 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.

  10. 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

    2016-01-01

    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.

  11. 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.

  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. 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.

  14. Influence of polyunsaturated fatty acids on vasoconstrictions induced by 8-iso-PGF(2alpha) and 8-iso-PGE(2).

    PubMed

    Sametz, W; Jeschek, M; Juan, H; Wintersteiger, R

    2000-04-01

    8-iso-PGF(2alpha) and 8-iso-PGE(2), which are released in vivo by free radical catalyzed peroxidation of arachidonic acid, are equipotent vasoconstrictors in vivo and in vitro. It is assumed that they exert this effect via activation of the thromboxane A(2) (TP) receptor or a TP-receptor-like isoprostane receptor. Increased levels of 8-iso-PGF(2alpha) have been detected in human cardiovascular diseases. It has been found that polyunsaturated fatty acids (PUFAs) have many beneficial effects in cardiovascular diseases, including antivasoconstrictor actions. Therefore, we investigated the influence of perfusions with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DGLA) at final concentrations of 3 and 30 micromol/l on vasoconstriction induced by 8-iso-PGF(2alpha), 8-iso-PGE(2) and the thromboxane A(2) mimetic U 46619 in the vasculature of the isolated perfused rabbit ear. Additionally, the effect of indomethacin (final concentration 3 micromol/l) on the effects of the PUFAs was investigated. Our results show that the PUFAs at a concentration of 30 micromol/l caused a significant inhibition of the vasoconstrictions induced by 8-iso-PGF(2alpha), 8-iso-PGE(2) and U 46619. Furthermore, it can be assumed that a part of the inhibitory effect of DGLA is due to the effect of a cyclooxygenase product, probably PGE(1), because indomethacin reduced the inhibitory effect of DGLA.

  15. 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... GRAS § 184.1165 n-Butane and iso-butane. (a) n-Butane and iso-butane (empirical formula C4H10, CAS...

  16. Three Quality Journeys - Capability Maturity Model Integration, Baldrige Performance Excellence Program, and ISO 9000 Series

    DTIC Science & Technology

    2012-04-26

    quality management practices. ISO 9001 :2008 has been implemented by over a million organizations in 176 countries. 14 Three Quality Journeys...University I S O 9 0 0 0 Initial Release of ISO 9000:1987 9001 :2000 amended to 9001 :2008 – quality management requirements 9004:2000 amended...clarifications of 9001 and 9004 occurred in 2008 and 2009, respectively o ISO 9001 :2000 - eight quality

  17. Implementation of ISO 9000 in the healthcare sector: a case study.

    PubMed

    Motwani, J G; Cheng, C H; Madan, M S

    1996-01-01

    In order to compete at the international level, companies are beginning to recognize ISO 9000 registration as a virtual necessity. As a result, the number of ISO certifications issued in the U.S. and Canada tripled between 1992 and 1994. By means of a case study, this paper describes how a large healthcare manufacturing organization recently achieved its ISO 9001 certification. Specifically, the strategies and the process used by the organization in obtaining the registration is explained.

  18. Impact of 50% Synthesized Iso-Paraffins (SIP) on Middle Distillate Fuel Filtration and Coalescence

    DTIC Science & Technology

    2014-10-30

    Impact of 50% Synthesized Iso -Paraffins (SIP) on Middle Distillate Fuel Filtration and Coalescence NF&LCFT REPORT 441/15-003 30 October 2014...negative structural impacts. An alternative sourced F-76 currently under-going qualification testing is Synthesized Iso -Paraffins (SIP). SIP fuels...are made from direct fermentation of sugar into olefinic hydrocarbons. The olefinic hydrocarbons are hydroprocessed to produce an iso -paraffinic

  19. [Approval of ISO/IEC 17025 and quality control of laboratory testing].

    PubMed

    Yamamoto, Shigeki; Asakura, Hiroshi; Machii, Kenji; Igimi, Shizunobu

    2010-01-01

    First section of Division of Biomedical Food Research, National Institute of Health Sciences (NIHS) was approved by ISO/IEC 17025 as a laboratory having an appropriate laboratory testing technique. NIHS is the first national laboratory approved by ISO/IEC 17025. NIHS has also been accepted the appropriate technique and facility for the BSL3 level pathogens by ISO/IEC 17025. NIHS is necessary to take an external audit almost every year. This approval is renewed every 4 years.

  20. 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.

  1. Water in K and M giant stars unveiled by ISO

    NASA Astrophysics Data System (ADS)

    Tsuji, T.

    2001-09-01

    Based on the spectra obtained with Infrared Space Observatory, ISO, we detected the 6.3 mu m bands of water in the late K giant Aldebaran (alpha Tau) and several early M giant stars (between M0 and M3.5), which have been deemed to be too warm for tri-atomic H2O molecule to reside in their photospheres. The water column densities range (0.2 - 2) *E18 molecules cm-2 in our sample of K and M giant stars and the excitation temperatures are 1500 K or higher. Thus, the water bands are not originating in cool stellar winds either. The presence of water in the K and early M giant stars was quite unexpected from the traditional picture of the atmosphere of the red giant star consisting of the photosphere, hot chromosphere, and cool wind. We confirm that a rather warm molecule forming region should exist as a new component of the atmosphere of red giant stars and that this should be a general phenomenon in late-type stars. Based on the data archives of ISO, an ESA project with instruments funded by ESA member states (especially the PI countries: France, Germany, The Netherlands, and the UK) and with the participation of ISAS and NASA.

  2. ISO 17025: practical benefits of implementing a quality system.

    PubMed

    Honsa, Julie D; McIntyre, Deborah A

    2003-01-01

    As a laboratory certified to ISO 9001:2000 and accredited to ISO 17025, rtech laboratories has incorporated an overall system for technical and quality management, which results in benefits observed in daily laboratory practices. Technical requirements were updated to include the addition of formal personnel training plans and detailed records, method development and validation procedures, measurement of method uncertainty, and a defined equipment calibration and maintenance program. In addition, a stronger definition of the sample preparation process was documented to maintain consistency in sampling, and a more rigorous quality control monitoring program was implemented for chemistry and microbiology. Management quality improvements focused on document control to maintain consistent analytical processes, improved monitoring of supplier performance, a contract review process for documenting customer requirements, and a system for handling customer comments and complaints, with continuous improvement through corrective and preventive action procedures and audits. Quarterly management review of corrective actions, nonconforming testing, and proficiency testing aid in determining long-term trending. The practical benefits of these technical and management quality improvements are seen on a daily basis in the laboratory. Faster identification and resolution of issues regarding methods, personnel or equipment, improved customer satisfaction, meeting quality requirements of specialized customers, and overall increased laboratory business are all the result of implementing an effective quality system.

  3. 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.

  4. 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.

  5. 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.

  6. Inhibition of secretory phospholipase A2 activity attenuates acute cardiogenic pulmonary edema induced by isoproterenol infusion in mice after myocardial infarction.

    PubMed

    Kawabata, Kenichi; Fujioka, Daisuke; Kobayashi, Tsuyoshi; Saito, Yukio; Obata, Jun-Ei; Nakamura, Takamitsu; Yano, Toshiaki; Watanabe, Kazuhiro; Watanabe, Yosuke; Mishina, Hideto; Kugiyama, Kiyotaka

    2010-10-01

    Several types of secretory phospholipase A2 (sPLA2) are expressed in lung tissue, yielding various eicosanoids that might cause pulmonary edema. This study examined whether inhibition of sPLA2 activity attenuates acute cardiogenic pulmonary edema in mice. Acute cardiogenic pulmonary edema was induced in C57BL/6J male mice by an increase in heart rate with continuous intravenous infusion of isoproterenol (ISP) (10 mg/kg/h) at 2 weeks after the creation of myocardial infarction by left coronary artery ligation. Just before ISP infusion, a single intraperitoneal injection of 100 mg/kg LY374388, a prodrug of LY329722 that inhibits sPLA2 activity, or vehicle was administered. The ISP infusion after myocardial infarction induced interstitial and alveolar edema on lung histology. Furthermore, it increased the lung-to-body weight ratio, pulmonary vascular permeability evaluated by the Evans blue extravasation method, lung activity of sPLA2, and lung content of thromboxane A2 and leukotriene B4. These changes were significantly attenuated by LY374388 treatment. In Kaplan-Meier analysis, the survival rate during the ISP infusion after myocardial infarction was significantly higher in LY374388- than in vehicle-treated mice. Similar results were obtained with another inhibitor of sPLA2 activity, para-bromophenacyl bromide. In conclusion, inhibition of sPLA2 activity suppressed acute cardiogenic pulmonary edema.

  7. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

    PubMed Central

    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

  8. ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and colon cancer models.

    PubMed

    Ioannou, Kyriaki; Cheng, Kai Fan; Crichlow, Gregg V; Birmpilis, Anastasios I; Lolis, Elias J; Tsitsilonis, Ourania E; Al-Abed, Yousef

    2014-10-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, whereas prolonged administration of ISO-66 in mice with established syngeneic melanoma or colon cancer was non-toxic and resulted in a significant decrease in tumor burden. Subsequent ex vivo analysis of mouse splenocytes revealed that the observed decrease in tumor growth rates was likely mediated by the selective in vivo expansion of antitumor-reactive effector cells induced by ISO-66. Compared to other MIF-inactivating strategies employed in vivo, the anticancer activity of ISO-66 is demonstrated to be of equal or better efficacy. Our findings suggest that targeting MIF, via highly specific and stable compounds, such as ISO-66, may be effective for cancer treatment and stimulation of anticancer immune responses.

  9. Global Impact Estimation of ISO 50001 Energy Management System for Industrial and Service Sectors

    SciTech Connect

    Aghajanzadeh, Arian; Therkelsen, Peter L.; Rao, Prakash; McKane, Aimee T.

    2016-08-01

    A methodology has been developed to determine the impacts of ISO 50001 Energy Management System (EnMS) at a region or country level. The impacts of ISO 50001 EnMS include energy, CO2 emissions, and cost savings. This internationally recognized and transparent methodology has been embodied in a user friendly Microsoft Excel® based tool called ISO 50001 Impact Estimator Tool (IET 50001). However, the tool inputs are critical in order to get accurate and defensible results. This report is intended to document the data sources used and assumptions made to calculate the global impact of ISO 50001 EnMS.

  10. 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

  11. Discovery of G Protein-Biased EP2 Receptor Agonists

    PubMed Central

    2016-01-01

    To identify G protein-biased and highly subtype-selective EP2 receptor agonists, a series of bicyclic prostaglandin analogues were designed and synthesized. Structural hybridization of EP2/4 dual agonist 5 and prostacyclin analogue 6, followed by simplification of the ω chain enabled us to discover novel EP2 agonists with a unique prostacyclin-like scaffold. Further optimization of the ω chain was performed to improve EP2 agonist activity and subtype selectivity. Phenoxy derivative 18a showed potent agonist activity and excellent subtype selectivity. Furthermore, a series of compounds were identified as G protein-biased EP2 receptor agonists. These are the first examples of biased ligands of prostanoid receptors. PMID:26985320

  12. Sports doping: emerging designer and therapeutic β2-agonists.

    PubMed

    Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

    2013-10-21

    Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future.

  13. Agonist-receptor-arrestin, an alternative ternary complex with high agonist affinity.

    PubMed

    Gurevich, V V; Pals-Rylaarsdam, R; Benovic, J L; Hosey, M M; Onorato, J J

    1997-11-14

    The rapid decrease of a response to a persistent stimulus, often termed desensitization, is a widespread biological phenomenon. Signal transduction by numerous G protein-coupled receptors appears to be terminated by a strikingly uniform two-step mechanism, most extensively characterized for the beta2-adrenergic receptor (beta2AR), m2 muscarinic cholinergic receptor (m2 mAChR), and rhodopsin. The model predicts that activated receptor is initially phosphorylated and then tightly binds an arrestin protein that effectively blocks further G protein interaction. Here we report that complexes of beta2AR-arrestin and m2 mAChR-arrestin have a higher affinity for agonists (but not antagonists) than do receptors not complexed with arrestin. The percentage of phosphorylated beta2AR in this high affinity state in the presence of full agonists varied with different arrestins and was enhanced by selective mutations in arrestins. The percentage of high affinity sites also was proportional to the intrinsic activity of an agonist, and the coefficient of proportionality varies for different arrestin proteins. Certain mutant arrestins can form these high affinity complexes with unphosphorylated receptors. Mutations that enhance formation of the agonist-receptor-arrestin complexes should provide useful tools for manipulating both the efficiency of signaling and rate and specificity of receptor internalization.

  14. Agonistic behavior in food animals: review of research and techniques.

    PubMed

    McGlone, J J

    1986-04-01

    One type of social behavior--agonistic behavior--is commonly observed among food animals. Agonistic behaviors are those behaviors which cause, threaten to cause or seek to reduce physical damage. Agonistic behavior is comprised of threats, aggression and submission. While any one of these divisions of agonistic behavior may be observed alone, they usually are found, in sequence, from the start to the end of an interaction. Food animals may show interspecific or intraspecific agonistic behaviors. Interspecific agonistic behavior has not been extensively studied but it is agriculturally important because farm workers may become injured or killed by aggressive food animals. Types of intraspecific agonistic behavior are: when animals are brought together, intermale fighting, resource defense, inter-gender fighting and aberrant aggression. Common pitfalls in research on agonistic behavior among food animals include too few replicates to detect a biological difference, the assumptions of the analysis are not met, only aggression and not submission or other agonistic behavior components are measured, incomplete description of the behaviors are reported and a complete, quantitive ethogram did not form the basis for selecting behavioral measures.

  15. 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.

  16. 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

  17. D-Cycloserine: Agonist turned antagonist.

    PubMed

    Lanthorn, T H

    1994-10-01

    D-Cycloserine can enhance activation of the NMDA receptor complex and could enhance the induction of long-term potentiation (LTP). In animals and humans, D-cycloserine can enhance performance in learning and memory tasks. This enhancing effect can disappear during repeated administration. The enhancing effects are also lost when higher doses are used, and replaced by behavioral and biochemical effects like those produced by NMDA antagonists. It has been reported that NMDA agonists, applied before or after tetanic stimulation, can block the induction of LTP. This may be the result of feedback inhibition of second messenger pathways stimulated by receptor activation. This may explain the antagonist-like effects of glycine partial agonists like D-cycloserine. In clinical trials of D-cycloserine in age-associated memory impairment (AAMI) and Alzheimer's disease, chronic treatment provided few positive effects on learning and memory. This may be due to inhibition of second messenger pathways following chronic stimulation of the receptor complex.

  18. Inverse agonist properties of atypical antipsychotic drugs.

    PubMed

    Akam, Elizabeth; Strange, Philip G

    2004-06-01

    Mechanisms of action of several atypical antipsychotic drugs have been examined at the D(2) dopamine receptor expressed in CHO cells. The drugs tested were found to exhibit inverse agonist activity at the D(2) dopamine receptor based on their effects to potentiate forskolin-stimulated cyclic AMP (cAMP) accumulation. Each of the antipsychotic drugs tested (clozapine, olanzapine, quetiapine and risperidone) increased cAMP accumulation to the same extent. The increase in cAMP was also similar to that seen with typical antipsychotic drugs. Inverse agonism at the D(2) dopamine receptor seems, therefore, to be a property common to all classes of antipsychotic drugs. The effect of sodium ions on the binding of the drugs to the receptor was also assessed. Each of the atypical antipsychotic drugs tested here bound with higher affinity in the absence of sodium ions. Previous studies have shown that some antipsychotic drugs are insensitive to sodium ions and some bind with higher affinity in the presence of sodium ions. Given that all of these antipsychotic drugs are inverse agonists, it may be concluded that this sodium ion sensitivity is unrelated to mechanisms of inverse agonism.

  19. 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.

  20. The ISO view of Palomar-Green quasars

    NASA Astrophysics Data System (ADS)

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

    2003-04-01

    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-)millimetre data. Since the PG quasars were selected optically, the high infrared detection rate of more than 80% suggests that every quasar possesses luminous to hyperluminous dust emission with dust masses comparable to Seyferts and ultraluminous 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. The power-law like near- to mid-IR SEDs (Fnu ~ nu alpha) are smooth up to far-infrared wavelengths, favouring dust heating by the central AGN, and we conclude that, in particular for our hyperluminous quasars at z=1, starbursts play only a minor role for powering the dust emission, even in the FIR. The IR spectral slopes alpha1-10 μm range from -0.9 to -2.2 with a mean of -1.3 +/- 0.3. They neither correlate with the optical spectral slope alpha0.3-1 μm, nor with the IR luminosity, nor with the FIR/MIR luminosity ratio, nor with inclination-dependent extinction effects in the picture of a dusty torus. 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. Strikingly, based on the sensitive ISO data now we do not only see the coarse IR differences between

  1. 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.

  2. Inheritance rules for Hierarchical Metadata Based on ISO 19115

    NASA Astrophysics Data System (ADS)

    Zabala, A.; Masó, J.; Pons, X.

    2012-04-01

    Mainly, ISO19115 has been used to describe metadata for datasets and services. Furthermore, ISO19115 standard (as well as the new draft ISO19115-1) includes a conceptual model that allows to describe metadata at different levels of granularity structured in hierarchical levels, both in aggregated resources such as particularly series, datasets, and also in more disaggregated resources such as types of entities (feature type), types of attributes (attribute type), entities (feature instances) and attributes (attribute instances). In theory, to apply a complete metadata structure to all hierarchical levels of metadata, from the whole series to an individual feature attributes, is possible, but to store all metadata at all levels is completely impractical. An inheritance mechanism is needed to store each metadata and quality information at the optimum hierarchical level and to allow an ease and efficient documentation of metadata in both an Earth observation scenario such as a multi-satellite mission multiband imagery, as well as in a complex vector topographical map that includes several feature types separated in layers (e.g. administrative limits, contour lines, edification polygons, road lines, etc). Moreover, and due to the traditional split of maps in tiles due to map handling at detailed scales or due to the satellite characteristics, each of the previous thematic layers (e.g. 1:5000 roads for a country) or band (Landsat-5 TM cover of the Earth) are tiled on several parts (sheets or scenes respectively). According to hierarchy in ISO 19115, the definition of general metadata can be supplemented by spatially specific metadata that, when required, either inherits or overrides the general case (G.1.3). Annex H of this standard states that only metadata exceptions are defined at lower levels, so it is not necessary to generate the full registry of metadata for each level but to link particular values to the general value that they inherit. Conceptually the metadata

  3. Crystal structure of iso-butyl-ammonium hydrogen oxalate hemihydrate.

    PubMed

    Dziuk, Błażej; Zarychta, Bartosz; Ejsmont, Krzysztof

    2014-11-01

    In the title hydrated mol-ecular salt, C4H12N(+)·C2HO4 (-)·0.5H2O, the O atom of the water mol-ecule lies on a crystallographic twofold axis. The dihedral angle between the CO2 and CO2H planes of the anion is 18.47 (8)°. In the crystal, the anions are connected to each other by strong near-linear O-H⋯O hydrogen bonds. The water mol-ecules are located between the chains of anions and iso-butyl-amine cations; their O atoms participate as donors and acceptors, respectively, in O-H⋯O and N-H⋯O hydrogen bonds, which form channels (dimensions = 4.615 and 3.387 Å) arranged parallel to [010].

  4. Standardization of discharge reports with the ISO 13606 norm.

    PubMed

    Moner, David; Maldonado, Jose A; Angulo, Carlos; Bosca, Diego; Perez, Daniel; Abad, Irene; Reig, Ernesto; Robles, Montserrat

    2008-01-01

    The International Organization for Standardization (ISO) has recently approved a new standard for the communication and semantic interoperability of electronic health record extracts. This standard is based on a dual model architecture, where a simple and generic reference model is defined for the representation of data and an archetype model is used for the representation of complex domain concepts of the electronic health record. By using this standard and a tool called LinkEHR-Ed, we have defined different types of hospital discharge reports in the form of archetypes and then we have normalized automatically discharge reports instances in a real environment following those archetype definitions. This work proves that it is possible to standardize legacy data automatically and enrich them with a semantic information layer by using archetypes as an integration and standardization mechanism.

  5. ISO Technical Specification for the Ionosphere -IRI Recent Activities

    NASA Astrophysics Data System (ADS)

    Bilitza, Dieter; Reinisch, Bodo; Tamara, Gulyaeva

    ISO Technical Specification TS 16457 recommends the International Reference Ionosphere (IRI) for the specification of ionospheric densities and temperatures. We review the latest develop-ments towards improving the IRI model and the newest version of the model IRI-2010. IRI-2010 includes several important improvements and additions. This presentation introduces these changes and discusses their benefits. The changes affect primarily the density profiles in the bottomside ionosphere and the density and height of the F2 peak, the point of highest density in the ionosphere. An important new addition to the model is the inclusion of auroral boundaries and their movement with magnetic activity. We will also discuss the status of other ongoing IRI activities and some of the recent applications of the IRI model. The homepage for the IRI project is at http://IRI.gsfc.nasa.gov/.

  6. 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.

  7. Fates of endocytosed somatostatin sst2 receptors and associated agonists.

    PubMed Central

    Koenig, J A; Kaur, R; Dodgeon, I; Edwardson, J M; Humphrey, P P

    1998-01-01

    Somatostatin agonists are rapidly and efficiently internalized with the somatostatin sst2 receptor. The fate of internalized agonists and receptors is of critical importance because the rate of ligand recycling back to the cell surface can limit the amount of radioligand accumulated inside the cells, whereas receptor recycling might be of vital importance in providing the cell surface with dephosphorylated, resensitized receptors. Furthermore the accumulation of radioisotope-conjugated somatostatin agonists inside cancer cells resulting from receptor-mediated internalization has been used as a treatment for cancers that overexpress somatostatin receptors. In the present study, radio-iodinated agonists at the sst2 somatostatin receptor were employed to allow quantitative analysis of the fate of endocytosed agonist. After endocytosis, recycling back to the cell surface was the main pathway for both 125I-labelled somatostatin-14 (SRIF-14) and the more stable agonist 125I-labelled cyclo(N-Me-Ala-Tyr-d-Trp-Lys-Abu-Phe) (BIM-23027; Abu stands for aminobutyric acid), accounting for 75-85% of internalized ligand when re-endocytosis of radioligand was prevented. We have shown that there is a dynamic cycling of both somatostatin agonist ligands and receptors between the cell surface and internal compartments both during agonist treatment and after surface-bound agonist has been removed, unless steps are taken to prevent the re-activation of receptors by recycled agonist. Internalization leads to increased degradation of 125I-labelled SRIF-14 but not 125I-labelled BIM-23027. The concentration of recycled agonist accumulating in the extracellular medium was sufficient to re-activate the receptor, as measured both by the inhibition of forskolin-stimulated adenylate cyclase and the recovery of surface receptor number after internalization. PMID:9820803

  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. ISO 14000: Origin, Structure, and Potential Barriers to Implementation.

    PubMed

    Casto; Ellisen; Trnovec; Kross; Ginter

    1996-04-01

    The ISO 14000 is likely to become the international standard for environmental management. At present, it is an evolving series of individual voluntary standards and guideline reference documents that provide business management with the structure for managing environmental impacts. These encompass environmental management systems, environmental audits, eco-labeling, environmental performance evaluations, life-cycle assessment, and environmental aspects in product standards. The authors present the rationale for the ISO 14000 and the steps in its evolution so far, as well as its present provisions and their implications and its position with regard to regulatory agencies. Particular attention is paid to the consequences of voluntary disclosure and correction of violations. Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996 April/June Perspectives on Rural Environmental Health in Central Europe 125 134 EN Tomas Trnovec Burton C. Kross CIREH-Room 352, International Center, University of Iowa, Iowa City, IA 52242, USA. Emil Ginter Life expectancy is about five to seven years less in Central European countries than in comparable countries in Western Europe. Environmental and occupational health risk factors, along with the socioeconomic and political conditions that have prevailed in this region for the past 40 years, are suspected contributing factors to this condition. The initial impression among observers was that environmental pollution by industry was the primary source of contamination leading to human health effects. Current thinking by the authors recognizes that combinations of personal habits, local environmental emissions (home heating), and occupational risk factors are more likely to be influencing the health of this region, particularly in rural areas. A predictive model for standard mortality rates determined that only three potential risk factors were statistically significant: consumption of alcoholic beverages, consumption of citrus

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

    PubMed

    Stoimenova, Assena; Stoilova, Ani; Petrova, Guenka

    2014-03-04

    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.

  11. 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

  12. 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…

  13. Integrating a Risk-based Approach and ISO 62304 into a Quality System for Medical Devices

    NASA Astrophysics Data System (ADS)

    Bianco, Celestina

    A recent standard for medical device software lifecycle processes, ISO/IEC 62304 (ISO 2006), assumes and specifies a software safety classification scheme, where documentation, verification and validation tasks to be carried out depend on the safety classification. This means that a risk-driven approach has become an accepted standard for medical devices.

  14. IsoWeb: a bayesian isotope mixing model for diet analysis of the whole food web.

    PubMed

    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.

  15. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission ISO New England Inc.; Notice of Initiation of Proceeding and Refund... existing tariff. Dominion Energy Marketing, Inc. and ISO New England Inc., 143 FERC ] 61,233 (2013)....

  16. 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...) filed a formal complaint against ISO New England Inc. (Respondent) alleging that certain newly...

  17. 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…

  18. 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…

  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. 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…

  1. 75 FR 51996 - Notice of Commission Staff Attendance at Midwest ISO Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ... Energy Regulatory Commission Notice of Commission Staff Attendance at Midwest ISO Meetings August 16... Commission staff may attend the following Midwest ISO-related meetings: Advisory Committee (10 a.m.-3 p.m.... Paul Hotel, 350 Market St., St. Paul, MN) September 15 October 20 November 17 December 1 Midwest...

  2. HL7 template model and EN/ISO 13606 archetype object model - a comparison.

    PubMed

    Bointner, Karl; Duftschmid, Georg

    2009-01-01

    HL7 Templates and EN/ISO 13606 Archetypes are essential components for a semantically interoperable exchange of electronic health record (EHR) data. In this article the underlying models from which Templates and Archetypes are instantiated, namely the HL7 Template Model and the EN/ISO 13606 Archetype Object Model will be compared to identify discrepancies and analogies.

  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. Strategies for Infusing ISO 19115 Metadata in Earth Science Data Systems

    NASA Astrophysics Data System (ADS)

    Hua, H.; Weiss, B.

    2011-12-01

    A major effort on the part of the NASA's Earth Science Data and Information System (ESDIS) project is the development of metadata that enables greater data interoperability among scientific data sets regardless of source or application. The International Standards Organization (ISO) metadata standards, specifically those in the ISO 19000 series, are currently emerging as the primary means to represent metadata associated with Geographic Information in Earth Science Data Products. This talk will focus on strategies to infuse some of the ISO 19000 series metadata into Earth Science Data Products. Part of the infusion requires development of tools that will enable ISO metadata to be generated for NASA data products, and then integration of these tools into a developing Science Data System. We will cover the use of ISO 19139 (Geographic Informatio--Metadata--XML Schema Implementation), along with XML Data Binding to generate APIs for ISO 19115 (Geographic Information--Metadata) in multiple languages. Different file representations of ISO 19115 encodings in data products will also be covered, including representations with HDF5. Other approaches, based on transforms, will be covered as a way to encode data product-specific variations of ISO 19139.

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

    PubMed

    Austin, Tony; Sun, Shanghua; Hassan, Taher; Kalra, Dipak

    2013-12-01

    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.

  6. The use of International Standards Organization ISO 9000 quality assurance standards in place of military standards

    NASA Astrophysics Data System (ADS)

    Beckerdite, Stanley M.

    1992-06-01

    The implementation of quality standards within the European Community by the creation of International Quality Standards 9000 is another step toward development of a global marketplace. It is in the interests of DoD to support this trend in order to help maintain the defense industrial base. The first part of this study performs a comparison of DoD quality standards to the ISO 9000 Standards. The second part of the study consists of a survey of U.S. firms that have become ISO 9000 registered. This survey is intended to provide an assessment of the current movement within the defense industrial base toward adoption of ISO 9000 Standards. The survey also attempts to identify potential implementation issues relating to adoption of ISO 9000 Standards in place of military standards. It is concluded that DoD should implement ISO 9000 and that the impact of this implementation will be favorable.

  7. Endogenous Bioactive Jasmonate Is Composed of a Set of (+)-7-iso-JA-Amino Acid Conjugates.

    PubMed

    Yan, Jianbin; Li, Suhua; Gu, Min; Yao, Ruifeng; Li, Yuwen; Chen, Juan; Yang, Mai; Tong, Jianhua; Xiao, Langtao; Nan, Fajun; Xie, Daoxin

    2016-12-01

    Jasmonates (JAs) regulate a wide range of plant defense and development processes. The bioactive JA is perceived by its receptor COI1 to trigger the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins and subsequently derepress the JAZ-repressed transcription factors for activation of expression of JA-responsive genes. So far, (+)-7-iso-JA-l-Ile has been the only identified endogenous bioactive JA molecule. Here, we designed coronafacic acid (CFA) conjugates with all the amino acids (CFA-AA) to mimic the JA amino acid conjugates, and revealed that (+)-7-iso-JA-Leu, (+)-7-iso-JA-Val, (+)-7-iso-JA-Met, and (+)-7-iso-JA-Ala are new endogenous bioactive JA molecules. Furthermore, our studies uncover the general characteristics for all the bioactive JA molecules, and provide a new strategy to synthetically generate novel active JA molecules.

  8. 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

  9. Outline of the International Organization for Standardization Standard for Circulatory Support Devices (ISO 14708-5).

    PubMed

    Imachi, Kou; Mussivand, Tofy

    2010-09-01

    The rapid progress of artificial heart and circulatory support devices enables us to apply them to severe heart failure patients. Many types of circulatory support devices have been developed in the United States, Europe, and Japan. This situation urged the establishment of an International Organization for Standardization (ISO) Standard for the circulatory support devices. A new work, "Cardiac Ventricular Assist Devices," was proposed to the ISO/TC150/SC6 (TC150: Technical Committee of Implants for Surgery, SC6: Sub-committee of Active Implants) in 2000, and the work was finalized for publication at a 2009 meeting of the ISO/TC150 in Kyoto. In this article, the authors would like to introduce the ISO system and the outline of the ISO Standard for Circulatory Support Devices.

  10. Implementation of ISO 10110 optics drawing standards for the National Ignition Facility

    SciTech Connect

    Aikens, D M; English, R E; Wang, D Y

    1999-07-01

    The National Ignition Facility (NIF) project elected to implement ISO 10110 standard for the specifications of NIF optics drawings in 1996. More than 7,000 NIF large optics and 20,000 NIF small optics will be manufactured based on ISO 10110 indications. ISO 10110 standard meets many of the needs of the NIF optics specifications. It allows the optical engineer to quantify and clearly communicate the desired optical specifications. While no single drawing standard specifies all the requirements of high energy laser system, a combination of ISO 10110 standard with detailed notes make it possible to apply international drawing standards to the NIF laser system. This paper will briefly describe LLNL's interpretation and implementation of the ISO 10110 drawing standard, present some examples of NIF optics drawings, and discuss pros and cons of the indications from the perspective of this application. Emphasis will be given to the surface imperfection specifications, known as 5/, for the NIF optics.

  11. Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration

    PubMed Central

    Chakrabarti, Mrinmay; Haque, Azizul; Banik, Naren L.; Nagarkatti, Prakash; Nagarkatti, Mitzi; Ray, Swapan K.

    2014-01-01

    Recent results from laboratory investigations and clinical trials indicate important roles for estrogen receptor (ER) agonists in protecting the central nervous system (CNS) from noxious consequences of neuroinflammation and neurodegeneration. Neurodegenerative processes in several CNS disorders including spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD) are associated with activation of microglia and astrocytes, which drive the resident neuroinflammatory response. During neurodegenerative processes, activated microglia and astrocytes cause deleterious effects on surrounding neurons. The inhibitory activity of ER agonists on microglia activation might be a beneficial therapeutic option for delaying the onset or progression of neurodegenerative injuries and diseases. Recent studies suggest that ER agonists can provide neuroprotection by modulation of cell survival mechanisms, synaptic reorganization, regenerative responses to axonal injury, and neurogenesis process. The anti-inflammatory and neuroprotective actions of ER agonists are mediated mainly via two ERs known as ERα and ERβ. Although some studies have suggested that ER agonists may be deleterious to some neuronal populations, the potential clinical benefits of ER agonists for augmenting cognitive function may triumph over the associated side effects. Also, understanding the modulatory activities of ER agonists on inflammatory pathways will possibly lead to the development of selective anti-inflammatory molecules with neuroprotective roles in different CNS disorders such as SCI, MS, PD, and AD in humans. Future studies should be concentrated on finding the most plausible molecular pathways for enhancing protective functions of ER agonists in treating neuroinflammatory and neurodegenerative injuries and diseases in the CNS. PMID:25245209

  12. 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...

  13. 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…

  14. 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.

  15. Neuroprotective effects of α-iso-cubebenol on glutamate-induced neurotoxicity.

    PubMed

    Park, Sun Young; Choi, Yung Hyun; Park, Geuntae; Choi, Young-Whan

    2015-09-01

    α-Iso-cubebenol is a natural compound isolated from Schisandra chinensis, and is reported to have beneficial bioactivity including anti-inflammatory and anti-tumor activities. Glutamate-induced oxidative neuronal damage has been implicated in a variety of neurodegenerative disorders. Here we investigated the mechanisms of α-iso-cubebenol protection of mouse hippocampus-derived neuronal cells (HT22 cells) from apoptotic cell death induced by the major excitatory neurotransmitter, glutamate. Pretreatment with α-iso-cubebenol markedly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase), in a dose-dependent manner. α-Iso-cubebenol significantly reduced glutamate-induced intracellular reactive oxygen species and calcium accumulation. Strikingly, α-iso-cubebenol inhibited glutamate-induced mitochondrial depolarization, which releases apoptosis-inducing factor from mitochondria. α-Iso-cubebenol also suppressed glutamate-induced phosphorylation of extracellular-signal-regulated kinases. Furthermore, α-iso-cubebenol induced CREB phosphorylation and Nrf-2 nuclear accumulation and increased the promoter activity of ARE and CREB in HT22 cells. α-Iso-cubebenol also upregulated the expression of phase-II detoxifying/antioxidant enzymes such as HO-1 and NQO1. Subsequent studies revealed that the inhibitory effects of α-iso-cubebenol on glutamate-induced apoptosis were abolished by small interfering RNA-mediated knockdown of CREB and Nrf-2. These findings suggest that α-iso-cubebenol prevents excitotoxin-induced oxidative damage to neurons by inhibiting apoptotic cell death, and might be a potential preventive or therapeutic agent for neurodegenerative disorders.

  16. 8-Iso-prostaglandin f(2alpha) reduces trophoblast invasion and matrix metalloproteinase activity.

    PubMed

    Staff, A C; Ranheim, T; Henriksen, T; Halvorsen, B

    2000-06-01

    Preeclampsia is a common pregnancy complication in the latter half of gestation diagnosed by hypertension and proteinuria. A key feature of preeclampsia is an altered placentation with reduced trophoblast invasion. Normal placentation requires controlled invasion of trophoblasts into the maternal uterine wall, with secretion of specific proteolytic enzymes able to degrade basement membranes and extracellular matrix, such as the matrix metalloproteinases (MMPs). 8-Iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo and is biologically active. We have recently reported an elevated content of free 8-iso-PGF(2alpha) in preeclamptic gestational tissue at delivery. Assuming an elevated level of 8-iso-PGF(2alpha) during the invasion period of the pregnancy, we hypothesized that 8-iso-PGF(2alpha) could reduce invasion of JAR cells, a choriocarcinoma cell line. We investigated JAR cell invasion with 2 types of Transwell assays and demonstrated that 8-iso-PGF(2alpha) (10 micromol/L) resulted in reduced cell invasion in both the colorimetric and radioactivity Transwell assays (P<0.01). Zymograms revealed reduced MMP-2 and MMP-9 activity in conditioned media from JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) (P<0.02). 8-Iso-PGF(2alpha) (10 micromol/L) also reduced the collagenase type IV activity in the conditioned media of JAR cells (P=0.04). No effects on MMP-2 and MMP-9 mRNA levels were observed after incubation with 8-iso-PGF(2alpha) (10 micromol/L), whereas protein levels were significantly decreased (P<0.02), suggesting a posttranscriptional regulation. We hypothesize a potential role for 8-iso-PGF(2alpha) in the reduced trophoblast invasion in preeclampsia.

  17. Activation of cerebral function by CS-932, a functionally selective M1 partial agonist: neurochemical characterization and pharmacological studies.

    PubMed

    Iwata, N; Kozuka, M; Hara, T; Kanek, T; Tonohiro, T; Sugimoto, M; Niitsu, Y; Kondo, Y; Yamamoto, T; Sakai, J; Nagano, M

    2000-11-01

    A newly synthesized agonist for muscarinic acetylcholine (ACh) receptors CS-932, (R)-3-(3-iso-xazoloxy)-1-azabicyclo-[2.2.2]octane hydrochloride, showed a relatively higher affinity for M1 than M2 receptors expressed in Chinese hamster ovary (CHO)-cells in comparison with ACh. CS-932 elevated the intracellular Ca2+ level only in M1-CHO cells, although ACh increased the level in both M1- and M3-CHO cells. CS-932 and ACh reduced forskolin-stimulated accumulation of cAMP in M2-CHO cells by 20% and 80%, respectively. This neurochemical profile of CS-932 indicates that the compound can activate M1-receptor-mediated functions selectively. CS-932 increased firing of cholinoceptive neurons in rat hippocampal slices, and this excitation was antagonized by pirenzepine, but not by AF-DX 116. CS-932 increased awake and decreased slow wave sleep episodes of daytime EEG in free-moving rats. It counteracted scopolamine-induced slow waves in rat cortical EEG. CS-932 also increased the power of alpha- and beta-waves, but decreased delta-wave of the cortical EEG in anesthetized monkeys. It ameliorated scopolamine-induced impairment of working memory in rats. Orally administered CS-932 had the best penetration into the brain among the muscarinic agonists tested and caused the least salivary secretion among the cholinomimetics examined. These results indicate that CS-932 has potential as a cognitive enhancer with fewer side effects in therapy for Alzheimer disease.

  18. Neuroprotection by Alpha 2-Adrenergic Agonists in Cerebral Ischemia

    PubMed Central

    Zhang, Yonghua; Kimelberg, Harold K.

    2005-01-01

    Ischemic brain injury is implicated in the pathophysiology of stroke and brain trauma, which are among the top killers worldwide, and intensive studies have been performed to reduce neural cell death after cerebral ischemia. Alpha 2-adrenergic agonists have been shown to improve the histomorphological and neurological outcome after cerebral ischemic injury when administered during ischemia, and recent studies have provided considerable evidence that alpha 2-adrenergic agonists can protect the brain from ischemia/reperfusion injury. Thus, alpha 2-adrenergic agonists are promising potential drugs in preventing cerebral ischemic injury, but the mechanisms by which alpha 2-adrenergic agonists exert their neuroprotective effect are unclear. Activation of both the alpha 2-adrenergic receptor and imidazoline receptor may be involved. This mini review examines the recent progress in alpha 2-adrenergic agonists - induced neuroprotection and its proposed mechanisms in cerebral ischemic injury. PMID:18369397

  19. 77 FR 12832 - Non-RTO/ISO Performance Metrics; Commission Staff Request Comments on Performance Metrics for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

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

  20. 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...

  1. 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

    ... Administration Staff; Medical Device ISO 13485:2003 Voluntary Audit Report Submission Pilot Program; Availability... (FDA) is announcing the availability of the guidance entitled ``Medical Device ISO 13485:2003 Voluntary... guidance document entitled ``Medical Device ISO 13485:2003 Voluntary Audit Report Submission Pilot...

  2. 90/10 JP5/Synthesized ISO-Paraffin Specification and Fit-for-Purpose Test Results

    DTIC Science & Technology

    2014-06-11

    90/10 JP5/SYNTHESIZED ISO -PARAFFIN SPECIFICATION AND FIT-FOR-PURPOSE TEST RESULTS NAVAIR SYSCOM REPORT 441/14-010 11 June 2014 Prepared By...3 3.1 Synthesized Iso -Paraffins (SIP) Procurement Specification Test Results...26 Appendix A: Procurement Specification for Synthesized Iso -Paraffins (SIP) ........................... A-1

  3. Quantifying agonist activity at G protein-coupled receptors.

    PubMed

    Ehlert, Frederick J; Suga, Hinako; Griffin, Michael T

    2011-12-26

    When an agonist activates a population of G protein-coupled receptors (GPCRs), it elicits a signaling pathway that culminates in the response of the cell or tissue. This process can be analyzed at the level of a single receptor, a population of receptors, or a downstream response. Here we describe how to analyze the downstream response to obtain an estimate of the agonist affinity constant for the active state of single receptors. Receptors behave as quantal switches that alternate between active and inactive states (Figure 1). The active state interacts with specific G proteins or other signaling partners. In the absence of ligands, the inactive state predominates. The binding of agonist increases the probability that the receptor will switch into the active state because its affinity constant for the active state (K(b)) is much greater than that for the inactive state (K(a)). The summation of the random outputs of all of the receptors in the population yields a constant level of receptor activation in time. The reciprocal of the concentration of agonist eliciting half-maximal receptor activation is equivalent to the observed affinity constant (K(obs)), and the fraction of agonist-receptor complexes in the active state is defined as efficacy (ε) (Figure 2). Methods for analyzing the downstream responses of GPCRs have been developed that enable the estimation of the K(obs) and relative efficacy of an agonist. In this report, we show how to modify this analysis to estimate the agonist K(b) value relative to that of another agonist. For assays that exhibit constitutive activity, we show how to estimate K(b) in absolute units of M(-1). Our method of analyzing agonist concentration-response curves consists of global nonlinear regression using the operational model. We describe a procedure using the software application, Prism (GraphPad Software, Inc., San Diego, CA). The analysis yields an estimate of the product of K(obs) and a parameter proportional to efficacy (

  4. Mid-infrared ISO spectroscopy of NGC 4945

    NASA Astrophysics Data System (ADS)

    Spoon, H. W. W.; Koornneef, J.; Moorwood, A. F. M.; Lutz, D.; Tielens, A. G. G. M.

    2000-05-01

    We have observed the central region of the nearby starburst galaxy NGC 4945 with the mid-infrared spectrometers SWS and PHT-S aboard ISO. We do not find any evidence for the existence of the powerful AGN, inferred from hard X-ray observations. The upper limits on our AGN tracers [ion {Ne}{v}] 14.32 mu m&24.3 mu m and [ion {Ne}{vi}] 7.65 mu m imply an A_V>160 towards the NLR, assuming the NLR to be of equal strength as in the Circinus galaxy. Other possibilities are discussed. The starburst excitation indicators [ion {Ne}{iii}]15.56 mu m/[ion {Ne}{ii}]12.81 mu m and L_bol/L_lyc suggest that the starburst in the central region is at least 5x106 yrs old, and that it accounts for at least half of the nuclear bolometric luminosity. The starburst might well power the entire bolometric luminosity, but the available constraints are also consistent with an up to 50% contribution of the embedded AGN. With PHT-S, at a resolution of ~90, we detect strong absorption features of water ice, and, for the first time in an external galaxy, of CO_2 and CO. The same PHT-S spectrum also reveals strong emission from the family of PAH features. Finally, we have observed and detected several pure rotational and ro-vibrational H_2 lines, two of which, the (0-0) S(0) & S(1) lines, allow us to determine the excitation temperature (160 K) and warm H_2 mass (2.4x107Msun). The low excitation temperature shows Orion-like shocks not to be representative for the entire emission of the central region of the galaxy and fairly normal PDRs to be perhaps more typical. Based on observations with ISO, an ESA project with instruments funded by ESA Member States (especially the PI countries: France, Germany, the Netherlands and the United Kingdom) and with the participation of ISAS and NASA

  5. Boreal Summer ISO hindcast experiment: preliminary results from SNU

    NASA Astrophysics Data System (ADS)

    Heo, S.; Kang, I.; Kim, D.; Ham, Y.

    2010-12-01

    As a part of internationally coordinated research program, hindcast experiments with focus on boreal summer intraseasonal oscillation (ISO) have been done in Seoul National University (SNU). This study aims to show preliminary results from SNU’s efforts. The ISO prediction system used in the hindcast experiment consists of SNU coupled model and SNU initialization method. The SNU coupled model is an ocean-atmosphere coupled model which couples the SNU Atmospheric GCM (SNU AGCM) to the Modular Ocean Model ver.2.2 (MOM2.2) Ocean GCM developed at Geophysical Fluid Dynamics Laboratory (GFDL). In the SNU initialization method, both atmospheric and oceanic states are nudged toward reanalysis data (ERAinterim and GODAS) before prediction starting date. For the results here, 2 ensemble members are generated by using different nudging period, 8 and 9 days, respectively. The initial dates of 45-day predictions are the 1st, 11th, 21st of months during boreal summer season (May to October). Prediction skills and its dependency on the initial amplitude, the initial phase, and the number of ensemble members are investigated using the Real-time Multivariate MJO (RMM) index suggested by Wheeler and Hendon (2004). It is shown in our hindcast experiment that, after 13 forecast lead days (the forecast skill is about 0.7), the prediction skill does not depend on the strength of the initial state. Also, we found that the prediction skill has a phase dependency. The prediction skill is particularly low when the convective center related to the MJO is over the Indian Ocean (phase 2). The ensemble prediction has more improved correlation skill than each member. To better understand the phase dependency, we compared the observed and predicted behavior of the MJO that propagates from different starting phases. The phase speed of the prediction is slower than the observation. The MJO in the hindcast experiment propagates with weaker amplitudes than observed except for initial phase 3. Also

  6. Agonistic behavior in males and females: effects of an estrogen receptor beta agonist in gonadectomized and gonadally intact mice

    PubMed Central

    Allen, Amy E. Clipperton; Cragg, Cheryl L.; Wood, Alexis J.; Pfaff, Donald W.; Choleris, Elena

    2010-01-01

    Summary Affiliative and agonistic social interactions are mediated by gonadal hormones. Research with estrogen receptor alpha (ERα) or beta (ERβ) knockout (KO) mice show that long-term inactivation of ERα decreases, while inactivation of ERβ increases, male aggression. Opposite effects were found in female αERKO and βERKO mice. The role of acute activation of ERα or ERβ in the agonistic responses of adult non-KO mice is unknown. We report here the effects of the ERβ selective agonist WAY-200070 on agonistic and social behavior in gonadally intact and gonadectomized (gonadex) male and female CD-1 mice towards a gonadex, same-sex intruder. All 15 min resident-intruder tests were videotaped for comprehensive behavioral analysis. Separate analyses assessed: 1) effects of WAY-200070 on each sex and gonadal condition; 2) differences between sexes, and between gonadally intact and gonadex mice, in untreated animals. Results show that in gonadally intact male and female mice WAY-200070 increased agonistic behaviors such as pushing down and aggressive grooming, while leaving attacks unaffected. In untreated mice, males attacked more than females, and gonadex animals showed less agonistic behavior than same-sex, gonadally intact mice. Overall, our detailed behavioral analysis suggested that in gonadally intact male and female mice, ERβ mediates patterns of agonistic behavior that are not directly involved in attacks. This suggests that specific aspects of aggressive behavior are acutely mediated by ERβ in adult mice. Our results also showed that, in resident-intruder tests, female mice spend as much time in intrasexual agonistic interactions as males, but use agonistic behaviors that involve extremely low levels of direct attacks. This non-attack aggression in females is increased by acute activation of ERβ. Thus, acute activation of ERβ similarly mediates agonistic behavior in adult male and female CD-1 mice. PMID:20129736

  7. Development of an ISO 9000 compatible occupational health standard: defining the issues.

    PubMed

    Dyjack, D T; Levine, S P

    1995-06-01

    Corporate ISO 9000 registration is gaining international acceptance as the hallmark of quality system achievement. The International Organization for Standardization (ISO) is currently drafting environmental standards that will complement ISO 9000. Should the international community also consider development of an ISO 9000-compatible occupational safety and health management standard (OSHMS)? To determine the advantages and disadvantages of this issue, the investigators conducted interviews with government and private sector experts, reviewed publicly accessible ISO documents, and evaluated published literature germane to the subject. Major advantages of an ISO OSHMS were the harmonization of national standards, maximizing Occupational Safety and Health Administration (OSHA) efficiency through third-party registration audits, and increased emphasis on employee-driven health and safety programs. Major disadvantages were the single vote of the American National Standards Institute at international proceedings, direct and indirect program development costs, potential unethical or incompetent conduct of registrars, and the logistics of developing an acceptable standard to all stakeholders. Some unresolved issues were the inevitability of an ISO OSHMS, auditor indemnification, and the scope of OSHA participation. Industrial health and safety professionals should initiate formal discussion on this issue to elaborate on findings presented here and to establish a consensus on future activities.

  8. ISO reference terminology models for nursing: applicability for natural language processing of nursing narratives.

    PubMed

    Bakken, Suzanne; Hyun, Sookyung; Friedman, Carol; Johnson, Stephen B

    2005-08-01

    Natural language processing (NLP) systems have demonstrated utility in parsing narrative texts for purposes such as surveillance and decision support. However, there has been little work related to NLP of nursing narratives. The purpose of this study was to compare the semantic categories of a NLP system (Medical Language Extraction and Encoding [MedLEE] system) with the semantic domains, categories, and attributes of the International Standards Organization (ISO) reference terminology models for nursing diagnoses and nursing actions. All but two MedLEE diagnosis and procedure-related semantic categories mapped to ISO models. In some instances, we found exact correspondence between the semantic structures of MedLEE and the ISO models. In other situations (e.g. aspects of Site or Location), the ISO model was not as granular as MedLEE. For clinical procedure and non-invasive examination, two ISO nursing action model components (Action and Target) mapped to a single MedLEE semantic category. The ISO models are applicable to NLP of nursing narratives. However, the ISO models require additional specification of selected semantic categories for the abstract semantic domains in order to achieve the objective of using NLP to parse and encode data from nursing narratives. Our analysis also suggests areas for extension of MedLEE particularly in regard to represent nursing actions.

  9. 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.

  10. The ISO 50001 Impact Estimator Tool (IET 50001 V1.1.4) - User Guide and Introduction to the ISO 50001 Impacts Methodology

    SciTech Connect

    Therkelsen, Peter L.; Rao, Prakash; Aghajanzadeh, Arian; McKane, Aimee T.

    2016-08-01

    ISO 50001-Energy management systems – Requirements with guidance for use, is an internationally developed standard that provides organizations with a flexible framework for implementing an energy management system (EnMS) with the goal of continual energy performance improvement. The ISO 50001 standard was first published in 2011 and has since seen growth in the number of certificates issued around the world, primarily in the industrial (agriculture, manufacturing, and mining) and service (commercial) sectors. Policy makers in many regions and countries are looking to or are already using ISO 50001 as a basis for energy efficiency, carbon reduction, and other energy performance improvement schemes. The Impact Estimator Tool 50001 (IET 50001 Tool) is a computational model developed to assist researchers and policy makers determine the potential impact of ISO 50001 implementation in the industrial and service (commercial) sectors for a given region or country. The IET 50001 Tool is based upon a methodology initially developed by the Lawrence Berkeley National Laboratory that has been improved upon and vetted by a group of international researchers. By using a commonly accepted and transparent methodology, users of the IET 50001 Tool can easily and clearly communicate the potential impact of ISO 50001 for a region or country.

  11. 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.

  12. 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.

  13. Does symbolism benefit environmental and business performance in the adoption of ISO 14001?

    PubMed

    Ferrón-Vílchez, Vera

    2016-12-01

    Much research has focused on the organisational and reputational benefits of ISO 14001. However, less discussed is the symbolic adoption that some firms are implementing without experiencing significant reductions in environmental impacts. This work analyses the relationships between the different ISO 14001 adoption profiles (from symbolic profile to factual approach) and both environmental performance and profitability. These relationships are examined using a sample of 1214 manufacturing firms in 7 OECD countries while controlling for selection bias. The results suggest that only ISO 14001 adopters that monitor an extensive set of negative environmental impacts are associated with real improvements in both environmental performance and business performance.

  14. A case study of ISO 11064 in control centre design in the Norwegian petroleum industry.

    PubMed

    Aas, Andreas Lumbe; Skramstad, Torbjørn

    2010-12-01

    In 2006-2008 we performed a case study for the purpose of assessing the industrial application of the seven part Control Centre (CC) design standard ISO 11064 to identify positive and negative experiences among stakeholders in the Norwegian petroleum sector. We mainly focussed on ISO 11064 Part 1, because this was the most commonly used among the identified stakeholders. ISO 11064 is generally appreciated and applied in the industry, but we did observe a significant variance in use between the different parts of the standard. We also identified potential areas for improvements, like scope and application adaptation. Thus we suggest a more goal-based approach based on one normative part only.

  15. 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.

  16. Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity

    PubMed Central

    Hu, Xiao; Liu, Xikui; Moisan, Jacques; Wang, Yahong; Lesch, Charles A.; Spooner, Chauncey; Morgan, Rodney W.; Zawidzka, Elizabeth M.; Mertz, David; Bousley, Dick; Majchrzak, Kinga; Kryczek, Ilona; Taylor, Clarke; Van Huis, Chad; Skalitzky, Don; Hurd, Alexander; Aicher, Thomas D.; Toogood, Peter L.; Glick, Gary D.; Paulos, Chrystal M.; Zou, Weiping; Carter, Laura L.

    2016-01-01

    ABSTRACT RORγt is the key transcription factor controlling the development and function of CD4+ Th17 and CD8+ Tc17 cells. Across a range of human tumors, about 15% of the CD4+ T cell fraction in tumor-infiltrating lymphocytes are RORγ+ cells. To evaluate the role of RORγ in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate RORγ to a greater extent than the endogenous agonist desmosterol. These RORγ agonists enhance effector function of Type 17 cells by increasing the production of cytokines/chemokines such as IL-17A and GM-CSF, augmenting expression of co-stimulatory receptors like CD137, CD226, and improving survival and cytotoxic activity. RORγ agonists also attenuate immunosuppressive mechanisms by curtailing Treg formation, diminishing CD39 and CD73 expression, and decreasing levels of co-inhibitory receptors including PD-1 and TIGIT on tumor-reactive lymphocytes. The effects of RORγ agonists were not observed in RORγ−/− T cells, underscoring the selective on-target activity of the compounds. In vitro treatment of tumor-specific T cells with RORγ agonists, followed by adoptive transfer to tumor-bearing mice is highly effective at controlling tumor growth while improving T cell survival and maintaining enhanced IL-17A and reduced PD-1 in vivo. The in vitro effects of RORγ agonists translate into single agent, immune system-dependent, antitumor efficacy when compounds are administered orally in syngeneic tumor models. RORγ agonists integrate multiple antitumor mechanisms into a single therapeutic that both increases immune activation and decreases immune suppression resulting in robust inhibition of tumor growth. Thus, RORγ agonists represent a novel immunotherapy approach for cancer. PMID:28123897

  17. 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.

  18. Understanding the LCA and ISO water footprint: A response to ...

    EPA Pesticide Factsheets

    Water footprinting has emerged as an important approach to assess water use related effects from consumption of goods and services. Assessment methods are proposed by two different communities, the Water Footprint Network (WFN) and the Life Cycle Assessment (LCA) community. The proposed methods are broadly similar and encompass both the computation of water use and its impacts, but differ in communication of a water footprint result. In this paper, we explain the role and goal of LCA and ISO-compatible water footprinting and resolve the six issues raised by Hoekstra (2016) in “A critique on the water-scarcity weighted water footprint in LCA”. By clarifying the concerns, we identify both the overlapping goals in the WFN and LCA water footprint assessments and discrepancies between them. The main differing perspective between the WFN and LCA-based approach seems to relate to the fact that LCA aims to account for environmental impacts, while the WFN aims to account for water productivity of global fresh water as a limited resource. We conclude that there is potential to use synergies in research for the two approaches and highlight the need for proper declaration of the methods applied. This paper advances efforts to understand ways to accurately capture use of water in life cycle analysis in other contexts. As the paper indicates, there is a discussion about whether quantities of water should be weighted by some local stress factor. This paper attempts to brid

  19. [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.

  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. [Histrelin acetate--the first once yearly LHRH agonist].

    PubMed

    Altarac, Silvio

    2011-01-01

    Long-acting synthetic luteinising hormone-releasing hormone agonists have become the mainstay for androgen-deprivation therapy, because they avoid the physical and psychological discomfort associated with orchidectomy and lack the potential cardiotoxicity associated with estrogens such as diethylstilbestrol. Currently available luteinising hormone-releasing hormone agonist analogues include leuprolide, goserelin, triptorelin, degarelix and buserelin were administered as either intramuscular or subcutaneous depot injections on a 1, 2, 3 or 6 months basis. Histrelin acetate is the first long-acting luteinising hormone-releasing hormone agonist available as a once-yearly subcutaneous implant.

  2. Toll-like receptor agonists in cancer therapy

    PubMed Central

    Adams, Sylvia

    2010-01-01

    Toll-like receptors (TLRs) are pattern-recognition receptors related to the Drosophila Toll protein. TLR activation alerts the immune system to microbial products and initiates innate and adaptive immune responses. The naturally powerful immunostimulatory property of TLR agonists can be exploited for active immunotherapy against cancer. Antitumor activity has been demonstrated in several cancers, and TLR agonists are now undergoing extensive clinical investigation. This review discusses recent advances in the field and highlights potential opportunities for the clinical development of TLR agonists as single agent immunomodulators, vaccine adjuvants and in combination with conventional cancer therapies. PMID:20563267

  3. 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

  4. Characterization of a novel bivalent morphinan possessing kappa agonist and micro agonist/antagonist properties.

    PubMed

    Mathews, Jennifer L; Peng, Xuemei; Xiong, Wennan; Zhang, Ao; Negus, S Stevens; Neumeyer, John L; Bidlack, Jean M

    2005-11-01

    Previous research has shown that compounds with mixed kappa and mu activity may have utility for the treatment of cocaine abuse and dependence. The present study characterizes the pharmacological profile of a bivalent morphinan that was shown to be a kappa opioid receptor agonist and a mu opioid receptor agonist/antagonist. MCL-145 [bis(N-cyclobutylmethylmorphinan) fumarate] is related to the morphinan cyclorphan and its N-cyclobutylmethyl derivative MCL-101 [3-hydroxy-N-cyclobutylmethyl morphinan S-(+)-mandelate]. MCL-145 consists of two morphinans connected by a spacer at the 3-hydroxy position. This compound had K(i) values of 0.078 and 0.20 nM for the kappa and mu opioid receptors, respectively, using radioligand binding assays as shown by Neumeyer et al. in 2003. In the guanosine 5'-O -(3-[(35) S]thiotriphosphate) binding assay, MCL-145 produced an E(max) value of 80% for the kappa opioid receptor and 42% for the mu opioid receptor. The EC(50) values obtained for this compound were 4.3 and 3.1 nM for the kappa and mu opioid receptors, respectively. In vivo MCL-145 produced a full dose-response curve in the 55 degrees C warm water tail-flick test and was equipotent to morphine. The agonist properties of MCL-145 were antagonized by the mu-selective antagonist beta-funaltrexamine and the kappa-selective antagonist nor-binaltorphimine. MCL-145 also acted as a mu antagonist, as measured by the inhibition of morphine-induced antinociception.

  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.

  6. Occupational health impacts of climate change: current and future ISO standards for the assessment of heat stress.

    PubMed

    Parsons, Ken

    2013-01-01

    The current system of International Standards (ISO) is assessed to consider whether standards are fit for purpose for the future in the context of climate change. ISO 7243, ISO 7933 and ISO 9886 provide the current ISO system for the assessment of heat stress. These involve a simple monitoring index, an analytical approach and physiological monitoring, respectively. The system relies on accurate measurement of the thermal conditions experienced by the worker (ISO 7726); and estimations of metabolic heat production due to work (ISO 8996) and the thermal properties of clothing (ISO 9920). As well as standards for heat stress assessment, the full range of ISO standards and the physical environment is listed as well as current work and proposed standards. A particular 'gap' in anticipating requirements for ISO standards in the future is the link between meteorological data and ISO standards. This is important for predicting the global consequences of a changing climate and anticipating potential impacts on occupational health across countries and cultures.

  7. [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].

  8. North American ginseng (Panax quinquefolius) suppresses β-adrenergic-dependent signalling, hypertrophy, and cardiac dysfunction.

    PubMed

    Tang, Xilan; Gan, Xiaohong Tracey; Rajapurohitam, Venkatesh; Huang, Cathy Xiaoling; Xue, Jenny; Lui, Edmund M K; Karmazyn, Morris

    2016-12-01

    There is increasing evidence for a beneficial effect of ginseng on cardiac pathology. Here, we determined whether North American ginseng can modulate the deleterious effects of the β-adrenoceptor agonist isoproterenol on cardiac hypertrophy and function using in vitro and in vivo approaches. Isoproterenol was administered for 2 weeks at either 25 mg/kg per day or 50 mg/kg per day (ISO25 or ISO50) via a subcutaneously implanted osmotic mini-pump to either control rats or those receiving ginseng (0.9 g/L in the drinking water ad libitum). Isoproterenol produced time- and dose-dependent left ventricular dysfunction, although these effects were attenuated by ginseng. Improved cardiac functions were associated with reduced heart masses, as well as prevention in the upregulation of the hypertrophy-related fetal gene expression. Lung masses were similarly attenuated, suggesting reduced pulmonary congestion. In in vitro studies, ginseng (10 μg/mL) completely suppressed the hypertrophic response to 1 μmol/L isoproterenol in terms of myocyte surface area, as well as reduction in the upregulation of fetal gene expression. These effects were associated with attenuation in both protein kinase A and cAMP response element-binding protein phosphorylation. Ginseng attenuates adverse cardiac adrenergic responses and, therefore, may be an effective therapy to reduce hypertrophy and heart failure associated with excessive catecholamine production.

  9. Parallel DNA double helices incorporating isoG or m5isoC bases studied by FTIR, CD and molecular modeling.

    PubMed

    Geinguenaud, F; Mondragon-Sanchez, J A; Liquier, J; Shchyolkina, A K; Klement, R; Arndt-Jovin, D J; Jovin, T M; Taillandier, E

    2005-02-01

    FTIR spectroscopy has been used to follow the formation of parallel stranded DNA duplexes incorporating isoG or m5isoC bases and determine their base pairing scheme. The results are discussed in comparison with data concerning anti-parallel duplexes with comparable base composition and sequence. In duplexes containing A-T and isoG-C or m5isoC-G base pairs shifts of the thymine C2=O2 and C4=O4 carbonyl stretching vibrations (to lower and higher wavenumbers, respectively, when compared to their positions in classical cis Watson-Crick (WC) base pairs) reflect the formation of trans Watson-Crick A-T base pairs. All carbonyl groups of cytosines, m5isocytosines, guanines and isoguanines are found to be involved in hydrogen bonds, indicative of the formation of isoG-C and m5isoC-G base pairs with three hydrogen bonds. Molecular modeling shows that both structures form regular right handed helices with C2'endo sugar puckers. The role of the water content on the helical conformation of the parallel duplexes has been studied by FTIR and CD. It is found that a conformational transition similar to the B --> A transition observed for anti-parallel duplexes induced by a decrease of the water content of the samples can occur for these parallel duplexes. Their helical flexibility has been evidenced by FTIR studies on hydrated films by the emergence of absorption bands characteristic of A type geometry, in particular by an S-type --> N-type repuckering of the deoxyribose. All sugars in the parallel duplex with alternating d(isoG-A)/d(C-T) sequence can adopt an N-type geometry in low water content conditions. The conformational transition of the parallel hairpin duplex with alternating d(isoG-A)/d(C-T) sequence was followed by circular dichroism in water/trifluoroethanol solutions and its free energy at 0 degrees C was estimated to be 6.6 +/- 0.3 kcal mol(-1).

  10. Conformational equilibrium and internal dynamics in the iso-propanol-water dimer.

    PubMed

    Evangelisti, Luca; Gou, Qian; Feng, Gang; Caminati, Walther; Mead, Griffin J; Finneran, Ian A; Carroll, P Brandon; Blake, Geoffrey A

    2016-12-21

    The molecular complex between iso-propanol and water has been investigated by Fourier transform microwave spectroscopy. Two distinct rotational spectra have been assigned, corresponding to two different isomers of the adduct. In both cases the water molecule acts as a proton donor to the alcoholic oxygen atom of iso-propanol in its gauche arrangement. The isomer in which the water molecule is oriented along the symmetry plane of the iso-propanol molecule (inner) is more stable than the second isomer, where the water is positioned outside the iso-propanol symmetry plane (outer). The rotational transitions of the inner isomer display a doubling, due to the two equivalent minima related to the internal rotation of the hydroxyl group (concerted with a rearrangement of the water unit). The tunneling splitting has been determined to be 25.16(8) GHz, corresponding to a B2 barrier of ∼440 cm(-1).

  11. 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.

  12. 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.

  13. Application of ISO 9002 and FDA's good manufacturing practices to general chemical manufacturing.

    PubMed

    Kauffman, J M; Weiler, E D

    1992-06-01

    Two manufacturing standards are discussed and compared, namely, the U.S. Food and Drug Administration's Good Manufacturing Practices and the International Standards Organization 9000 (ISO 9000) series. Conclusions are drawn relative to quality improvement strategies.

  14. [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.

  15. International standards on mental work-load--the ISO 10,075 series.

    PubMed

    Nachreiner, F

    1999-04-01

    After a short review of the history and an introduction into the background of standardization in the field of mental work-load an overview over the ISO 10,075 series of standards on ergonomic principles related to mental work-load is given. The review also presents relationships of these standards with some other ergonomic standards and some of the problems associated with standardization in the field of mental work-load. The stress-strain model, the concepts and the terminology used in ISO 10,075 are presented in the overview, together with the basic ideas and the frame of reference of the design guidelines provided by ISO 10,075-2. An outline of the state of discussion and possible developments of a working draft for ISO 10,075-3 on diagnostic methods concludes the presentation of the international standards on mental work-load.

  16. Mapping 'hydroscapes' along the iso- to anisohydric continuum of stomatal regulation of plant water status.

    PubMed

    Meinzer, Frederick C; Woodruff, David R; Marias, Danielle E; Smith, Duncan D; McCulloh, Katherine A; Howard, Ava R; Magedman, Alicia L

    2016-11-01

    The concept of iso- vs. anisohydry has been used to describe the stringency of stomatal regulation of plant water potential (ψ). However, metrics that accurately and consistently quantify species' operating ranges along a continuum of iso- to anisohydry have been elusive. Additionally, most approaches to quantifying iso/anisohydry require labour-intensive measurements during prolonged drought. We evaluated new and previously developed metrics of stringency of stomatal regulation of ψ during soil drying in eight woody species and determined whether easily-determined leaf pressure-volume traits could serve as proxies for their degree of iso- vs. anisohydry. Two metrics of stringency of stomatal control of ψ, (1) a 'hydroscape' incorporating the landscape of ψ over which stomata control ψ, and (2) the slope of the daily range of ψ as pre-dawn ψ declined, were strongly correlated with each other and with the leaf osmotic potential at full and zero turgor derived from pressure-volume curves.

  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. [Quality assurance and certification of a hemodialysis unit according to the ISO-9001-2000 standards].

    PubMed

    Arenas, M D; Gil, M T; Egea, J J; Sirvent, A E; Giménez, A

    2003-01-01

    We report the experience of three hemodialysis centers registered with the ISO 9001-2000 standard, regarding the development of a quality measure system and providing an analysis of this system and its advantages and disadvantages.

  19. 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

    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.

  20. Octopaminergic agonists for the cockroach neuronal octopamine receptor.

    PubMed

    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.

  1. (R)-(-)-10-methyl-11-hydroxyaporphine: a highly selective serotonergic agonist.

    PubMed

    Cannon, J G; Mohan, P; Bojarski, J; Long, J P; Bhatnagar, R K; Leonard, P A; Flynn, J R; Chatterjee, T K

    1988-02-01

    Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

  2. 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.

  3. Agonist Replacement for Stimulant Dependence: A Review of Clinical Research

    PubMed Central

    Stoops, William W.; Rush, Craig R.

    2013-01-01

    Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and clinical trials to determine whether agonist replacement therapy is a viable strategy for managing cocaine and/or amphetamine use disorders. The extant literature suggests that agonist replacement therapy may be effective for managing stimulant use disorders, however, the clinical selection of an agonist replacement medication likely needs to be based on the pharmacological mechanism of the medication and the stimulant abused by patients. Specifically, dopamine releasers appear most effective for reducing cocaine use whereas dopamine reuptake inhibitors appear most effective for reducing amphetamine use. PMID:23574440

  4. 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.

  5. 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

  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... Listing of Specific Substances Affirmed as GRAS § 184.1165 n-Butane and iso-butane. (a) n-Butane and...

  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. Impact of 50% Synthesized Iso-Paraffins (SIP) on F-76 Fuel Coalescence

    DTIC Science & Technology

    2013-12-16

    time required to flow the entire volume of fluid in a container, also known as residence time (volume of fuel ÷ volumetric flow rate ) NF...petroleum JP-5 and Synthesized Iso-Paraffins (SIP). SIP fuels are made from direct fermentation of sugar into olefinic hydrocarbons. The olefinic...5 and Synthesized Iso-Paraffins (SIP). SIP fuels are made from direct fermentation of sugar into olefinic hydrocarbons. The olefinic hydrocarbons

  9. The process of implementing an ISO 9001 quality management system in a school of nursing.

    PubMed

    Lett, M

    2000-01-01

    This paper documents the process undertaken during the establishment of an ISO 9000 series quality management system by a School of Nursing. Further discussion centres around the reasons why an ISO quality management system was implemented, the lessons learnt during the process and the benefits that accreditation has brought to the School of Nursing. The lessons learnt during the process could be of help to other organisations wishing to achieve a similar accreditation status.

  10. 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...

  11. An Approach to Combining Results From Multiple Methods Motivated by the ISO GUM.

    PubMed

    Levenson, M S; Banks, D L; Eberhardt, K R; Gill, L M; Guthrie, W F; Liu, H K; Vangel, M G; Yen, J H; Zhang, N F

    2000-01-01

    The problem of determining a consensus value and its uncertainty from the results of multiple methods or laboratories is discussed. Desirable criteria of a solution are presented. A solution motivated by the ISO Guide to the Expression of Uncertainty in Measurement (ISO GUM) is introduced and applied in a detailed worked example. A Bayesian hierarchical model motivated by the proposed solution is presented and compared to the solution.

  12. Cross-conjugated chromophores: synthesis of iso-polydiacetylenes with Donor/Acceptor substitution

    PubMed

    Ciulei; Tykwinski

    2000-11-16

    The iterative construction of cross-conjugated donor (D), acceptor (A), and donor-acceptor (D-A) substituted iso-polydiacetylene (iso-PDA) oligomers has been achieved utilizing palladium-catalyzed cross-coupling techniques. Structure-property relationships for these compounds have been analyzed for cross-conjugated pi-electronic communication as a result of contributions from donor, acceptor, or donor-acceptor functionalization.

  13. 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...

  14. Beta2-agonists and exercise-induced asthma.

    PubMed

    Anderson, Sandra D; Caillaud, Corinne; Brannan, John D

    2006-01-01

    Beta2-agonists taken immediately before exercise provide significant protection against exercise- induced asthma (EIA) in most patients. However, when they are taken daily, there are some negative aspects regarding severity, control, and recovery from EIA. First, there is a significant minority (15-20%) of asthmatics whose EIA is not prevented by beta2-agonists, even when inhaled corticosteroids are used concomitantly. Second, with daily use, there is a decline in duration of the protective effect of long-acting beta2-agonists. Third, if breakthrough EIA occurs, recovery of lung function is slower in response to a beta2-agonist, and additional doses are often required to achieve pre-exercise values. If a person who takes a beta2-agonist daily experiences problems with exercise, then the physician should consider changing the treatment regimen to achieve better control of EIA. These problems likely result from desensitization of the beta2-receptor on the mast cell, which enhances mediator release, and on the bronchial smooth muscle, which enhances the bronchoconstrictor response and delays recovery from EIA. These effects are reversed within 72 h after cessation of a beta2-agonists. The important clinical question is: Are we actually compromising the beneficial effects of beta2-agonists on the prevention and recovery from EIA by prescribing them daily? Patients with EIA need to ensure that their doses of inhaled corticosteroid or other anti-inflammatory therapy are optimized so that, if necessary, a beta2-agonist can be used intermittently as prophylactic medication with greater confidence in the outcome.

  15. [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.

  16. [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.

  17. 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.

  18. Opioid receptor agonists reduce brain edema in stroke.

    PubMed

    Yang, Li; Wang, Hezhen; Shah, Kaushik; Karamyan, Vardan T; Abbruscato, Thomas J

    2011-04-06

    Cerebral edema is a leading cause of mortality in stroke patients. The purpose of this study was to assess a non-selective opioid receptor agonist, biphalin, in decreasing reducing brain edema formation using both in vitro and in vivo models of stroke. For the in situ model of ischemia, hippocampal slices were exposed to oxygen glucose deprivation (OGD) conditions and we observed that hippocampal water content was increased, compared to normoxia. Treatment with the mu agonist, Tyr-D-Ala', N-CH, -Phe4, Glyol-Enkephalin (DAMGO), delta opioid agonists, D-pen(2), D-phe(5) enkephalin (DPDPE), and kappa agonist, U50 488, all significantly decreased brain slice water gain. Interestingly, the non-selective agonist, biphalin, exhibited a statistically significant (P<0.01) greater effect in decreasing water content in OGD-exposed hippocampal slices, compared with mu, delta, and kappa selective opioid agonists. Moreover, biphalin exhibited anti-edematous effects in a dose responsive manner. The non-selective opioid antagonist, naloxone, returned the water content nearly back to original OGD values for all opioid agonist treatments, supporting that these effects were mediated by an opioid receptor pathway. Furthermore, biphalin significantly decreased edema (53%) and infarct (48%) ratios, and neuronal recovery from stroke, compared with the vehicle-treated groups in a 12h permanent middle cerebral artery occlusion (MCAO) model of focal ischemia. Biphalin also significantly decreased the cell volume increase in primary neuronal cells exposed to OGD condition. These data suggest that opioid receptor activation may provide neuroprotection during stroke and further investigations are needed in the development of novel opioid agonist as efficacious treatments for brain ischemia.

  19. 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.

  20. NAP alpha-aminoisobutyric acid (IsoNAP).

    PubMed

    Gozes, Illana; Schirer, Yulie; Idan-Feldman, Anat; David, Merav; Furman-Assaf, Sharon

    2014-01-01

    We set out to identify NAP (davunetide) analogs, providing neuroprotection and reducing tau pathology, specifically addressing protection against protein misfolding. NAP (NAPVSIPQ, intranasal formulation AL-108) is a drug candidate that (1) had a statistically significant impact on two measures, namely digit span and delayed-match-to-sample, tests of verbal recall and visual working memory, respectively, in patient population of mild cognitive impairment [preceding Alzheimer's disease (AD)] and (2) protected functional activities of daily living in schizophrenia patients. Previous preclinical studies have shown that stabilization of NAP by replacement of all L-amino acids by D-amino acids resulted in an active peptide, D-NAP. Other NAP mimetics are now explored. A new NAP analog was designed that included replacement of the proline residues by alpha-aminoisobutyric acid to enhance β-sheet breaker characteristics, thereby reducing protein misfolding. Three lines of investigations were chosen: (1) protection against the AD-associated amyloid β (1-42), Aβ1-42, peptide toxicity in cell cultures; (2) inhibition of AD-associated tau aggregation in vitro; and (3) cognitive protection in a mouse model of deficiencies of the NAP parent protein, activity-dependent neuroprotective protein (ADNP), exhibiting tau pathology and neurodegeneration. NAP alpha-aminoisobutyric acid (IsoNAP) protected neurons against AD-associated Aβ1-42-toxicity, inhibited the aggregation of the tau-derived peptide VQIVYK (important for the aggregation of tau into paired helical filaments, which form the tangles found in AD and related disorders), and protected cognitive functions in a model of ADNP deficiency. With AD being the major tauopathy, novel NAP derivatives that reduce tauopathy and provide neuroprotection as well as cognitive protection are of scientific and clinical interest.

  1. ISO spectroscopic observations of short-period comets

    NASA Astrophysics Data System (ADS)

    Crovisier, J.; Encrenaz, Th.; Lellouch, E.; Bockelée-Morvan, D.; Altieri, B.; Leech, K.; Salama, A.; Griffin, M. J.; de Graauw, Th.; van Dishoeck, E. F.; Knacke, R.; Brooke, T. Y.

    1999-03-01

    Two Infrared Space Observatory programmes (guaranteed time and open time) were devoted to high-resolution spectroscopic observations of short-period comets. 22P/Kopff was observed on October-December 1996 with SWS and LWS. Due to the weakness of the object, only the ν3 ro-vibrational lines of water were detected, with SWS. Comet 103P/Hartley 2 was observed close to its perihelion (at 1.04 AU from Sun and 0.82 AU from Earth) on January 1998 with SWS, LWS and CAM. The bands of H2O and CO2 at 2.7 and 4.3 μm are detected, with [CO2]/[H2O] = 10 %. The 2.7 μm band of H2O is observed with a high signal-to-noise ratio with SWS, which permits to evaluate the rotational temperature of water to 16-20 K and its ortho-to-para ratio to ~ 2.7, corresponding to a spin temperature of ~ 35 K. The 5-17 μm spectrum of comet Hartley 2 observed with CAM-CVF shows the 9-12 μm signature of silicates. Silicate emission around 10 μm is present at a level of about 20 % of the continuum, with a peak at 11.3 μm indicative of crystalline silicates. This is the first time crystalline silicates are found in a short-period comet. The ISO observations of the Jupiter-family comet P/Hartley 2, presumably originating from the Edgeworth-Kuiper belt, are compared to those of comet Hale-Bopp which came from the Oort cloud.

  2. Framework for establishing records control in hospitals as an ISO 9001 requirement.

    PubMed

    Al-Qatawneh, Lina

    2017-02-13

    Purpose The purpose of this paper is to present the process followed to control records in a Jordanian private community hospital as an ISO 9001:2008 standard requirement. Design/methodology/approach Under the hospital quality council's supervision, the quality management and development office staff were responsible for designing, planning and implementing the quality management system (QMS) using the ISO 9001:2008 standard. A policy for records control was established. An action plan for establishing the records control was developed and implemented. On completion, a coding system for records was specified to be used by hospital staff. Finally, an internal audit was performed to verify conformity to the ISO 9001:2008 standard requirements. Findings Successful certification by a neutral body ascertained that the hospital's QMS conformed to the ISO 9001:2008 requirements. A framework was developed that describes the records controlling process, which can be used by staff in any healthcare organization wanting to achieve ISO 9001:2008 accreditation. Originality/value Given the increased interest among healthcare organizations to achieve the ISO 9001 certification, the proposed framework for establishing records control is developed and is expected to be a valuable management tool to improve and sustain healthcare quality.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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..

  8. [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.

  9. Behavioural effects of selective tachykinin agonists in midbrain dopamine regions.

    PubMed

    Stoessl, A J; Szczutkowski, E; Glenn, B; Watson, I

    1991-11-29

    The effects of selective NK-1, NK-2 and NK-3 tachykinin agonists in midbrain dopamine cell containing regions were investigated in the rat. The NK-3 agonist senktide induced locomotion, rearing and sniffing following infusion into the substantia nigra pars compacta, and to a lesser extent in the ventral tegmental area. These behavioural responses were not seen following infusion of the selective NK-1 agonist [Sar9,Met (O2)11]SP or the NK-2 agonist [N1e10]NKA4-10. In contrast, grooming was induced only by the NK-1 agonist administered into the substantia nigra. Yawning, chewing mouth movements and wet dog shakes were all seen following infusion of senktide into the ventral tegmental area. These findings suggest that (i) dopamine-mediated behavioural responses seen following tachykinin administration into the midbrain are dependent upon stimulation of NK-3 tachykinin receptors, (ii) tachykinin-induced grooming is mediated by stimulation of NK-1 receptors and (iii) some of the previously described 5-HT mediated behaviours seen following administration of NK-3 tachykinin agonists are probably generated by stimulation of 5-HT cell bodies in the ventral tegmental area.

  10. Histamine H3-receptor inverse agonists as novel antipsychotics.

    PubMed

    Ito, Chihiro

    2009-06-01

    Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.

  11. 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

  12. 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

  13. The neuroprotective effects of α-iso-cubebene on dopaminergic cell death: involvement of CREB/Nrf2 signaling.

    PubMed

    Park, Sun Young; Son, Beung Gu; Park, Young Hoon; Kim, Cheol-Min; Park, Geuntae; Choi, Young-Whan

    2014-09-01

    As a part of ongoing studies to elucidate pharmacologically active components of Schisandra chinensis, we isolated and studied α-iso-cubebene. The neuroprotective mechanisms of α-iso-cubebene in human neuroblastoma SH-SY5Y cells were investigated. α-Iso-cubebene significantly inhibited cytotoxicity and apoptosis due to 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in dopaminergic SH-SY5Y cells. Pretreatment of cells with α-iso-cubebene reduced intracellular accumulation of ROS and calcium in response to 6-OHDA. The neuroprotective effects of α-iso-cubebene were found to result from protecting the mitochondrial membrane potential. Notably, α-iso-cubebene inhibited the release of apoptosis-inducing factor from the mitochondria into the cytosol and nucleus after 6-OHDA treatment. α-Iso-cubebene also induced the activation of PKA/PKB/CREB/Nrf2 and suppressed 6-OHDA-induced neurotoxicity. α-Iso-cubebene was found to induce phosphorylation of PKA and PKB and activate Nrf2 and CREB signaling pathways in a dose-dependent manner. Additionally, α-iso-cubebene stimulated the expression of the antioxidant response genes NQO1 and HO-1. Finally, α-iso-cubebene-mediated neuroprotective effects were found to be reversible after transfection with CREB and Nrf2 small interfering RNAs.

  14. 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.

  15. 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

  16. 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

  17. α-Iso-cubebene exerts neuroprotective effects in amyloid beta stimulated microglia activation.

    PubMed

    Park, Sun Young; Park, Se Jin; Park, Nan Jeong; Joo, Woo Hong; Lee, Sang-Joon; Choi, Young-Whan

    2013-10-25

    Schisandra chinensis is commonly used for food and as a traditional remedy for the treatment of neuronal disorders. However, it is unclear which component of S. chinensis is responsible for its neuropharmacological effects. To answer this question, we isolated α-iso-cubebene, a dibenzocyclooctadiene lignin, from S. chinensis and determined if it has any anti-neuroinflammatory and neuroprotective properties against amyloid β-induced neuroinflammation in microglia. Microglia that are stimulated by amyloid β increased their production of pro-inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO) and reactive oxygen species (ROS) and the enzymatic activity of matrix metalloproteinase 9 (MMP-9). We found this was all inhibited by α-iso-cubebene. Consistent with these results, α-iso-cubebene inhibited the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and MMP-9 in amyloid β-stimulated microglia. Subsequent mechanistic studies revealed that α-iso-cubebene inhibited the phosphorylation and degradation of IκB-α, the phosphorylation and transactivity of NF-κB, and the phosphorylation of MAPK in amyloid β-stimulated microglia. These results suggest that α-iso-cubebene impairs the amyloid β-induced neuroinflammatory response of microglia by inhibiting the NF-κB and MAPK signaling pathways. Importantly, α-iso-cubebene can provide critical neuroprotection for primary cortical neurons against amyloid β-stimulated microglia-mediated neurotoxicity. To the best of our knowledge, this is the first report showing that α-iso-cubebene can provide neuroprotection against, and influence neuroinflammation triggered by, amyloid β activation of microglia.

  18. Pressure-dependent kinetics of initial reactions in iso-octane pyrolysis.

    PubMed

    Ning, HongBo; Gong, ChunMing; Li, ZeRong; Li, XiangYuan

    2015-05-07

    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.

  19. 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

    2015-01-08

    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. 

  20. Evaluation of PC-ISO for customized, 3D printed, gynecologic 192Ir 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. PACS number: none.