Sample records for accelerate catecholamine release

  1. Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

    PubMed

    Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

    2015-01-01

    In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

  2. Effect of quinine on the release of catecholamines from bovine cultured chromaffin cells.

    PubMed Central

    Tang, R.; Novas, M. L.; Glavinovic, M. I.; Trifaró, J. M.

    1990-01-01

    1. The effects of quinine on catecholamine release from cultured bovine chromaffin cells were studied. 2. Quinine (25-400 microM) produced a dose-related inhibition of catecholamine release in response to depolarizing concentrations (12.5-50 mM) of K+. 3. The inhibition of the secretory response to high K+ produced by quinine decreased with the increase in the extracellular concentration of Ca2+. 4. Stimulation of cultured chromaffin cells with 50 mM K+ produced a significant increase in Ca2+ influx. In the presence of 100 microM quinine a 54% inhibition of the K(+)-induced Ca2+ influx was observed. 5. Quinine treatment of chromaffin cell cultures produced a small but significant decrease in membrane resting potential and a less pronounced depolarization in response to 50 mM K+. 6. The results suggest that the inhibition of the K(+)-evoked release of catecholamines produced by quinine is at least partly due to a decrease in Ca2+ influx. Ca2+ influx is lower because quinine reduces the sensitivity of the membrane potential to changes in extracellular K+ but direct effects of quinine on Ca2+ channels cannot be excluded. PMID:2158846

  3. Magnetron sputtered diamond-like carbon microelectrodes for on-chip measurement of quantal catecholamine release from cells

    PubMed Central

    Gao, Yuanfang; Chen, Xiaohui; Gupta, Sanju; Gillis, Kevin D.; Gangopadhyay, Shubhra

    2008-01-01

    Carbon electrodes are widely used in electrochemistry due to their low cost, wide potential window, and low and stable background noise. Carbon-fiber electrodes (CFE) are commonly used to electrochemically measure “quantal” catecholamine release via exocytosis from individual cells, but it is difficult to integrate CFEs into lab-on-a-chip devices. Here we report the development of nitrogen doped diamond-like carbon (DLC:N) microelectrodes on a chip to monitor quantal release of catecholamines from cells. Advantages of DLC:N microelectrodes are that they are batch producible at low cost, and are harder and more durable than graphite films. The DLC:N microelectrodes were prepared by a magnetron sputtering process with nitrogen doping. The 30 μm by 40 μm DLC:N microelectrodes were patterned onto microscope glass slides by photolithography and lift-off technology. The properties of the DLC:N microelectrodes were characterized by AFM, Raman spectroscopy and cyclic voltammetry. Quantal catecholamine release was recorded amperometrically from bovine adrenal chromaffin cells on the DLC:N microelectrodes. Amperometric spikes due to quantal release of catecholamines were similar in amplitude and area as those recorded using CFEs and the background current and noise levels of microchip DLC:N electrodes were also comparable to CFEs. Therefore, DLC:N microelectrodes are suitable for microchip-based high-throughput measurement of quantal exocytosis with applications in basic research, drug discovery and cell-based biosensors. PMID:18493856

  4. Effects of catecholamines on rat myocardial metabolism. II. Influence of catecholamines on 32p-incorporation into rat myocardial adenylic nucleotides and their turn-over.

    PubMed

    Merouze, P; Gaudemer, Y; Gautheron, D

    1975-01-01

    1. The influence of catecholamines (adrenaline and noradrenaline) on 32Pi incorporation into intracellular phosphate and adenylic nucleotides has been studied on rat myocardium slices; consequently, the turn-over of nucleotides could be determined and compared under the influence of these two hormones. 2. In order to specify the site of action of these catecholamines, several inhibitors and activators of energetic metabolism were included in the incubation medium: 3'5'-AMP, caffein, ouabain, oligomycin, rotenone + antimycin. 3. Both catecholamines favour Pi exchanges between intra and extracellular spaces; ATP turn-over is greatly increased, while ADP turn-over is slightly decreased, and 32P-incorporation into ADP is increased. 4. 3'5'-AMP and caffein are without effect on Pi penetration; however, caffein increases catecholamine effects on this penetration. ATP turn-over is slightly increased by 3'5'-AMP or caffein. 5. Ouabain decreases ATP turn-over but does not prevent the adrenaline induced acceleration. Inhibitors of oxidative phosphorylation and electron transport decrease ATP-turn-over severely; this inhibition is not released by catecholamines. 6. It is concluded that the catecholamine effects observed are dependent on the oxidative phosphorylations process. The increase of Pi exchange by catecholamines may be related to the increase of extracellular space and cation translocations we observed with the hormones.

  5. Inhibition of Ca2+ channels and adrenal catecholamine release by G protein coupled receptors.

    PubMed

    Currie, Kevin P M

    2010-11-01

    Catecholamines and other transmitters released from adrenal chromaffin cells play central roles in the "fight-or-flight" response and exert profound effects on cardiovascular, endocrine, immune, and nervous system function. As such, precise regulation of chromaffin cell exocytosis is key to maintaining normal physiological function and appropriate responsiveness to acute stress. Chromaffin cells express a number of different G protein coupled receptors (GPCRs) that sense the local environment and orchestrate this precise control of transmitter release. The primary trigger for catecholamine release is Ca2+ entry through voltage-gated Ca2+ channels, so it makes sense that these channels are subject to complex regulation by GPCRs. In particular G protein βγ heterodimers (Gbc) bind to and inhibit Ca2+ channels. Here I review the mechanisms by which GPCRs inhibit Ca2+ channels in chromaffin cells and how this might be altered by cellular context. This is related to the potent autocrine inhibition of Ca2+ entry and transmitter release seen in chromaffin cells. Recent data that implicate an additional inhibitory target of Gβγ on the exocytotic machinery and how this might fine tune neuroendocrine secretion are also discussed.

  6. Tyrosine - Effects on catecholamine release

    NASA Technical Reports Server (NTRS)

    Acworth, Ian N.; During, Matthew J.; Wurtman, Richard J.

    1988-01-01

    Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.

  7. A toxin fraction (FTX) from the funnel-web spider poison inhibits dihydropyridine-insensitive Ca2+ channels coupled to catecholamine release in bovine adrenal chromaffin cells.

    PubMed

    Duarte, C B; Rosario, L M; Sena, C M; Carvalho, A P

    1993-03-01

    In adrenal chromaffin cells, depolarization-evoked Ca2+ influx and catecholamine release are partially blocked by blockers of L-type voltage-sensitive Ca2+ channels. We have now evaluated the sensitivity of the dihydropyridine-resistant components of Ca2+ influx and catecholamine release to a toxin fraction (FTX) from the funnel-web spider poison, which is known to block P-type channels in mammalian neurons. FTX (1:4,000 dilution, with respect to the original fraction) inhibited K(+)-depolarization-induced Ca2+ influx by 50%, as monitored with fura-2, whereas nitrendipine (0.1-1 microM) and FTX (3:3), a synthetic FTX analogue (1 mM), blocked the [Ca2+]i transients by 35 and 30%, respectively. When tested together, FTX and nitrendipine reduced the [Ca2+]i transients by 70%. FTX or nitrendipine reduced adrenaline and noradrenaline release by approximately 80 and 70%, respectively, but both substances together abolished the K(+)-evoked catecholamine release, as measured by HPLC. The omega-conotoxin GVIA (0.5 microM) was without effect on K(+)-stimulated 45Ca2+ uptake. Our results indicate that FTX blocks dihydropyridine- and omega-conotoxin-insensitive Ca2+ channels that, together with L-type voltage-sensitive Ca2+ channels, are coupled to catecholamine release.

  8. Kv7(KCNQ)-K+-Channels Influence Total Peripheral Resistance in Female but Not Male Rats, and Hamper Catecholamine Release in Hypertensive Rats of Both Sexes

    PubMed Central

    Berg, Torill

    2018-01-01

    K+-channels of the Kv7/KCNQ-family hyperpolarize and stabilize excitable cells such as autonomic neurons and vascular smooth muscle cells (VSMC). Kv7 may therefore play a role in blood pressure (BP) homeostasis, and prevent a high total peripheral vascular resistance (TPR), a hallmark of hypertensive disease. The present study analyzed if Kv7 channels influence catecholamine release and TPR in normotensive (WKY) and spontaneously hypertensive rats (SHR), and if they may contribute to the antihypertensive protection seen in young, female SHR. Tyramine-stimulated norepinephrine release evokes an adrenergic cardiovascular response, and also allows modulation of release to be reflected in the overflow to plasma. The experiment itself activated some secretion of epinephrine. The results show: (1) XE-991 (Kv7.1-7.4-inhibitor), but not chromanol 293B (Kv7.1-inhibitor), increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in both sexes in SHR, but not WKY. (2) Surprisingly, the Kv7-openers retigabine (Kv7.2-7.5) and ICA-27243 (Kv7.2-7.3-preferring) increased catecholamine release in female SHR. (3) The rise in TPR following tyramine-stimulated norepinephrine release was increased by XE-991 but not chromanol in the female WKY only. (4) Retigabine and ICA-27243 reduced the TPR-response to tyramine in the female SHR only. These results suggested: (1) Up-regulation of Kv7.2-7.3 function in sympathetic neurons and chromaffin cells hampered catecholamine release in SHR of both sexes. (2) The increase catecholamine release observed after channel openers in the female SHR may possibly involve reduced transmission in cholinergic neurons which hamper catecholamine release. These two mechanisms may serve to counter-act the hyperadrenergic state in SHR. (3) Kv7.4, most likely in the vasculature, opposed the tension-response to norepinephrine in the female WKY. (4) Vascular Kv7.4-7.5 could be stimulated and then opposed norepinephrine-induced vasoconstriction

  9. Kv7(KCNQ)-K+-Channels Influence Total Peripheral Resistance in Female but Not Male Rats, and Hamper Catecholamine Release in Hypertensive Rats of Both Sexes.

    PubMed

    Berg, Torill

    2018-01-01

    K + -channels of the Kv7/KCNQ-family hyperpolarize and stabilize excitable cells such as autonomic neurons and vascular smooth muscle cells (VSMC). Kv7 may therefore play a role in blood pressure (BP) homeostasis, and prevent a high total peripheral vascular resistance (TPR), a hallmark of hypertensive disease. The present study analyzed if Kv7 channels influence catecholamine release and TPR in normotensive (WKY) and spontaneously hypertensive rats (SHR), and if they may contribute to the antihypertensive protection seen in young, female SHR. Tyramine-stimulated norepinephrine release evokes an adrenergic cardiovascular response, and also allows modulation of release to be reflected in the overflow to plasma. The experiment itself activated some secretion of epinephrine. The results show: (1) XE-991 (Kv7.1-7.4-inhibitor), but not chromanol 293B (Kv7.1-inhibitor), increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in both sexes in SHR, but not WKY. (2) Surprisingly, the Kv7-openers retigabine (Kv7.2-7.5) and ICA-27243 (Kv7.2-7.3-preferring) increased catecholamine release in female SHR. (3) The rise in TPR following tyramine-stimulated norepinephrine release was increased by XE-991 but not chromanol in the female WKY only. (4) Retigabine and ICA-27243 reduced the TPR-response to tyramine in the female SHR only. These results suggested: (1) Up-regulation of Kv7.2-7.3 function in sympathetic neurons and chromaffin cells hampered catecholamine release in SHR of both sexes. (2) The increase catecholamine release observed after channel openers in the female SHR may possibly involve reduced transmission in cholinergic neurons which hamper catecholamine release. These two mechanisms may serve to counter-act the hyperadrenergic state in SHR. (3) Kv7.4, most likely in the vasculature, opposed the tension-response to norepinephrine in the female WKY. (4) Vascular Kv7.4-7.5 could be stimulated and then opposed norepinephrine

  10. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    PubMed

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  11. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    PubMed Central

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  12. Catecholamines release mediators in the opossum oesophageal circular smooth muscle.

    PubMed Central

    Daniel, E E; Jager, L P; Jury, J

    1987-01-01

    1. Effects of catecholamines applied exogenously to the circular smooth muscle layer of the body of the oesophagus of the opossum (Didelphis marsupialis) were studied, simultaneously measuring changes in the membrane potential, the membrane conductance and the contractility of the muscle, using the double sucrose-gap technique. 2. Superfusion of the smooth muscle with Krebs solution at 27 degrees C containing dopamine (10(-6)-10(-4) M) dose-dependently caused a hyperpolarization of the smooth muscle cells and an increased membrane resistance followed after gradual repolarization by oscillations of the membrane potential, often accompanied by muscle action potentials. During the hyperpolarization, the tendency for the membrane potential to sag during prolonged application of hyperpolarizing currents was reduced and the 'off' depolarization following such currents was increased. This muscle did not develop active tension prior to treatment; it therefore did not relax during the hyperpolarizations, but contracted following the depolarized phase of oscillations. 3. The non-adrenergic, non-cholinergic nerve-mediated inhibitory junction potential (i.j.p.) showed a small reduction in amplitude during superfusion with dopamine, explicable as a result of the drug-induced hyperpolarization. The 'off' response following the i.j.p., decreased transiently when the membrane potential was hyperpolarized to its maximum value. Then it increased to values larger than control as the membrane repolarized. Vasoactive intestinal polypeptide (VIP, 10(-6) M) produced a similar response but hyperpolarizations were smaller. 4. Of the tested catecholamines, isoprenaline, phenylephrine, butylated hydroxytoluene-920 (BHT-920) and clonidine were ineffective whereas the potency order for other catecholamines was dopamine greater than noradrenaline greater than or equal to adrenaline greater than DOPA. The catecholamine-induced responses were not affected by alpha- or beta

  13. Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.

    PubMed

    Lee, Byung-Hwan; Kim, Jisu; Lee, Ra Mi; Choi, Sun-Hye; Kim, Hyeon-Joong; Hwang, Sung-Hee; Lee, Myung Koo; Bae, Chun-Sik; Kim, Hyoung-Chun; Rhim, Hyewon; Lim, Kiwon; Nah, Seung-Yeol

    2016-01-26

    Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. (-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

    PubMed

    Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

    2016-09-01

    A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

  15. The effects of C-type natriuretic peptide on catecholamine release in the pacific spiny dogfish (Squalus acanthias).

    PubMed

    Montpetit, C J; McKendry, J; Perry, S F

    2001-08-01

    The interaction between homologous C-type natriuretic peptide (dfCNP) and catecholamine release in cardiovascular control was assessed in the marine dogfish (Squalus acanthias). This was accomplished by evaluation of the dynamics of the dfCNP-elicited secretion of catecholamines in situ and in vivo. With an in situ saline-perfused postcardinal sinus preparation, it was demonstrated that perfusion with saline containing dfCNP (10(-9) mol x L(-1)) did not affect the secretion of either noradrenaline or adrenaline. However, the presence of dfCNP in the perfusate significantly enhanced carbachol-evoked secretion of noradrenaline. In vivo, intravascular injection of dfCNP (10(-9) mol x kg(-1)) caused a biphasic pressor-depressor response consisting of a brief increase in caudal artery blood pressure (P(CA)) followed by a prolonged reduction in P(CA). Furthermore, although systemic resistance initially increased, it was subsequently maintained at baseline values in the face of persistent decreases in both P(CA) and cardiac output. Bolus injection of dfCNP elicited significant increases in plasma noradrenaline levels that peaked within 10 min; plasma adrenaline levels were unaffected. The release of noradrenaline elicited by dfCNP was unaffected by prior blockade of the renin-angiotensin system (RAS) (with the angiotensin converting enzyme inhibitor lisinopril) or by pretreatment with the nicotinic receptor blocker hexamethonium. The delayed decrease in P(CA) was not observed in the hexamethonium-treated fish. Prior blockade of beta-adrenoreceptors (with sotalol) or alpha-adrenoreceptors (with prazosin) either significantly reduced (sotalol) or abolished (prazosin) the increase in plasma noradrenaline levels after dfCNP injection. The results of this investigation demonstrate that the elevation of plasma noradrenaline levels observed in vivo following dfCNP injection is not caused by a direct effect of dfCNP on catecholamine secretion from axillary body chromaffin cells

  16. Do alterations in prostanoid or catecholamine release influence the antiarrhythmic activity of nicergoline?

    PubMed

    Williams, F M; Coker, S J; Dean, H G; Kane, K A; Parratt, J R

    1986-01-01

    We examined the effects of nicergoline, an alpha-adrenoceptor blocking drug and an inhibitor of platelet phospholipase, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid and catecholamine release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Twenty-five minutes after commencing the intravenous infusion of nicergoline (50 micrograms kg-1 min-1) there were significant reductions in heart rate, arterial blood pressure, left ventricular dP/dtmax, and cardiac output. Nicergoline also increased the 0(2) extraction by the myocardium both before and during coronary artery occlusion. In contrast to control animals, heart rate decreased but there were no further reductions in arterial blood pressure during the occlusion period. Nicergoline improved survival (from 17 in control dogs to 50%) following the combined period of myocardial ischaemia and reperfusion and appeared to suppress the phase 1b occlusion-induced arrhythmias. The release of thromboxane B2 from the ischaemic myocardium was partially suppressed by nicergoline, and the ratio of 6-keto PGF1 alpha/thromboxane B2 (the stable breakdown products of prostacyclin and thromboxane A2, respectively) was increased. The washout of noradrenaline and adrenaline from the ischaemic myocardium following release of the occlusion was slightly enhanced by nicergoline. It is concluded that the beneficial metabolic and prostacyclin-promoting properties of nicergoline may be opposed by its action on noradrenaline washout, thus limiting its antiarrhythmic effectiveness.

  17. Selective stimulation of catecholamine release from bovine adrenal chromaffin cells by an ionotropic purinergic receptor sensitive to 2-methylthio ATP.

    PubMed

    Tomé, Angelo R; Castro, Enrique; Santos, Rosa M; Rosário, Luís M

    2007-06-20

    2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca2+ influx and evokes catecholamine release from adrenal chromaffin cells. These cells express P2Y and P2X (ionotropic) purinoceptors, with the latter providing an important Ca2+ influx pathway. Using single cell calcium imaging techniques, we have determined whether 2-MeSATP might be a specific P2X receptor agonist in bovine chromaffin cells and assessed the relative role of P2X and P2Y receptors on catecholamine secretion from these cells. ATP raised the [Ca2+]i in ~50% of the cells. Removing extracellular Ca2+ suppressed the [Ca2+]i-raising ability of 2-MeSATP, observed in ~40% of the ATP-sensitive cells. This indicates that 2-MeSATP behaves as a specific ionotropic purinoceptor agonist in bovine chromaffin cells. The 2-MeSATP-induced [Ca2+]i-rises were suppressed by PPADS. UTP raised the [Ca2+]i in ~40% of the ATP-sensitive cells, indicating that these expressed Ca2+-mobilizing P2Y receptors. UTP-sensitive receptors may not be the only P2Y receptors present, as suggested by the observation that ~20% of the ATP-sensitive pool did not respond to either 2-MeSATP or UTP. The average sizes of the ATP- and 2-MeSATP-evoked [Ca2+]i responses were identical in UTP-insensitive cells. 2-MeSATP stimulated Ca2+ influx and evoked catecholamine release, whereas UTP elicited Ca2+ release from intracellular stores but did not evoke secretion. 2-MeSATP-induced secretion was strongly inhibited by Cd2+ and suppressed by extracellular Ca2+ or Na+ removal. TTX inhibited 2-MeSATP-evoked secretion by ~20%. 2-MeSATP is a specific P2X purinoceptor agonist and a potent secretagogue in bovine chromaffin cells. Activation of 2-MeSATP-sensitive receptors stimulates Ca2+ influx mainly via voltage-sensitive Ca2+ channels. For the most part, these are activated by the depolarization brought about by Na+ influx across P2X receptor pores.

  18. Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells.

    PubMed

    Gomes, Andreia; Correia, Gustavo; Coelho, Marisa; Araújo, João Ricardo; Pinho, Maria João; Teixeira, Ana Luisa; Medeiros, Rui; Ribeiro, Laura

    2015-05-01

    Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres.

    PubMed

    Andhariya, Janki V; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J; Shen, Jie

    2017-03-30

    The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol ® ) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37°C) and "accelerated" (45°C), respectively. The USP apparatus 4 method was more reproducible than the sample-and-separate method. In addition, the accelerated release profile obtained using USP apparatus 4 had a shortened release duration (within seven days), and good correlation with the "real-time" release profile. Lastly, the discriminatory ability of the developed accelerated release method was assessed using compositionally equivalent naltrexone microspheres with different release characteristics. The developed accelerated USP apparatus 4 release method was able to detect differences in the release characteristics of the prepared naltrexone microspheres. Moreover, a linear correlation was observed between the "real-time" and accelerated release profiles of all the formulations investigated, suggesting that the release mechanism(s) may be similar under both conditions. These results indicate that the developed accelerated USP apparatus 4 method has the potential to be an appropriate fast quality control tool for long-acting naltrexone PLGA microspheres. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fish in hot water: hypoxaemia does not trigger catecholamine mobilization during heat shock in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Currie, S; Ahmady, E; Watters, M A; Perry, S F; Gilmour, K M

    2013-06-01

    Rainbow trout (Oncorhynchus mykiss) exposed to an acute heat shock (1 h at 25 °C after raising water temperature from 13 °C to 25 °C over 4 h) mount a significant catecholamine response. The present study investigated the proximate mechanisms underlying catecholamine mobilization. Trout exposed to heat shock in vivo exhibited a significant reduction in arterial O(2) tension, but arterial O(2) concentration was not affected by heat shock, nor was catecholamine release during heat shock prevented by prior and concomitant exposure to hyperoxia (to prevent the fall in arterial O(2) tension). Thus, catecholamine mobilization probably was not triggered by impaired blood O(2) transport. Heat-shocked trout also exhibited an elevation of arterial CO(2) tension coupled with a fall in arterial pH, but these factors are not expected to trigger catecholamine release. The changes in blood O(2) and CO(2) tension occurred despite a significant hyperventilatory response to heat shock. Future studies should investigate whether catecholamine mobilization during heat shock in rainbow trout is triggered by a specific effect of high temperature activating the sympathetic nervous system via a thermosensitive transient receptor potential channel. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. A novel accelerated in vitro release method to evaluate the release of thymopentin from PLGA microspheres.

    PubMed

    Xie, Xiangyang; Li, Zhiping; Zhang, Ling; Chi, Qiang; Yang, Yanfang; Zhang, Hui; Yang, Yang; Mei, Xingguo

    2015-01-01

    A novel accelerated method of good correlations with "real-time" release to evaluate in vitro thymopentin release from poly (D, L-lactide-co-glycolide) (PLGA) microsphere was developed. Thymopentin-loaded microspheres were made from three types of PLGA, and peptide release was studied in various conditions. Incomplete release of peptide (<60%) from microspheres was found in accelerated testing with two typical release media. This problem was circumvented by adding organic solvents to the release media and varying the temperature in the media heating process. Release media containing three kinds of organic solvents at 50 °C were tested, respectively, and hydro-alcoholic solution was selected for further study. After the surfactant concentration (0.06%, W/V) and ethanol concentration (20%, V/V) were fixed, a gradient heating program, consisting of three stages and each stage with a different temperature, was introduced to enhance the correlations between the short- and long-term release. After adjusting the heating time of each stage, a good correlation (R(2) = 9896, formulation 8 K; R(2) = 0.9898, formulation 13 K; R(2) = 0.9886, formulation 28 K) between accelerated and "real-time" release was obtained. By optimizing the conditions as ethanol concentration and temperature gradients, this accelerated method may be appropriate for similar peptide formulations that not well correlate with "real-time" release.

  2. An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

    PubMed

    Hu, Xiaoqin; Zhang, Jianwei; Tang, Xuemei; Li, Mingyuan; Ma, Siyu; Liu, Cheng; Gao, Yue; Zhang, Yue; Liu, Yan; Yu, Fanglin; Yang, Yang; Guo, Jia; Li, Zhiping; Mei, Xingguo

    2018-01-01

    A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release

  3. DISTRIBUTION OF ATRAZINE IN PC12 CELLS AND MODULATION OF CATECHOLAMINE SYNTHESIS

    EPA Science Inventory

    Previously, we reported that atrazine disrupts ovarian function by altering hypothalamic catecholamine (CA) concentrations and the consequent regulation of pituitary LH release and prolactin secretion in the young female rat. We also showed that atrazine directly interacts with t...

  4. Effects of their nutrient precursors on the synthesis and release of serotonin, the catecholamines, and acetylcholine - Implications for behavioral disorders

    NASA Technical Reports Server (NTRS)

    Wurtman, Richard J.

    1988-01-01

    Authentic foods affect brain serotonin synthesis by modifying brain tryptophan levels, carbohydrates increasing and proteins decreasing these levels. The carbohydrate-induced rise in brain serotonin tends to diminish the likelihood that one carbohydrate-rich, protein-poor meal or snack will be followed by another. This mechanism is apparently disturbed in carbohydrate-craving obesity, which may explain why this syndrome responds well to d-fenfluramine, a serotoninergic drug. Pure nutrients like tyrosine or choline can also affect the rates at which their neurotransmitter products, the catecholamines and acetylcholine, are synthesized in and released from nerve terminals, suggesting that these compounds may find uses as drugs.

  5. Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry

    PubMed Central

    Smith, Amanda R.; Garris, Paul A.; Casto, Joseph M.

    2015-01-01

    Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of

  6. Catecholamines - urine

    MedlinePlus

    Dopamine - urine test; Epinephrine - urine test; Adrenalin - urine test; Urine metanephrine; Normetanephrine; Norepinephrine - urine test; Urine catecholamines; VMA; HVA; Metanephrine; Homovanillic ...

  7. The effect of salts on catecholamine fluxes and adenosine triphosphatase activity in storage vesicles from the adrenal medulla

    PubMed Central

    Taugner, G.

    1971-01-01

    1. Influx and efflux of catecholamine and adenosine triphosphatase activity in storage vesicles from the adrenal medulla were studied with dl-[14C]adrenaline in different media. 2. The lowest values for flux and adenosine triphosphatase activity were observed in sucrose media in which an ATP-dependent influx of catecholamine compensated for an efflux of the same magnitude. Efflux in the presence or absence of ATP was similar. 3. In media containing sodium succinate or glutarate adenosine triphosphatase activity was higher and the ATP-dependent influx of catecholamine was about twice that observed in iso-osmotic sucrose medium. In the presence of ATP influx and efflux of catecholamine were balanced; in its absence there was a net release of catecholamine, since efflux was more than twice the influx. Efflux in the presence or absence of ATP was similar. 4. In media containing sodium or potassium chloride and in the presence of ATP influx and adenosine triphosphatase activity were further enhanced, but in the absence of ATP there was no further increase in influx, since catecholamine was released with or without ATP at the same rate. Efflux was therefore twice as high in the presence of ATP as in its absence. 5. Sodium nitrate suppressed the ATP-dependent influx nearly completely, but caused a greatly enhanced efflux, which was twice as high in the presence of ATP as in its absence. 6. The extinction of vesicular suspensions remained unchanged in the presence of ATP under conditions where the catecholamine efflux was balanced by the influx. Under conditions where the efflux was not compensated by influx, the extinction of the suspensions decreased in the presence of ATP more than in its absence. PMID:4256794

  8. Plasma renin activity, aldosterone and catecholamine levels when swimming and running.

    PubMed

    Guezennec, C Y; Defer, G; Cazorla, G; Sabathier, C; Lhoste, F

    1986-01-01

    The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.

  9. Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

    PubMed

    Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

    2017-01-01

    Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

    PubMed

    Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

    2013-11-01

    The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

  11. GABAA receptor: a unique modulator of excitability, Ca2+ signaling, and catecholamine release of rat chromaffin cells.

    PubMed

    Alejandre-García, Tzitzitlini; Peña-Del Castillo, Johanna G; Hernández-Cruz, Arturo

    2018-01-01

    The role of gamma-aminobutyric acid (GABA) in adrenal medulla chromaffin cell (CC) function is just beginning to unfold. GABA is stored in catecholamine (CA)-containing dense core granules and is presumably released together with CA, ATP, and opioids in response to physiological stimuli, playing an autocrine-paracrine role on CCs. The reported paradoxical "dual action" of GABA A -R activation (enhancement of CA secretion and inhibition of synaptically evoked CA release) is only one aspect of GABA's multifaceted actions. In this review, we discuss recent physiological experiments on rat CCs in situ which suggest that GABA regulation of CC function may depend on the physiological context: During non-stressful conditions, GABA A -R activation by endogenous GABA tonically inhibits acetylcholine release from splanchnic nerve terminals and decreases spontaneous Ca 2+ fluctuations in CCs, preventing unwanted CA secretion. During intense stress, splanchnic nerve terminals release acetylcholine, which depolarizes CCs and allows the Ca 2+ influx that triggers the release of CA and GABA. With time, CA secretion declines, due to voltage-independent inhibition of Ca 2+ channels and desensitization of cholinergic nicotinic receptors. Nonetheless, acute activation of GABA A -R is depolarizing in about 50% of CCs, and thus GABA, acting as an autocrine/paracrine mediator, could help to maintain CA exocytosis under stress. GABA A -R activation is not excitatory in about half of CCs' population because it hyperpolarizes them or elicits no response. This percentage possibly varies, depending on functional demands, since GABA A -R-mediated actions are determined by the intracellular chloride concentration ([Cl - ] i ) and therefore on the activity of cation-chloride co transporters, which is functionally regulated. These findings underscore a potential importance of a novel and complex GABA-mediated regulation of CC function and of CA secretion.

  12. Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry.

    PubMed

    Smith, Amanda R; Garris, Paul A; Casto, Joseph M

    2015-01-01

    Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of

  13. Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

    1993-01-01

    Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

  14. PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

    PubMed Central

    Pacak, Karel

    2012-01-01

    The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla — an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called “attacks” or “spells”. Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto

  15. Catecholamines and obesity: effects of exercise and training.

    PubMed

    Zouhal, Hassane; Lemoine-Morel, Sophie; Mathieu, Marie-Eve; Casazza, Gretchen A; Jabbour, Georges

    2013-07-01

    Excess body fat in obese individuals can affect the catecholamine response to various stimuli. Indeed, several studies report lower plasma catecholamine concentrations in obese subjects compared with nonobese subjects in response to submaximal or maximal exercise. This low catecholamine response reflects decreased sympathetic nervous system (SNS) activity. Although the relationship between the SNS and obesity is not well established, some authors have suggested that low SNS activity may contribute to the development of obesity. A decreased catecholamine response could affect α- and β-adrenoceptor sensitivity in adipose tissue, reducing lipolysis and increasing fat stores. Few studies have examined the effects of obesity on the plasma catecholamine response at rest and during exercise in adolescents. It is interesting to note that the effects of age, sex, and degree of obesity and the impact of very intense exercise on the catecholamine response have not yet been well examined. Moreover, the hormonal concentrations measured in the majority of obesity studies did not take into account plasma volume changes. This methodological factor can also undoubtedly influence plasma catecholamine results.

  16. A reproducible accelerated in vitro release testing method for PLGA microspheres.

    PubMed

    Shen, Jie; Lee, Kyulim; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

    2016-02-10

    The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 °C) and accelerated (45 °C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures). Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings

    PubMed Central

    Shen, Jie; Burgess, Diane J.

    2011-01-01

    Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under “real-time” and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to “real-time” conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict “real-time” release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under “real-time” and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. PMID:22016033

  18. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings.

    PubMed

    Shen, Jie; Burgess, Diane J

    2012-01-17

    Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

    PubMed Central

    Wenisch, C; Parschalk, B; Weiss, A; Zedwitz-Liebenstein, K; Hahsler, B; Wenisch, H; Georgopoulos, A; Graninger, W

    1996-01-01

    Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood. PMID:8807207

  20. ALTERATION OF CATECHOLAMINES IN PHOECHROMOCYTOMA (PC12) CELLS IN VITRO BY THE METABOLITES OF CHLOROTRIAZINE HERBICIDE

    EPA Science Inventory

    The effects of four major chlorotriazine metabolites on the constitutive synthesis of the catecholamines dopamine (DA) and norepinephrine (NE) were examined using undifferentiated PC12 cells. NE release and intracellular DA and NE concentrations were quantified following treatme...

  1. Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma.

    PubMed

    Salmasi, Vafi; Schiavi, Adam; Binder, Zev A; Ruzevick, Jacob; Orr, Brent A; Burger, Peter C; Ball, Douglas W; Blitz, Ari M; Koch, Wayne M; Ishii, Masaru; Gallia, Gary L

    2015-06-01

    Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed an intraoperative hypertensive crisis. A patient with a history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Workup revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade before the second stage. Serum catecholamine levels after this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. © 2015 Wiley Periodicals, Inc.

  2. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis

    PubMed Central

    Fischer, Katrin; Ruiz, Henry H.; Jhun, Kevin; Finan, Brian; Oberlin, Douglas J.; van der Heide, Verena; Kalinovich, Anastasia V.; Petrovic, Natasa; Wolf, Yochai; Clemmensen, Christoffer; Shin, Andrew C.; Divanovic, Senad; Brombacher, Frank; Glasmacher, Elke; Keipert, Susanne; Jastroch, Martin; Nagler, Joachim; Schramm, Karl-Werner; Medrikova, Dasa; Collden, Gustav; Woods, Stephen C.; Herzig, Stephan; Homann, Dirk; Jung, Steffen; Nedergaard, Jan; Cannon, Barbara; Tschöp, Matthias H.

    2017-01-01

    Adaptive thermogenesis is the process of heat generation in response to cold stimulation and is under the control of the sympathetic nervous system whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta3 adrenergic receptors to activate brown adipose tissue and by “browning” white adipose tissue. Recent studies reported that the alternative activation of macrophages in response to IL-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and to provide an alternative source of locally produced catecholamines during the thermogenic process. We here report that the deletion of Th in hematopoetic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with Interleukin-4 (IL-4), and conditioned media from IL-4 stimulated macrophages failed to induce expression of thermogenic genes, such as the one for uncoupling protein 1 (Ucp1) in adipocytes cultured with the conditioned media. Further, chronic IL-4 treatment failed to increase energy expenditure in WT, Ucp1-/- and Il4ra-/- mice. Consistent with these findings, adipose tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines and hence are not likely to play a direct role in adipocyte metabolism or adaptive thermogenesis. PMID:28414329

  3. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.

    PubMed

    Fischer, Katrin; Ruiz, Henry H; Jhun, Kevin; Finan, Brian; Oberlin, Douglas J; van der Heide, Verena; Kalinovich, Anastasia V; Petrovic, Natasa; Wolf, Yochai; Clemmensen, Christoffer; Shin, Andrew C; Divanovic, Senad; Brombacher, Frank; Glasmacher, Elke; Keipert, Susanne; Jastroch, Martin; Nagler, Joachim; Schramm, Karl-Werner; Medrikova, Dasa; Collden, Gustav; Woods, Stephen C; Herzig, Stephan; Homann, Dirk; Jung, Steffen; Nedergaard, Jan; Cannon, Barbara; Tschöp, Matthias H; Müller, Timo D; Buettner, Christoph

    2017-05-01

    Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1 -/- and interleukin-4 receptor-α double-negative (Il4ra -/- ) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.

  4. Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma

    PubMed Central

    Salmasi, Vafi; Schiavi, Adam; Binder, Zev A.; Ruzevick, Jacob; Orr, Brent A.; Burger, Peter C.; Ball, Douglas W.; Blitz, Ari M.; Koch, Wayne M.; Ishii, Masaru; Gallia, Gary L.

    2015-01-01

    Background Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. Methods We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed intraoperative hypertensive crisis. Results A patient with history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Work-up revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade prior to the second stage. Serum catecholamine levels following this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in cathecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Conclusion Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. PMID:25352487

  5. Controlled On-chip Stimulation of Quantal Catecholamine Release from Chromaffin Cells Using Photolysis of Caged Ca2+ on Transparent Indium-Tin-Oxide Microchip Electrodes

    PubMed Central

    Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D.

    2008-01-01

    Photorelease of caged Ca2+ is a uniquely powerful tool to study the dynamics of Ca2+-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca2+ together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm - thick transparent Indium-Tin-Oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (∼20 μm by 20 μm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca2+ cage NP-EGTA and Ca2+ indicator dye Fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca2+, a uniform rise of [Ca2+]i within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca2+]i and a “priming” effect of sub-stimulatory [Ca2+]i on the response of cells to subsequent [Ca2+]i elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca2+ is a suitable stimulation technique for higher-throughput studies of Ca2+-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

  6. A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells.

    PubMed

    Ges, Igor A; Brindley, Rebecca L; Currie, Kevin P M; Baudenbacher, Franz J

    2013-12-07

    Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped "cell traps", each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion/repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time.

  7. Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Ludwig, D. A.; Gray, B. D.; Vernikos, J.

    1998-01-01

    We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

  8. Plasma free metanephrines are superior to urine and plasma catecholamines and urine catecholamine metabolites for the investigation of phaeochromocytoma.

    PubMed

    Hickman, Peter E; Leong, Michelle; Chang, Julia; Wilson, Susan R; McWhinney, Brett

    2009-02-01

    To compare the relative diagnostic efficacy of several different tests used to establish a diagnosis of phaeochromocytoma, in patients with a proven diagnosis of phaeochromocytoma, and in hospital patients with significant disease of other types. We prospectively compared biochemical markers of catecholamine output and metabolism in plasma and urine in 22 patients with histologically proven phaeochromocytoma, 15 intensive care unit (ICU) patients, 30 patients on chronic haemodialysis and both hypertensive (n = 10) and normotensive (n = 16) controls. Receiver operating characteristic curves were plotted. At the point of maximum efficiency, plasma free metanephrines showed 100% sensitivity and 97.6% specificity, compared with plasma catecholamines (78.6% and 70.7%), urine catecholamines (78.6% and 87.8%), urine metanephrines (85.7% and 95.1%), and urine hydroxymethoxymandelic acid (HMMA or VMA) (93.0% and 75.8%). All patients with phaeochromocytoma had plasma free metanephrine concentrations at least 27% above the upper limit of the reference range. Only three other patients (two on haemodialysis and one in ICU) had PFM concentrations more than 50% above the upper limit of the reference range. In patients with phaeochromocytoma, plasma free metanephrines displayed superior diagnostic sensitivity and specificity compared with other biochemical markers of catecholamine output and metabolism.

  9. The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue.

    PubMed Central

    Kalsner, S

    1976-01-01

    The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue. PMID:974389

  10. Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats.

    PubMed

    Li, Ai-Jun; Wang, Qing; Elsarelli, Megan M; Brown, R Lane; Ritter, Sue

    2015-08-01

    Hindbrain catecholamine neurons are required for elicitation of feeding responses to glucose deficit, but the forebrain circuitry required for these responses is incompletely understood. Here we examined interactions of catecholamine and orexin neurons in eliciting glucoprivic feeding. Orexin neurons, located in the perifornical lateral hypothalamus (PeFLH), are heavily innervated by hindbrain catecholamine neurons, stimulate food intake, and increase arousal and behavioral activation. Orexin neurons may therefore contribute importantly to appetitive responses, such as food seeking, during glucoprivation. Retrograde tracing results showed that nearly all innervation of the PeFLH from the hindbrain originated from catecholamine neurons and some raphe nuclei. Results also suggested that many catecholamine neurons project collaterally to the PeFLH and paraventricular hypothalamic nucleus. Systemic administration of the antiglycolytic agent, 2-deoxy-D-glucose, increased food intake and c-Fos expression in orexin neurons. Both responses were eliminated by a lesion of catecholamine neurons innervating orexin neurons using the retrogradely transported immunotoxin, anti-dopamine-β-hydroxylase saporin, which is specifically internalized by dopamine-β-hydroxylase-expressing catecholamine neurons. Using designer receptors exclusively activated by designer drugs in transgenic rats expressing Cre recombinase under the control of tyrosine hydroxylase promoter, catecholamine neurons in cell groups A1 and C1 of the ventrolateral medulla were activated selectively by peripheral injection of clozapine-N-oxide. Clozapine-N-oxide injection increased food intake and c-Fos expression in PeFLH orexin neurons as well as in paraventricular hypothalamic nucleus neurons. In summary, catecholamine neurons are required for the activation of orexin neurons during glucoprivation. Activation of orexin neurons may contribute to appetitive responses required for glucoprivic feeding.

  11. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

    PubMed Central

    Janagam, Dileep R.; Wang, Lizhu; Ananthula, Suryatheja; Johnson, James R.; Lowe, Tao L.

    2016-01-01

    Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98) well with that under real-time conditions at four months. PMID:27598191

  12. GLUCOCORTICOID TREATMENT—EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

    PubMed Central

    Sharara-Chami, Rana I.; Joachim, Maria; Pacak, Karel; Majzoub, Joseph A.

    2016-01-01

    Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal

  13. A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells

    PubMed Central

    Ges, Igor A.; Brindley, Rebecca L.; Currie, Kevin P.M.; Baudenbacher, Franz J.

    2013-01-01

    Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped “cell traps”, each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion / repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time. PMID:24126415

  14. Catecholamines and cognition after traumatic brain injury

    PubMed Central

    Jenkins, Peter O.; Mehta, Mitul A.

    2016-01-01

    Abstract Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

  15. Effects of active recovery during interval training on plasma catecholamines and insulin.

    PubMed

    Nalbandian, Harutiun M; Radak, Zsolt; Takeda, Masaki

    2018-06-01

    BACKGROUNDː Active recovery has been used as a method to accelerate the recovery during intense exercise. It also has been shown to improve performance in subsequent exercises, but little is known about its acute effects on the hormonal and metabolic profile. The aim of this research was to study the effects of active recovery on plasma catecholamines and plasma insulin during a high-intensity interval exercise. METHODSː Seven subjects performed two high-intensity interval training protocols which consisted of three 30-second high-intensity bouts (constant intensity), separated by a recovery of 4 minutes. The recovery was either active recovery or passive recovery. During the main test blood samples were collected and plasma insulin, plasma catecholamines and blood lactate were determined. Furthermore, respiratory gasses were also measured. RESULTSː Plasma insulin and blood lactate were significantly higher in the passive recovery trial, while plasma adrenaline was higher in the active recovery. Additionally, VO2 and VCO2 were significantly more increased during the active recovery trials. CONCLUSIONSː These results suggest that active recovery affects the hormonal and metabolic responses to high-intensity interval exercise. Active recovery produces a hormonal environment which may favor lipolysis and oxidative metabolism, while passive recovery may be favoring glycolysis.

  16. Seasonal variation in plasma catecholamines and adipose tissue lipolysis in adult female green sea turtles (Chelonia mydas).

    PubMed

    Hamann, Mark; Limpus, Colin J; Whittier, Joan M

    2003-02-15

    We investigated three aspects of potential interrenal regulation of reproduction in female green sea turtles, Chelonia mydas. First, seasonal trends in plasma catecholamines were examined from female C. mydas at different stages of their reproductive cycles. Second, variation in catecholamine levels during a nesting season were analysed in relation to restraint time, and ecological variables such as nesting habitat, body size, and reproductive investment. Third, catecholamine and corticosterone (CORT) induced lipolysis was investigated with adipose tissue collected from gravid green turtles, using in vitro incubations. Plasma epinephrine (EPI) was lowest in non-vitellogenic (1.55 +/- 0.26 ng/ml) and post-breeding (1.57 +/- 0.22 ng/ml) females, and highest in courting females (2.87 +/- 0.28). Concentrations of norepinephrine (NE) and EPI were relatively constant throughout a nesting season, and not significantly related to restraint time, reproductive investment or nesting habitat. In vitro concentrations of CORT (>3 ng/ml) and NE (2 ng/ml) induced significant release of glycerol after 6h of incubation. Epinephrine tended to induce an antilipolytic affect at low concentrations (0.25 ng/ml) and a net lipolytic response at higher concentrations (>1 ng/ml). Our data suggest that EPI may play a role in regulating body condition during vitellogenesis, and maintaining energy stores during prolonged aphagia during courtship and nesting in female green sea turtles. Furthermore, we provide preliminary evidence that suggests that catecholamine production may be either down regulated or de-sensitised in gravid female C. mydas. Copyright 2003 Elsevier Science (USA)

  17. Insights into accelerated liposomal release of topotecan in plasma monitored by a non-invasive fluorescence spectroscopic method

    PubMed Central

    Fugit, Kyle D.; Jyoti, Amar; Upreti, Meenakshi; Anderson, Bradley D.

    2014-01-01

    A non-invasive fluorescence method was developed to monitor liposomal release kinetics of the anticancer agent topotecan (TPT) in physiological fluids and subsequently used to explore the cause of accelerated release in plasma. Analyses of fluorescence excitation spectra confirmed that unencapsulated TPT exhibits a red shift in its spectrum as pH is increased. This property was used to monitor TPT release from actively loaded liposomal formulations having a low intravesicular pH. Mathematical release models were developed to extract reliable rate constants for TPT release in aqueous solutions monitored by fluorescence and release kinetics obtained by HPLC. Using the fluorescence method, accelerated TPT release was observed in plasma as previously reported in the literature. Simulations to estimate the intravesicular pH were conducted to demonstrate that accelerated release correlated with alterations in the low intravesicular pH. This was attributed to the presence of ammonia in plasma samples rather than proteins and other plasma components generally believed to alter release kinetics in physiological samples. These findings shed light on the critical role that ammonia may play in contributing to the preclinical/clinical variability and performance seen with actively-loaded liposomal formulations of TPT and other weakly-basic anticancer agents. PMID:25456833

  18. Aortoarteritis: Could it be a form of catecholamine-induced vasculitis?

    PubMed Central

    Sarathi, Vijaya; Lila, Anurag R.; Bandgar, Tushar R.; Shah, Nalini S.

    2013-01-01

    Catecholamine-induced vasculitis is a well known but rarely described entity. However, aortoarteritis as a manifestation of catecholamine-induced vasculitis is not described in the literature. We have reported two patients in whom pheochromocytoma coexisted with aortoarteritis. Both patients were young females with history of bilateral pheochromocytomas in more than one first-degree relative. Both patients also had bilateral adrenal pheochromocytomas (second patient also had paraganglioma at left renal hilum) with elevation of plasma free normetanephrine levels. We conclude that there may be an association between pheochromocytoma and aortoarteritis, and that catecholamine excess may have a role in the etiopathogenesis of aortoarteritis in these patients. PMID:23776874

  19. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

    PubMed

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

    2014-07-01

    The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  20. On-column reduction of catecholamine quinones in stainless steel columns during liquid chromatography.

    PubMed

    Xu, R; Huang, X; Kramer, K J; Hawley, M D

    1995-10-10

    The chromatographic behavior of quinones derived from the oxidation of dopamine and N-acetyldopamine has been studied using liquid chromatography (LC) with both a diode array detector and an electrochemical detector that has parallel dual working electrodes. When stainless steel columns are used, an anodic peak for the oxidation of the catecholamine is observed at the same retention time as a cathodic peak for the reduction of the catecholamine quinone. In addition, the anodic peak exhibits a tail that extends to a second anodic peak for the catecholamine. The latter peak occurs at the normal retention time of the catecholamine. The origin of this phenomenon has been studied and metallic iron in the stainless steel components of the LC system has been found to reduce the quinones to their corresponding catecholamines. The simultaneous appearance of a cathodic peak for the reduction of catecholamine quinone and an anodic peak for the oxidation of the corresponding catecholamine occurs when metallic iron in the exit frit reduces some of the quinones as the latter exits the column. This phenomenon is designated as the "concurrent anodic-cathodic response." It is also observed for quinones of of 3,4-dihydroxybenzoic acid and probably occurs with o- or p-quinones of other dihydroxyphenyl compounds. The use of nonferrous components in LC systems is recommended to eliminate possible on-column reduction of quinones.

  1. Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.

    PubMed

    Oh, Jae-Young; Yu, Bum-Hee; Heo, Jung-Yoon; Yoo, Ikki; Song, Hyemin; Jeon, Hong Jin

    2015-02-28

    Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

    PubMed

    Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

    2009-01-01

    Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

  3. Management of an acute catecholamine-induced cardiomyopathy and circulatory collapse: a multidisciplinary approach

    PubMed Central

    Challis, B G; Pitfield, D; Mahroof, R M; Jamieson, N; Bhagra, C J; Vuylsteke, A; Pettit, S J; Chatterjee, K C

    2017-01-01

    A phaeochromocytoma (PC) is a rare, catecholamine-secreting neuroendocrine tumour arising from the adrenal medulla. Presenting symptoms of this rare tumour are highly variable but life-threatening multiorgan dysfunction can occur secondary to catecholamine-induced hypertension or hypotension and subsequent cardiovascular collapse. High levels of circulating catecholamines can induce an acute stress cardiomyopathy, also known as Takotsubo cardiomyopathy. Recent studies have focused on early diagnosis and estimation of the prevalence of acute stress cardiomyopathy in patients with PC, but very little is reported about management of these complex cases. Here, we report the case of a 38-year-old lady who presented with an acute Takotsubo or stress cardiomyopathy and catecholamine crisis, caused by an occult left-sided 5 cm PC. The initial presenting crisis manifested with symptoms of severe headache and abdominal pain, triggered by a respiratory tract infection. On admission to hospital, the patient rapidly deteriorated, developing respiratory failure, cardiogenic shock and subsequent cardiovascular collapse due to further exacerbation of the catecholamine crisis caused by a combination of opiates and intravenous corticosteroid. An echocardiogram revealed left ventricular apical hypokinesia and ballooning, with an estimated left ventricular ejection fraction of 10–15%. Herein, we outline the early stabilisation period, preoperative optimisation and intraoperative management, providing anecdotal guidance for the management of this rare life-threatening complication of PC. Learning points: A diagnosis of phaeochromocytoma should be considered in patients presenting with acute cardiomyopathy or cardiogenic shock without a clear ischaemic or valvular aetiology. Catecholamine crisis is a life-threatening medical emergency that requires cross-disciplinary expertise and management to ensure the best clinical outcome. After initial resuscitation, treatment of acute

  4. Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

    PubMed Central

    2016-01-01

    As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:22297542

  5. Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

    PubMed Central

    2017-01-01

    As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:21615193

  6. Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

    PubMed

    Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

    2014-03-01

    Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  7. Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.

    PubMed

    Limesand, Sean W; Rozance, Paul J

    2017-08-01

    Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  8. Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

    PubMed

    Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

    2016-05-30

    The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. 18F-FDOPA PET/CT uptake parameters correlate with catecholamines secretion in human pheochromocytomas.

    PubMed

    Moog, Sophie; Moog, Sophie; Houy, Sébastien; Chevalier, Elodie; Ory, Stéphane; Weryha, Georges; Rame, Marion; Klein, Marc; Brunaud, Laurent; Gasman, Stéphane; Cuny, Thomas

    2018-06-27


    Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging for the diagnosis of pheochromocytomas (PHEO). However, its utility as a predictive factor of the secretion of catecholamines remains poorly studied. Thirty-nine histologically-confirmed PHEO were included in this retrospective monocentric study. Patients underwent 18F-FDOPA PET/CT before surgery with evaluation of several uptake parameters (SUVmax, SUVmean and the metabolic burden [MB] calculated as follows: MB = SUVmean x tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM) and chromogranin A (CGA). Thirty-five patients were screened for germline mutations in RET, SDHx and VHL genes. Once resected, primary cultures of 5 PHEO were used for real time measurement of catecholamines release by carbon fiber amperometry. The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r=0.64, p<0.0001), MN (r=0.49, p=0.002), combined MN and NM (r=0.75, p<0,0001) and eventually plasma free levels of NM (r=0.55 p=0.006). In mutated-patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL and 3 RET), a similar correlation was observed between the MB and the 24h-urinary combined MN and NM (r=0.86, p=0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p=0.01). While the 18F-FDOPA PET/CT metabolic burden of PHEO strongly correlates with the concentration of metanephrines, amperometric recordings suggest that the 18F-FDOPA uptake could be enhanced by the overactivity of the catecholamines exocytosis.
    . ©2018S. Karger AG, Basel.

  10. A SERS protocol as a potential tool to access 6-mercaptopurine release accelerated by glutathione-S-transferase.

    PubMed

    Wang, Ying; Sun, Jie; Yang, Qingran; Lu, Wenbo; Li, Yan; Dong, Jian; Qian, Weiping

    2015-11-21

    The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.

  11. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders.

    PubMed

    Goldstein, David S; Kopin, Irwin J; Sharabi, Yehonatan

    2014-12-01

    Several neurodegenerative diseases involve loss of catecholamine neurons-Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of "autotoxicity"-inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the "catecholaldehyde hypothesis" for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. Published by Elsevier Inc.

  12. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders☆

    PubMed Central

    Goldstein, David S.; Kopin, Irwin J.; Sharabi, Yehonatan

    2015-01-01

    Several neurodegenerative diseases involve loss of catecholamine neurons—Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of “autotoxicity”—inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the “catecholaldehyde hypothesis” for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. PMID:24945828

  13. Evidence That High Catecholamine Levels Produced by Pheochromocytoma May be Responsible for Tako-Tsubo Cardiomyopathy.

    PubMed

    Sharkey, Scott W; McAllister, Nancy; Dassenko, David; Lin, David; Han, Kelly; Maron, Barry J

    2015-06-01

    Tako-tsubo cardiomyopathy (TC) is a novel form of acute heart failure, characterized by regional left ventricular dysfunction without coronary artery obstruction, and usually triggered by a stressful event. Excessive circulating catecholamines have been implicated in the pathophysiology of this condition. This report documents the unusual occurrence of acute TC events in 2 male subjects of disparate ages, 16 and 66 years, for whom subsequent investigation in both led to the unexpected discovery of catecholamine-producing pheochromocytoma. Marked elevation of plasma catecholamines (epinephrine, norepinephrine, and dopamine) was present in both subjects and were remarkably similar to those previously reported in female patients with TC triggered by emotional stress. These observations show a common link between TC occurrence and elevated catecholamine levels in both male and female patients and, therefore, support the hypothesis that excessive levels of catecholamines may be involved in the pathophysiology of TC independent of age or gender. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Role of catecholamines in maternal-fetal stress transfer in sheep.

    PubMed

    Rakers, Florian; Bischoff, Sabine; Schiffner, Rene; Haase, Michelle; Rupprecht, Sven; Kiehntopf, Michael; Kühn-Velten, W Nikolaus; Schubert, Harald; Witte, Otto W; Nijland, Mark J; Nathanielsz, Peter W; Schwab, Matthias

    2015-11-01

    We sought to evaluate whether in addition to cortisol, catecholamines also transfer psychosocial stress indirectly to the fetus by decreasing uterine blood flow (UBF) and increasing fetal anaerobic metabolism and stress hormones. Seven pregnant sheep chronically instrumented with uterine ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of psychosocial stress by isolation. We used adrenergic blockade with labetalol to examine whether decreased UBF is catecholamine mediated and to determine to what extent stress transfer from mother to fetus is catecholamine dependent. Stress induced transient increases in maternal cortisol and norepinephrine (NE). Maximum fetal plasma cortisol concentrations were 8.1 ± 2.1% of those in the mother suggesting its maternal origin. In parallel to the maternal NE increase, UBF decreased by maximum 22% for 30 minutes (P < .05). Fetal NE remained elevated for >2 hours accompanied by a prolonged blood pressure increase (P < .05). Fetuses developed a delayed and prolonged shift toward anaerobic metabolism in the presence of an unaltered oxygen supply. Adrenergic blockade prevented the stress-induced UBF decrease and, consequently, the fetal NE and blood pressure increase and the shift toward anaerobic metabolism. We conclude that catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress transfer. It may explain the influence of maternal stress on fetal development and on programming of adverse health outcomes in later life especially during early pregnancy when fetal glucocorticoid receptor expression is limited. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

    PubMed

    Wagner, Isabella C; van Buuren, Mariët; Bovy, Leonore; Morris, Richard G; Fernández, Guillén

    2017-02-01

    Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

  16. Phentolamine tests and catecholamine levels in normotensive CVA patients.

    PubMed

    Favazza, A R

    1974-11-01

    Ten normotensive patients diagnosed as having a CVA had Regitine tests and urinary VMA and catecholamine determinations during the first day of hospitalization. The VMA and catecholamine levels were all within normal limits (except for one elevated VMA level) but did not correlate well with each other. The average response to phentolamine was an average drop in blood pressure of 30mm. Hg systolic and 19 mm. Hg diastolic. Mechanisms by which hypertensive states or cerebral damage might effect blood pressure are discussed. It is suggested that CNS damage might induce a vasolabile or hypersensitive state via connections and consequent alterations in the autonomic vasomotor system.

  17. Catecholamine crisis during induction of general anesthesia : A case report.

    PubMed

    Sonntagbauer, M; Koch, A; Strouhal, U; Zacharowski, K; Weber, C F

    2018-03-01

    Catecholamine crises associated with pheochromocytoma may cause life-threatening cardiovascular conditions. We report the case of a 75-year-old male who developed a hypertensive crisis during induction of general anesthesia for elective resection of a cervical neuroma due to an undiagnosed pheochromocytoma. Hemodynamic instability occurred immediately after the injection of fentanyl, propofol and rocuronium, prior to laryngoscopy and in the absence of any manipulation of the abdomen. In this case report, we present the management of this incident and discuss the underlying pathophysiology triggering a catecholamine crisis.

  18. Reactivity of catecholamine-driven Fenton reaction and its relationships with iron(III) speciation.

    PubMed

    Melin, Victoria; Henríquez, Adolfo; Freer, Juanita; Contreras, David

    2015-03-01

    Fenton reaction is the main source of free radicals in biological systems. The reactivity of this reaction can be modified by several factors, among these iron ligands are important. Catecholamine (dopamine, epinephrine, and norepinephrine) are able to form Fe(III) complexes whose extension in the coordination number depends upon the pH. Fe(III)-catecholamine complexes have been related with the development of several pathologies. In this work, the ability of catecholamines to enhance the oxidative degradation of an organic substrate (veratryl alcohol, VA) through Fenton and Fenton-like reactions was studied. The initial VA degradation rate at different pH values and its relationship to the different iron species present in solution were determined. Furthermore, the oxidative degradation of VA after 24 hours of reaction and its main oxidation products were also determined. The catecholamine-driven Fenton and Fenton-like systems showed higher VA degradation compared to unmodified Fenton or Fenton-like systems, which also showed an increase in the oxidation state of the VA degradation product. All of this oxidative degradation takes place at pH values lower than 5.50, where the primarily responsible species would be the Fe(III) mono-complex. The presence of Fe(III) mono-complex is essential in the ability of catecholamines to increase the oxidative capacity of Fenton systems.

  19. Fatigue and stress studies : an improved semi-automated procedure for flurometric determination of plasma catecholamines.

    DOT National Transportation Integrated Search

    1966-04-01

    A semiautomated technique is described for the estimation of total catecholamines in plasma by the trihydroxyindole procedure. The method utilizes conventional alumina-column chromatography for isolation of the amines. Catecholamine oxidation, tautom...

  20. Evaluation of the effects of zilpateral hydrochloride supplementation on catecholamin response and other blood metabolites following a combined corticotropin releasing hormone and vasopressin challenge

    USDA-ARS?s Scientific Manuscript database

    The stress response of cattle supplemented with zilpaterol hydrochloride (ZH) has become a topic due to anecdotal claims of supplemented cattle responding poorly to stress. This study was designed to determine if differences exist in the catecholamine and blood metabolite response of ZH-supplemente...

  1. Channelled tablets: An innovative approach to accelerating drug release from 3D printed tablets.

    PubMed

    Sadia, Muzna; Arafat, Basel; Ahmed, Waqar; Forbes, Robert T; Alhnan, Mohamed A

    2018-01-10

    Conventional immediate release dosage forms involve compressing the powder with a disintegrating agent that enables rapid disintegration and dissolution upon oral ingestion. Among 3D printing technologies, the fused deposition modelling (FDM) 3D printing technique has a considerable potential for patient-specific dosage forms. However, the use of FDM 3D printing in tablet manufacturing requires a large portion of polymer, which slows down drug release through erosion and diffusion mechanisms. In this study, we demonstrate for the first time the use of a novel design approach of caplets with perforated channels to accelerate drug release from 3D printed tablets. This strategy has been implemented using a caplet design with perforating channels of increasing width (0.2, 0.4, 0.6, 0.8 or 1.0mm) and variable length, and alignment (parallel or at right angle to tablet long axis). Hydrochlorothiazide (BCS class IV drug) was chosen as the model drug as enhanced dissolution rate is vital to guarantee oral bioavailability. The inclusion of channels exhibited an increase in the surface area/volume ratio, however, the release pattern was also influenced by the width and the length of the channel. A channel width was ≥0.6mm deemed critical to meet the USP criteria of immediate release products. Shorter multiple channels (8.6mm) were more efficient at accelerating drug release than longer channels (18.2mm) despite having comparable surface area/mass ratio. This behaviour may be linked to the reduced flow resistance within the channels and the faster fragmentation during dissolution of these tablets. In conclusion, the width and length of the channel should be carefully considered in addition to surface area/mass when optimizing drug release from 3D printed designs. The incorporation of short channels can be adopted in the designs of dosage forms, implants or stents to enhance the release rate of eluting drug from polymer-rich structures. Copyright © 2017 Elsevier B.V. All

  2. Accelerated anaerobic release of K, Mg and P from surplus activated sludge for element recovery and struvite formation inhibition.

    PubMed

    Ito, A; Kawakami, H; Ishikawa, N; Ito, M; Oikawa, T; Sato, A; Umita, T

    2017-05-01

    Accelerated release of potassium (K), magnesium (Mg) and phosphorus (P) from surplus activated sludge (SAS) was investigated to develop a new system for the recovery of the elements. Anaerobic cultivation of SAS during 24 h released 78% of K and about 50% of Mg and P from SAS more effectively compared to aerobic cultivation (K: 40%, Mg: 15%, P: 15%). Furthermore, the addition of sodium acetate as an organic carbon source remarkably accelerated the release of K, Mg and P from SAS under anaerobic condition. However, no increase in the maximum release efficiencies was observed. The elements released from SAS could be transferred to separate liquid with the existing mechanical thickener and be recovered as MgKPO 4 by some additional process. Furthermore, the removal of the elements from SAS would inhibit the formation of struvite causing the blockage of sludge transport pipe after anaerobic digestion process of thickened sludge.

  3. Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

    PubMed

    Spasojevic, Natasa; Jovanovic, Predrag; Dronjak, Sladjana

    2015-03-01

    We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

  4. Effects of catecholamines on rat myocardial metabolism. I. Influence of catecholamines on energy-rich nucleotides and phosphorylated fraction contents.

    PubMed

    Merouze, P; Gaudemer, Y

    1975-01-01

    1. The influence of catecholamines (adrenaline and noradrenaline) on energy metabolism of the rat myocardium has been studied by incubating slices of this tissue with these hormones and by following the levels of the different phosphorylated fractions and adenylic nucleotides. 2. Similar effects are obtained with both hormones, adrenaline being more effective. 3. Catecholamines decrease significantly the total amount of phosphate while Pi content increases during the first 10 minutes of incubation; labile and residual phosphate contents increase at the beginning of incubation and decrease to the initial values afterwards. 4. ATP and ADP levels decrease significantly with both hormones; however, the effect of noradrenalin on the ATP level needs a longer time of incubation. The ATP/ADP ratios decrease after 5 minutes incubation and the total adenylic nucleotide content is severely decreased (35 per cent with adrenalin, after 20 minutes incubation). 5. Similar results have been obtained with other tissues; these results can explain the decrease of aerobic metabolism we observed under the same conditions.

  5. [Urinary excretion of catecholamines in obese subjects and in diabetics (author's transl)].

    PubMed

    Giorgino, R; Nardelli, G M; Scardapane, R

    1976-03-01

    95 obese subjects, 40 diabetics and 22 normal controls were investigated. The weight of all obese subjects was at least 20% higher than the ideal weight. Catecholamine excretion was determined a few days after hospitalization to minimize the influence of environmental changes. Spectrofluorimetric estimation of adrenaline and noradrenaline in the urine was carried out according to the method of von Euler and Lihajko. Statistical analysis of the results showed a significant increase in both adrenaline and noradrenaline excretion in the group of obeses subjects compared with the diabetics. The increased catecholamine excretion may represent the response of the adrenal medulla to the stress of the disease. Such an increase may be responsible for perpheral insulin resistence and hence acts as a diabetogenic factor. The results obtained emphasize the influence of catecholamines on insulin responsiveness, possibly constituting a major contribution to the diabetic state.

  6. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis in the aged

    PubMed Central

    Camell, Christina D.; Sander, Jil; Spadaro, Olga; Lee, Aileen; Nguyen, Kim Y.; Wing, Allison; Goldberg, Emily L.; Youm, Yun-Hee; Brown, Chester W.; Elsworth, John; Rodeheffer, Matthew S.; Schultze, Joachim L.; Dixit, Vishwa Deep

    2017-01-01

    Catecholamine-induced lipolysis, the first step in generation of energy substrates through hydrolysis of triglycerides (TGs) 1, declines with age 2,3. The defect in mobilization of free fatty acids (FFA) in elderly is accompanied with increased visceral adiposity, lower exercise capacity, failure to maintain core body temperature during cold stress, and reduced ability to survive starvation. While catecholamine signaling in adipocytes is normal in elderly, how lipolysis is impaired in aging remains unknown 2,4. Here we uncover that the adipose tissue macrophages (ATMs) regulate age-related reduction in adipocyte lipolysis by lowering the bioavailability of norepinephrine (NE). Unexpectedly, unbiased whole transcriptome analyses of adipose macrophages revealed that aging upregulates genes controlling catecholamine degradation in an NLRP3 inflammasome-dependent manner. Deletion of NLRP3 in aging restored catecholamine-induced lipolysis through downregulation of growth differentiation factor-3 (GDF3) and monoamine oxidase-a (MAOA) that is known to degrade NE. Consistent with this, deletion of GDF3 in inflammasome-activated macrophages improved lipolysis by decreasing MAOA and caspase-1. Furthermore, inhibition of MAOA reversed age-related reduction in adipose tissue NE concentration and restored lipolysis with increased levels of key lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Our study reveals that targeting neuro-innate signaling between sympathetic nervous system and macrophages may offer new approaches to mitigate chronic inflammation-induced metabolic impairment and functional decline. PMID:28953873

  7. Mechanisms of cardiac cell damage due to catecholamines: significance of drugs regulating central sympathetic outflow.

    PubMed

    Rupp, H; Dhalla, K S; Dhalla, N S

    1994-01-01

    A chronically increased rate of catecholamine release has various deleterious actions. Isoproterenol injections (80 mg/kg body weight) resulted in depressed Ca2+ transport in the sarcolemma (ATP-dependent Ca2+ uptake, Na(+)-dependent Ca2+ uptake) and sarcoplasmic reticulum (Ca2+ uptake) of rat heart. The formation of malondialdehyde owing to lipid peroxidation was increased. Pretreatment with vitamin E (10-25 mg/kg/day) strongly inhibited the membrane damage. The toxic effects of catecholamines arise most probably from their oxidation, and it is therefore important either to reduce the central sympathetic outflow or to prevent the oxidation. An inappropriately high sympathetic outflow is a typical feature of Western affluent societies, and is linked to psychosocial stress and hypercaloric nutrition. However, established pharmacologic interventions to reduce sympathetic outflow have proven not practicable because of marked side effects. Using radiotelemetry for monitoring cardiovascular parameters of spontaneously hypertensive rats treated with clonidine or moxonidine, we showed that clonidine, unlike moxonidine, resulted in rebound hypertension after drug withdrawal. Because the rebound blood pressure and the typical side effects of clonidine associated with low patient compliance are mainly mediated by alpha-adrenoceptors, it can be inferred that the I1-imidazoline agonist moxonidine does not exhibit the side effects commonly seen with clonidine and therefore represents a promising approach for reducing an inappropriately high central sympathetic outflow.

  8. If and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells

    PubMed Central

    Gao, Zhan; Chen, Biyi; Joiner, Mei-ling A.; Wu, Yuejin; Guan, Xiaoqun; Koval, Olha M.; Chaudhary, Ashok K.; Cunha, Shane R.; Mohler, Peter J.; Martins, James B.; Song, Long-Sheng; Anderson, Mark E.

    2010-01-01

    Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a ‘voltage clock’ and a Ca2+ dependent process, or ‘Ca2+ clock.’ The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (If) is thought to be particularly important. A Ca2+ dependent process triggers APs when sarcoplasmic reticulum (SR) Ca2+ release activates inward current carried by the forward mode of the electrogenic Na+/Ca2+ exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca2+ clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective If antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest (∼14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca2+ release, but did not affect basal or isoproterenol-enhanced If. Taken together, these results indicate that voltage and Ca2+ dependent automaticity mechanisms coexist in canine SAN cells, and suggest If and SR Ca2+ release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells. PMID:20380837

  9. Growth Stimulation by Catecholamines in Plant Tissue/Organ Cultures 1

    PubMed Central

    Protacio, Calixto M.; Dai, Yao-ren; Lewis, Eldrin F.; Flores, Hector E.

    1992-01-01

    Addition of catecholamines at micromolar concentrations caused a dramatic stimulation of growth of tobacco (Nicotiana tabacum) thin cell layers (TCLs) and Acmella oppositifolia “hairy” root cultures. A threefold increase in the rate of ethylene evolution was observed in the catecholamine-treated explants. Aminooxyacetic acid and silver thiosulfate, inhibitors of ethylene biosynthesis and action, respectively, reduced the growth-promoting effect of dopamine. However, these compounds alone could also inhibit the growth of the TCL explants. When ethylene in the culture vessel was depleted by trapping with mercuric perchlorate, dopamine-stimulated growth was still obtained, suggesting that ethylene does not mediate the dopamine effect. Dopamine potentiated the growth of TCLs grown in Murashige and Skoog medium supplemented with indoleacetic acid (IAA) and kinetin. When IAA was replaced by 2,4-dichlorophenoxyacetic acid, dopamine addition showed no growth-promoting effect. Instead, 2,4-dichlorophenoxyacetic acid stimulated the growth of TCL explants to the same extent as that obtained with IAA plus dopamine. Because synthetic auxins do not appear to be substrates for IAA oxidizing enzymes, we hypothesized that catecholamines exert their effect by preventing IAA oxidation. Consistent with this explanation, dopamine (25 micromolar) inhibited IAA oxidase activity by 60 to 100% in crude enzyme extracts from tobacco roots and etiolated corn coleoptiles, but had no effect on peroxidase activity in the same extracts. Furthermore, addition of dopamine to TCL cultures resulted in a fourfold reduction in the oxidative degradation of [1-14C]IAA fed to the explants. Because the growth enhancement by catecholamines is observed in both IAA-requiring and IAA-independent cultures, we suggest that these aromatic amines may have a role in the regulation of IAA levels in vivo. ImagesFigure 2 PMID:16668653

  10. Involvement of multiple distinct Bordetella receptor proteins in the utilization of iron liberated from transferrin by host catecholamine stress hormones

    PubMed Central

    Armstrong, Sandra K.; Brickman, Timothy J.; Suhadolc, Ryan J.

    2012-01-01

    Summary Bordetella bronchiseptica is a pathogen that can acquire iron using its native alcaligin siderophore system, but can also use the catechol xenosiderophore enterobactin via the BfeA outer membrane receptor. Transcription of bfeA is positively controlled by a regulator that requires induction by enterobactin. Catecholamine hormones also induce bfeA transcription and B. bronchiseptica can use the catecholamine norepinephrine for growth on transferrin. In this study, B. bronchiseptica was shown to use catecholamines to obtain iron from both transferrin and lactoferrin in the absence of siderophore. In the presence of siderophore, norepinephrine augmented transferrin utilization by B. bronchiseptica, as well as siderophore function in vitro. Genetic analysis identified BfrA, BfrD and BfrE as TonB dependent outer membrane catecholamine receptors. The BfeA enterobactin receptor was found to not be involved directly in catecholamine utilization; however, the BfrA, BfrD and BfrE catecholamine receptors could serve as receptors for enterobactin and its degradation product 2,3-dihydroxybenzoic acid. Thus, there is a functional link between enterobactin-dependent and catecholamine-dependent transferrin utilization. This investigation characterizes a new B. bronchiseptica mechanism for iron uptake from transferrin that uses host stress hormones that not only deliver iron directly to catecholamine receptors, but also potentiate siderophore activity by acting as iron shuttles. PMID:22458330

  11. Thyrotropin-releasing hormone and its analogs accelerate wound healing.

    PubMed

    Nie, Chunlei; Yang, Daping; Liu, Nan; Dong, Deli; Xu, Jin; Zhang, Jiewu

    2014-06-15

    Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The effect of morphine on the biosynthesis of catecholamines in the rat brain.

    PubMed

    Malini, M; Kwan, T K; Perumal, R

    1994-02-01

    In vivo studies involved monitoring the effect of morphine administration on catecholamine biosynthesis by the brain while in vitro studies involved studying the effect of morphine on the uptake of tritiated tyrosine by synaptosomes and its subsequent incorporation into the catecholamines. The extremely low levels of these endogenous compounds required the use of High Performance Liquid Chromatography with electrochemical detection. Intra-peritoneal injection of morphine at a dosage of 10 mg/kg did not produce appreciable changes in the catecholamine levels but a dosage of 30 mg/kg morphine was found to elevate dihydroxy phenylacetic acid content. At a dosage of 60 mg/kg, dopamine levels were elevated while noradrenaline was depleted. Morphine, at a concentration of 1 x 10(-5)M increases the incorporation of tritiated tyrosine into dopamine and dihydroxy phenylacetic acid in synaptosomal preparations.

  13. Reduced catecholamine response to exercise in amenorrheic athletes

    USDA-ARS?s Scientific Manuscript database

    Studies have found an array of endocrine disturbances related to energy deprivation in women with functional hypothalamic amenorrhea. Purpose: We examined the catecholamine response to exercise in five eumenorrheic (EU) and five amenorrheic (AM) athletes, matched by age (mean T SEM: EU = 29.8 T 2.5 ...

  14. 21 CFR 862.1165 - Catecholamines (total) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  15. 21 CFR 862.1165 - Catecholamines (total) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  16. 21 CFR 862.1165 - Catecholamines (total) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  17. 21 CFR 862.1165 - Catecholamines (total) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  18. 21 CFR 862.1165 - Catecholamines (total) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  19. Leisure Activities, Caregiving Demands, and Catecholamine Levels in Dementia Caregivers

    PubMed Central

    Chattillion, Elizabeth A.; Mausbach, Brent T.; Roepke, Susan K.; von Känel, Roland; Mills, Paul J.; Dimsdale, Joel E.; Allison, Matthew; Ziegler, Michael G.; Patterson, Thomas L.; Ancoli-Israel, Sonia; Grant, Igor

    2012-01-01

    This study examined whether satisfaction from leisure activities moderates the relationship between caregiving demands (i.e., hours per day spent caring for a spouse with dementia) and resting levels of the catecholamines norepinephrine (NE) and epinephrine (EPI). Spousal caregivers (N=107; mean age 73.95±8.12 years) were assessed in home for plasma levels of NE and EPI, amount of care provided, and leisure satisfaction. Regression was used to determine whether leisure satisfaction moderated the relationship between hours providing care per day and catecholamine levels. A significant interaction was found between hours caregiving and leisure satisfaction for NE, but not for EPI. Post hoc regressions were conducted for both NE and EPI. At low leisure satisfaction, time spent caring for a spouse was positively associated with plasma NE (β = .41; p = .005) and EPI (β = .44; p = .003). In contrast, at high levels of satisfaction, time caregiving was not significantly associated with plasma NE (β = −.08; p = .57) or EPI (β = .23; p = .12). These findings suggest that leisure satisfaction may protect caregivers from increases in catecholamines, which have been implicated in cardiovascular risk. Further support for these findings may impact psychological treatments for distressed caregivers. PMID:22149759

  20. Prevention moderates associations between family risks and youth catecholamine levels.

    PubMed

    Brody, Gene H; Yu, Tianyi; Chen, Edith; Miller, Gregory E

    2014-11-01

    The purpose of this study was to establish, using a quasi-experimental design, whether 2 family risk factors, parental psychological dysfunction and nonsupportive parenting, during preadolescence could longitudinally predict elevated sympathetic nervous system (SNS) activity 9 years later, and to determine whether participation in an efficacious family centered prevention program could moderate these associations if they emerged. Rural African American preadolescents (N = 476) were assigned randomly to the Strong African American Families (SAAF) program or to a control condition. When youths were 11 years of age (M = 11.2 years), primary caregivers provided data on their own depressive symptoms and self-esteem, and youths provided data on their receipt of nonsupportive parenting. When the youths were 20 years of age, indicators of SNS activity, the catecholamines epinephrine and norepinephrine, were assayed from their overnight urine voids. Parental psychological dysfunction and nonsupportive parenting forecast elevated catecholamine levels for youths in the control condition, but not for those in the SAAF condition. The demonstration that a prevention program can induce reduction of catecholamine levels is important from both theoretical and public health perspectives, because it shows that the developmental progression from family risk factors to heightened sympathetic nervous system activity is not immutable. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  1. Perioperative management of paraganglioma and catecholamine-induced cardiomyopathy in child- a case report and review of the literature.

    PubMed

    Jia, Xixi; Guo, Xiangyang; Zheng, Qing

    2017-10-17

    Paragangliomas are catecholamine-secreting tumors of the paraganglia. Perioperative mortality of children with paraganglioma is high, but preoperative therapy and anesthetic management of paraganglioma resection are controversial in children. The literatures on catecholamine-induced cardiomyopathy are limited to several case reports,with few reports of studies on children. Here we report the anesthetic management of a child with paraganglioma and catecholamine-induced cardiomyopathy, and the possible perioperative anesthesia problems of the paraganglioma resection are discussed. Preoperative and intraoperative anesthetic management of Pheochromocytomas children should follow the same principles as for adults, The most important aspects are the control of blood pressure liability and maintenance of adequate blood volume. Pheochromocytomas patient may have cardiomoyopathy due to myocardial toxicity of excessive circulating catecholamines level. The perioperative management of catecholamine-induced cardiomyopathy should include lowering sympathetic activation by means of α-and β-adrenergic receptor blocker and diuretics administration in case of volume overload.

  2. Role of catecholamines and nitric oxide on pigment displacement of the chromatophores of freshwater snakehead teleost fish, Channa punctatus.

    PubMed

    Biswas, Saikat P; Jadhao, Arun G; Palande, Nikhil V

    2014-04-01

    We are reporting for the first time that the catecholamines (adrenaline and noradrenaline) inhibit the effect of nitric oxide (NO) on melanosome dispersion in freshly isolated scales of the freshwater snakehead fish, Channa punctatus. We studied the effect of NO and catecholamines on the pigment displacement by observing the changes in the melanophore index. The scales when treated with solution containing NO donor sodium nitroprusside (SNP) showed dispersion of melanosomes, whereas NO synthase blocker N-omega-Nitro-L-arginine suppresses this action of SNP. Treatment with adrenaline and noradrenaline on the isolated scales caused aggregation of melanosomes. Scales treated with solution containing catecholamines and SNP resulted in aggregation of melanosomes suggesting that catecholamines mask the effect of SNP. These results suggest that the catecholamines are inhibiting the effect of NO and causing the aggregation of the melanosomes may be via surface receptors.

  3. Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

    PubMed

    Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

    2008-09-01

    Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

  4. Neural response to catecholamine depletion in remitted bulimia nervosa: Relation to depression and relapse.

    PubMed

    Mueller, Stefanie Verena; Mihov, Yoan; Federspiel, Andrea; Wiest, Roland; Hasler, Gregor

    2017-07-01

    Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has involved the behavioral and neural responses to experimental catecholamine depletion. The purpose of this study was to examine the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its relationship to relapse. In a randomized, double-blind and crossover study design, catecholamine depletion was achieved by using the oral administration of alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up telephone interview, bulimic relapse was assessed. Following AMPT, rBN participants revealed an increased vigor reduction and CBF decreases in the pallidum and posterior midcingulate cortex (pMCC) relative to HC participants showing no CBF changes in these regions. These results indicated that the pallidum and the pMCC are the functional neural correlates of the dysregulated catecholamine system in bulimia nervosa. Bulimic relapse was associated with increased depressive symptoms and CBF reduction in the hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced increased CBF in this region predicted staying in remission. These findings demonstrated the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Catecholamines and in vitro growth of pathogenic bacteria: enhancement of growth varies greatly among bacterial species

    NASA Technical Reports Server (NTRS)

    Belay, Tesfaye; Aviles, Hernan; Vance, Monique; Fountain, Kimberly; Sonnenfeld, Gerald

    2003-01-01

    The purpose of this study was to examine the effects of catecholamines on in vitro growth of a range of bacterial species, including anaerobes. Bacteria tested included: Porphyromonas gingivalis, Bacteriodes fragilis, Shigella boydii, Shigella sonnie, Enterobacter Sp, and Salmonella choleraesuis. The results of the current study indicated that supplementation of bacterial cultures in minimal medium with norepinephrine or epinephrine did not result in increased growth of bacteria. Positive controls involving treatment of Escherichia coli with catecholamines did result in increased growth of that bacterial species. The results of the present study extend previous observations that showed differential capability of catecholamines to enhance bacterial growth in vitro.

  6. Reserpine-induced Reduction in Norepinephrine Transporter Function Requires Catecholamine Storage Vesicles

    PubMed Central

    Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A.

    2010-01-01

    Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5 min decreased [3H]NE uptake capacity, an effect characterized by a robust decrease in the Vmax of the transport of [3H]NE. As expected, reserpine did not displace the binding of [3H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [3H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [3H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca2+/Ca2+-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [3H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, α-methyl-p-tyrosine, increased [3H]NE uptake and eliminated the inhibitory effects of reserpine on [3H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca2+-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. PMID:20176067

  7. Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles.

    PubMed

    Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A

    2010-01-01

    Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5min decreased [(3)H]NE uptake capacity, an effect characterized by a robust decrease in the V(max) of the transport of [(3)H]NE. As expected, reserpine did not displace the binding of [(3)H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [(3)H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [(3)H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca(2+)/Ca(2+)-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [(3)H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, alpha-methyl-p-tyrosine, increased [(3)H]NE uptake and eliminated the inhibitory effects of reserpine on [(3)H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca(2+)-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Systematic Morphometry of Catecholamine Nuclei in the Brainstem.

    PubMed

    Bucci, Domenico; Busceti, Carla L; Calierno, Maria T; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

    2017-01-01

    Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology.

  9. Systematic Morphometry of Catecholamine Nuclei in the Brainstem

    PubMed Central

    Bucci, Domenico; Busceti, Carla L.; Calierno, Maria T.; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

    2017-01-01

    Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology. PMID:29163071

  10. Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness.

    PubMed

    Arnsten, Amy F T

    2007-09-01

    Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal levels of DA D1 receptor stimulation decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive levels of catecholamine release during stress impair working memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental illnesses are associated with extracellular changes in these pathways: Attention Deficit Hyperactivity Disorder is linked to genetic changes that reduce catecholamine transmission to suboptimal levels and is treated with agents that increase catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is associated with amplified noradrenergic transmission that impairs PFC but strengthens amygdala function. PTSD is now treated with agents that block alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, schizophrenia and bipolar disorder, are associated with genetic changes in molecules regulating intracellular signaling pathways activated by stress. Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein signaling 4 inhibits PI signaling. Loss of function in these genes may render patients vulnerable to profound stress-induced PFC dysfunction including symptoms of thought disorder.

  11. Effect of betel quid on catecholamine secretion from adrenal chromaffin cells.

    PubMed

    Wang, C K; Hwang, L S

    1997-10-01

    Health damage and environmental pollution are serious problems caused by betel quid chewing in Taiwan. Many people acquire the habit of chewing betel quid due to its physiological effects, including increased stamina and a general feeling of well-being. In this study, a sympathetic model system of adrenal chromaffin cells and sensory evaluation were used to examine the physiological effects of betel quid and the interaction of all the ingredients (areca fruit, Piper betle inflorescence and red time paste) in betel quid. Physiological effects of cardioacceleration, a slightly drunk feeling, sweating and salivation occurred during the chewing of betel quid (a mixture of areca fruit, Piper betle inflorescence and red lime paste) and a mixture of areca fruit and red lime paste. Both induced much more basal catecholamine secretion from adrenal chromaffin cells than did other ingredients and combinations of ingredients. It was evident that the responses in the sympathetic model system were closely correlated with the physiological feeling of well-being. The inhibitory effects of all the chewing juices on catecholamine secretion evoked by carbachol and a high concentration of potassium (high K+) showed that they perhaps affected the calcium influx through voltage-sensitive channels or the steps involved in secretion after calcium entry to stimulate basal catecholamine secretion from chromaffin cells.

  12. Potentiometric and NMR complexation studies of phenylboronic acid PBA and its aminophosphonate analog with selected catecholamines

    NASA Astrophysics Data System (ADS)

    Ptak, Tomasz; Młynarz, Piotr; Dobosz, Agnieszka; Rydzewska, Agata; Prokopowicz, Monika

    2013-05-01

    Boronic acids are a class of intensively explored compounds, which according to their specific properties have been intensively explored in last decades. Among them phenylboronic acids and their derivatives are most frequently examined as receptors for diverse carbohydrates. In turn, there is a large gap in basic research concerning complexation of catecholamines by these compounds. Therefore, we decided to undertake studies on interaction of chosen catecholamines, namely: noradrenaline (norephinephrine), dopamine, L-DOPA, DOPA-P (phosphonic analog of L-DOPA) and catechol, with simple phenyl boronic acid PBA by means of potentiometry and NMR spectroscopy. For comparison, the binding properties of recently synthesized phenylboronic receptor 1 bearing aminophosphonate function in meta-position were investigated and showed promising ability to bind catecholamines. The protonation and stability constants of PBA and receptor 1 complexes were examined by potentiometry. The obtained results demonstrated that PBA binds the catecholamines with the following affinity order: noradrenaline ⩾ dopamine ≈ L-DOPA > catechol > DOPA-P, while its modified analog 1 reveals slightly different preferences: dopamine > noradrenaline > catechol > L-DOPA > DOPA-P.

  13. Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives.

    PubMed

    Sun, Wu-Ping; Li, Da; Lun, Yong-Zhi; Gong, Xiao-Jie; Sun, Shen-Xia; Guo, Ming; Jing, Li-Xin; Zhang, Li-Bin; Xiao, Fu-Cheng; Zhou, Shi-Sheng

    2012-02-01

    Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N(1)-methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N(1)-methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamide-loading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy

  14. Lower catecholamine activity is associated with greater levels of anger in adults.

    PubMed

    Schwartz, Joseph A; Portnoy, Jill

    2017-10-01

    Previous research has revealed a consistent association between heart rate at rest and during stress and behavioral problems, potentially implicating autonomic nervous system (ANS) functioning in the etiological development of antisocial behavior. A complementary line of research has focused on the potential independent and interactive role of the two subsystems that comprise the ANS, the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS), on behavioral problems. The current study aims to contribute to the existing literature by examining the influence of heart rate (HR) reactivity, high-frequency heart rate variability (HF-HRV) reactivity, and catecholamine activity on a comprehensive measure of anger in a large, nationally-representative sample of adults from the United States. Results from a series of structural equation models (SEMs) revealed that catecholamine activity was most consistently linked to anger, while associations involving HR and HF-HRV reactivity were nonsignificant. Additional analyses revealed that HF-HRV did not significantly moderate the association between catecholamine activity and anger. These findings highlight the importance of SNS activity in the development of more reactive forms of aggression such as anger. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Concepts of scientific integrative medicine applied to the physiology and pathophysiology of catecholamine systems.

    PubMed

    Goldstein, David S

    2013-10-01

    This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body's monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems-especially Parkinson disease-and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era. Published 2013. Compr Physiol 3:1569-1610, 2013.

  16. Concepts of Scientific Integrative Medicine Applied to the Physiology and Pathophysiology of Catecholamine Systems

    PubMed Central

    Goldstein, David S.

    2016-01-01

    This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body’s monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems—especially Parkinson disease—and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era. PMID:24265239

  17. Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning.

    PubMed

    Highland, Krista B; Costanzo, Michelle E; Jovanovic, Tanja; Norrholm, Seth D; Ndiongue, Rochelle B; Reinhardt, Brian J; Rothbaum, Barbara; Rizzo, Albert A; Roy, Michael J

    2015-01-01

    Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness.

  18. Effect of hypoxia and hypercapnia on catecholamine content in cat carotid body.

    PubMed

    Fitzgerald, R S; Garger, P; Hauer, M C; Raff, H; Fechter, L

    1983-05-01

    The purpose of this study was to determine the content of catecholamines (CA) in the cat carotid body before and after 0.5 h exposures to normoxic normocapnia [arterial O2 partial pressure (Pao2) 126 +/- 28 Torr, arterial CO2 partial pressure (Paco2) 36.4 +/- 1.5 Torr], hypoxic normocapnia (Pao2 25 +/- 3 Torr, Paco2 36.7 +/- 3.3 Torr), and normoxic hypercapnia (Pao2 132 +/- 13 Torr, Paco2 = 98.2 +/- 7.6 Torr). CA synthesis was blocked using alpha-methylparatyrosine methyl ester (AMPT) prior to alterations in the inspired air. There was a significant decrease in carotid body content of dopamine (DA), norepinephrine (NE), and epinephrine (E) 1 h after AMPT administration. Analysis of variance and Duncan new multiple range procedures revealed that during the subsequent 0.5-h exposures to normoxia, hypoxia, or hypercapnia, only the decrease in DA during hypoxia was significantly greater than that during normoxia; the loss during hypercapnia was not. The decreases in NE during the three exposures were indistinguishable among themselves as were the decreases in E. The decrease in CA content is probably attributable to increased release. The data reveal that the release of CAs during the chemoreception of hypoxia is different from that during the chemoreception of hypercapnia and support the concept of different mechanisms for the chemoreception of hypoxia and hypercapnia.

  19. The content of catecholamines in the adrenal glands and sections of the brain under hypokinesia and injection of some neurotropic agents

    NASA Technical Reports Server (NTRS)

    Melnik, B. E.; Paladiy, E. S.

    1980-01-01

    The dynamics of catecholamine content were studied in the adrenal glands and in various region of the brain of white rats under hypokinesia and injections of neurotropic agents. Profound changes in body catecholamine balance occured as a result of prolonged acute restriction of motor activity. Adrenalin retention increased and noradrenanalin retention decreased in the adrenal glands, hypothalamus, cerebral hemispheres, cerebellum and medulla oblongata. Observed alterations in catecholamine retention varied depending upon the type of neurotropic substance utilized. Mellipramine increased catecholamine retention in the tissues under observation while spasmolytin brought about an increase in adrenalin concentration in the adrenals and a decrease in the brain.

  20. The catecholamine response to spaceflight: role of diet and gender

    NASA Technical Reports Server (NTRS)

    Stein, T. P.; Wade, C. E.

    2001-01-01

    Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

  1. The catecholamine response to spaceflight: role of diet and gender.

    PubMed

    Stein, T P; Wade, C E

    2001-09-01

    Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

  2. Photoaffinity labelling of MSH receptors on Anolis melanophores: effects of catecholamines, calcium and forskolin.

    PubMed

    Eberle, A N; Girard, J

    1985-01-01

    Photoaffinity labelling of MSH receptors on Anolis melanophores was used as a tool for studying the effects of catecholamines, calcium and forskolin on hormone-receptor interaction and receptor-adenylate cyclase coupling. Covalent attachment of photoreactive alpha-MSH to its receptor was suppressed in calcium-free buffer but was hardly influenced by catecholamines or forskolin. The longlasting signal generated by the covalent MSH-receptor complex was readily and reversibly abolished by adrenaline, noradrenaline, dopamine or clonidine or by the absence of calcium. The suppression of pigment dispersion by catecholamines was blocked by the simultaneous presence of yohimbine but not prazosin, indicating that the catecholamines antagonize the alpha-MSH signal by inhibitory action on the adenylate cyclase system through an alpha-2 receptor. Forskolin, which stimulates melanophores by direct action on the catalytic unit of the adenylate cyclase and at about the same speed as alpha-MSH, produced a slower and weaker response in the presence of noradrenaline. If MSH receptors were covalently labelled and then exposed to noradrenaline, the characteristics of the forskolin-induced response were identical to those of unlabelled cells that had not been exposed to noradrenaline. This may point to a partial restoration of receptor-adenylate cyclase coupling by forskolin. The results show that the longlasting stimulation of Anolis melanophores by photoaffinity labelling proceeds via a permanently stimulated adenylate-cyclase system whose coupling to the receptor depends on calcium and is abolished by alpha-2 receptor agonists. Calcium is also essential for hormone-receptor binding.

  3. Synergic effect studies of the bi-enzymatic system laccase-peroxidase in a voltammetric biosensor for catecholamines.

    PubMed

    Leite, Oldair D; Lupetti, Karina O; Fatibello-Filho, Orlando; Vieira, Iolanda C; Barbosa, Aneli de M

    2003-04-10

    Several bi-enzymatic carbon paste biosensors modified with enzymes laccase from Pleurotus ostreatus fungi and peroxidase from zucchini (Cucurbita pepo) were constructed for evaluating the synergic effect of the two enzymes on the voltammetric biosensor response for various catecholamines. Initially was investigated the effect of pH from 5.0 to 7.5, temperature from 25 to 50 degrees C, initial stirring time from 30 to 150 s, scan rate from 10 to 60 mVs(-1) and potential pulse amplitude from 10 to 60 mV on the biosensor response for several catecholamines such as dopamine, adrenaline, isoprenaline and l-dopa. It was observed a biosensor signal increase employing both enzymes, indicating thus there is a synergic effect between laccase and peroxidase, verified also in spectrophotometric studies, in the determination of these catecholamines.

  4. Multifunctional Polyphenols- and Catecholamines-Based Self-Defensive Films for Health Care Applications.

    PubMed

    Dhand, Chetna; Harini, Sriram; Venkatesh, Mayandi; Dwivedi, Neeraj; Ng, Alice; Liu, Shouping; Verma, Navin Kumar; Ramakrishna, Seeram; Beuerman, Roger W; Loh, Xian Jun; Lakshminarayanan, Rajamani

    2016-01-20

    In an era of relentless evolution of antimicrobial resistance, there is an increasing demand for the development of efficient antimicrobial coatings or surfaces for food, biomedical, and industrial applications. This study reports the laccase-catalyzed room-temperature synthesis of mechanically robust, thermally stable, broad spectrum antimicrobial films employing interfacial interactions between poly(vinyl alcohol), PVA, and 14 naturally occurring catecholamines and polyphenols. The oxidative products of catecholamines and polyphenols reinforce the PVA films and also alter their surface and bulk properties. Among the catecholamines-reinforced films, optimum surface and bulk properties can be achieved by the oxidative products of epinephrine. For polyphenols, structure-property correlation reveals an increase in surface roughness and elasticity of PVA films with increasing number of phenolic groups in the precursors. Interestingly, PVA films reinforced with oxidized/polymerized products of pyrogallol (PG) and epinephrine (EP) display potent antimicrobial activity against pathogenic Gram-positive and Gram-negative strains, whereas hydroquinone (HQ)-reinforced PVA films display excellent antimicrobial properties against Gram-positive bacteria only. We further demonstrate that HQ and PG films retain their antimicrobial efficacy after steam sterilization. With an increasing trend of giving value to natural and renewable resources, our results have the potential as durable self-defensive antimicrobial surfaces/films for advanced healthcare and industrial applications.

  5. The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa.

    PubMed

    Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

    2014-12-07

    A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; P<.0001). The plasma leptin levels were higher under catecholamine depletion compared with placebo in the whole sample (treatment effect; P=.0004). This study reports on preliminary findings that suggest a catecholamine-dependent association of plasma BDNF and reward learning in subjects with remitted bulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  6. Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons.

    PubMed

    Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Powers, Bethany R; Ritter, Sue

    2014-02-15

    Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component.

  7. Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons

    PubMed Central

    Wang, Qing; Dinh, Thu T.; Powers, Bethany R.; Ritter, Sue

    2013-01-01

    Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component. PMID:24381177

  8. Electroporation followed by electrochemical measurement of quantal transmitter release from single cells using a patterned microelectrode.

    PubMed

    Ghosh, Jaya; Liu, Xin; Gillis, Kevin D

    2013-06-07

    An electrochemical microelectrode located immediately adjacent to a single neuroendocrine cell can record spikes of amperometric current that result from exocytosis of oxidizable transmitter from individual vesicles, i.e., quantal exocytosis. Here, we report the development of an efficient method where the same electrochemical microelectrode is used to electropermeabilize an adjacent chromaffin cell and then measure the consequent quantal catecholamine release using amperometry. Trains of voltage pulses, 5-7 V in amplitude and 0.1-0.2 ms in duration, were used to reliably trigger release from cells using gold electrodes. Amperometric spikes induced by electropermeabilization had similar areas, peak heights and durations as amperometric spikes elicited by depolarizing high K(+) solutions, therefore release occurs from individual secretory granules. Uptake of trypan blue stain into cells demonstrated that the plasma membrane is permeabilized by the voltage stimulus. Voltage pulses did not degrade the electrochemical sensitivity of the electrodes assayed using a test analyte. Surprisingly, robust quantal release was elicited upon electroporation in the absence of Ca(2+) in the bath solution (0 Ca(2+)/5 mM EGTA). In contrast, electropermeabilization-induced transmitter release required Cl(-) in the bath solution in that bracketed experiments demonstrated a steep dependence of the rate of electropermeabilization-induced transmitter release on [Cl(-)] between 2 and 32 mM. Using the same electrochemical electrode to electroporate and record quantal release of catecholamines from an individual chromaffin cell allows precise timing of the stimulus, stimulation of a single cell at a time, and can be used to load membrane-impermeant substances into a cell.

  9. The apelinergic system as an alternative to catecholamines in low-output septic shock.

    PubMed

    Coquerel, David; Sainsily, Xavier; Dumont, Lauralyne; Sarret, Philippe; Marsault, Éric; Auger-Messier, Mannix; Lesur, Olivier

    2018-01-19

    Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the "maintaining blood pressure" paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

  10. Hypoxic alligator embryos: chronic hypoxia, catecholamine levels and autonomic responses of in ovo alligators.

    PubMed

    Eme, John; Altimiras, Jordi; Hicks, James W; Crossley, Dane A

    2011-11-01

    Hypoxia is a naturally occurring environmental challenge for embryonic reptiles, and this is the first study to investigate the impact of chronic hypoxia on the in ovo development of autonomic cardiovascular regulation and circulating catecholamine levels in a reptile. We measured heart rate (f(H)) and chorioallantoic arterial blood pressure (MAP) in normoxic ('N21') and hypoxic-incubated ('H10'; 10% O(2)) American alligator embryos (Alligator mississippiensis) at 70, 80 and 90% of development. Embryonic alligator responses to adrenergic blockade with propranolol and phentolamine were very similar to previously reported responses of embryonic chicken, and demonstrated that embryonic alligator has α and β-adrenergic tone over the final third of development. However, adrenergic tone originates entirely from circulating catecholamines and is not altered by chronic hypoxic incubation, as neither cholinergic blockade with atropine nor ganglionic blockade with hexamethonium altered baseline cardiovascular variables in N21 or H10 embryos. In addition, both atropine and hexamethonium injection did not alter the generally depressive effects of acute hypoxia - bradycardia and hypotension. However, H10 embryos showed significantly higher levels of noradrenaline and adrenaline at 70% of development, as well as higher noradrenaline at 80% of development, suggesting that circulating catecholamines reach maximal levels earlier in incubation for H10 embryos, compared to N21 embryos. Chronically elevated levels of catecholamines may alter the normal balance between α and β-adrenoreceptors in H10 alligator embryos, causing chronic bradycardia and hypotension of H10 embryos measured in normoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock

    PubMed Central

    Macarthur, Heather; Westfall, Thomas C.; Riley, Dennis P.; Misko, Thomas P.; Salvemini, Daniela

    2000-01-01

    A major feature of septic shock is the development of a vascular crisis characterized by nonresponsiveness to sympathetic vasoconstrictor agents and the subsequent irreversible fall in blood pressure. In addition, sepsis, like other inflammatory conditions, results in a large increase in the production of free radicals, including superoxide anions (O2⨪) within the body. Here we show that O2⨪ reacts with catecholamines deactivating them in vitro. Moreover, this deactivation would appear to account for the hyporeactivity to exogenous catecholamines observed in sepsis, because administration of a superoxide dismutase (SOD) mimetic to a rat model of septic shock to remove excess O2⨪ restored the vasopressor responses to norepinephrine. This treatment with the SOD mimetic also reversed the hypotension in these animals; suggesting that deactivation of endogenous norepinephrine by O2⨪ contributes significantly to this aspect of the vascular crisis. Indeed, the plasma concentrations of both norepinephrine and epinephrine in septic rats treated with the SOD mimetic were significantly higher than in untreated rats. Interestingly, the plasma concentrations for norepinephrine and epinephrine were inversely related to the plasma concentrations of adrenochromes, the product of the autoxidation of catecholamines initiated by O2⨪. We propose, therefore, that the use of a SOD mimetic represents a new paradigm for the treatment of septic shock. By removing O2⨪, exogenous and endogenous catecholamines are protected from autoxidation. As a result, both hyporeactivity and hypotension are reversed, generation of potentially toxic adrenochromes is reduced, and survival rate is improved. PMID:10944234

  12. The novel iron chelator, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone, reduces catecholamine-mediated myocardial toxicity.

    PubMed

    Mladĕnka, Premysl; Kalinowski, Danuta S; Haskova, Pavlína; Bobrovová, Zuzana; Hrdina, Radomír; Simůnek, Tomás; Nachtigal, Petr; Semecký, Vladimĺr; Vávrová, Jaroslava; Holeckova, Magdaléna; Palicka, Vladimir; Mazurová, Yvona; Jansson, Patric J; Richardson, Des R

    2009-01-01

    Iron (Fe) chelators are used clinically for the treatment of Fe overload disease. Iron also plays a role in the pathology of many other conditions, and these potentially include the cardiotoxicity induced by catecholamines such as isoprenaline (ISO). The current study examined the potential of Fe chelators to prevent ISO cardiotoxicity. This was done as like other catecholamines, ISO contains the classical catechol moiety that binds Fe and may form redox-active and cytotoxic Fe complexes. Studies in vitro used the cardiomyocyte cell line, H9c2, which was treated with ISO in the presence or absence of the chelator, desferrioxamine (DFO), or the lipophilic ligand, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH). Both of these chelators were not cardiotoxic and significantly reduced ISO cardiotoxicity in vitro. However, PCTH was far more effective than DFO, with the latter showing activity only at a high, clinically unachievable concentration. Further studies in vitro showed that interaction of ISO with Fe(II)/(III) did not increase cytotoxic radical generation, suggesting that this mechanism was not involved. Studies in vivo were initiated using rats pretreated intravenously with DFO or PCTH before subcutaneous administration of ISO (100 mg/kg). DFO at a clinically used dose (50 mg/kg) failed to reduce catecholamine cardiotoxicity, while PCTH at an equimolar dose totally prevented catecholamine-induced mortality and reduced cardiotoxicity. This study demonstrates that PCTH reduced ISO-induced cardiotoxicity in vitro and in vivo, demonstrating that Fe plays a role, in part, in the pathology observed.

  13. Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients.

    PubMed

    Verly, Iedan R N; van Kuilenburg, André B P; Abeling, Nico G G M; Goorden, Susan M I; Fiocco, Marta; Vaz, Frédéric M; van Noesel, Max M; Zwaan, C Michel; Kaspers, GertJan L; Merks, Johannes H M; Caron, Huib N; Tytgat, Godelieve A M

    2017-02-01

    Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients. Elevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel. Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

    NASA Technical Reports Server (NTRS)

    Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

    1980-01-01

    The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

  15. Effects of Mind-Body Training on Cytokines and Their Interactions with Catecholamines.

    PubMed

    Jang, Joon Hwan; Park, Hye Yoon; Lee, Ui Soon; Lee, Kyung-Jun; Kang, Do-Hyung

    2017-07-01

    Mind-body training (MBT) may control reactions to stress and regulate the nervous and immune systems. The present study was designed to assess the effects of MBT on plasma cytokines and their interactions with catecholamines. The study group consisted of 80 subjects who practice MBT and a control group of 62 healthy subjects. Plasma catecholamine (norepinephrine, NE; epinephrine, E; and dopamine, DA) and cytokine (TNF-alpha, IL-6, IFN-gamma, and IL-10) levels were measured, and the differences between the MBT and control groups and the interactions of cytokines with catecholamines were investigated. A significant increase in IL-10+IFN-gamma was found in females of the MBT group compared with controls. Also, a significant increase of IL-10 (anti-inflammatory cytokine) in the MBT group was shown in a specific condition in which TNF-alpha and IL-6 (pro-inflammatory cytokines) are almost absent (≤1 ng/L) compared with controls. In the MBT group, significant positive correlations were found between IL-10 and the NE/E ratio and between IL-10 and the DA/E ratio, whereas the control group did not show any such correlations. MBT may increase IL-10, under specific conditions such as a decrease of pro-inflammatory cytokines or E, which may regulate the stress response and possibly contribute to effective and beneficial interactions between the nervous and immune systems.

  16. Reduction in total plasma ghrelin levels following catecholamine depletion: relation to bulimic and depressive symptoms.

    PubMed

    Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Hasler, Gregor

    2013-09-01

    There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

    PubMed Central

    Nguyen, Khoa D.; Qiu, Yifu; Cui, Xiaojin; Goh, Y.P. Sharon; Mwangi, Julia; David, Tovo; Mukundan, Lata; Brombacher, Frank; Locksley, Richard M.; Chawla, Ajay

    2011-01-01

    All homeotherms utilize thermogenesis to maintain core body temperature, ensuring that cellular functions and physiologic processes can ensue in cold environments1-3. In the prevailing model, when the hypothalamus senses cold temperatures, it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue (BAT) and white adipose tissue (WAT)4,5. Acting via the β3-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes6, whereas it stimulates the expression of thermogenic genes, such as PPARγ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1), and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes7-9. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report an unexpected requirement for the interleukin 4 (IL4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Cold exposure rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in BAT and lipolysis in WAT. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL4 increased thermogenic gene expression, fatty acid mobilization, and energy expenditure, all in a macrophage-dependent manner. We have thus discovered a surprising role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold. PMID:22101429

  18. Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

    PubMed

    Goggins, Sean; Marsh, Barrie J; Lubben, Anneke T; Frost, Christopher G

    2015-08-01

    Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.

  19. Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.

    PubMed

    Li, Xiaojia; Toyohira, Yumiko; Horisita, Takafumi; Satoh, Noriaki; Takahashi, Keita; Zhang, Han; Iinuma, Munekazu; Yoshinaga, Yukari; Ueno, Susumu; Tsutsui, Masato; Sata, Takeyoshi; Yanagihara, Nobuyuki

    2015-12-01

    Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 μM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 μM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 μM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 μM and 10-100 μM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

  20. Calorigenic effect of glucagon and catecholamines in king penguin chicks.

    PubMed

    Barre, H; Rouanet, J L

    1983-06-01

    The calorigenic action of glucagon and catecholamine infusion was evaluated in winter-acclimatized king penguin chicks at 20 and 0 degrees C ambient temperature (Ta). At Ta = 20 degrees C the mean increase in metabolic rate was 0.73 W . kg-1 for epinephrine (80 micrograms . kg-1), 0.42 W . kg-1 for norepinephrine (150 micrograms . kg-1), and 1.16 W . kg-1 for glucagon (0.75 micrograms . kg-1); i.e., respectively 30, 17, and 47% of the control value. The maximum response to glucagon reached 89% over control. At Ta = 0 degrees C, for the same glucagon infusion, the mean increase in specific metabolic rate was 0.84 W . kg-1, 27% of control rate. In the cold, glucagon infusion inhibited shivering and substituted its calorigenic action, resulting in a less apparent effect. In contrast with the negligible effect of catecholamines, glucagon infused at low doses exerted a powerful calorigenic action in young king penguins and could be considered as a possible nonshivering thermogenesis mediator.

  1. Preservation of urine free catecholamines and their free O-methylated metabolites with citric acid as an alternative to hydrochloric acid for LC-MS/MS-based analyses.

    PubMed

    Peitzsch, Mirko; Pelzel, Daniela; Lattke, Peter; Siegert, Gabriele; Eisenhofer, Graeme

    2016-01-01

    Measurements of urinary fractionated metadrenalines provide a useful screening test to diagnose phaeochromocytoma. Stability of these compounds and their parent catecholamines during and after urine collection is crucial to ensure accuracy of the measurements. Stabilisation with hydrochloric acid (HCl) can promote deconjugation of sulphate-conjugated metadrenalines, indicating a need for alternative preservatives. Urine samples with an intrinsically acidic or alkaline pH (5.5-6.9 or 7.1-8.7, respectively) were used to assess stability of free catecholamines and their free O-methylated metabolites over 7 days of room temperature storage. Stabilisation with HCl was compared with ethylenediaminetetraacetic acid/metabisulphite and monobasic citric acid. Catecholamines and metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Free catecholamines and their O-methylated metabolites were stable in acidic urine samples over 7 days of room temperature storage, independent of the presence or absence of any stabilisation method. In contrast, free catecholamines, but not the free O-methylated metabolites, showed rapid degradation within 24 h and continuing degradation over 7 days in urine samples with an alkaline pH. Adjustment of alkaline urine samples to a pH of 3-5 with HCl or 4.8-5.4 with citric acid completely blocked degradation of catecholamines. Ethylenediaminetetraacetic acid/metabisulphite, although reducing the extent of degradation of catecholamines in alkaline urine, was largely ineffectual as a stabiliser. Citric acid is equally effective as HCl for stabilisation of urinary free catecholamines and minimises hazards associated with use of strong inorganic acids while avoiding deconjugation of sulphate-conjugated metabolites during simultaneous LC-MS/MS measurements of free catecholamines and their free O-methylated metabolites.

  2. L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.

    PubMed

    Brodnik, Zachary D; Double, Manda; España, Rodrigo A; Jaskiw, George E

    2017-09-01

    We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated. Published by Elsevier Ltd.

  3. Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats.

    PubMed

    Dronjak, S; Gavrilovic, L

    2006-06-01

    Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days) and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4 degrees C, 2 h), were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(3H-methyl)-methionine was used. The O-methylated derivatives were oxidized to 3H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18%) and hippocampal dopamine (about 20%) stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39%) in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20%) as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

  4. Consideration of the degree of increase in urine metadrenalines provides superior specificity in the diagnosis of phaeochromocytoma than additional urine catecholamine measurement.

    PubMed

    Scargill, J J; Reed, P; Kane, J

    2013-01-01

    Measurement of fractionated plasma or urine metadrenalines is the recommended screening test in the diagnosis of phaeochromocytoma, with clinical cut-offs geared towards diagnostic sensitivity. Current practice at Salford Royal Hospital is to add urine catecholamines onto samples with raised urine metadrenalines, with the aim of adding specificity to a diagnosis of phaeochromocytoma. This practice was reviewed by identifying a series of patients with raised urine metadrenalines who had catecholamines reflectively added. A total of 358 samples were identified from 242 patients, of which 228 had urine catecholamines measured. A diagnosis of 'phaeochromocytoma' (n = 41) or 'no phaeochromocytoma' (n = 90) was obtained in 131 of 228 patients, giving raised urine metadrenalines a positive predictive value for phaeochromocytoma of 31%. The finding of increased urine catecholamines in samples with raised urine metadrenalines increased specificity for phaeochromocytoma to 70%. However, 95% diagnostic specificity for phaeochromocytoma could be achieved by the introduction of a second cut-off for urine metadrenalines geared towards maximizing specificity. Consideration of the degree of increase in urine metadrenalines is a superior method of determining the likelihood of phaeochromocytoma than measurement of urine catecholamines.

  5. Diurnal Salivary Cortisol and Urinary Catecholamines Are Associated With Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Champaneri, Shivam; Xu, Xiaoqiang; Carnethon, Mercedes R.; Bertoni, Alain G.; Seeman, Teresa; Roux, Ana Diez; Golden, Sherita Hill

    2011-01-01

    Objective To examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status. Methods Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1,002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose ≥126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response (CAR), early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine. Results Participants with diabetes had significantly lower CAR (β=−0.19; 95% CI: −0.34 to −0.04) than those without diabetes in multivariable models. While men with diabetes had a non-significant trend toward lower total AUC (β=−1.56; 95% CI: −3.93 to 0.80), women with diabetes had significantly higher total AUC (β=2.62; 95% CI: 0.72 to 4.51) (p=0.02 for interaction) compared to those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines, compared to those without diabetes (p<0.05). Conclusions Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes. PMID:22209664

  6. Effect of consecutive cooling and immobilization on catecholamine metabolism in rat tissues

    NASA Technical Reports Server (NTRS)

    Matlina, E. S.; Waysman, S. M.; Zaydner, I. G.; Kogan, B. M.; Nozdracheva, L. V.

    1979-01-01

    The combined effect of two stressor stimuli--cooling and immobilization--acting successively on the sympathetic-adrenaline system was studied experimentally in rats that were cooled for 8 hours at 7 C on the first day and immobilized for 6 hours on the next day. The biochemical and histochemical methods used and the experimental technique involved are described in detail. The following conclusions were formulated: (1) the successive action of cooling and immobilization results in a stronger decrease in the adrenaline and noradrenaline content in the adrenal gland than that which could be due to a simple summation of the cooling and immobilization effects; (2) successive cooling and immobilization are followed by activation of catecholamine synthesis in the adrenal gland; and (3) 1-DOPA administration (45 mg/kg 3 times in 2 days) intraabdominally activated catecholamine synthesis in the adrenal glands in both the control and test animals.

  7. β1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating β1-Adrenoceptors in Normotensive and Hypertensive Rats

    PubMed Central

    Berg, Torill

    2014-01-01

    Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here the author tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood–brain barrier, reduced norepinephrine overflow after adrenalectomy (AdrX), AdrX + ganglion blockade, losartan, or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1 receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as

  8. Occupational EMF exposure from radar at X and Ku frequency band and plasma catecholamine levels.

    PubMed

    Singh, Sarika; Kapoor, Neeru

    2015-09-01

    Workers in certain occupations such as the military may be exposed to technical radiofrequency radiation exposure above current limits, which may pose a health risk. The present investigation intended to find the effect of chronic electromagnetic field (EMF) exposure from radar on plasma catecholamines in the military workforce. In the study, 166 male personnel selected randomly were categorized into three groups: control (n = 68), exposure group-I (X-band, 8-12 GHz, n = 40), and exposure group-II (Ku-band, 12.5-18 GHz, n = 58). The three clusters were further divided into two groups according to their years of service (YOS) (up to 9 years and ≥10 years) to study the effect of years of radar exposure. Enzyme immunoassay was employed to assess catecholamine concentrations. EMF levels were recorded at different occupational distances from radar. Significant adrenaline diminution was registered in exposure group-II with no significant difference in exposure group-I when both groups were weighed against control. Nor-adrenaline and dopamine levels did not vary significantly in both exposure groups when compared to controls. Exposure in terms of YOS also did not yield any significant alteration in any of the catecholamines and in any of the exposure groups when compared with their respective control groups. The shift from baseline catecholamine values due to stress has immense significance for health and well-being. Their continual alteration may prove harmful in due course. Suitable follow-up studies are needed to further strengthen these preliminary observations and for now, exposures should be limited as much as possible with essential safeguards. © 2015 Wiley Periodicals, Inc.

  9. DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis

    PubMed Central

    Piston, Dominik; Alvarez-Erviti, Lydia; Bansal, Vikas; Gargano, Daniela; Yao, Zhi; Szabadkai, Gyorgy; Odell, Mark; Puno, M Rhyan; Björkblom, Benny; Maple-Grødem, Jodi; Breuer, Peter; Kaut, Oliver; Larsen, Jan Petter; Bonn, Stefan; Møller, Simon Geir; Wüllner, Ullrich; Schapira, Anthony H V

    2017-01-01

    Abstract DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson’s disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease. PMID:29016861

  10. Catecholamine-Induced β2-adrenergic receptor activation mediates desensitization of gastric cancer cells to trastuzumab by upregulating MUC4 expression.

    PubMed

    Shi, Ming; Yang, Zhengyan; Hu, Meiru; Liu, Dan; Hu, Yabin; Qian, Lu; Zhang, Wei; Chen, Hongyu; Guo, Liang; Yu, Ming; Song, Lun; Ma, Yuanfang; Guo, Ning

    2013-06-01

    Trastuzumab is currently used for patients with Her2(+) advanced gastric cancer. However, the response rate to trastuzumab among the patients is low. The molecular mechanisms underlying trastuzumab resistance in gastric cancer are unknown. Our in vitro data show that activation of β2-adrenergic receptor (β2-AR) triggered by catecholamine caused "targeting failure" of trastuzumab in gastric cancer cells. The antitumor activities of trastuzumab were significantly impeded by chronic catecholamine stimulation in gastric cancer cells and in the mice bearing human gastric cancer xenografts. Mechanistically, catecholamine induced upregulation of the MUC4 expression at both transcription and protein levels via activating STAT3 and ERK. The effects of catecholamine could be effectively blocked by β2-AR antagonist ICI-118,551, indicating that β2-AR-mediated signaling pathway plays a key role in upregulation of MUC4, which was previously demonstrated to interfere with the recognition and physical binding of trastuzumab to Her2 molecules. Moreover, a significant elevation of the MUC4 level was observed in the xenograft tissues in nude mice chronically treated with isoproterenol. Knockdown of MUC4 restored the binding activities of trastuzumab to Her2-overexpressing gastric cancer cells. In addition, coexpression of β2-AR and MUC4 were observed in gastric cancer tissues. Our data indicated a novel trastuzumab resistance mechanism, by which catecholamine-induced β2-AR activation mediates desensitization of gastric cancer cells to trastuzumab through upregulating the MUC4 expression.

  11. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

    PubMed

    Johansson, P I; Ostrowski, S R

    2010-12-01

    Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    PubMed

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto

    2016-01-01

    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large

  13. Analysis of catecholamines in urine by unique LC/MS suitable ion-pairing chromatography.

    PubMed

    Bergmann, Marianne L; Sadjadi, Seyed; Schmedes, Anne

    2017-07-01

    The catecholamines, epinephrine (E) and norepinephrine (NE) are small polar, hydrophilic molecules, posing significant challenges to liquid chromatography - tandem mass spectrometry (LC-MS/MS) method development. Specifically, these compounds show little retention on conventional reversed-phase liquid chromatography columns. This work presents development and validation of an LC-MS/MS method for determining catecholamines in urine, based on a new approach to ion-pairing chromatography (IPC), in which the ion-pairing reagent (IPR), 1-Heptane Sulfonic Acid (HSA), is added to the extracted samples instead of the mobile phases. A Hamilton STARlet workstation carried out the solid phase extraction of urine samples. The extracted samples were diluted with 60mmol/L HSA and injected on a Kinetex core-shell biphenyl column with conventional LC-MS/MS suitable mobile phases. Chromatographic separation of E and NE was achieved successfully with very stable retention times (RT). In 484 injections, the RTs were steady with a CV of less than ±4%. Furthermore, HSA was separated from E and NE, allowing HSA to be diverted to waste instead of entering the mass spectrometer ion chamber. The method was validated with good analytical performance, and even though the analysis for urinary catecholamines is increasingly being replaced by plasma free metanephrines in diagnosing pheochromocytomas, this work represents the application of a new analytical technique that can be transferred to other small polar molecules, that are difficult to chromatograph on traditional reversed phase columns. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Behavioral and perceived stressor effects on urinary catecholamine excretion in adult Samoans.

    PubMed

    Bergey, Meredith R; Steele, Matthew S; Bereiter, David A; Viali, Satupaitea; McGarvey, Stephen T

    2011-01-01

    The effects of perceptions and behaviors related to culturally patterned socioeconomic obligations on catecholamine excretion rates were studied in a cross-sectional sample of Samoan adults. A total of 378 participants, ages 29-62 years, from 9 villages throughout Samoa, provided timed overnight urine specimens, and self-reported perceptions and behaviors associated with contributions to one's family, aiga, and chief, matai, and communal gift exchanges, fa'alavelave. Urinary norepinephrine and epinephrine excretion rates were measured by high performance liquid chromatography with electrochemical detection. Age (≤40 vs. >40 years) and gender-specific regression models were estimated to detect associations with catecholamine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who view their contribution to their matai to be "just right," had significantly higher residence-adjusted norepinephrine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who consider their contribution to their aiga not to be a burden, had higher epinephrine excretion. Older men who contribute more to their aiga and who perceive their contribution to their aiga to be "just right" had increased residence-adjusted epinephrine excretion. Individual-level perceptions and behaviors related to traditional socioeconomic obligations are a significant correlate of increased overnight catecholamine excretion rates. Higher excretion rates may be attributed to psychosocial stress arousal associated with a discordance between personal desires for upward social mobility, and family and community-based socioeconomic obligations. Changes in patterns of individual-level psychosocial stress arousal may contribute to cardiovascular disease risk in modernizing Samoans. Copyright © 2011 Wiley-Liss, Inc.

  15. Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

    PubMed

    Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

    1980-01-01

    The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.

  16. [Studies on the relationship between beta-adrenergic receptor density on cell wall lymphocytes, total serum catecholamine level and heart rate in patients with hyperthyroidism].

    PubMed

    Gajek, J; Zieba, I; Zyśko, D

    2000-08-01

    Hyperthyreosis mimics the hyperadrenergic state and its symptoms were though to be dependent on increased level of catecholamines. Another reason for the symptoms could be the increased density or affinity of beta-adrenergic receptors to catecholamines. The aim of the study was to examine the elements of sympathetic nervous system, thyroid hormones level and their influence on heart rate control in patients with hyperthyreosis. The study was carried out in 18 women, mean age 48.9 +/- 8.7 yrs and 6 men, mean age 54.2 +/- 8.7 yrs. The control group consisted of 30 healthy persons matched for age and sex. We examined the density of beta-adrenergic receptors using radioligand labelling method with 125I-cyanopindolol, serum total catecholamines level with radioenzymatic assay kit, the levels of free thyroid hormones using radioimmunoassays and thyreotropine level with immunoradiometric assay. Maximal, minimal and mean heart rate were studied using Holter monitoring system. The density of beta-adrenergic receptors in hyperthyreosis was 37.3 +/- 21.7 vs 37.2 +/- 18.1 fmol/mg in the control group (p = NS). Total catecholamines level was significantly decreased in hyperthyreosis group: 1.5 +/- 0.89 vs 1.9 +/- 0.73 pmol/ml (p < 0.05). There was significantly higher minimal, maximal and mean heart rate in hyperthyreosis group (p < 0.0001, p < 0.0001 and p < 0.05 respectively). There was a weak inverse correlation between minimum heart rate and triiodothyronine level (r = -0.38, p < 0.05). An inverse correlation between triiodothyronine and catecholamines level (r = -0.49, p < 0.05) was observed. Beta-adrenergic receptors density is unchanged and catecholamines level is decreased in hyperthyreosis when compared to normal subjects. There is no correlation between minimal heart rate and adrenergic receptors density or catecholamines level in hyperthyreosis.

  17. L-DOPA therapy interferes with urine catecholamine analysis in children with suspected neuroblastoma: a case series.

    PubMed

    Kelly, Alison U; Srivastava, Rajeev; Dow, Ellie; Davidson, D Fraser

    2017-09-01

    Neuroblastoma is the most common solid extracranial malignancy diagnosed in childhood. Clinical presentation is variable, and metastatic disease is common at diagnosis. Analyses of urinary catecholamines and their metabolites are commonly requested as a first-line investigation when clinical suspicion exists. Levodopa (L-Dopa) therapy is utilized as a treatment for a number of disorders in childhood, including Dopa-responsive dystonia. Neuroblastoma may mimic some of the clinical features of this disorder. L-Dopa can interfere with analysis of urinary catecholamines and their metabolites and complicate the interpretation of results. We present the cases of three children who were prescribed L-dopa at the time of analysis of urinary catecholamines and metabolites as a screen for neuroblastoma, but who did not have the disease. Comparison of their results with those from cases with true neuroblastoma reveal that it is impossible to reliably distinguish true neuroblastoma from L-Dopa therapy using these tests. We recommend that patients should be off L-dopa therapy, if possible when these tests are performed. These cases illustrate the importance of providing clinical details and drug history to the laboratory in order to avoid diagnostic confusion.

  18. Anticipatory responses of catecholamines on muscle force production.

    PubMed

    French, Duncan N; Kraemer, William J; Volek, Jeff S; Spiering, Barry A; Judelson, Daniel A; Hoffman, Jay R; Maresh, Carl M

    2007-01-01

    Few data exist on the temporal relationship between catecholamines and muscle force production in vivo. The purpose of this study was to examine the influence of preexercise arousal on sympathoadrenal neurohormones on muscular force expression during resistance exercise. Ten resistance-trained men completed two experimental conditions separated by 7 days: 1) acute heavy resistance exercise protocol (AHREP; 6 x 10 repetitions parallel squats, 80% 1 repetition maximum) and 2) control (Cont; rest). Peak force (F(peak)) was recorded during a maximal isometric squat preceding each set and mean force (F(mean)) was measured during each set. Serial venous blood samples were collected before the AHREP and immediately preceding each set. Blood collection times were matched during Cont. Preexercise epinephrine (Epi), norepinephrine (NE), and dopamine (DA) increased (P or= 0.05) in muscular performance (F(peak), F(mean)) during AHREP and that five subjects (F(reducers)) had significant reductions in F(peak) and F(mean). Integrated area under the curve for Epi, NE, and F(peak) were greater (P < 0.02) for F(maintainers) than F(reducers). In conclusion, an anticipatory rise in catecholamines existed, which may be essential for optimal force production at the onset of exercise.

  19. Catecholamine levels in the brain of rats exposed by inhalation to benzalkonium chloride.

    PubMed

    Swiercz, Radosław; Grzelińska, Zofia; Gralewicz, Sławomir; Wasowicz, Wojciech

    2009-01-01

    The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.

  20. Sympathetic neural control of indoleamine metabolism in the rat pineal gland

    NASA Technical Reports Server (NTRS)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

    1975-01-01

    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  1. Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets.

    PubMed

    Arafat, Basel; Wojsz, Magdalena; Isreb, Abdullah; Forbes, Robert T; Isreb, Mohammad; Ahmed, Waqar; Arafat, Tawfiq; Alhnan, Mohamed A

    2018-06-15

    Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure

    PubMed Central

    Fargali, Samira; Garcia, Angelo L.; Sadahiro, Masato; Jiang, Cheng; Janssen, William G.; Lin, Wei-Jye; Cogliani, Valeria; Elste, Alice; Mortillo, Steven; Cero, Cheryl; Veitenheimer, Britta; Graiani, Gallia; Pasinetti, Giulio M.; Mahata, Sushil K.; Osborn, John W.; Huntley, George W.; Phillips, Greg R.; Benson, Deanna L.; Bartolomucci, Alessandro; Salton, Stephen R.

    2014-01-01

    Secretion of proteins and neurotransmitters from large dense core vesicles (LDCVs) is a highly regulated process. Adrenal LDCV formation involves the granin proteins chromogranin A (CgA) and chromogranin B (CgB); CgA- and CgB-derived peptides regulate catecholamine levels and blood pressure. We investigated function of the granin VGF (nonacronymic) in LDCV formation and the regulation of catecholamine levels and blood pressure. Expression of exogenous VGF in nonendocrine NIH 3T3 fibroblasts resulted in the formation of LDCV-like structures and depolarization-induced VGF secretion. Analysis of germline VGF-knockout mouse adrenal medulla revealed decreased LDCV size in noradrenergic chromaffin cells, increased adrenal norepinephrine and epinephrine content and circulating plasma epinephrine, and decreased adrenal CgB. These neurochemical changes in VGF-knockout mice were associated with hypertension. Germline knock-in of human VGF1–615 into the mouse Vgf locus rescued the hypertensive knockout phenotype, while knock-in of a truncated human VGF1–524 that lacks several C-terminal peptides, including TLQP-21, resulted in a small but significant increase in systolic blood pressure compared to hVGF1–615 mice. Finally, acute and chronic administration of the VGF-derived peptide TLQP-21 to rodents decreased blood pressure. Our studies establish a role for VGF in adrenal LDCV formation and the regulation of catecholamine levels and blood pressure.—Fargali, S., Garcia, A. L., Sadahiro, M., Jiang, C., Janssen, W. G., Lin, W.-J., Cogliani, V., Elste, A., Mortillo, S., Cero, C., Veitenheimer, B., Graiani, G., Pasinetti, G. M., Mahata, S. K., Osborn, J. W., Huntley, G. W., Phillips, G. R., Benson, D. L., Bartolomucci, A., Salton, S. R. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. PMID:24497580

  3. Development of Sensitive and Direct Methods for Measuring Plasma Aldosterone and Catecholamine Concentrations

    NASA Technical Reports Server (NTRS)

    Haber, E.

    1972-01-01

    Radioimmunoassays for renin activity, angiotensin 1, and angiotensin 2 in the study of vasomotor regulation give new insight into the role of the renin system in maintaining postural homeostatsis. Similar laboratory procedures for specific assays of aldosterone and catecholamines achieve accurate determinations in small human blood samples.

  4. The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

    PubMed

    Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

    2017-09-01

    The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few

  5. Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

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

    Mao, Haoping; Wang, Hong; Ma, Shangwei

    2014-01-01

    Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectionalmore » regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p < 0.01), while it reduced 300 μM acetylcholine (ACh) (p < 0.01), 100 μM veratridine (Ver) (p < 0.01) and 56 mM K{sup +} (p < 0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p < 0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56 mM K{sup +} induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine

  6. Circulating catecholamine and glucose concentrations in Japanese toads (Bufo japonicus) during the breeding season.

    PubMed

    Wilson, J X; Sawai, H; Kikuchi, M; Kubokawa, K; Ishii, S

    1995-06-01

    We investigated the relationship between catecholamine neurohormones and glucose during seasonal reproductive activity in Japanese toads (Bufo japonicus). Field studies found that plasma epinephrine concentration increased as toads migrated to their breeding ponds, where amplexus most frequently took place. Blood glucose concentration also increased as toads arrived at the ponds, even though these animals did not eat during the breeding season, and there was a positive correlation between epinephrine and glucose levels. Blood glucose concentration was higher in amplectic than in solitary males, whereas this relationship did not occur in females. For both males and females, plasma epinephrine concentration was elevated during amplexus. The plasma concentration of norepinephrine was lower than that of epinephrine and did not correlate with either the proximity of the animal to the breeding ponds or the blood glucose concentration. Laboratory experiments showed that systemic injection of [Trp7,Leu8]gonadotropin-releasing hormone (sGnRH) increased plasma epinephrine to levels characteristic of amplectic feral toads. These results suggest that a physiological role of GnRH-like peptides may be to stimulate epinephrine secretion and consequently to increase glucose production in toads under the starvation conditions associated with the breeding migration.

  7. Overnight Changes of Immune Parameters and Catecholamines Are Associated With Mood and Stress

    PubMed Central

    Rief, Winfried; Mills, Paul J.; Ancoli-Israel, Sonia; Ziegler, Michael G.; Pung, Meredith A.; Dimsdale, Joel E.

    2011-01-01

    Objectives To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables. Methods A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day. Results The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue rp = −.25 to −.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable. Conclusions The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted. PMID:20841563

  8. Overnight changes of immune parameters and catecholamines are associated with mood and stress.

    PubMed

    Rief, Winfried; Mills, Paul J; Ancoli-Israel, Sonia; Ziegler, Michael G; Pung, Meredith A; Dimsdale, Joel E

    2010-10-01

    To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables. A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day. The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue r(p) = -.25 to -.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable. The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted.

  9. Corticotropin-releasing factor accelerates metamorphosis in Bufo arenarum: effect on pituitary ACTH and TSH cells.

    PubMed

    Miranda, L A; Affanni, J M; Paz, D A

    2000-04-01

    The actions of several neuropeptides as hypothalamic mediators in the regulation of Bufo arenarum metamorphosis were investigated. Prometamorphic larvae were injected with 1.5 microg thyrotropin-releasing hormone (TRH), 2 microg ovine corticotropin-releasing factor (oCRF), 2 microg mammalian gonadotropin-releasing hormone (mGnRH), 2 microg human growth hormone-releasing hormone (hGHRH), or Holtfreter solution (control group). Larvae received two injections with the same dose: one at the beginning of the experiment and the other 7 days later. Several morphologic parameters (total length, tail length, wet weight, hind limb length, and metamorphic stages) were measured as indicators of growth and metamorphic development. These measurements were taken in 20 larvae per treatment or control group at the beginning of the experiment, at day 7 and at day 14 when the experiment ended. We observed that only the administration of exogenous CRF stimulated resorption of the tail and accelerated the rate of metamorphosis. In the pituitary of CRF-treated larvae we observed that thyrotropin (TSH) and adrenocorticotropic hormone (ACTH) producing cells showed a weaker immunoreactivity, a decrease in cell number and a reduction of volume density when compared with normal larvae. In conclusion, the results obtained indicate a possible role for CRF in Bufo arenarum metamorphosis. CRF may regulate interrenal and thyroid activity by acting directly upon TSH and ACTH cells. On the other hand, TRH, GnRH and GHRH were inactive in stimulating growth or metamorphosis of Bufo arenarum. J. Exp. Zool. 286:473-480, 2000. Copyright 2000 Wiley-Liss, Inc.

  10. Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

    PubMed

    Trump, D L; Livingston, J N; Baylin, S B

    1977-10-01

    A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

  11. DIFFERENTIAL MODULATION OF CATECHOLAMINES BY CHLOROTRIAZINE HERBICIDES IN PHEOCHROMOCYTOMA (PC12) CELLS IN VITRO

    EPA Science Inventory

    Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.

    Das PC, McElroy WK, Cooper RL.

    Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.

    Epidemiological, wildlife, and lab...

  12. POTENTIAL MECHANISMS RESPONSIBLE FOR CHLOROTRIAZINE-INDUCED ALTERATIONS IN CATECHOLAMINES IN PHEOCHROMOCYTOMA (PC12) CELLS

    EPA Science Inventory

    ABSTRACT

    Potential Mechanisms Responsible for Chlorotriazine-induced Changes in Catecholamine Metabolism in Pheochromocytoma (PC12) Cells*
    PARIKSHIT C. DAS1, WILLIAM K. McELROY2 , AND RALPH L. COOPER2+
    1Curriculum in Toxicology, University of North Carolina, Chape...

  13. Potential of Sulphur-containing Amino Acids in the Prevention of Catecholamine-induced Arrhythmias.

    PubMed

    Adameova, Adriana; Tappia, Paramjit S; Hatala, Robert; Dhalla, Naranjan S

    2018-01-30

    Various physiological and pathological stimuli can hypersensitize the sympathetic nervous system resulting in a substantial release of catecholamines (CA) and consequent alterations in excitation-contraction coupling and excitation-transcription coupling. It has been shown that oxidation products of CA, rather than CA themselves, are responsible for such adaptation to a new equilibrium. While chronic, sustained accumulation of CA and their toxic products are associated with the depression in cardiac contractile force and remodeling, acute excessive release of CA can result in brief oxidative bursts and serious damage leading in lethal arrhythmias. In response to such oxidative stress, dysregulation of ion homeostasis, activation of neurohumoral system, immune and inflammatory responses, are augmented. These events are inter-related, and as a complex promote electrical instability. Likewise, remodeling occurring after the loss of cardiomyocytes, induces the development of a proarrhythmogenic environment. Thus, CA oxidation products may be involved in triggering arrhythmias as a result of both changes in cardiac cell automaticity and conduction velocity. In contrast, sulphur-containing amino acids (S-AA), in particular taurine and its precursor cysteine have been shown to modulate redox state of the heart. However, the multiple anti-oxidant properties of S-AA are unlikely to be exclusively responsible for their anti-arrhythmic action. They also possess additional cytoprotective effects which can stabilize electrical activity of the heart. It is concluded that specific S-AA may attenuate deleterious effects of supraphysiological levels of CA and this could serve as an important mechanism for the treatment and/or prevention of arrhythmogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Release of Phosphorylated HSP27 (HSPB1) from Platelets Is Accompanied with the Acceleration of Aggregation in Diabetic Patients.

    PubMed

    Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Kojima, Akiko; Doi, Tomoaki; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Iwama, Toru; Tanikawa, Takahisa; Ishikawa, Kei; Kojima, Kumi; Kozawa, Osamu

    2015-01-01

    We investigated the relationship between HSP27 phosphorylation and collagen-stimulated activation of platelets in patients with diabetes mellitus (DM). Platelet-rich plasma was prepared from blood of type 2 DM patients. The platelet aggregation was analyzed in size of aggregates by an aggregometer using a laser scattering method. The protein phosphorylation was analyzed by Western blotting. Phosphorylated-HSP27 and PDGF-AB released from platelets were measured by ELISA. The phosphorylated-HSP27 levels at Ser-78 and Ser-82 induced by collagen were directly proportional to the platelet aggregation. Total HSP27 levels in platelets were decreased concomitantly with the phosphorylation. The released HSP27 levels were significantly correlated with the phosphorylated levels of HSP27 in the platelets stimulated by 0.3 μg/ml collagen. The low dose collagen-stimulated release of HSP27 was detected but relatively small in healthy donors. The released levels of PDGF-AB were in parallel with the levels of released HSP27. Area under the curve (AUC) of small aggregation (9-25 μm) induced by 0.3 μg/ml collagen was inversely proportional to the levels of released HSP27. AUC of large aggregation (50-70 μm) was directly proportional to the levels of released HSP27. Exogenous recombinant phosphorylated- HSP27 hardly affected the aggregation or the released levels of PDGF-AB induced by collagen. These results strongly suggest that HSP27 is released from human platelets accompanied with its phosphorylation induced by collagen, which is correlated with the acceleration of platelet aggregation in type 2 DM patients.

  15. Inhibitory effects of pine nodule extract and its component, SJ-2, on acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal medullary cells.

    PubMed

    Li, Xiaojia; Horishita, Takafumi; Toyohira, Yumiko; Shao, Hui; Bai, Jie; Bo, Haixia; Song, Xinbo; Ishikane, Shin; Yoshinaga, Yukari; Satoh, Noriaki; Tsutsui, Masato; Yanagihara, Nobuyuki

    2017-04-01

    Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3-100 μM), but not the other three, concentration-dependently inhibited catecholamine secretion induced by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003-0.005%) and SJ-2 (0.3-100 μM) also inhibited 45 Ca 2+ influx induced by acetylcholine in a concentration-dependent manner, similar to its effect on catecholamine secretion. They also suppressed 14 C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, matsufushi extract (0.00003-0.001%) and SJ-2 (1-100 μM) directly inhibited the current evoked by acetylcholine. The present findings suggest that SJ-2, as well as matsufushi extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  16. Night-rest urinary catecholamine excretion in relation to aspects of free time, work and background data in a teacher group.

    PubMed

    Kinnunen, U; Vihko, V

    1991-01-01

    Free time, work and background data were related to night-rest catecholamine excretion rates in a teacher group (n = 137) during an autumn term. The explained interindividual variance increased slightly towards the end of the term. Adrenaline excretion was predicted better than noradrenaline, notedly by coffee consumption, amount of physical activity, and subjective stress feelings which explained 16% of the variance in adrenaline excretion during night rest. However, the results indicated that the differences in catecholamine excretion during night rest remained mostly unpredictable.

  17. Differential effects of catecholamines on in vitro growth of pathogenic bacteria

    NASA Technical Reports Server (NTRS)

    Belay, Tesfaye; Sonnenfeld, Gerald

    2002-01-01

    Supplementation of minimal medium inoculated with bacterial cultures with norepinephrine, epinephrine, dopamine, or isoproterenol resulted in marked increases in growth compared to controls. Norepinephrine and dopamine had the greatest enhancing effects on growth of cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae, while epinephrine and isoproterenol also enhanced growth to a lesser extent. The growth of Escherichia coli in the presence of norepinephrine was greater than growth in the presence of the three other neurochemicals used in the study. Growth of Staphylococcus aureus was also enhanced in the presence of norepinephrine, but not to the same degree as was the growth of gram negative bacteria. Addition of culture supernatants from E. coli cultures that had been grown in the presence of norepinephrine was able to enhance the growth of K. pneumoniae. Addition of the culture supernatant fluid culture from E. coli cultures that had been grown in the presence of norepinephrine did not enhance growth of P. aeruginosa or S. aureus. Culture supernatant fluids from bacteria other than E. coli grown in the presence of norepinephrine were not able to enhance the growth of any bacteria tested. The results suggest that catecholamines can enhance growth of pathogenic bacteria, which may contribute to development of pathogenesis; however, there is no uniform effect of catecholamines on bacterial growth.

  18. Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells.

    PubMed

    Pasquali, Daniela; Rossi, Valentina; Conzo, Giovanni; Pannone, Giuseppe; Bufo, Pantaleo; De Bellis, Annamaria; Renzullo, Andrea; Bellastella, Giuseppe; Colao, Annamaria; Vallone, Gianfranco; Bellastella, Antonio; Sinisi, Antonio A

    2008-06-01

    Surgery is the primary therapy for pheochromocytoma (PHEO), a catecholamine-producing tumor. Benign and malignant PHEO could develop recurrences, and the intraoperative risk of recurrent PHEO is an important unresolved issue. Non-surgical treatments of PHEO recurrence would therefore better prepare patients for reintervention as well as provide them with palliative management. We investigated the effects of the new somatostatin analog (pasireotide) SOM230 versus octreotide (OCT) in primary PHEO cell cultures (Pheo-c). Pheo-c from six benign surgical samples were set up and characterized by immunocytochemistry. Real-time PCR, using both PHEO tissues and Pheo-c, showed different levels of somatostatin receptor(1-5) mRNA expression. Cells treated with various doses of OCT or SOM230 for 48 and 72 h were analyzed to assess their effects on cell proliferation and apoptosis and catecholamine levels. Even if reduction of cell viability was observed in Pheo-c treated for 48 h with either OCT or SOM230 and this effect increased after 72 h, a more significant inhibition of cell growth as well as a significantly higher induction of apoptosis was seen in Pheo-c treated with SOM230 versus OCT. In particular, apoptosis in Pheo-c was detected after 48 h and was associated with increased expression and activation of caspase-3 and cleaved poly(ADP-ribose) polymerase. OCT 10(-6) M and SOM230 10(-7) M significantly reduced catecholamine levels. Our results indicate that while both OCT and SOM230 modulate cell growth and apoptosis and catecholamine levels in Pheo-c through specific receptors, SOM230 is more effective. This improves our knowledge on the mechanism of SOM230 action in PHEO and supports a possible therapeutic use in benign PHEO recurrence.

  19. In Vivo Comparison of Norepinephrine and Dopamine Release in Rat Brain by Simultaneous Measurements with Fast-Scan Cyclic Voltammetry

    PubMed Central

    Park, Jinwoo; Takmakov, Pavel; Wightman, R. Mark

    2011-01-01

    Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. Here, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry (FSCV) at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle (VNB), the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra (VTA/SN), the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode FSCV technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures. PMID:21933188

  20. Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

    PubMed

    Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

    2016-01-01

    The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

  1. Dynamin and myosin regulate differential exocytosis from mouse adrenal chromaffin cells.

    PubMed

    Chan, Shyue-An; Doreian, Bryan; Smith, Corey

    2010-11-01

    Neuroendocrine chromaffin cells of the adrenal medulla represent a primary output for the sympathetic nervous system. Chromaffin cells release catecholamine as well as vaso- and neuro-active peptide transmitters into the circulation through exocytic fusion of large dense-core secretory granules. Under basal sympathetic activity, chromaffin cells selectively release modest levels of catecholamines, helping to set the "rest and digest" status of energy storage. Under stress activation, elevated sympathetic firing leads to increased catecholamine as well as peptide transmitter release to set the "fight or flight" status of energy expenditure. While the mechanism for catecholamine release has been widely investigated, relatively little is known of how peptide transmitter release is regulated to occur selectively under elevated stimulation. Recent studies have shown selective catecholamine release under basal stimulation is accomplished through a transient, restricted exocytic fusion pore between granule and plasma membrane, releasing a soluble fraction of the small, diffusible molecules. Elevated cell firing leads to the active dilation of the fusion pore, leading to the release of both catecholamine and the less diffusible peptide transmitters. Here we propose a molecular mechanism regulating the activity-dependent dilation of the fusion pore. We review the immediate literature and provide new data to formulate a working mechanistic hypothesis whereby calcium-mediated dephosphorylation of dynamin I at Ser-774 leads to the recruitment of the molecular motor myosin II to actively dilate the fusion pore to facilitate release of peptide transmitters. Thus, activity-dependent dephosphorylation of dynamin is hypothesized to represent a key molecular step in the sympatho-adrenal stress response.

  2. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure.

    PubMed

    Fargali, Samira; Garcia, Angelo L; Sadahiro, Masato; Jiang, Cheng; Janssen, William G; Lin, Wei-Jye; Cogliani, Valeria; Elste, Alice; Mortillo, Steven; Cero, Cheryl; Veitenheimer, Britta; Graiani, Gallia; Pasinetti, Giulio M; Mahata, Sushil K; Osborn, John W; Huntley, George W; Phillips, Greg R; Benson, Deanna L; Bartolomucci, Alessandro; Salton, Stephen R

    2014-05-01

    Secretion of proteins and neurotransmitters from large dense core vesicles (LDCVs) is a highly regulated process. Adrenal LDCV formation involves the granin proteins chromogranin A (CgA) and chromogranin B (CgB); CgA- and CgB-derived peptides regulate catecholamine levels and blood pressure. We investigated function of the granin VGF (nonacronymic) in LDCV formation and the regulation of catecholamine levels and blood pressure. Expression of exogenous VGF in nonendocrine NIH 3T3 fibroblasts resulted in the formation of LDCV-like structures and depolarization-induced VGF secretion. Analysis of germline VGF-knockout mouse adrenal medulla revealed decreased LDCV size in noradrenergic chromaffin cells, increased adrenal norepinephrine and epinephrine content and circulating plasma epinephrine, and decreased adrenal CgB. These neurochemical changes in VGF-knockout mice were associated with hypertension. Germline knock-in of human VGF1-615 into the mouse Vgf locus rescued the hypertensive knockout phenotype, while knock-in of a truncated human VGF1-524 that lacks several C-terminal peptides, including TLQP-21, resulted in a small but significant increase in systolic blood pressure compared to hVGF1-615 mice. Finally, acute and chronic administration of the VGF-derived peptide TLQP-21 to rodents decreased blood pressure. Our studies establish a role for VGF in adrenal LDCV formation and the regulation of catecholamine levels and blood pressure.

  3. An amplified chemiluminescence system based on Si-doped carbon dots for detection of catecholamines.

    PubMed

    Amjadi, Mohammad; Hallaj, Tooba; Manzoori, Jamshid L; Shahbazsaghir, Tahmineh

    2018-08-05

    We report on a chemiluminescence (CL) system based on simultaneous enhancing effect of Si-doped carbon dots (Si-CDs) and cetyltrimethylammonium bromide (CTAB) on HCO 3 - -H 2 O 2 reaction . The possible CL mechanism is investigated and discussed. Excited-state Si-CDs was found to be the final emitting species, which are probably produced via electron and hole injection by oxy-radicals. The effect of several other heteroatom-doped CDs and undoped CDs was also investigated and compared with Si-CDs. Furthermore, it was found that catecholamines such as dopamine, adrenaline and noradrenaline remarkably diminish the CL intensity of Si-CD-HCO 3 - -H 2 O 2 -CTAB system. By taking advantage of this fact, a sensitive probe was designed for determination of dopamine, adrenaline and noradrenaline with a limit of detection of 0.07, 0.60 and 0.01 μM, respectively. The method was applied to the determination of catecholamines in human plasma samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Evaluation and validation of a method for determining platelet catecholamine in patients with obstructive sleep apnea and arterial hypertension.

    PubMed

    Feres, Marcia C; Cintra, Fatima D; Rizzi, Camila F; Mello-Fujita, Luciane; Lino de Souza, Altay A; Tufik, Sergio; Poyares, Dalva

    2014-01-01

    Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions. In this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls. In the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension. A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05). Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.

  5. Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

    PubMed

    Gaykema, Ronald P A; Goehler, Lisa E

    2011-03-01

    Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from

  6. Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

    PubMed Central

    Gaykema, Ronald P.A.; Goehler, Lisa E.

    2010-01-01

    Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from

  7. Release of Phosphorylated HSP27 (HSPB1) from Platelets Is Accompanied with the Acceleration of Aggregation in Diabetic Patients

    PubMed Central

    Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Kojima, Akiko; Doi, Tomoaki; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Iwama, Toru; Tanikawa, Takahisa; Ishikawa, Kei; Kojima, Kumi; Kozawa, Osamu

    2015-01-01

    We investigated the relationship between HSP27 phosphorylation and collagen-stimulated activation of platelets in patients with diabetes mellitus (DM). Platelet-rich plasma was prepared from blood of type 2 DM patients. The platelet aggregation was analyzed in size of aggregates by an aggregometer using a laser scattering method. The protein phosphorylation was analyzed by Western blotting. Phosphorylated-HSP27 and PDGF-AB released from platelets were measured by ELISA. The phosphorylated-HSP27 levels at Ser-78 and Ser-82 induced by collagen were directly proportional to the platelet aggregation. Total HSP27 levels in platelets were decreased concomitantly with the phosphorylation. The released HSP27 levels were significantly correlated with the phosphorylated levels of HSP27 in the platelets stimulated by 0.3 μg/ml collagen. The low dose collagen-stimulated release of HSP27 was detected but relatively small in healthy donors. The released levels of PDGF-AB were in parallel with the levels of released HSP27. Area under the curve (AUC) of small aggregation (9-25 μm) induced by 0.3 μg/ml collagen was inversely proportional to the levels of released HSP27. AUC of large aggregation (50-70 μm) was directly proportional to the levels of released HSP27. Exogenous recombinant phosphorylated- HSP27 hardly affected the aggregation or the released levels of PDGF-AB induced by collagen. These results strongly suggest that HSP27 is released from human platelets accompanied with its phosphorylation induced by collagen, which is correlated with the acceleration of platelet aggregation in type 2 DM patients. PMID:26046355

  8. Determination of catecholamine in human serum by a fluorescent quenching method based on a water-soluble fluorescent conjugated polymer-enzyme hybrid system.

    PubMed

    Huang, Hui; Gao, Yuan; Shi, Fanping; Wang, Guannan; Shah, Syed Mazhar; Su, Xingguang

    2012-03-21

    In this paper, a sensitive water-soluble fluorescent conjugated polymer biosensor for catecholamine (dopamine DA, adrenaline AD and norepinephrine NE) was developed. In the presence of horse radish peroxidase (HRP) and H(2)O(2), catecholamine could be oxidized and the oxidation product of catecholamine could quench the photoluminescence (PL) intensity of poly(2,5-bis(3-sulfonatopropoxy)-1,4-phenylethynylenealt-1,4-poly(phenylene ethynylene)) (PPESO(3)). The quenching PL intensity of PPESO(3) (I(0)/I) was proportional to the concentration of DA, AD and NE in the concentration ranges of 5.0 × 10(-7) to 1.4 × 10(-4), 5.0 × 10(-6) to 5.0 × 10(-4), and 5.0 × 10(-6) to 5.0 × 10(-4) mol L(-1), respectively. The detection limit for DA, AD and NE was 1.4 × 10(-7) mol L(-1), 1.0 × 10(-6) and 1.0 × 10(-6) mol L(-1), respectively. The PPESO(3)-enzyme hybrid system based on the fluorescence quenching method was successfully applied for the determination of catecholamine in human serum samples with good accuracy and satisfactory recovery. The results were in good agreement with those provided by the HPLC-MS method.

  9. Modulation of key reactions of the catecholamine metabolism by extracts from Eschscholtzia californica and Corydalis cava.

    PubMed

    Kleber, E; Schneider, W; Schäfer, H L; Elstner, E F

    1995-02-01

    Aqueous-alcoholic extracts from Eschscholtzia californica inhibit the enzymatic degradation of catecholamines as well as the synthesis of adrenaline, whereas aqueous-ethanolic extracts from Corydalis cava enhance the chemical oxidation of adrenaline and the synthesis of melanine from dihydroxyphenylalanine (DOPA). Both extracts dramatically shorten the lag phase in the catalysis of phenolase probably due to their o-diphenol content, where the Corydalis extracts are 10 times more active than the Eschscholtzia preparations. Dopamine beta-hydroxylase and monoamine oxidase (MAO-B) are especially inhibited by Eschscholtzia extracts. Diamine oxidases are inhibited by both preparations to a similar extent. The results of this study may be interpreted as a cooperative function of the two preparations in establishing and preserving high catecholamine levels thus explaining their sedative, antidepressive and hypnotic activities.

  10. Monitoring the Secretory Behavior of the Rat Adrenal Medulla by High-Performance Liquid Chromatography-Based Catecholamine Assay from Slice Supernatants

    PubMed Central

    De Nardi, Frédéric; Lefort, Claudie; Bréard, Dimitri; Richomme, Pascal; Legros, Christian; Guérineau, Nathalie C.

    2017-01-01

    Catecholamine (CA) secretion from the adrenal medullary tissue is a key step of the adaptive response triggered by an organism to cope with stress. Whereas molecular and cellular secretory processes have been extensively studied at the single chromaffin cell level, data available for the whole gland level are much scarcer. We tackled this issue in rat by developing an easy to implement experimental strategy combining the adrenal acute slice supernatant collection with a high-performance liquid chromatography-based epinephrine and norepinephrine (NE) assay. This technique affords a convenient method for measuring basal and stimulated CA release from single acute slices, allowing thus to individually address the secretory function of the left and right glands. Our data point that the two glands are equally competent to secrete epinephrine and NE, exhibiting an equivalent epinephrine:NE ratio, both at rest and in response to a cholinergic stimulation. Nicotine is, however, more efficient than acetylcholine to evoke NE release. A pharmacological challenge with hexamethonium, an α3-containing nicotinic acetylcholine receptor antagonist, disclosed that epinephrine- and NE-secreting chromaffin cells distinctly expressed α3 nicotinic receptors, with a dominant contribution in NE cells. As such, beyond the novelty of CA assays from acute slice supernatants, our study contributes at refining the secretory behavior of the rat adrenal medullary tissue, and opens new perspectives for monitoring the release of other hormones and transmitters, especially those involved in the stress response. PMID:28993760

  11. Accelerated Episodic LH Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca mulatta) Exposed to Testosterone During Early-to-Mid Gestation.

    PubMed

    Abbott, David H; Vepraskas, Sarah H; Horton, Teresa H; Terasawa, Ei; Levine, Jon E

    2018-06-15

    Ovarian theca cell hyperandrogenism in women with PCOS is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic LH release. The resultant LH hypersecretion, likely the product of accelerated episodic release of GnRH from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized female monkeys (PA) exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels. This study tests the hypothesis that progesterone resistance-associated acceleration in episodic LH release contributes to PA monkey LH excess. 4 PA and 3 regularly cycling, healthy control adult female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h, frequent intravenous sampling assessment for LH episodic release, immediately followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH responsiveness, and subsequently (3) an SC injection of a progesterone receptor antagonist, mifepristone, to examine LH responses to blockade of progesterone-mediated action. Compared to controls, the relatively hyperandrogenic PA females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater increase (p = 0.034) in acute (0--10 min) LH responses to exogenous GnRH, and an absence (p = 0.008) of modest LH elevation following acute progesterone receptor blockade suggestive of diminished progesterone negative feedback. Such dysregulation of LH release in PCOS-like monkeys implicates impaired feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS neuroendocrinopathy. 2018 S. Karger AG, Basel.

  12. Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs

    PubMed Central

    Yu, Byung-Sik; Na, Duck-Mi; Kang, Mi-Young

    2009-01-01

    The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 µg/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K+ (56 mM), DMPP (100 µM) and McN-A-343 (100 µM). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 µg/ml), the CA secretory responses to veratridine (a selective Na+ channel activator (10 µM), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10 µM) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 µg/ml) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 µg/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase. PMID:20054501

  13. Modulation of the caveolin-3 localization to caveolae and STAT3 to mitochondria by catecholamine-induced cardiac hypertrophy in H9c2 cardiomyoblasts

    PubMed Central

    Jeong, Kyuho; Kwon, Hayeong; Min, Chanhee

    2009-01-01

    We investigated the effect of phenylephrine (PE)- and isoproterenol (ISO)-induced cardiac hypertrophy on subcellular localization and expression of caveolin-3 and STAT3 in H9c2 cardiomyoblast cells. Caveolin-3 localization to plasma membrane was attenuated and localization of caveolin-3 to caveolae in the plasma membrane was 24.3% reduced by the catecholamine-induced hypertrophy. STAT3 and phospho-STAT3 were up-regulated but verapamil and cyclosporin A synergistically decreased the STAT3 and phospho-STAT3 levels in PE- and ISO-induced hypertrophic cells. Both expression and activation of STAT3 were increased in the nucleus by the hypertrophy. Immunofluorescence analysis revealed that the catecholamine-induced hypertrophy promoted nuclear localization of pY705-STAT3. Of interest, phosphorylation of pS727-STAT3 in mitochondria was significantly reduced by catecholamine-induced hypertrophy. In addition, mitochondrial complexes II and III were greatly down-regulated in the hypertrophic cells. Our data suggest that the alterations in nuclear and mitochondrial activation of STAT3 and caveolae localization of caveolin-3 are related to the development of the catecholamine-induced cardiac hypertrophy. PMID:19299911

  14. Energy balance studies and plasma catecholamine values for patients with healed burns.

    PubMed

    Wallace, B H; Cone, J B; Caldwell, F T

    1991-01-01

    We report heat balance studies and plasma catecholamine values for 49 children and young adults with healed burn wounds (age range 0.6 to 31 years and burn range 1% to 82% body surface area burned; mean 41%). All measurements were made during the week of discharge. Heat production for patients with healed burns was not significantly different from predicted normal values. However, compartmented heat loss demonstrated a persistent increment in evaporative heat loss that was secondary to continued elevation of cutaneous water vapor loss immediately after wound closure. A reciprocal decrement in dry heat loss was demonstrated (as a result of a cooler average surface temperature, 0.84 degree C cooler than the average integrated skin temperature of five normal volunteers who were studied in our unit under similar environmental conditions). Mean values for plasma catecholamines were in the normal range: epinephrine = 56 +/- 37 pg/ml, norepinephrine = 385 +/- 220 pg/ml, and dopamine = 34 +/- 29 pg/ml. In conclusion, patients with freshly healed burn wounds have normal rates of heat production; however, there is a residual increment in transcutaneous water vapor loss, which produces surface cooling and decreased average surface temperature, which in turn lowers dry heat loss by an approximately equivalent amount.

  15. The Control of Responsiveness in ADHD by Catecholamines: Evidence for Dopaminergic, Noradrenergic and Interactive Roles

    ERIC Educational Resources Information Center

    Oades, Robert D.; Sadile, Adolfo G.; Sagvolden, Terje; Viggiano, Davide; Zuddas, Alessandro; Devoto, Paola; Aase, Heidi; Johansen, Espen B.; Ruocco, Lucia A.; Russell, Vivienne A.

    2005-01-01

    We explore the neurobiological bases of attention deficit hyperactivity disorder (ADHD) from the viewpoint of the neurochemistry and psychopharmacology of the catecholamine-based behavioural systems. The contributions of dopamine (DA) and noradrenaline (NA) neurotransmission to the motor and cognitive symptoms of ADHD (e.g. hyperactivity, variable…

  16. Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

    PubMed

    Nichols, Blake; Kubis, Sherri; Hewlett, Jennifer; Yehya, Nadir; Srinivasan, Vijay

    2017-09-01

    The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. Retrospective cohort study. Non-cardiac PICU. Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. None. The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 μg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 μg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 μg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 μg/dL; p = 0.69). In children with random serum total cortisol less than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In

  17. Synergy between growth factors and transmitters required for catecholamine differentiation in brain neurons.

    PubMed

    Du, X; Iacovitti, L

    1995-07-01

    The phenotypically plastic neurons of the embryonic mouse striatum were used to explore mechanisms of catecholamine differentiation in culture. De novo transcription and translation of the CA biosynthetic enzyme, tyrosine hydroxylase (TH), was induced in striatal neurons exposed, simultaneously or sequentially, to the growth factor, acidic fibroblast growth factor (aFGF) and a catecholamine. Although dopamine was the most potent aFGF partner (ED50 = 4 microM), a number of substances, including dopamine (D1) receptor agonists, beta-adrenoceptor agonists, and dopamine uptake inhibitors also trigger TH induction when accompanied by aFGF. However, since none of the receptor antagonists nor transport blockers tested could inhibit dopamine's action, the mechanism remains obscure. Structure-activity analysis suggests that effective aFGF partners all contain an amine group separated from a catechol nucleus by two carbons. Thus, TH expression can be novelly induced by the synergistic interaction of aFGF, and to a lesser extent basic FGF, and a variety of CA-containing partner molecules. We speculate that a similar association between growth factor and transmitter may be required in development for the differentiation of a CA phenotype in brain neurons.

  18. Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy.

    PubMed

    Tidholm, Anna; Häggström, Jens; Hansson, Kerstin

    2005-10-01

    To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.

  19. Subclinical Phaeochromocytoma

    PubMed Central

    Mannelli, Massimo; Lenders, Jacques W.M.; Pacak, Karel; Parenti, Gabriele; Eisenhofer, Graeme

    2012-01-01

    Phaeochromocytomas and paragangliomas are neural crest-derived tumours. Autopsy studies indicate that relatively large numbers of these tumours remain undiagnosed during life. This may reflect non-specific signs and symptoms and low medical alertness in evaluating the clinical picture or it may reflect a silent clinical presentation - the subclinical phaeochromocytoma. The associated clinical picture depends on the capacity of the tumours to release catecholamines and sometimes biologically active peptides. Hypertension is the hallmark of catecholamine release, but the amount, type and pattern of catecholamine secretion is extremely variable. Some tumours have low or intermittent secretory activity, some produce mainly or solely dopamine, while others very rarely do not synthesize or release any catecholamines (non-secretory or non-functional tumours). Such tumours may present with mild or even absent signs and symptoms of catecholamine excess. Low secretory activity may reflect small tumour size or differences in secretory phenotypes associated with the biochemical and genetic background of the tumours. Tumours due to succinate dehydrogenase subunit B mutations are often subclinical, poorly differentiated, contain low amounts of catecholamines, and are usually malignant at diagnosis. Adrenoceptor desensitization can result in a subclinical presentation, even when catecholamine levels are high. Subclinical phaeochromocytomas are often discovered as incidentalomas during radiological procedures or during routine screening for phaeochromocytoma in carriers of mutations in one of the ten currently identified tumour susceptibility genes. Undiagnosed phaeochromocytomas, whether or not subclinical and even if biologically benign, may cause extremely deleterious consequences or even death, following abrupt release of catecholamines. PMID:22863392

  20. Subclinical phaeochromocytoma.

    PubMed

    Mannelli, Massimo; Lenders, Jacques W M; Pacak, Karel; Parenti, Gabriele; Eisenhofer, Graeme

    2012-08-01

    Phaeochromocytomas and paragangliomas are neural crest-derived tumours. Autopsy studies indicate that relatively large numbers of these tumours remain undiagnosed during life. This may reflect non-specific signs and symptoms and low medical alertness in evaluating the clinical picture or it may reflect a silent clinical presentation - the subclinical phaeochromocytoma. The associated clinical picture depends on the capacity of the tumours to release catecholamines and sometimes biologically active peptides. Hypertension is the hallmark of catecholamine release, but the amount, type and pattern of catecholamine secretion is extremely variable. Some tumours have low or intermittent secretory activity, some produce mainly or solely dopamine, while others very rarely do not synthesize or release any catecholamines (non-secretory or non-functional tumours). Such tumours may present with mild or even absent signs and symptoms of catecholamine excess. Low secretory activity may reflect small tumour size or differences in secretory phenotypes associated with the biochemical and genetic background of the tumours. Tumours due to succinate dehydrogenase subunit B mutations are often subclinical, poorly differentiated, contain low amounts of catecholamines, and are usually malignant at diagnosis. Adrenoceptor desensitization can result in a subclinical presentation, even when catecholamine levels are high. Subclinical phaeochromocytomas are often discovered as incidentalomas during radiological procedures or during routine screening for phaeochromocytoma in carriers of mutations in one of the ten currently identified tumour susceptibility genes. Undiagnosed phaeochromocytomas, whether or not subclinical and even if biologically benign, may cause extremely deleterious consequences or even death, following abrupt release of catecholamines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Catecholamine-Independent Heart Rate Increases Require CaMKII

    PubMed Central

    Gao, Zhan; Singh, Madhu V; Hall, Duane D; Koval, Olha M.; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Chen, Biyi; Wu, Yuejin; Chaudhary, Ashok K; Martins, James B; Hund, Thomas J; Mohler, Peter J; Song, Long-Sheng; Anderson, Mark E.

    2011-01-01

    Background Catecholamines increase heart rate by augmenting the cAMP responsive HCN4 ‘pacemaker current’ (If) and/or by promoting inward Na+/Ca2+ exchanger current (INCX), by a ‘Ca2+ clock’ mechanism in sinoatrial nodal cells (SANCs). The importance, identity and function of signals that connect If and Ca2+ clock mechanisms are uncertain and controversial, but the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) is required for physiological heart rate responses to β-adrenergic receptor (β-AR) stimulation. The aim of this stuy is to measure the contribution of the Ca2+ clock and CaMKII to cardiac pacing independent of β-AR agonist stimulation. Methods and Results We used the L-type Ca2+ channel agonist BayK 8644 (BayK) to activate the SANC Ca2+ clock. BayK and isoproterenol were similarly effective in increasing rates in SANCs and Langendorff-perfused hearts from WT control mice. In contrast, SANCs and isolated hearts from mice with CaMKII inhibition by transgenic expression of an inhibitory peptide (AC3-I) were resistant to rate increases by BayK. BayK only activated CaMKII in control SANCs, but increased ICa equally in all SANCs, indicating that increasing ICa was insufficient and suggesting CaMKII activation was required for heart rate increases by BayK. BayK did not increase If or protein kinase A (PKA)-dependent phosphorylation of phospholamban (at Ser16), indicating that increased SANC Ca2+ by BayK did not augment cAMP/PKA signaling at these targets. Late diastolic intracellular Ca2+ release and INCX were significantly reduced in AC3-I SANCs and the response to BayK was eliminated by ryanodine in all groups. Conclusions The Ca2+ clock is capable of supporting physiological fight or flight responses, independent of β-AR stimulation or If increases. Complete Ca2+ clock and β-AR stimulation responses require CaMKII. PMID:21406683

  2. Postnatal development of EEG patterns, catecholamine contents and myelination, and effect of hyperthyroidism in Suncus brain.

    PubMed

    Takeuchi, T; Sitizyo, K; Harada, E

    1998-03-01

    The postnatal development of the central nervous system (CNS) in house musk shrew in the early stage of maturation was studied. The electroencephalogram (EEG) and visual evoked potential (VEP) in association with catecholamine contents and myelin basic protein (MBP) immunoreactivity were carried out from the 1st to the 20th day of postnatal age. Different EEG patterns which were specific to behavioral states (awake and drowsy) were first recorded on the 5th day, and the total power which was obtained by power spectrum analysis increased after this stage. The latencies of all peaks in VEP markedly shortened between the 5th and the 7th day. Noradrenalin (NA) content of the brain showed a slight increase after the 3rd day, and reached maximum levels on the 7th day, which was delayed a few days compared to dopamine (DA). In hyperthyroidism, the peak latency of VEP was shortened and biosynthesis of NA in cerebral cortex and DA in hippocampus was accelerated. The most obvious change in MBP-immunoreactivity of the telencephalon occurred from the 7th to the 10th day. These morphological changes in the brain advanced at the identical time-course to those in the electrophysiological development and increment of DA and NA contents.

  3. Excessive Catecholamine Secretion and the Activation of the Renin-Angiotensin-Aldosterone-System in Patients with Pheochromocytoma: A Single Center Experience and Overview of the Literature.

    PubMed

    Haase, Matthias; Dringenberg, Till; Allelein, Stephanie; Willenberg, Holger S; Schott, Matthias

    2017-10-01

    Catecholamines stimulate renin-secretion in the juxtaglomerular cells of the kidney and a number of case reports suggest an association between pheochromocytoma and activation of the RAAS. Therefore, it could be asked whether patients suffering from pheochromocytoma with high concentrations of circulating catecholamines present with oversecretion of renin and aldosterone. We identified twelve patients with excessive catecholamine secretion due to pheochromocytoma and compared them to a group of twelve patients with essential hypertension (EH) with regard to the activation of the renin-angiotensin-aldosterone-system (RAAS). The PubMed database was screened for studies that investigate the association between pheochromocytoma and activation of the RAAS. The plasma concentrations of metanephrines (19.9-fold) and normetanephrines (29.5-fold) were significantly higher in the pheochromocytoma group than in the EH group. Renin and aldosterone levels were 1.3-fold and 1.6-fold higher, respectively, as compared to the EH group, whereas the differences were not statistically significant. There was no significant correlation between plasma metanephrine or normetanephrine levels and the plasma renin concentration (r s =0.077, r s =0.049, respectively) in our patients. The data from our institution and from review of literature suggest that an association between pheochromocytoma in the context of high plasma catecholamine levels and activation of the RAAS is present. However, results have not been consistent. Thus, other causes of RAAS-activation should be considered also in the presence of pheochromocytoma or reinvestigation for aldosteronism should be offered to such patients after removal of the catecholamine-producing tumour. © Georg Thieme Verlag KG Stuttgart · New York.

  4. A Potential Benefit of Albinism in Astyanax Cavefish: Downregulation of the oca2 Gene Increases Tyrosine and Catecholamine Levels as an Alternative to Melanin Synthesis

    PubMed Central

    Parkhurst, Amy; Jeffery, William R.

    2013-01-01

    Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax mexicanus, which has a pigmented surface dwelling form (surface fish) and several albino cave-dwelling forms (cavefish), albinism is caused by loss of function mutations in the oca2 gene, which operates during the first step of the melanin synthesis pathway. In addition to albinism, cavefish have evolved differences in behavior, including feeding and sleep, which are under the control of the catecholamine system. The catecholamine and melanin synthesis pathways diverge after beginning with the same substrate, L-tyrosine. Here we describe a novel relationship between the catecholamine and melanin synthesis pathways in Astyanax. Our results show significant increases in L-tyrosine, dopamine, and norepinephrine in pre-feeding larvae and adult brains of Pachón cavefish relative to surface fish. In addition, norepinephrine is elevated in cavefish adult kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal cells. We further show that the oca2 gene is expressed during surface fish development but is downregulated in cavefish embryos. A key finding is that knockdown of oca2 expression in surface fish embryos delays the development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We conclude that a potential evolutionary benefit of albinism in Astyanax cavefish may be to provide surplus L-tyrosine as a precursor for the elevated catecholamine synthesis pathway, which could be important for adaptation to the challenging cave environment. PMID:24282555

  5. Caffeine accelerates recovery from general anesthesia

    PubMed Central

    Wang, Qiang; Fong, Robert; Mason, Peggy; Fox, Aaron P.

    2013-01-01

    General anesthetics inhibit neurotransmitter release from both neurons and secretory cells. If inhibition of neurotransmitter release is part of an anesthetic mechanism of action, then drugs that facilitate neurotransmitter release may aid in reversing general anesthesia. Drugs that elevate intracellular cAMP levels are known to facilitate neurotransmitter release. Three cAMP elevating drugs (forskolin, theophylline, and caffeine) were tested; all three drugs reversed the inhibition of neurotransmitter release produced by isoflurane in PC12 cells in vitro. The drugs were tested in isoflurane-anesthetized rats. Animals were injected with either saline or saline containing drug. All three drugs dramatically accelerated recovery from isoflurane anesthesia, but caffeine was most effective. None of the drugs, at the concentrations tested, had significant effects on breathing rates, O2 saturation, heart rate, or blood pressure in anesthetized animals. Caffeine alone was tested on propofol-anesthetized rats where it dramatically accelerated recovery from anesthesia. The ability of caffeine to accelerate recovery from anesthesia for different chemical classes of anesthetics, isoflurane and propofol, opens the possibility that it will do so for all commonly used general anesthetics, although additional studies will be required to determine whether this is in fact the case. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in human patients. PMID:24375022

  6. Relationship of Sleep Quantity and Quality with 24-Hour Urinary Catecholamines and Salivary Awakening Cortisol in Healthy Middle-Aged Adults

    PubMed Central

    Zhang, Jihui; Ma, Ronald C.W.; Kong, Alice P.S.; So, Wing Yee; Li, Albert M.; Lam, Sui Ping; Li, Shirley Xin; Yu, Mandy W.M.; Ho, Chung Shun; Chan, Michael H.M.; Zhang, Bin; Wing, Yun Kwok

    2011-01-01

    Objectives: a. Explore the stability in sleep/wake patterns of middle-aged adults over a 3-year follow-up period. b. Explore the relationship between objectively measured sleep indices, urinary catecholamines, and salivary cortisol. Design: Naturalistic follow-up for sleep/wake patterns (n = 114) by 2-week sleep log and cross-sectional design for objective sleep assessments and hormonal measures (n = 96) at follow-up period nearly 3 years after baseline measurements. Setting: Community Participants: Healthy middle-aged adults Interventions: N/A Measurements and Results: There were high correlations between baseline and follow-up period (2.6 ± 0.5 years) on sleep/wake patterns (r = 0.6–0.79) as measured by 2-week sleep log. For wave 2 cross-sectional study, objective poor sleepers (3-day actigraphy sleep efficiency < 85%) had a higher 24-h urinary norepinephrine (NE) level (205.7 ± 105 nmol/d vs 162.1 ± 55.6 nmol/d, P = 0.03) and a nearly significantly higher 24-h urinary epinephrine (E) level (P = 0.12) than good sleepers. There were no differences in 3-day mean salivary awakening cortisol and 24-h urinary catecholamines (NE and E) between short and normal/long sleepers. Linear regression results, however, showed that shorter time in bed and actual sleep time, longer sleep onset latency, and lower sleep efficiency were correlated with higher 24-h urinary E and NE (all P < 0.05) but not salivary cortisol. The effect of poor sleep quality on 24-h urinary catecholamines was stronger in males than females. Conclusions: Increased sympathetic activity as measured by 24-h urinary catecholamines might play a critical role in the pathogenesis mediating the relationship of insufficient sleep (quantity and quality) with subsequent cardiovascular and metabolic complications. Salivary awakening cortisol was not associated with sleep quantity and quality in healthy middle-aged adults. Citation: Zhang J; Ma RCW; Kong APS; So WY; Li AM; Lam SP; Li SX; Yu MWM; Ho CS; Chan MHM

  7. Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

    NASA Technical Reports Server (NTRS)

    Aviles, Hernan; Belay, Tesfaye; Vance, Monique; Sonnenfeld, Gerald

    2005-01-01

    The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

  8. Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

    PubMed

    Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

    2014-07-01

    Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine. Copyright © 2014. Published by Elsevier B.V.

  9. The choice of catecholamines in septic shock: more and more good arguments to strengthen the known position, but don't lose the faith!

    PubMed

    Meier-Hellmann, Andreas

    2006-01-01

    The choice of catecholamines for hemodynamic stabilisation in septic shock patients has been an ongoing debate for several years. Several studies have investigated the regional effects in septic patients. Because of an often very small sample size, because of inconsistent results and because of methodical problems in the monitoring techniques used in these studies, however, it is not possible to provide clear recommendations concerning the use of catecholamines in sepsis. Prospective and adequate-sized studies are necessary because outcome data are completely lacking.

  10. Probing the magnetosphere using chemical releases from the Combined Release and Radiation Effects Satellite

    NASA Technical Reports Server (NTRS)

    Bernhardt, P. A.

    1992-01-01

    An overview is presented of the chemical release experiments from NASA's Combined Release and Radiation Effects Satellite (CRRES) program. Preliminary results are given for the CRRES investigations of (1) stimulated electron and ion precipitation, (2) ion transport in the magnetotail, (3) critical ionization velocity, (4) field line tracing and parallel acceleration, (5) diamagnetic cavity formation and collapse, and (6) plasma instabilities. The chemical vapor properties from a thermite release mechanism are also briefly described.

  11. No Elevated Plasma Catecholamine Levels during Sleep in Newly Diagnosed, Untreated Hypertensives

    PubMed Central

    Rasch, Björn; Dodt, Christoph; Sayk, Friedhelm; Mölle, Matthias; Born, Jan

    2011-01-01

    The sympatho-adrenergic system is highly involved in regulating sleep, wake and arousal states, and abnormalities in this system are regarded as a key factor in the development and progression of arterial hypertension. While hypertension is associated with a hyperadrenergic state during wakefulness, the effect of hypertension on plasma-catecholamine levels during sleep is not yet known. Twelve young participants with newly diagnosed, untreated hypertension and twelve healthy controls slept for 7 hours in the sleep laboratory. Before and after sleep, subjects rested in a supine position for 3-h periods of wakefulness. We sampled blood at a fast rate (1/10 min) and monitored blood pressure and heart rate continuously. We show that plasma NE and E levels did not differ between hypertensives and normotensive during sleep as well as before and after sleep. Blood pressure was higher in hypertensives, reaching the largest group difference in the morning after sleep. Unlike in the normotensives, in the hypertensive participants the morning rise in blood pressure did not correlate with the rise in catecholamine levels at awakening. Our results suggest that hypertension in its early stages is not associated with a strong hyperadrenergic state during sleep. In showing a diminished control of blood pressure through sympatho-adrenergic signals in hypertensive participants, our data point towards a possible involvement of dysfunctional sleep-related blood pressure regulation in the development of hypertension. PMID:21695061

  12. Testing the accelerating moment release (AMR) hypothesis in areas of high stress

    NASA Astrophysics Data System (ADS)

    Guilhem, Aurélie; Bürgmann, Roland; Freed, Andrew M.; Ali, Syed Tabrez

    2013-11-01

    Several retrospective analyses have proposed that significant increases in moment release occurred prior to many large earthquakes of recent times. However, the finding of accelerating moment release (AMR) strongly depends on the choice of three parameters: (1) magnitude range, (2) area being considered surrounding the events and (3) the time period prior to the large earthquakes. Consequently, the AMR analysis has been criticized as being a posteriori data-fitting exercise with no new predictive power. As AMR has been hypothesized to relate to changes in the state of stress around the eventual epicentre, we compare here AMR results to models of stress accumulation in California. Instead of assuming a complete stress drop on all surrounding fault segments implied by a back-slip stress lobe method, we consider that stress evolves dynamically, punctuated by the occurrence of earthquakes, and governed by the elastic and viscous properties of the lithosphere. We study the seismicity of southern California and extract events for AMR calculations following the systematic approach employed in previous studies. We present several sensitivity tests of the method, as well as grid-search analyses over the region between 1955 and 2005 using fixed magnitude range, radius of the search area and period of time. The results are compared to the occurrence of large events and to maps of Coulomb stress changes. The Coulomb stress maps are compiled using the coseismic stress from all M > 7.0 earthquakes since 1812, their subsequent post-seismic relaxation, and the interseismic strain accumulation. We find no convincing correlation of seismicity rate changes in recent decades with areas of high stress that would support the AMR hypothesis. Furthermore, this indicates limited utility for practical earthquake hazard analysis in southern California, and possibly other regions.

  13. A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites.

    PubMed

    Xie, Li; Chen, Liqin; Gu, Pan; Wei, Lanlan; Kang, Xuejun

    2018-03-01

    The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and related diseases, but their precise measurement is still a challenge. Many protocols have been described for neurotransmitter measurement by a variety of instruments, including high-pressure liquid chromatography (HPLC). However, there are shortcomings, such as complicated operation or hard-to-detect multiple targets, which cannot be avoided, and presently, the dominant analysis technique is still HPLC coupled with sensitive electrochemical or fluorimetric detection, due to its high sensitivity and good selectivity. Here, a detailed protocol is described for the pretreatment and detection of catecholamines with high pressure liquid chromatography with electrochemical detection (HPLC-ECD) in real urine samples of infants, using electrospun composite nanofibers composed of polymeric crown ether with polystyrene as adsorbent, also known as the packed-fiber solid phase extraction (PFSPE) method. We show how urine samples can be easily precleaned by a nanofiber-packed solid phase column, and how the analytes in the sample can be rapidly enriched, desorbed, and detected on an ECD system. PFSPE greatly simplifies the pretreatment procedures for biological samples, allowing for decreased time, expense, and reduction of the loss of targets. Overall, this work illustrates a simple and convenient protocol for solid-phase extraction coupled to an HPLC-ECD system for simultaneous determination of three monoamine neurotransmitters (norepinephrine (NE), epinephrine (E), dopamine (DA)) and two of their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC)) in infants' urine. The established protocol was applied to assess the differences of urinary catecholamines and their metabolites between high-risk infants with perinatal brain damage and healthy controls. Comparative analysis revealed a

  14. Stress response of wild bottlenose dolphins (Tursiops truncatus) during capture-release health assessment studies.

    PubMed

    Fair, Patricia A; Schaefer, Adam M; Romano, Tracy A; Bossart, Gregory D; Lamb, Stephen V; Reif, John S

    2014-09-15

    There is a growing concern about the impacts of stress in marine mammals as they face a greater array of threats. The stress response of free-ranging dolphins (Tursiops truncatus) was examined by measuring their physiologic response to capture and handling. Samples were collected from 168 dolphins during capture-release health assessments 2003-2007 at two study sites: Charleston, SC (CHS) and the Indian River Lagoon, FL (IRL). Adrenocorticotropic hormone (ACTH), cortisol, aldosterone (ALD) and catecholamines (epinephrine (EPI), norepinephrine (NOR), dopamine (DA)), were measured in blood and cortisol in urine. Mean time to collect pre-examination samples after netting the animals was 22min; post-examination samples were taken prior to release (mean 1h 37min). EPI and DA concentrations decreased significantly with increased time to blood sampling. ACTH and cortisol levels increased from the initial capture event to the post-examination sample. EPI concentrations increased significantly with increasing time to the pre-examination sample and decreased significantly with time between the pre- and post-examination sample. Cortisol concentrations increased between the pre- and post-examination in CHS dolphins. Age- and sex-adjusted mean pre-examination values of catecholamines were significantly higher in CHS dolphins; ALD was higher in IRL dolphins. Significant differences related to age or sex included higher NOR concentrations in males; higher ALD and urine cortisol levels in juveniles than adults. Wild dolphins exhibited a typical mammalian response to acute stress of capture and restraint. Further studies that relate hormone levels to biological and health endpoints are warranted. Published by Elsevier Inc.

  15. Acetylcholine release from the rabbit isolated superior cervical ganglion preparation.

    PubMed

    Dawes, P M; Vizi, E S

    1973-06-01

    1. The rabbit isolated superior cervical ganglion preparation has been used to measure the release of acetylcholine from the tissue at rest and during preganglionic nerve stimulation.2. In the presence of physostigmine, the resting release of acetylcholine was 0.13 +/- 0.01 (nmol/g)/min (10 experiments) and that during stimulation with 300 shocks at 10 Hz was 3.1 +/- 0.4 (pmol/g)/volley in 4 experiments (means +/- S.E.M.). The volley output was independent of the frequency of stimulation over the range 1 to 10 Hz but was higher at 0.3 Hz.3. Tetrodotoxin, 0.8 muM, had no effect on the resting release of acetylcholine but reduced the stimulated release below detectable levels (2 pmol). Lowering the temperature of the bathing fluid to 5 degrees C reduced to below detectable levels both the resting release and that produced by nerve stimulation.4. The resting release of acetylcholine was increased by a potassium-rich (49.4 mM K(+)) bathing solution and by replacing the sodium chloride in the solution with lithium chloride (113 mM Li(+)).5. (-)-Noradrenaline bitartrate, 3 muM, and (+/-)-adrenaline bitartrate, 1.5 muM, reduced by 70% the output of acetylcholine induced by stimulation at 0.3 Hz, but failed to reduce the resting release or that evoked by stimulation at 10 Hz. The inhibition was reversed by phentolamine.6. It is concluded that the rabbit superior cervical ganglion in vitro is a suitable preparation for studying transmitter release and that the ganglion blocking effect of catecholamines is due to a reduction in transmitter release.

  16. Price To Be Paid for Two-Metal Catalysis: Magnesium Ions That Accelerate Chemistry Unavoidably Limit Product Release from a Protein Kinase

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

    Jacobsen, Douglas M.; Bao, Zhao-Qin; O'’Brien, Patrick

    Incorporation of divalent metal ions into an active site is a fundamental catalytic tool used by diverse enzymes. Divalent cations are used by protein kinases to both stabilize ATP binding and accelerate chemistry. Kinetic analysis establishes that Cyclin-dependent kinase 2 (CDK2) requires simultaneous binding of two Mg 2+ ions for catalysis of phosphoryl transfer. This tool, however, comes with a price: the rate-acceleration effects are opposed by an unavoidable rate-limiting consequence of the use of two Mg 2+ ions by CDK2. The essential metal ions stabilize ADP product binding and limit the overall rate of the reaction. We demonstrate thatmore » product release is rate limiting for activated CDK2 and evaluate the effects of the two catalytically essential Mg 2+ ions on the stability of the ADP product within the active site. We present two new crystal structures of CDK2 bound to ADP showing how the phosphate groups can be coordinated by either one or two Mg 2+ ions, with the occupancy of one site in a weaker equilibrium. Molecular dynamics simulations indicate that ADP phosphate mobility is more restricted when ADP is coordinated by two Mg 2+ ions compared to one. The structural similarity between the rigid ADP·2Mg product and the cooperatively assembled transition state provides a mechanistic rational for the rate-limiting ADP release that is observed. We demonstrate that although the simultaneous binding of two Mg 2+ ions is essential for efficient phosphoryl transfer, the presence of both Mg 2+ ions in the active site also cooperatively increases ADP affinity and opposes its release. Evolution of protein kinases must have involved careful tuning of the affinity for the second Mg 2+ ion in order to balance the needs to stabilize the chemical transition state and allow timely product release. The link between Mg 2+ site affinity and activity presents a chemical handle that may be used by regulatory factors as well as explain some mutational effects.« less

  17. Types of aggressiveness and catecholamine response in essential hypertensives and healthy controls.

    PubMed

    Netter, P; Neuhäuser-Metternich, S

    1991-01-01

    Relationships between plasma catecholamine responses, and levels and types of aggression in hyper- and normotensives were investigated by analyses of data obtained in a large psychophysiological experiment on 97 hypertensives (EH) and 98 normotensives (CO) each. Subjects were divided according to levels (high vs low) and types (repressed vs manifest) of aggressiveness according to self rating questionnaire scores. Their plasma catecholamine responses to defined stressors indicating sympathetic arousability were compared by four factor analyses of covariance adjusting for age. Repressed aggression was significantly more frequent among male EH, whereas manifest aggression was significantly more frequent among the male COs. High as compared to low hostility was associated with significantly elevated values of plasma epinephrine in EH but not in CO. The immediate norepinephrine stress response was blunted but showed a delayed increase during the subsequent period of rest in high aggressives of both the EH and CO group, a pattern particularly pronounced in repressed aggressive hypertensives. Neither cardiovascular reactions nor speed of performance were observed to be substantially different in subjects of repressed and of manifest hostility. It was concluded that aggression in general is characterized by a delayed norepinephrine stress response and that an association with high epinephrine is typical for aggressiveness in hypertensives. Repressed hostility, however, does not produce a sympathomedullary pattern substantially different from that of manifest aggression thus casting doubt on the physiological significance of repression claimed by Alexander.

  18. The role of prefrontal catecholamines in attention and working memory

    PubMed Central

    Clark, Kelsey L.; Noudoost, Behrad

    2014-01-01

    While much progress has been made in identifying the brain regions and neurochemical systems involved in the cognitive processes disrupted in mental illnesses, to date, the level of detail at which neurobiologists can describe the chain of events giving rise to cognitive functions is very rudimentary. Much of the intense interest in understanding cognitive functions is motivated by the hope that it might be possible to understand these complex functions at the level of neurons and neural circuits. Here, we review the current state of the literature regarding how modulations in catecholamine levels within the prefrontal cortex (PFC) alter the neuronal and behavioral correlates of cognitive functions, particularly attention and working memory. PMID:24782714

  19. Structural and functional analysis of a FeoB A143S G5 loop mutant explains the accelerated GDP release rate.

    PubMed

    Guilfoyle, Amy P; Deshpande, Chandrika N; Vincent, Kimberley; Pedroso, Marcelo M; Schenk, Gerhard; Maher, Megan J; Jormakka, Mika

    2014-05-01

    GTPases (G proteins) hydrolyze the conversion of GTP to GDP and free phosphate, comprising an integral part of prokaryotic and eukaryotic signaling, protein biosynthesis and cell division, as well as membrane transport processes. The G protein cycle is brought to a halt after GTP hydrolysis, and requires the release of GDP before a new cycle can be initiated. For eukaryotic heterotrimeric Gαβγ proteins, the interaction with a membrane-bound G protein-coupled receptor catalyzes the release of GDP from the Gα subunit. Structural and functional studies have implicated one of the nucleotide binding sequence motifs, the G5 motif, as playing an integral part in this release mechanism. Indeed, a Gαs G5 mutant (A366S) was shown to have an accelerated GDP release rate, mimicking a G protein-coupled receptor catalyzed release state. In the present study, we investigate the role of the equivalent residue in the G5 motif (residue A143) in the prokaryotic membrane protein FeoB from Streptococcus thermophilus, which includes an N-terminal soluble G protein domain. The structure of this domain has previously been determined in the apo and GDP-bound states and in the presence of a transition state analogue, revealing conformational changes in the G5 motif. The A143 residue was mutated to a serine and analyzed with respect to changes in GTPase activity, nucleotide release rate, GDP affinity and structural alterations. We conclude that the identity of the residue at this position in the G5 loop plays a key role in the nucleotide release rate by allowing the correct positioning and hydrogen bonding of the nucleotide base. © 2014 FEBS.

  20. Acetylcholine release from the rabbit isolated superior cervical ganglion preparation

    PubMed Central

    Dawes, P. M.; Vizi, E. S.

    1973-01-01

    1. The rabbit isolated superior cervical ganglion preparation has been used to measure the release of acetylcholine from the tissue at rest and during preganglionic nerve stimulation. 2. In the presence of physostigmine, the resting release of acetylcholine was 0·13 ± 0·01 (nmol/g)/min (10 experiments) and that during stimulation with 300 shocks at 10 Hz was 3·1 ± 0·4 (pmol/g)/volley in 4 experiments (means ± S.E.M.). The volley output was independent of the frequency of stimulation over the range 1 to 10 Hz but was higher at 0·3 Hz. 3. Tetrodotoxin, 0·8 μM, had no effect on the resting release of acetylcholine but reduced the stimulated release below detectable levels (2 pmol). Lowering the temperature of the bathing fluid to 5° C reduced to below detectable levels both the resting release and that produced by nerve stimulation. 4. The resting release of acetylcholine was increased by a potassium-rich (49·4 mM K+) bathing solution and by replacing the sodium chloride in the solution with lithium chloride (113 mM Li+). 5. (-)-Noradrenaline bitartrate, 3 μM, and (±)-adrenaline bitartrate, 1·5 μM, reduced by 70% the output of acetylcholine induced by stimulation at 0·3 Hz, but failed to reduce the resting release or that evoked by stimulation at 10 Hz. The inhibition was reversed by phentolamine. 6. It is concluded that the rabbit superior cervical ganglion in vitro is a suitable preparation for studying transmitter release and that the ganglion blocking effect of catecholamines is due to a reduction in transmitter release. PMID:4733726

  1. Critical study of common conditions of storage of glucocorticoids and catecholamines in 24-h urine collected during resting and exercising conditions.

    PubMed

    Gouarne, C; Foury, A; Duclos, M

    2004-10-01

    Except immediate freezing of the samples, no practical method has been validated for preservation of glucocorticoids and catecholamines in 24-h urine collection. Furthermore, the influence of urine storage at bladder temperature during periods of different lengths and the effect of prior exercise on preservation of these hormones in the bladder have not been investigated until now. Ten healthy volunteers collected their urine both after a resting and after an exercise session. Urine was aliquoted into tubes which were stored during 24 h in the presence or in the absence of preservatives and at different temperatures. Two samples were stored either 3 or 9 h at 37 degrees C (bladder temperature) without additive. When collecting 24-h urine samples for glucocorticoids determination, sample can be stored at room temperature during the 24-h collection period without compromising glucocorticoids preservation. When collecting 24-h urine samples for catecholamines determination, samples have to be chilled without preservative during the whole of the collection period. If the samples have to be stored at room temperature, HCl should be used. Moreover, we report for the first time that catecholamines can be degraded in the bladder and therefore that subjects should urinate every 3 h during either a resting or an exercising day.

  2. Release Accelerates Growth of Yellow-Poplar -- an 18-Year Look

    Treesearch

    Robert D. Williams

    1976-01-01

    Yellow-poplar seedlings that germinated and were completely released from woody competition in 1957 (the first year after a harvest cut) were four times taller and five times larger in diameter after the 1973 growing season than seedlings that were not released.

  3. EGR-1 Expression in Catecholamine-synthesizing Neurons Reflects Auditory Learning and Correlates with Responses in Auditory Processing Areas.

    PubMed

    Dai, Jennifer B; Chen, Yining; Sakata, Jon T

    2018-05-21

    Distinguishing between familiar and unfamiliar individuals is an important task that shapes the expression of social behavior. As such, identifying the neural populations involved in processing and learning the sensory attributes of individuals is important for understanding mechanisms of behavior. Catecholamine-synthesizing neurons have been implicated in sensory processing, but relatively little is known about their contribution to auditory learning and processing across various vertebrate taxa. Here we investigated the extent to which immediate early gene expression in catecholaminergic circuitry reflects information about the familiarity of social signals and predicts immediate early gene expression in sensory processing areas in songbirds. We found that male zebra finches readily learned to differentiate between familiar and unfamiliar acoustic signals ('songs') and that playback of familiar songs led to fewer catecholaminergic neurons in the locus coeruleus (but not in the ventral tegmental area, substantia nigra, or periaqueductal gray) expressing the immediate early gene, EGR-1, than playback of unfamiliar songs. The pattern of EGR-1 expression in the locus coeruleus was similar to that observed in two auditory processing areas implicated in auditory learning and memory, namely the caudomedial nidopallium (NCM) and the caudal medial mesopallium (CMM), suggesting a contribution of catecholamines to sensory processing. Consistent with this, the pattern of catecholaminergic innervation onto auditory neurons co-varied with the degree to which song playback affected the relative intensity of EGR-1 expression. Together, our data support the contention that catecholamines like norepinephrine contribute to social recognition and the processing of social information. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Changes of catecholamine excretion during long-duration confinement.

    PubMed

    Kraft, N; Inoue, N; Ohshima, H; Sekiguchi, C

    2002-06-01

    Simulation studies have become the main source of data about small group interactions during prolonged isolation, from which it should be possible to anticipate crew problems during actual space missions. International Space Station (ISS) astronauts and cosmonauts will form one international crew, although living in different national modules. They will have joint flight protocols, and at the same time, fulfill a number of different tasks in accord with their national flight programs. Consistent with these concepts, we studied two simultaneously functioning groups in a simulation of ISS flight. The objective of this study was to investigate physiological parameters (such as catecholamine excretions) related to long-duration confinement in the hermetic chamber, simulating International Space Station flight conditions. We also planned to evaluate the relationship between epinephrine/norepinephrine with group dynamics and social events to predict unfavorable changes in health and work capability of the subjects related to psychological interaction in the isolation chamber.

  5. Clozapine response and plasma catecholamines and their metabolites.

    PubMed

    Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J

    1993-02-01

    The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.

  6. Urban commuting: crowdedness and catecholamine excretion.

    PubMed

    Lundberg, U

    1976-09-01

    Male passengers regularly commuting by train on the Stockholm-Nynäshamn line were investigated on two morning trips to Stockholm. These trips were made under different levels of crowding, before (Trip 1) and after (Trip 2) a period of gas rationing during the oil crisis in 1974. However, seats were available for almost everyone during both trips. One group of subjects boarded the train at its first stop (Nynäshamn), the other midway on its route (Västerhaninge). Physiological reactions were assessed from the rate of catecholamine excretion in urine and subjective experiences were measured by self-ratings. The results showed that feelings of discomfort grew more intense as the train approached Stockholm and the number of passengers increased. Perceived crowdedness increased as the square of the number of passengers. During both trips the subjects from Nynäshamn (longer trip) had a lower rate of adrenaline and noradrenaline excretion on the train than those from Västerhaninge. Furthermore, it was found that the rate of adrenaline excretion was higher for both groups during Trip 2, when the train was more crowded. The results support previous findings indicating that the stress involved in travelling by train varies more with the social and ecological conditions of the trip than with its length or duration.

  7. Experimental Evidence of Accelerated Seismic Release without Critical Failure in Acoustic Emissions of Compressed Nanoporous Materials

    NASA Astrophysics Data System (ADS)

    Baró, Jordi; Dahmen, Karin A.; Davidsen, Jörn; Planes, Antoni; Castillo, Pedro O.; Nataf, Guillaume F.; Salje, Ekhard K. H.; Vives, Eduard

    2018-06-01

    The total energy of acoustic emission (AE) events in externally stressed materials diverges when approaching macroscopic failure. Numerical and conceptual models explain this accelerated seismic release (ASR) as the approach to a critical point that coincides with ultimate failure. Here, we report ASR during soft uniaxial compression of three silica-based (SiO2 ) nanoporous materials. Instead of a singular critical point, the distribution of AE energies is stationary, and variations in the activity rate are sufficient to explain the presence of multiple periods of ASR leading to distinct brittle failure events. We propose that critical failure is suppressed in the AE statistics by mechanisms of transient hardening. Some of the critical exponents estimated from the experiments are compatible with mean field models, while others are still open to interpretation in terms of the solution of frictional and fracture avalanche models.

  8. Inhibition of radioemesis by disruption of catecholamines in dogs

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

    Luthra, Y.K.; Mattsson, J.L.; Yochmowitz, M.G.

    1981-03-01

    Dogs were treated 30 min to 1 h before x irradiation with ..cap alpha..-methyl-p-tyrosine or 6-hydroxydopamine. A third group of dogs was given a known antiradioemetic drug, haloperidol to verify the sensitivity of the procedure. Irradiated but untreated controls were also used. Light methoxyflurane anesthesia was used for restraint during the exposure. Exposure dose was 800 rad kerma delivered at 50 rad/min to a 10 x 10-cm area covering the abdominal area from xiphoid to pubis. Haloperidol and 6-hydroxydopamine significantly reduced the number of emetic episodes and delayed the onset time to the first episode, ..cap alpha..-Methyl-p-tyrosine caused no significantmore » changes. The effectiveness of 6-hydroxydopamine indicates that catecholaminergic neurons are involved in radioemesis, whereas haloperidol and phenothiazine-derivative tranquilizers inhibit radiomesis by blocking catecholamine receptor neurons.« less

  9. Accelerated Seismic Release and Related Aspects of Seismicity Patterns on Earthquake Faults

    NASA Astrophysics Data System (ADS)

    Ben-Zion, Y.; Lyakhovsky, V.

    2001-05-01

    Observational studies indicate that large earthquakes are sometimes preceded by phases of accelerated seismic release (ASR) characterized by cumulative Benioff strain following a power law time-to-failure relation with a term (tf - t)m, where tf is the failure time of the large event and observed values of m are close to 0.3. We discuss properties of ASR and related aspects of seismicity patterns associated with several theoretical frameworks, with a focus on models of heterogeneous faults in continuum solids. Using stress and earthquake histories simulated by the model of Ben-Zion (1996) for a discrete fault with quenched heterogeneities in a 3D elastic half space, we show that large model earthquakes are associated with non-repeating cyclical establishment and destruction of long-range stress correlations, accompanied by non-stationary cumulative Benioff strain release. We then analyze results associated with a regional lithospheric model consisting of a seismogenic upper crust governed by the damage rheology of Lyakhovsky et al. (1997) over a viscoelastic substrate. We demonstrate analytically for a simplified 1D case that the employed damage rheology leads to a singular power law equation for strain proportional to (tf - t)-1/3, and a non-singular power law relation for cumulative Benioff strain proportional to (tf - t)1/3. A simple approximate generalization of the latter for regional cumulative Benioff strain is obtained by adding to the result a linear function of time representing a stationary background release. To go beyond the analytical expectations, we examine results generated by various realizations of the regional lithospheric model producing seismicity following the characteristic frequency-size statistics, Gutenberg-Richter power law distribution, and mode switching activity. We find that phases of ASR exist only when the seismicity preceding a given large event has broad frequency-size statistics. In such cases the simulated ASR phases can be

  10. Effect of Leu-enkephalin and delta sleep inducing peptide (DSIP) on endogenous noradrenaline release by rat brain synaptosomes

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

    Lozhanets, V.V.; Anosov, A.K.

    1986-01-01

    The nonapeptide delta-sleep inducing peptide (DSIP) causes specific changes in the encephalogram of recipient animals: It prolongs the phase of long-wave or delta sleep. The cellular mechanism of action of DSIP has not yet been explained. To test the hyporhesis that this peptide or its degradation product may be presynaptic regulators of catecholamine release, the action of Leu-enkephaline, DSIP, and amino acids composing DSIP on release of endogenous noradrenalin (NA) from synaptosomes during depolarization was compared. Subcellular fractions from cerebral hemisphere of noninbred male albino rats were isolated. Lactate dehydrogenase activity was determined in the suspension of synaptosomes before andmore » after addition of 0.5% Triton X-100. The results were subjected to statistical analysis, using the Wilcoxon-Mann-Whitney nonparametric test.« less

  11. [Premature immunosenescence in catecholamines syntesis deficient mice. Effect of social environment].

    PubMed

    Garrido, Antonio; Cruces, Julia; Iriarte, Idoia; Hernández-Sánchez, Catalina; de Pablo, Flora; de la Fuente, Mónica

    Healthy state depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune systems) and the correct communication between them. The functional and redox state of the immune system is an excellent marker of health, and animals with premature immunosenescence show a shorter lifespan. Since catecholamines modulate the function of immune cells, the alteration in their synthesis could provoke immunosenescence. The social environment could be a strategy for modulating this immunosenescence. To determine if an haploinsufficiency of tyrosine hydroxylase (TH), the limiting enzyme of synthesis of catecholamines, may produce a premature immunosenescence and if this immunosenescence could be modulated by the social environment. Adult (9±1 months) male ICR-CD1 mice with deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase enzyme (TH-HZ) and wild-type (WT) mice were used. Animals were housed in four subgroups: WT>50% (in the cage, the proportion of WT mice was higher than 50% in relation to TH-HZ), WT<50%, TH-HZ<50% and TH-HZ>50%. Peritoneal leukocytes were collected and phagocytosis, chemotaxis and proliferation of lymphocytes in the presence of lipopolysaccharide were analyzed. Glutathione reductase and glutathione peroxidase activities as well as oxidized/reduced glutathione ratio were studied. TH-HZ>50% mice showed a deteriorated function and redox state in leukocytes respect to WT>50% and similar to old mice. However, TH-HZ<50% animals had similar values to those found in WT<50% mice. The haploinsufficiency of TH generates premature immunosenescence, which appears to be compensated by living together with an appropriate number of WT animals. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Transient ischemia reduces norepinephrine release during sustained ischemia. Neural preconditioning in isolated rat heart.

    PubMed

    Seyfarth, M; Richardt, G; Mizsnyak, A; Kurz, T; Schömig, A

    1996-04-01

    Endogenous catecholamine release may play a role in ischemic preconditioning either as a trigger or as a target within the process of myocardial preconditioning. Therefore, we investigated the effect of transient ischemia (TI) on norepinephrine release during sustained ischemia in isolated rat hearts. TI was induced by multiple cycles of global ischemia followed by reperfusion with a duration of 5 minutes each, comparable to ischemic preconditioning protocols. After TI, norepinephrine release was evoked by either sustained global ischemia, anoxia, cyanide intoxication, tyramine, or electrical stimulation. During TI, no washout of norepinephrine was observed, and tissue concentrations of norepinephrine were not changed. TI, however, reduced norepinephrine overflow after 20 minutes of sustained ischemia from 239 +/- 26 pmol/g (control) to 79+/-8 pmol/g (67% reduction, P <.01 ). A similar reduction of ischemia-induced norepinephrine release from 192 +/- 22 pmol/g (control) to 90 +/- 15 pmol/g was observed when hearts underwent transient anoxia without glucose (P < .05). When reperfusion between TI and sustained ischemia was prolonged from 5 to 90 minutes, the inhibitory effect of TI on norepinephrine release was gradually lost. Susceptibility to TI was a unique feature of norepinephrine release induced by sustained ischemia, since release of norepinephrine evoked by anoxia, cyanide intoxication, tyramine, or electrical stimulation remained unaffected by TI. We propose a protective effect of TI on neural tissue, which may reduce norepinephrine-induced damage during prolonged myocardial ischemia.

  13. Disruption of the Axonal Trafficking of Tyrosine Hydroxylase mRNA Impairs Catecholamine Biosynthesis in the Axons of Sympathetic Neurons.

    PubMed

    Aschrafi, Armaz; Gioio, Anthony E; Dong, Lijin; Kaplan, Barry B

    2017-01-01

    Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3'untranslated region (3'UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal. Toward this end, a targeted deletion of the axonal transport sequence element was developed, using the lentiviral delivery of the CRISPR/Cas9 system, and two guide RNA (gRNA) sequences flanking the 50-bp cis- acting regulatory element in rat superior cervical ganglion (SCG) neurons. Deletion of the axonal transport element reduced TH mRNA levels in the distal axons and reduced the axonal protein levels of TH and TH activity as measured by phosphorylation of SER40 in SCG neurons. Moreover, deletion of the zip-code diminished the axonal levels of dopamine (DA) and norepinephrine (NE). Conversely, the local translation of exogenous TH mRNA in the distal axon enhanced TH levels and activity, and elevated axonal NE levels. Taken together, these results provide direct evidence to support the hypothesis that TH mRNA trafficking and local synthesis of TH play an important role in the synthesis of catecholamines in the axon and presynaptic terminal.

  14. [Catecholamines and their metabolites in children with Asperger and Kanner syndromes].

    PubMed

    Gorina, A S; Kolesnichenko, L S; Mikhnovich, V I

    2011-01-01

    Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

  15. Effects of water immersion on plasma catecholamines in normal humans

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Johnson, G.; Denunzio, A. G.

    1983-01-01

    An investigation was conducted in order to determine whether water immersion to the neck (NI) alters plasma catecholamines in normal humans. Eight normal subjects were studied during a seated control study (C) and during 4 hr of NI, and the levels of norepinephrine (NE) and epinephrine (E) as determined by radioenzymatic assay were measured hourly. Results show that despite the induction of a marked natriuresis and diuresis indicating significant central hypervolemia, NI failed to alter plasma NE or E levels compared with those of either C or the corresponding prestudy 1.5 hr. In addition, the diuresis and natriuresis was found to vary independently of NE. These results indicate that the response of the sympathetic nervous system to acute volume alteration may differ from the reported response to chronic volume expansion.

  16. Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer.

    PubMed

    James, P; Rivier, C; Lee, S

    2008-02-01

    Our laboratory has shown that male testosterone levels are not solely controlled by the release of hypothalamic gonadotrophin-releasing hormone and pituitary luteinising hormone, but are also regulated by a multisynaptic pathway connecting the brain and the testis that interferes with the testosterone response to gonadotrophins. This pathway, which is independent of the pituitary gland, is activated by an i.c.v. injection of either the stress-related peptide corticotrophin-releasing factor (CRF) or of beta-adrenoceptor agonists, both of which alter androgen release and decrease levels of the peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein within Leydig cells. Our original studies used the retrograde transganglionic tracer pseudorabies virus (PRV) to map progression of the virus from the testes to upper brain levels. The present study aimed to extend this work by identifying the regions where CRF and catecholamine neurones represented components of the stress-activated, brain-testicular pathway that prevents testosterone increases. To this end, anaesthetised adult male rats received an intra-testicular injection of PRV. Using immunofluorescence, we identified co-labelling of PRV and either CRF or tyrosine hydroxylase (TH), the enzyme responsible for biogenic amine synthesis. Co-labelling of PRV and CRF was found in the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus (PVN) and the central amygdala. Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kölliker-Fuse area, area of A5, locus coeruleus, nucleus of solitary tract, area of C3, area of C2 and the area of C1/A1. These results indicate that most cell groups of the ventral noradrenergic pathway have neurones that are a part of the brain-testicular pathway. This suggests that the stress hormones CRF and catecholamines may act as neurotransmitters that signal the pathway to inhibit increases in plasma testosterone levels.

  17. PHEOCHROMOCYTOMA: AN ENDOCRINE STRESS MIMICKING DISORDER

    PubMed Central

    Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

    2008-01-01

    Pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. PMID:19120142

  18. Pyroclast acceleration and energy partitioning in fake explosive eruptions

    NASA Astrophysics Data System (ADS)

    Gaudin, Damien; Taddeucci, Jacopo; Scheu, Bettina; Valentine, Greg; Capponi, Antonio; Kueppers, Ulrich; Graettiger, Allison; Sonder, Ingo

    2014-05-01

    Explosive eruptions are characterized by the fast release of energy, with gas expansion playing a lead role. An excess of pressure may be generated either by the exsolution and accumulation of volatiles (e.g., vulcanian and strombolian explosions) or by in situ vaporization of water (e.g., phreato-magmatic explosions). The release of pressurized gas ejects magma and country rock pyroclasts at velocities that can reach several hundred of meters per second. The amount and velocity of pyroclasts is determined not only by the total released energy, but also by the system-specific dynamics of the energy transfer from gas to pyroclasts. In this context, analogue experiments are crucial, since the amount of available energy is determined. Here, we analyze three different experiments, designed to reproduce different aspects of explosive volcanism, focusing on the acceleration phase of the pyroclasts, in order to compare how the potential energy is transferred to the pyroclasts in different systems. In the first, shock-tube-type experiment, salt crystals resting in a pressurized Plexiglas cylinder are accelerated when a diaphragm set is suddenly opened, releasing the gas. In the second experiment, a pressurized air bubble is released in a water-filled Plexiglas pipe; diaphragm opening causes sudden expansion and bursting of the bubble and ejection of water droplets. In the last experiment, specifically focusing on phreatomagmatic eruptions, buried explosive charges accelerate the overlying loose material. All experiments were monitored by multiple high speed cameras and a variety of sensors. Despite the largely differing settings and processes, particle ejection velocity above the vent from the three experiments share a non-linear decay over time. Fitting this decay allows to estimate a characteristic depth that is related to the specific acceleration processes. Given that the initial available energy is experimentally controlled a priori, the information on the

  19. Brain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency.

    PubMed

    Korner, Germaine; Noain, Daniela; Ying, Ming; Hole, Magnus; Flydal, Marte I; Scherer, Tanja; Allegri, Gabriella; Rassi, Anahita; Fingerhut, Ralph; Becu-Villalobos, Damasia; Pillai, Samyuktha; Wueest, Stephan; Konrad, Daniel; Lauber-Biason, Anna; Baumann, Christian R; Bindoff, Laurence A; Martinez, Aurora; Thöny, Beat

    2015-10-01

    Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, the rate-limiting step in the synthesis of catecholamines. Mutations in the TH gene encoding tyrosine hydroxylase are associated with the autosomal recessive disorder tyrosine hydroxylase deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, to complex encephalopathy with perinatal onset, termed type B. We generated homozygous Th knock-in mice with the mutation Th-p.R203H, equivalent to the most recurrent human mutation associated with type B tyrosine hydroxylase deficiency (TH-p.R233H), often unresponsive to l-DOPA treatment. The Th knock-in mice showed normal survival and food intake, but hypotension, hypokinesia, reduced motor coordination, wide-based gate and catalepsy. This phenotype was associated with a gradual loss of central catecholamines and the serious manifestations of motor impairment presented diurnal fluctuation but did not improve with standard l-DOPA treatment. The mutant tyrosine hydroxylase enzyme was unstable and exhibited deficient stabilization by catecholamines, leading to decline of brain tyrosine hydroxylase-immunoreactivity in the Th knock-in mice. In fact the substantia nigra presented an almost normal level of mutant tyrosine hydroxylase protein but distinct absence of the enzyme was observed in the striatum, indicating a mutation-associated mislocalization of tyrosine hydroxylase in the nigrostriatal pathway. This hypomorphic mouse model thus provides understanding on pathomechanisms in type B tyrosine hydroxylase deficiency and a platform for the evaluation of novel therapeutics for movement disorders with loss of dopaminergic input to the striatum. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Load-Unload Response Ratio (LURR), Accelerating Moment/Energy Release (AM/ER) and State Vector Saltation as Precursors to Failure of Rock Specimens

    NASA Astrophysics Data System (ADS)

    Yin, Xiang-Chu; Yu, Huai-Zhong; Kukshenko, Victor; Xu, Zhao-Yong; Wu, Zhishen; Li, Min; Peng, Keyin; Elizarov, Surgey; Li, Qi

    2004-12-01

    In order to verify some precursors such as LURR (Load/Unload Response Ratio) and AER (Accelerating Energy Release) before large earthquakes or macro-fracture in heterogeneous brittle media, four acoustic emission experiments involving large rock specimens under tri-axial stress, have been conducted. The specimens were loaded in two ways: monotonous or cycling. The experimental results confirm that LURR and AER are precursors of macro-fracture in brittle media. A new measure called the state vector has been proposed to describe the damage evolution of loaded rock specimens.

  1. Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

    PubMed

    Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

    2015-10-01

    Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  2. Disruption of the Axonal Trafficking of Tyrosine Hydroxylase mRNA Impairs Catecholamine Biosynthesis in the Axons of Sympathetic Neurons

    PubMed Central

    Gioio, Anthony E.

    2017-01-01

    Abstract Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3′untranslated region (3’UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal. Toward this end, a targeted deletion of the axonal transport sequence element was developed, using the lentiviral delivery of the CRISPR/Cas9 system, and two guide RNA (gRNA) sequences flanking the 50-bp cis-acting regulatory element in rat superior cervical ganglion (SCG) neurons. Deletion of the axonal transport element reduced TH mRNA levels in the distal axons and reduced the axonal protein levels of TH and TH activity as measured by phosphorylation of SER40 in SCG neurons. Moreover, deletion of the zip-code diminished the axonal levels of dopamine (DA) and norepinephrine (NE). Conversely, the local translation of exogenous TH mRNA in the distal axon enhanced TH levels and activity, and elevated axonal NE levels. Taken together, these results provide direct evidence to support the hypothesis that TH mRNA trafficking and local synthesis of TH play an important role in the synthesis of catecholamines in the axon and presynaptic terminal. PMID:28630892

  3. The effects of mind-body training on stress reduction, positive affect, and plasma catecholamines.

    PubMed

    Jung, Ye-Ha; Kang, Do-Hyung; Jang, Joon Hwan; Park, Hye Yoon; Byun, Min Soo; Kwon, Soo Jin; Jang, Go-Eun; Lee, Ul Soon; An, Seung Chan; Kwon, Jun Soo

    2010-07-26

    This study was designed to assess the association between stress, positive affect and catecholamine levels in meditation and control groups. The meditation group consisted of 67 subjects who regularly engaged in mind-body training of "Brain-Wave Vibration" and the control group consisted of 57 healthy subjects. Plasma catecholamine (norepinephrine (NE), epinephrine (E), and dopamine (DA)) levels were measured, and a modified form of the Stress Response Inventory (SRI-MF) and the Positive Affect and Negative Affect Scale (PANAS) were administered. The meditation group showed higher scores on positive affect (p=.019) and lower scores on stress (p<.001) compared with the control group. Plasma DA levels were also higher in the meditation (p=.031) than in the control group. The control group demonstrated a negative correlation between stress and positive affects (r=-.408, p=.002), whereas this correlation was not observed in the meditation group. The control group showed positive correlations between somatization and NE/E (r=.267, p=.045) and DA/E (r=.271, p=.042) ratios, whereas these correlations did not emerge in the meditation group. In conclusion, these results suggest that meditation as mind-body training is associated with lower stress, higher positive affect and higher plasma DA levels when comparing the meditation group with the control group. Thus, mind-body training may influence stress, positive affect and the sympathetic nervous system including DA activity. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

    PubMed

    Ohara, Nobumasa; Uemura, Yasuyuki; Mezaki, Naomi; Kimura, Keita; Kaneko, Masanori; Kuwano, Hirohiko; Ebe, Katsuya; Fujita, Toshio; Komeyama, Takeshi; Usuda, Hiroyuki; Yamazaki, Yuto; Maekawa, Takashi; Sasano, Hironobu; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-10-12

    and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.

  5. Aging and unusual catecholamine-containing structures in the mouse brain.

    PubMed

    Masuoka, D T; Jonsson, G; Finch, C E

    1979-06-22

    Brains of C57BL/6J mice, aged 4, 8 and 20--29 months, were examined by the Falck-Hillarp histochemical fluorescence technique. Numerous large, intensely fluorescent green to yellow-green spots (LIFS) were observed in the brains of senescent mice. LIFS were generally round to ovoid in shape and ranged in size from about 10 micrometer to about 30 micrometer. Histochemical and pharmacological procedures and spectral analysis indicated that the formaldehyde-induced fluorescence of the LIFS was due to the presence of catecholamines (CA) rather than aging pigment. Their distribution in the brain suggests an association with nerve axons or terminals rather than cell bodies. The number of LIFS in the hypothalamus increased progressively during aging. It is proposed that LIFS may represent age-related, unusual CA accumulation in enlargements proximal to axonal or terminal portions undergoing spontaneous degeneration.

  6. Annually-layered lake sediments reveal strongly increased release of persistent chemicals due to accelerated glacier melting

    NASA Astrophysics Data System (ADS)

    Anselmetti, Flavio S.; Blüthgen, Nancy; Bogdal, Christian; Schmid, Peter

    2010-05-01

    Melting glaciers may represent a secondary source of chemical pollutants that have previously been incorporated and stored in the ice. Of particular concern are persistent organic pollutants (POPs), such as the insecticide dichlorodiphenyl trichloroethane (DDT) and industrial chemicals like polychlorinated biphenyls (PCBs), which are hazardous environmental contaminants due to their persistent, bioaccumulative and toxic properties. They were introduced in the 1930s and eventually banned in the 1970s. After release into the environment these chemicals were atmospherically transported to even remote areas such as the Alps and were deposited and stored in glaciers. Ongoing drastic glacier melting due to global warming, which is expected to further accelerate, implies the significance of studying the fate of these 'legacy pollutants'. Proglacial lake sediments provide well-dated and high-resolution archives to reconstruct timing and quantities of such a potentially hazardous remobilization. The goal of this study is to reconstruct the historical inputs of POPs into remote alpine lakes and to investigate the accelerated release of POPs from melting glaciers. Due to their lipophilic character, these chemicals exhibit a high tendency to adsorb to particles whereas concentrations in water are expected to be low. Therefore, quantitative determination in annually-layered lake sediment provides an excellent way to investigate the temporal trend of inputs into lakes that act as particle sinks. For this purpose, sediment cores were sampled from proglacial lakes in the Bernese Alps (Switzerland), which are exclusively fed by glacial melt waters. For comparison, cores were also taken from nearby high-alpine lakes located in non-glaciated catchments, which only should record the initial atmospheric fall-out. Sediment layers were dated by annual varve counting and radionuclide measurements; they cover the time period from the mid 20th century to today. The measured time series of

  7. Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction.

    PubMed

    Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok

    2016-03-01

    The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.

  8. Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors.

    PubMed

    Combet, Emilie; Lean, Michael E J; Boyle, James G; Crozier, Alan; Davidson, D Fraser

    2011-01-14

    Urinary homovanillic acid (HVA) measurement is used routinely as a marker of the first test for the screening of catecholamine-secreting tumors and dopamine metabolism, but generates a large number of false-positive results. With no guidelines for dietary restrictions prior to the test, we hypothesize that consumption of flavonol-rich foods (such as onions, tomatoes, tea) prior to urinary catecholamine screening could be responsible for false-positive urinary HVA in healthy subjects. A randomized, crossover dietary intervention was carried out in healthy subjects (n=17). Volunteers followed either a low or high-flavonol diet, for a duration of 3 days, prior to providing a 24-h urine sample for HVA measurement using a routine, validated liquid chromatography method as well as a gas chromatography-mass spectrometry method. Dietary flavonol intake significantly increased urinary HVA excretion (p < 0.001), with 3 out of 17 volunteers (20%) exceeding the 40 μmol/24 h upper limit of normal for HVA excretion (false-positive result). Dietary flavonols commonly found in foodstuff such as tomatoes, onions, and tea, interfered with the routine urinary HVA screening test and should be avoided in the three-day run-up to the test. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. In vitro Catecholamine Exposure Produces Variable Effects on the B7 Costimulatory Pathway in Human Monocytic Cells

    NASA Technical Reports Server (NTRS)

    Salicru, A. N.; Crucian, B.; Sams, Clarence; Actor, J. K.; Marshall, G. D., Jr.

    2006-01-01

    Catecholamines have been associated with immunomodulation of the adaptive immune system towards a Th2 response in vitro. We therefore examined the role of in vitro epinephrine (EPI) and norepinephrine (NE) exposure on the B7 costimulatory expression of antigen presenting cells (APC) from human monocytic cell lines and human peripheral blood mononuclear cells (PBMC). THP1 monocytic cells and CD14+ cells from normal human PBMC were stimulated with lipopolysaccharide (LPS) and incubated with physiologic stress levels (10(exp -6) - 10(exp -8)M) of EPI or NE for 24 hours. Cells were subsequently stained with CD80 FITC, CD86 PE, and CD14 PC5 antibodies and analyzed by flow cytometry for changes in fluorescence and mean fluorescence intensity (MFI). Exposure of THP1 to EPI in vitro at concentrations of 10(exp -6), 10(exp -7) and 10(exp -8)M significantly decreased mean CD80 from 42 plus or minus 0.7% to 11 plus or minus 0.44%, 19.1 plus or minus 2.0%, and 30.7 plus or minus 2.1% expression, respectively (p less than 0.01). In addition, CD86 expression increased with EPI at 10(exp -6), 10(exp -7) and 10(exp -8) M from 9.2 plus or minus 0.52% to 41 plus or minus 3.8%, 26.4 plus or minus 1.9%, and 15.74 plus or minus 1.8% expression, respectively (p less than 0.01). Similar results for mean CD80 and CD86 percent expression were observed for CD14+ cells from PBMC with a sample size of N = 6 and for NE when substituted for EPI. The data show that in vitro exposure to catecholamines significantly decreases %CD86 expression and significantly increases %CD86 expression in THP1 cells and human CD14+ APC. Previous studies have suggested an association between increased CD86 expression and TH2 activity. Thus, these data suggest that immunomodulation by catecholamines results in part by the variable effects of the B7 costimulatory pathway in APC.

  10. On the mechanism of tachyphylaxis to tyramine in the isolated rat heart

    PubMed Central

    Axelrod, J.; Gordon, Edna; Hertting, G.; Kopin, I. J.; Potter, L. T.

    1962-01-01

    Tyramine was shown to release [3H]-catecholamines from an isolated rat heart previously perfused with [3H]-noradrenaline. With successive injections of tyramine the amount of [3H]-catecholamine released fell progressively and there was a parallel decrease in the increment of amplitude and rate of contraction of the heart. Reserpinized hearts were shown to take up less [3H]-noradrenaline than normal hearts. Release of radioactivity and loss of responsiveness to tyramine occurred more rapidly in the reserpinized heart. In the same preparation the uptake of [14C]-tyramine exceeded the quantity of the noradrenaline released. ImagesFig. 4 PMID:13863453

  11. The effect of adaptive servo-ventilation on dyspnoea, haemodynamic parameters and plasma catecholamine concentrations in acute cardiogenic pulmonary oedema.

    PubMed

    Nakano, Shintaro; Kasai, Takatoshi; Tanno, Jun; Sugi, Keiki; Sekine, Yasumasa; Muramatsu, Toshihiro; Senbonmatsu, Takaaki; Nishimura, Shigeyuki

    2015-08-01

    Adaptive servo-ventilation has a potential sympathoinhibitory effect in acute cardiogenic pulmonary oedema (ACPO). To evaluate the acute effects of adaptive servo-ventilation in patients with ACPO. Fifty-eight consecutive patients with ACPO were divided into those who underwent adaptive servo-ventilation and those who received oxygen therapy alone as part of their immediate care. Visual analogue scale, vital signs, blood gas data and plasma catecholamine concentrations at baseline and 1 h during emergency care, and subsequent clinical events (death within 30 days, intubation within seven days or between seven and 30 days, and length of hospital stay) were assessed. Pre-matched and post-propensity score (PS)-matched datasets were analysed. During the first hour of adaptive servo-ventilation, plasma catecholamine concentrations fell significantly (baseline versus 1 h: epinephrine p = 0.003, norepinephrine p < 0.001, dopamine p < 0.001), with falls in blood pressure, heart rate, respiratory rate and pCO2, and rise in HCO3 and pH. In the PS-matched model, visual analogue scale (p = 0.036), systolic blood pressure (from 153.8 ± 30.7 to 133.1 ± 16.3 mmHg; p = 0.025) and plasma dopamine concentration (p = 0.034) fell significantly in the adaptive servo-ventilation group compared with the oxygen therapy alone group. The clinical outcomes between the groups were comparable. In patients with ACPO, emergency care using adaptive servo-ventilation attenuated plasma catecholamine concentrations and led to the improvement of dyspnoea, vital signs and acid-base balance, without adversely influencing clinical outcomes. Using adaptive servo-ventilation, rather than standard oxygen alone, may relieve dyspnoea and improve haemodynamic status, possibly by modulating sympathetic nerve activity. © The European Society of Cardiology 2014.

  12. Chronic lithium treatment up-regulates cell surface Na(V)1.7 sodium channels via inhibition of glycogen synthase kinase-3 in adrenal chromaffin cells: enhancement of Na(+) influx, Ca(2+) influx and catecholamine secretion after lithium withdrawal.

    PubMed

    Yanagita, Toshihiko; Maruta, Toyoaki; Nemoto, Takayuki; Uezono, Yasuhito; Matsuo, Kiyotaka; Satoh, Shinya; Yoshikawa, Norie; Kanai, Tasuku; Kobayashi, Hideyuki; Wada, Akihiko

    2009-09-01

    In cultured bovine adrenal chromaffin cells expressing Na(V)1.7 isoform of voltage-dependent Na(+) channels, we have previously reported that lithium chloride (LiCl) inhibits function of Na(+) channels independent of glycogen synthase kinase-3 (GSK-3) (Yanagita et al., 2007). Here, we further examined the effects of chronic lithium treatment on Na(+) channels. LiCl treatment (1-30 mM, > or = 12 h) increased cell surface [(3)H]saxitoxin ([(3)H]STX) binding by approximately 32% without altering the affinity of [(3)H]STX binding. This increase was prevented by cycloheximide and actinomycin D. SB216763 and SB415286 (GSK-3 inhibitors) also increased cell surface [(3)H]STX binding by approximately 31%. Simultaneous treatment with LiCl and SB216763 or SB415286 did not produce an increased effect on [(3)H]STX binding compared with either treatment alone. LiCl increased Na(+) channel alpha-subunit mRNA level by 32% at 24 h. LiCl accelerated alpha-subunit gene transcription by 35% without altering alpha-subunit mRNA stability. In LiCl-treated cells, LiCl inhibited veratridine-induced (22)Na(+) influx as in untreated cells. However, washout of LiCl after chronic treatment enhanced veratridine-induced (22)Na(+) influx, (45)Ca(2+) influx and catecholamine secretion by approximately 30%. Washout of LiCl after 24 h treatment shifted concentration-response curve of veratridine upon (22)Na(+) influx upward, without altering its EC(50) value. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced (22)Na(+) influx by two-fold in untreated and LiCl-treated cells. Whole-cell patch-clamp analysis indicated that I-V curve and steady-state inactivation/activation curves were comparable between untreated and LiCl-treated cells. Thus, GSK-3 inhibition by LiCl up-regulated cell surface Na(V)1.7 via acceleration of alpha-subunit gene transcription, enhancing veratridine-induced Na(+) influx, Ca(2+) influx and catecholamine secretion.

  13. Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells

    PubMed Central

    Raghupathi, Ravinarayan; Duffield, Michael D; Zelkas, Leah; Meedeniya, Adrian; Brookes, Simon J H; Sia, Tiong Cheng; Wattchow, David A; Spencer, Nick J; Keating, Damien J

    2013-01-01

    The major source of serotonin (5-HT) in the body is the enterochromaffin (EC) cells lining the intestinal mucosa of the gastrointestinal tract. Despite the fact that EC cells synthesise ∼95% of total body 5-HT, and that this 5-HT has important paracrine and endocrine roles, no studies have investigated the mechanisms of 5-HT release from single primary EC cells. We have developed a rapid primary culture of guinea-pig and human EC cells, allowing analysis of single EC cell function using electrophysiology, electrochemistry, Ca2+ imaging, immunocytochemistry and 3D modelling. Ca2+ enters EC cells upon stimulation and triggers quantal 5-HT release via L-type Ca2+ channels. Real time amperometric techniques reveal that EC cells release 5-HT at rest and this release increases upon stimulation. Surprisingly for an endocrine cell storing 5-HT in large dense core vesicles (LDCVs), EC cells release 70 times less 5-HT per fusion event than catecholamine released from similarly sized LDCVs in endocrine chromaffin cells, and the vesicle release kinetics instead resembles that observed in mammalian synapses. Furthermore, we measured EC cell density along the gastrointestinal tract to create three-dimensional (3D) simulations of 5-HT diffusion using the minimal number of variables required to understand the physiological relevance of single cell 5-HT release in the whole-tissue milieu. These models indicate that local 5-HT levels are likely to be maintained around the activation threshold for mucosal 5-HT receptors and that this is dependent upon stimulation and location within the gastrointestinal tract. This is the first study demonstrating single cell 5-HT release in primary EC cells. The mode of 5-HT release may represent a unique mode of exocytosis amongst endocrine cells and is functionally relevant to gastrointestinal sensory and motor function. PMID:24099799

  14. IR, UV-Vis, magnetic and thermal characterization of chelates of some catecholamines and 4-aminoantipyrine with Fe(III) and Cu(II)

    NASA Astrophysics Data System (ADS)

    Mohamed, Gehad G.; Zayed, M. A.; El-Dien, F. A. Nour; El-Nahas, Reham G.

    2004-07-01

    The dopamine derivatives participate in the regulation of wide variety of physiological functions in the human body and in medication life. Increase and/or decrease in the concentration of dopamine in human body reflect an indication for diseases such as Schizophrenia and/or Parkinson diseases. α-Methyldopa (α-MD) in tablets is used in medication of hypertension. The Fe(III) and Cu(II) chelates with coupled products of adrenaline hydrogen tartarate (AHT), levodopa (LD), α-MD and carbidopa (CD) with 4-aminoantipyrine (4-AAP) are prepared and characterized. Different physico-chemical methods like IR, magnetic and UV-Vis spectra are used to investigate the structure of these chelates. Fe(III) form 1:2 (M:catecholamines) chelates while Cu(II) form 1:1 chelates. Catecholamines behave as a bidentate mono- or dibasic ligands in binding to the metal ions. IR spectra show that the catecholamines are coordinated to the metal ions in a bidentate manner with O,O donor sites of the phenolic - OH. Magnetic moment measurements reveal the presence of Fe(III) chelates in octahedral geometry while the Cu(II) chelates are square planar. The thermal decomposition of Fe(III) and Cu(II) complexes is studied using thermogravimetric (TGA) and differential thermal analysis (DTA) techniques. The water molecules are removed in the first step followed immediately by decomposition of the ligand molecules. The activation thermodynamic parameters, such as, energy of activation, enthalpy, entropy and free energy change of the complexes are evaluated and the relative thermal stability of the complexes are discussed.

  15. Haloperidol response and plasma catecholamines and their metabolites.

    PubMed

    Green, A I; Alam, M Y; Boshes, R A; Waternaux, C; Pappalardo, K M; Fitzgibbon, M E; Tsuang, M T; Schildkraut, J J

    1993-06-01

    Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.

  16. Catecholamines of the adrenal medula and their morphological changes during adaptation to repeated immobilization stress

    NASA Technical Reports Server (NTRS)

    Kvetnansky, R.; Mitro, A.; Mikulaj, L.; Hocman, G.

    1980-01-01

    Changes of the adrenal medulla of rats were studied in the course of adaptation to repeated immobilization stress. An increase in the number of cells in the adrenal medulla was found in the adapted animals; this increase was confirmed by weight indices of the medulla and by cell counts per surface unit. Simultaneous karyometric measurements of the nuclei of adrenal medulla cells and an analysis of the catecholamine contents in the adrenals explain the increased activity of the adrenal medulla in the course of adaptation.

  17. [The catecholamine content of the hypothalamus during the modelling of the ulcer process in the gastroduodenal area].

    PubMed

    Iemel'ianenko, I V; Sultanova, I D; Voronych, N M

    1995-01-01

    The content of catecholamines in rat hypothalamus in experimental ulcer process in gastroduodenal region has been studied in experiments on rats. It was determined that under these conditions the content of hypothalamus adrenalin increases and the content of noradrenalin decreases. The level of dofamin and DOFA in this brain structure changes in phases. The mentioned shifts depended on the duration and character of the pathological process in the gastroduodenal region.

  18. Alpha-1-Adrenergic Receptors in Heart Failure: The Adaptive Arm of the Cardiac Response to Chronic Catecholamine Stimulation

    PubMed Central

    Jensen, Brian C.; O'Connell, Timothy D.; Simpson, Paul C.

    2013-01-01

    Alpha-1-adrenergic receptors are G-protein coupled receptors (GPCRs) activated by catecholamines. The alpha-1A and alpha-1B subtypes are expressed in mouse and human myocardium, whereas the alpha-1D protein is found only in coronary arteries. There are far fewer alpha-1-ARs than beta-ARs in the non-failing heart, but their abundance is maintained or increased in the setting of heart failure, which is characterized by pronounced chronic elevation of catecholamines and b□eta-AR dysfunction. Decades of evidence from gain- and loss-of-function studies in isolated cardiac myocytes and numerous animal models demonstrate important adaptive functions for cardiac alpha-1-ARs, to include physiological hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Clinical trial data indicate that blocking alpha-1-ARs is associated with incident heart failure in patients with hypertension. Collectively, these findings suggest that alpha-1-AR activation might mitigate the well-recognized toxic effects of beta-ARs in the hyperadrenergic setting of chronic heart failure. Thus, exogenous cardioselective activation of alpha-1-ARs might represent a novel and viable approach to the treatment of heart failure. PMID:24145181

  19. The Solar Flare: A Strongly Turbulent Particle Accelerator

    NASA Astrophysics Data System (ADS)

    Vlahos, L.; Krucker, S.; Cargill, P.

    The topics of explosive magnetic energy release on a large scale (a solar flare) and particle acceleration during such an event are rarely discussed together in the same article. Many discussions of magnetohydrodynamic (MHD) mod- eling of solar flares and/or CMEs have appeared (see [143] and references therein) and usually address large-scale destabilization of the coronal mag- netic field. Particle acceleration in solar flares has also been discussed exten- sively [74, 164, 116, 166, 87, 168, 95, 122, 35] with the main emphasis being on the actual mechanisms for acceleration (e.g., shocks, turbulence, DC electric fields) rather than the global magnetic context in which the acceleration takes place.

  20. Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction

    PubMed Central

    Kim, Nahyun; Hughes, Tonda L.; Park, Chang G.; Quinn, Laurie

    2016-01-01

    Abstract The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ2-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t =−6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents. PMID:26849530

  1. Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia.

    PubMed

    Ishikawa, Takaki; Yoshida, Chiemi; Michiue, Tomomi; Perdekamp, Markus Grosse; Pollak, Stefan; Maeda, Hitoshi

    2010-05-01

    Catecholamines are involved in various stress responses. Previous studies have suggested applicability of the postmortem blood levels to investigations of physical stress responses or toxic/hyperthermic neuronal dysfunction during death process. The present study investigated cellular immunopositivity for adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) in the hypothalamus, adenohypophysis and adrenal medulla with special regard to fatal hypothermia (cold exposure) and hyperthermia (heat stroke) to examine forensic pathological significance. Medicolegal autopsy cases (n=290, within 3 days postmortem) were examined. The proportions of catecholamine (Adr, Nad and DA)-positive cells (% positivity) in each tissue were quantitatively estimated using immunostaining. Hyperthermia cases (n=12) showed a lower neuronal DA-immunopositivity in the hypothalamus than hypothermia cases (n=20), while Nad- and DA-immunopositivities in the adrenal medulla were higher for hyperthermia than for hypothermia. Rates of Nad-immunopositivity in the adrenal medulla were very low for hypothermia. No such difference between hypothermia and hyperthermia was seen in the adenohypophysis. In hypothermia cases, cellular Nad-immunopositivity in the adrenal medulla correlated with the Nad level in cerebrospinal fluid (r=0.591, p<0.01). These observations suggest a characteristic immunohistochemical pattern of systemic stress response to fatal hypothermia and hyperthermia, involving the hypothalamus and adrenal medulla. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Neuromuscular Control of Rapid Linear Accelerations in Fish

    DTIC Science & Technology

    2016-06-22

    2014 30-Apr-2015 Approved for Public Release; Distribution Unlimited Final Report: Neuromuscular Control of Rapid Linear Accelerations in Fish The...it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. Tufts University Research... Control of Rapid Linear Accelerations in Fish Report Title In this project, we measured muscle activity, body movements, and flow patterns during linear

  3. Self-Replenishing Vascularized Fouling-Release Surfaces

    DOE PAGES

    Howell, Caitlin; Vu, Thy L.; Lin, Jennifer J.; ...

    2014-08-13

    Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the selfreplenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectiousmore » bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella salina, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.« less

  4. Nicotine promotes cell proliferation via {alpha}7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

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

    Wong, Helen Pui Shan; Yu Le; Lam, Emily Kai Yee

    Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a {beta}{sub 1}- and {beta}{sub 2}-selective antagonist, respectively, suggesting the role of {beta}-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-{beta}-hydroxylase (D{beta}H) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferationmore » and adrenaline production. Expression of {alpha}7-nicotinic acetylcholine receptor ({alpha}7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an {alpha}7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and D{beta}H expression as well as adrenaline production. Taken together, through the action on {alpha}7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and {beta}-adrenergic activation. These data reveal the contributory role {alpha}7-nAChR and {beta}-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer.« less

  5. Flow-injection analysis of catecholamine secretion from bovine adrenal medulla cells on microbeads.

    PubMed

    Herrera, M; Kao, L S; Curran, D J; Westhead, E W

    1985-01-01

    Bovine adrenal medullary cells have been cultured on microbeads which are placed in a low-volume flow system for measurements of stimulation-response parameters. Electronically controlled stream switching allows stimulation of cells with pulse lengths from 1 s to many minutes; pulses may be repeated indefinitely. Catecholamines secreted are detected by an electrochemical detector downstream from the cells. This flow-injection analysis technique provides a new level of sensitivity and precision for measurement of kinetic parameters of secretion. A manual injection valve allows stimulation by higher levels of stimulant in the presence of constant low levels of stimulant. Such experiments show interesting differences between the effects of K+ and acetylcholine on cells partially desensitized to acetylcholine.

  6. Acceleration of barium ions near 8000 km above an aurora

    NASA Technical Reports Server (NTRS)

    Stenbaek-Nielsen, H. C.; Hallinan, T. J.; Wescott, E. M.; Foeppl, H.

    1984-01-01

    A barium shaped charge, named Limerick, was released from a rocket launched from Poker Flat Research Range, Alaska, on March 30, 1982, at 1033 UT. The release took place in a small auroral breakup. The jet of ionized barium reached an altitude of 8100 km 14.5 min after release, indicating that there were no parallel electric fields below this altitude. At 8100 km the jet appeared to stop. Analysis shows that the barium at this altitude was effectively removed from the tip. It is concluded that the barium was actually accelerated upward, resulting in a large decrease in the line-of-sight density and hence the optical intensity. The parallel electric potential in the acceleration region must have been greater than 1 kV over an altitude interval of less than 200 km. The acceleration region, although presumably auroral in origin, did not seem to be related to individual auroral structures, but appeared to be a large-scale horizontal structure. The perpendicular electric field below, as deduced from the drift of the barium, was temporally and spatially very uniform and showed no variation related to individual auroral structures passing through.

  7. Strategies for enhancing catecholamine-mediated neurotransmission

    NASA Technical Reports Server (NTRS)

    Wurtman, Richard J.

    1992-01-01

    Major findings made during this project period included the following observations: changes in tyrosine availability do affect brain dopamine release, as assessed by in vivo microdialysis, but that neuronal feedback mechanisms limit the durations of this effect except when dopaminergic neurotransmission has been deficient; the circulating hormone TRH markedly stimulates brain dopamine release, an effect probably mediated by its diketopiperazine metabolite; the amount of circulating L-dopa which enters the brain is both enhanced by carbohydrate consumption and suppressed by protein intake (both nutritional effects can be damaging, inasmuch as a sudden rush of L-dopa into the brain can facilitate dyskinesias, while the inhibition of brain L-dopa uptake by proteins suppresses its conversion to brain dopamine; an appropriate mixture of dietary proteins and carbohydrates can obviate both effects); serotonin release from superfused hypothalamic slices is a linear function of available tryptophan levels throughout the normal dynamic range; the daily rhythm in plasma melatonin levels is abnormal both in the sudden infant death syndrome and in women with secondary amenorrhea; tyrosine can potentiate the anorectic effects of widely-used sympathomimetic drugs; newly-described COMT inhibitors can enhance brain dopamine release in vivo; and a cell culture system, based on Y-79 (retinoblast) cells, exists in which melatonin reliably suppresses dopamine release.

  8. Prefrontal/accumbal catecholamine system processes high motivational salience

    PubMed Central

    Puglisi-Allegra, Stefano; Ventura, Rossella

    2012-01-01

    Motivational salience regulates the strength of goal seeking, the amount of risk taken, and the energy invested from mild to extreme. Highly motivational experiences promote highly persistent memories. Although this phenomenon is adaptive in normal conditions, experiences with extremely high levels of motivational salience can promote development of memories that can be re-experienced intrusively for long time resulting in maladaptive outcomes. Neural mechanisms mediating motivational salience attribution are, therefore, very important for individual and species survival and for well-being. However, these neural mechanisms could be implicated in attribution of abnormal motivational salience to different stimuli leading to maladaptive compulsive seeking or avoidance. We have offered the first evidence that prefrontal cortical norepinephrine (NE) transmission is a necessary condition for motivational salience attribution to highly salient stimuli, through modulation of dopamine (DA) in the nucleus accumbens (NAc), a brain area involved in all motivated behaviors. Moreover, we have shown that prefrontal-accumbal catecholamine (CA) system determines approach or avoidance responses to both reward- and aversion-related stimuli only when the salience of the unconditioned stimulus (UCS) is high enough to induce sustained CA activation, thus affirming that this system processes motivational salience attribution selectively to highly salient events. PMID:22754514

  9. Accelerated drug release and clearance of PEGylated epirubicin liposomes following repeated injections: a new challenge for sequential low-dose chemotherapy

    PubMed Central

    Yang, Qiang; Ma, Yanling; Zhao, Yongxue; She, Zhennan; Wang, Long; Li, Jie; Wang, Chunling; Deng, Yihui

    2013-01-01

    Background Sequential low-dose chemotherapy has received great attention for its unique advantages in attenuating multidrug resistance of tumor cells. Nevertheless, it runs the risk of producing new problems associated with the accelerated blood clearance phenomenon, especially with multiple injections of PEGylated liposomes. Methods Liposomes were labeled with fluorescent phospholipids of 1,2-dipalmitoyl-snglycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) and epirubicin (EPI). The pharmacokinetics profile and biodistribution of the drug and liposome carrier following multiple injections were determined. Meanwhile, the antitumor effect of sequential low-dose chemotherapy was tested. To clarify this unexpected phenomenon, the production of polyethylene glycol (PEG)-specific immunoglobulin M (IgM), drug release, and residual complement activity experiments were conducted in serum. Results The first or sequential injections of PEGylated liposomes within a certain dose range induced the rapid clearance of subsequently injected PEGylated liposomal EPI. Of note, the clearance of EPI was two- to three-fold faster than the liposome itself, and a large amount of EPI was released from liposomes in the first 30 minutes in a complement-activation, direct-dependent manner. The therapeutic efficacy of liposomal EPI following 10 days of sequential injections in S180 tumor-bearing mice of 0.75 mg EPI/kg body weight was almost completely abolished between the sixth and tenth day of the sequential injections, even although the subsequently injected doses were doubled. The level of PEG-specific IgM in the blood increased rapidly, with a larger amount of complement being activated while the concentration of EPI in blood and tumor tissue was significantly reduced. Conclusion Our investigation implied that the accelerated blood clearance phenomenon and its accompanying rapid leakage and clearance of drug following sequential low-dose injections may reverse the unique

  10. Neuroanatomical Evidence for Catecholamines as Modulators of Audition and Acoustic Behavior in a Vocal Teleost.

    PubMed

    Forlano, Paul M; Sisneros, Joseph A

    2016-01-01

    The plainfin midshipman fish (Porichthys notatus) is a well-studied model to understand the neural and endocrine mechanisms underlying vocal-acoustic communication across vertebrates. It is well established that steroid hormones such as estrogen drive seasonal peripheral auditory plasticity in female Porichthys in order to better encode the male's advertisement call. However, little is known of the neural substrates that underlie the motivation and coordinated behavioral response to auditory social signals. Catecholamines, which include dopamine and noradrenaline, are good candidates for this function, as they are thought to modulate the salience of and reinforce appropriate behavior to socially relevant stimuli. This chapter summarizes our recent studies which aimed to characterize catecholamine innervation in the central and peripheral auditory system of Porichthys as well as test the hypotheses that innervation of the auditory system is seasonally plastic and catecholaminergic neurons are activated in response to conspecific vocalizations. Of particular significance is the discovery of direct dopaminergic innervation of the saccule, the main hearing end organ, by neurons in the diencephalon, which also robustly innervate the cholinergic auditory efferent nucleus in the hindbrain. Seasonal changes in dopamine innervation in both these areas appear dependent on reproductive state in females and may ultimately function to modulate the sensitivity of the peripheral auditory system as an adaptation to the seasonally changing soundscape. Diencephalic dopaminergic neurons are indeed active in response to exposure to midshipman vocalizations and are in a perfect position to integrate the detection and appropriate motor response to conspecific acoustic signals for successful reproduction.

  11. N-(4-Trifluoromethylphenyl)amide group of the synthetic histamine receptor agonist inhibits nicotinic acetylcholine receptor-mediated catecholamine secretion.

    PubMed

    Kim, Dong-Chan; Park, Yong-Soo; Jun, Dong-Jae; Hur, Eun-Mi; Kim, Sun-Hee; Choi, Bo-Hwa; Kim, Kyong-Tai

    2006-02-28

    The therapeutic targeting of nicotinic receptors requires the identification of drugs that selectively activate or inhibit a limited range of nicotine acetylcholine receptors (nAChRs). In this study, we identified N-(4-trifluoromethylphenyl)amide group of the synthetic histamine receptor ligands, histamine-trifluoromethyltoluide, that act as potent inhibitors of nAChRs in bovine adrenal chromaffin cells. Catecholamine secretion induced by the nAChRs agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), was significantly inhibited by histamine-trifluoromethyltoluide. Real time carbon-fiber amperometry confirmed the ability of histamine-trifluoromethyltoluide to inhibit DMPP-induced exocytosis in single chromaffin cells. We also found that histamine-trifluoromethyltoluide inhibited DMPP-induced [Ca(2+)](i) and [Na(+)](i) increases, as well as DMPP-induced inward currents in the absence of extracellular calcium. Histamine-trifluoromethyltoluide had no effect on [(3)H]nicotine binding or on calcium increases induced by high K(+), bradykinin, veratridine, histamine, and benzoylbenzoyl ATP. Among the synthetic histamine receptor ligands, clobenpropit exhibited similarity. In addition, 4'-nitroacetanilide also significantly attenuated nAChR-mediated catecholamine secretion. In conclusion, the N-(4-trifluoromethylphenyl)amide group of the histamine-trifluoromethyltoluide might be the critical moiety in the inhibition of nAChR-mediated CA secretion.

  12. Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

    PubMed Central

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. PMID:25032843

  13. Catecholamine-mediated arrhythmias in acute myocardial infarction. Experimental evidence and role of beta-adrenoceptor blockade.

    PubMed

    Opie, L H; Lubbe, W F

    1979-11-24

    Ventricular fibrillation is a major mechanism of sudden death. The cellular link between catecholamine activity and the development of serious ventricular arrhythmias may be in the formation of cyclic adenosine monophosphate (cAMP). Cyclic AMP and agents promoting cAMP accumulation allow development of slow responses which, especially in the presence of regional ischaemia, could develop into ventricular fibrillation. The role of beta-antagonist agents in the therapy of acute myocardial infarction is analysed in relation to the hypothesis linking cAMP and ventricular fibrillation. Reasons for the limited effectiveness of anti-arrhythmic therapy with beta-antagonist agents are given.

  14. 5-s-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons.

    PubMed

    Spencer, Jeremy P E; Whiteman, Matthew; Jenner, Peter; Halliwell, Barry

    2002-04-01

    A decrease in reduced glutathione levels in dopamine containing nigral cells in Parkinson's disease may result from the formation of cysteinyl-adducts of catecholamines, which in turn exert toxicity on nigral cells. We show that exposure of neurons (CSM 14.1) to 5-S-cysteinyl conjugates of dopamine, L-DOPA, DOPAC or DHMA causes neuronal damage, increases in oxidative DNA base modification and an elevation of caspase-3 activity in cells. Damage to neurons was apparent 12-48 h of post-exposure and there were increases in caspase-3 activity in neurons after 6 h. These changes were paralleled by large increases in pyrimidine and purine base oxidation products, such as 8-OH-guanine suggesting that 5-S-cysteinyl conjugates of catecholamines are capable of diffusing into cells and stimulating the formation of reactive oxygen species (ROS), which may then lead to a mechanism of cell damage involving caspase-3. Indeed, intracellular ROS were observed to rise sharply on exposure to the conjugates. These results suggest one mechanism by which oxidative stress may occur in the substantia nigra in Parkinson's disease.

  15. Environmental Impact From Accelerator Operation at SLAC

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

    Liu, James C

    1999-03-22

    Environmental impacts from electron accelerator operations at the Stanford Linear Accelerator Center, which is located near populated areas, are illustrated by using examples of three different accelerator facilities: the low power (a few watts) SSRL, the high power (a few kilowatts) PEP-II, and the 50-kW SLC. Three types of major impacts are discussed: (1) off-site doses from skyshine radiation, mainly neutrons, (2) off-site doses from radioactive air emission, mainly {sup 13}N, and (3) radioactivities, mainly {sup 3}H, produced in the groundwater. It was found that, from SSRL operation, the skyshine radiation result in a MEI (Maximum Exposed Individual) of 0.3more » {mu}Sv/y while a conservative calculation using CAP88 showed a MEI of 0.36 {mu}Sv/y from radioactive air releases. The calculated MEI doses due to future PEP-II operation are 30 {mu}Sv/y from skyshine radiation and 2 {mu}Sv/y from air releases. The population doses due to radioactive air emission are 0.5 person-mSv from SSRL and 12 person-mSv from PEP-II. Because of the stronger decrease of skyshine dose as the distance increases, the population dose from skyshine radiation are smaller than that from air release. The third environmental impact, tritium activity produced in the groundwater, was also demonstrated to be acceptable from both the well water measurements and the FLUKA calculations for the worst case of the SLC high-power dump.« less

  16. Impacts of soil petroleum contamination on nutrient release during litter decomposition of Hippophae rhamnoides.

    PubMed

    Zhang, Xiaoxi; Liu, Zengwen; Luc, Nhu Trung; Yu, Qi; Liu, Xiaobo; Liang, Xiao

    2016-03-01

    Petroleum exploitation causes contamination of shrub lands close to oil wells. Soil petroleum contamination affects nutrient release during the litter decomposition of shrubs, which influences nutrient recycling and the maintenance of soil fertility. Hence, this contamination may reduce the long-term growth and stability of shrub communities and consequently, the effects of phytoremediation. Fresh foliar litter of Hippophae rhamnoides, a potential phytoremediating species, was collected for this study. The litter was placed in litterbags and then buried in different petroleum-polluted soil media (the petroleum concentrations were 15, 30, and 45 g kg(-1) dry soil, which were considered as slightly, moderately and seriously polluted soil, respectively) for a decomposition test. The impacts of petroleum contamination on the release of nutrients (including N, P, K, Cu, Zn, Fe, Mn, Ca and Mg) were assessed. The results showed that (1) after one year of decomposition, the release of all nutrients was accelerated in the slightly polluted soil. In the moderately polluted soil, P release was accelerated, while Cu, Zn and Mn release was inhibited. In the seriously polluted soil, Cu and Zn release was accelerated, while the release of the other nutrients was inhibited. (2) The effect of petroleum on nutrient release from litter differed in different periods during decomposition; this was mainly due to changes in soil microorganisms and enzymes under the stress of petroleum contamination. (3) To maintain the nutrient cycling and the soil fertility of shrub lands, H. rhamnoides is only suitable for phytoremediation of soils containing less than 30 g kg(-1) of petroleum.

  17. COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

    PubMed

    Zumárraga, Mercedes; Arrúe, Aurora; Basterreche, Nieves; Macías, Isabel; Catalán, Ana; Madrazo, Arantza; Bustamante, Sonia; Zamalloa, María I; Erkoreka, Leire; Gordo, Estibaliz; Arnaiz, Ainara; Olivas, Olga; Arroita, Ariane; Marín, Elena; González-Torres, Miguel A

    2016-06-01

    We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.

  18. Calcium-dependent transferrin receptor recycling in bovine chromaffin cells.

    PubMed

    Knight, Derek E

    2002-04-01

    The release of regulated secretory granules is known to be calcium dependent. To examine the Ca2+-dependence of other exocytic fusion events, transferrin recycling in bovine chromaffin cells was examined. Internalised 125I-transferrin was released constitutively from cells with a half-time of about 7 min. Secretagogues that triggered catecholamine secretion doubled the rate of 125I-transferrin release, the time courses of the two triggered secretory responses being similar. The triggered 125I-transferrin release came from recycling endosomes rather than from sorting endosomes or a triggered secretory vesicle pool. Triggered 125I-transferrin release, like catecholamine secretion from the same cells, was calcium dependent but the affinities for calcium were very different. The extracellular calcium concentrations that gave rise to half-maximal evoked secretion were 0.1 mm for 125I-transferrin and 1.0 mm for catecholamine, and the intracellular concentrations were 0.1 microm and 1 microm, respectively. There was significant 125I-transferrin recycling in the virtual absence of intracellular Ca2+, but the rate increased when Ca2+ was raised above 1 nm, and peaked at 1 microm when the rate had doubled. Botulinum toxin type D blocked both transferrin recycling and catecholamine secretion. These results indicate that a major component of the vesicular transport required for the constitutive recycling of transferrin in quiescent cells is calcium dependent and thus under physiological control, and also that some of the molecular machinery involved in transferrin recycling/fusion processes is shared with that for triggered neurosecretion.

  19. Stimulus-secretion coupling in chromaffin cells isolated from bovine adrenal medulla

    PubMed Central

    Schneider, Allan S.; Herz, Ruth; Rosenheck, Kurt

    1977-01-01

    Bovine adrenal chromaffin cells were isolated by removal of the cortex and sequential collagenase digestion of the medulla. The catecholamine secretory function of these cells was characterized with respect to acetylcholine stimulation, cation requirements, and cytoskeletal elements. The dose-response curve for stimulated release had its half-maximum value at 10-5 M acetylcholine, and maximum secretion was on the average 7 times that of control basal secretion. The differential release of epinephrine versus norepinephrine after stimulation with 0.1 mM acetylcholine occurred in proportion to their distribution in the cell suspension. The cholinergic receptors were found to be predominantly nicotinic. The kinetics of catecholamine release were rapid, with significant secretion occurring in less than 60 sec and 85% of maximum secretion within 5 min. A critical requirement for calcium in the extracellular medium was demonstrated, and 80% of maximum secretion was achieved at physiologic calcium concentrations. Stimulation by excess potassium (65 mM KCl) also induced catecholamine secretion which differed from acetylcholine stimulation in being less potent, in having a different dependence on calcium concentration, and in its response to the local anesthetic tetracaine. Tetracaine, which is thought to inhibit membrane cation permeability, was able to block acetylcholine-stimulated but not KCl-stimulated secretion. The microtubule disrupting agent vinblastine was able to block catecholamine release whereas the microfilament disrupter cytochalasin B had little effect. The results show the isolated bovine chromaffin cells to be viable, functioning, and available in large quantity. These cells now provide an excellent system for studying cell surface regulation of hormone and neurotransmitter release. PMID:270738

  20. Modeling drug release from functionalized magnetic nanoparticles actuated by non-heating low frequency magnetic field

    NASA Astrophysics Data System (ADS)

    Golovin, Y.; Golovin, D.; Klyachko, N.; Majouga, A.; Kabanov, A.

    2017-02-01

    Various plausible acceleration mechanisms of drug release from nanocarriers composed of a single-domain magnetic nanoparticle core with attached long macromolecule chains activated by low frequency non-heating alternating magnetic field (AMF) are discussed. The most important system characteristics affecting the AMF exposure impact are determined. Impact of several reasonable mechanisms is estimated analytically or obtained using numerical modeling. Some conditions providing manifold release acceleration as a result from exposure in AMF are found.

  1. High-Energy Aspects of Small-Scale Energy Release at the Sun

    NASA Astrophysics Data System (ADS)

    Glesener, L.; Vievering, J. T.; Wright, P. J.; Hannah, I. G.; Panchapakesan, S. A.; Ryan, D.; Krucker, S.; Hudson, H. S.; Grefenstette, B.; White, S. M.; Smith, D. M.; Marsh, A.; Kuhar, M.; Christe, S.; Buitrago-Casas, J. C.; Musset, S.; Inglis, A. R.

    2017-12-01

    Large, powerful solar flares have been investigated in detail for decades, but it is only recently that high-energy aspects of small flares could be measured. These small-scale energy releases offer the opportunity to examine how particle acceleration characteristics scale down, which is critical for constraining energy transfer theories such as magnetic reconnection. Probing to minuscule flare sizes also brings us closer to envisioning the characteristics of the small "nanoflares" that may be responsible for heating the corona. A new window on small-scale flaring activity is now opening with the use of focusing hard X-ray instruments to observe the Sun. Hard X-rays are emitted by flare-accelerated electrons and strongly heated plasma, providing a relatively direct method of measuring energy release and particle acceleration properties. This work will show the first observations of sub-A class microflares using the FOXSI sounding rocket and the NuSTAR astrophysics spacecraft, both of which directly focus hard X-rays but have limited observing time on the Sun. These instruments serve as precursors to a spacecraft version of FOXSI, which will explore energy release across the entire range of flaring activity.

  2. A modified acceleration-based monthly gravity field solution from GRACE data

    NASA Astrophysics Data System (ADS)

    Chen, Qiujie; Shen, Yunzhong; Chen, Wu; Zhang, Xingfu; Hsu, Houze; Ju, Xiaolei

    2015-08-01

    This paper describes an alternative acceleration approach for determining GRACE monthly gravity field models. The main differences compared to the traditional acceleration approach can be summarized as: (1) The position errors of GRACE orbits in the functional model are taken into account; (2) The range ambiguity is eliminated via the difference of the range measurements and (3) The mean acceleration equation is formed based on Cowell integration. Using this developed approach, a new time-series of GRACE monthly solution spanning the period January 2003 to December 2010, called Tongji_Acc RL01, has been derived. The annual signals from the Tongji_Acc RL01 time-series agree well with those from the GLDAS model. The performance of Tongji_Acc RL01 shows that this new model is comparable with the RL05 models released by CSR and JPL as well as with the RL05a model released by GFZ.

  3. Catecholamine exocytosis during low frequency stimulation in mouse adrenal chromaffin cells is primarily asynchronous and controlled by the novel mechanism of Ca2+ syntilla suppression

    PubMed Central

    Lefkowitz, Jason J; DeCrescenzo, Valerie; Duan, Kailai; Bellve, Karl D; Fogarty, Kevin E; Walsh, John V; ZhuGe, Ronghua

    2014-01-01

    Adrenal chromaffin cells (ACCs), stimulated by the splanchnic nerve, generate action potentials (APs) at a frequency near 0.5 Hz in the resting physiological state, at times described as ‘rest and digest’. How such low frequency stimulation in turn elicits sufficient catecholamine exocytosis to set basal sympathetic tone is not readily explained by the classical mechanism of stimulus–secretion coupling, where exocytosis is synchronized to AP-induced Ca2+ influx. By using simulated action potentials (sAPs) at 0.5 Hz in isolated patch-clamped mouse ACCs, we show here that less than 10% of all catecholaminergic exocytosis, measured by carbon fibre amperometry, is synchronized to an AP. The asynchronous phase, the dominant phase, of exocytosis does not require Ca2+ influx. Furthermore, increased asynchronous exocytosis is accompanied by an AP-dependent decrease in frequency of Ca2+ syntillas (i.e. transient, focal Ca2+ release from internal stores) and is ryanodine sensitive. We propose a mechanism of disinhibition, wherein APs suppress Ca2+ syntillas, which themselves inhibit exocytosis as they do in the case of spontaneous catecholaminergic exocytosis. PMID:25128575

  4. The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus: a possible link between cytokine production and sympathetic transmission.

    PubMed

    Donoso, Verónica; Gomez, Christian R; Orriantia, Miguel Angel; Pérez, Viviana; Torres, Claudio; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Morales, Bernardo; Fernandez, Ricardo; Imarai, Mónica; Huidobro-Toro, Juan Pablo; Sierra, Felipe; Acuña-Castillo, Claudio

    2008-12-01

    Aging results in a general decline in the response to external insults, including acute inflammatory challenges. In young animals, the inflammatory response requires activation of the sympathetic system, including neurotransmitters such as ATP, and catecholamines (epinephrine and norepinephrine). To test whether aging affects activation of this axis, and whether this in turn might affect cytokine release, we administered lipopolysaccharide (LPS) i.p. to adult, middle-aged and aged Fisher 344 rats (6-, 15- and 23-month old, respectively) and evaluated the early (0-12h) serum levels of Neuropeptide-Y (NP-Y), ATP and vanillyl mandelic acid (VMA, as an indirect measurement of catecholamine levels). In addition, we evaluated the association between these factors and serum levels of the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL-10). Induction of both ATP and NP-Y was markedly reduced in the serum of aged animals, when compared to their younger counterparts, while induction of VMA was not affected by age. In spite of these changes, serum levels of TNFalpha and IL-10 were strongly hyper induced and delayed in aged rats. The results suggest that during aging there is a dysregulation in sympathetic neurotransmitter regulatory mechanisms, and this might play a role in the impairment of the inflammatory response.

  5. The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus. A possible link between cytokine production and sympathetic transmission

    PubMed Central

    Donoso, Verónica; Gomez, Christian R.; Orriantia, Miguel Ángel; Pérez, Viviana; Torres, Claudio; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Morales, Bernardo; Fernandez, Ricardo; Imarai, Mónica; Huidobro-Toro, Juan Pablo; Sierra, Felipe; Acuña-Castillo, Claudio

    2009-01-01

    Aging results in a general decline in the response to external insults, including acute inflammatory challenges. In young animals, the inflammatory response requires activation of the sympathetic system, including neurotransmitters such as ATP, and catecholamines (epinephrine and norepinephrine). To test whether aging affects activation of this axis, and whether this in turn might affect cytokine release, we administered lipopolysaccharide (LPS) i.p. to adult, middle-aged and aged Fisher 344 rats (6, 15 and 23-month old, respectively) and evaluated the early (0–12 hours) serum levels of Neuropeptide-Y (NP-Y), ATP and vanillyl mandelic acid (VMA, as an indirect measurement of catecholamine levels). In addition, we evaluated the association between these factors and serum levels of the cytokines tumor necrosis factor-alpha (TNFα)3 and interleukin-10 (IL-10). Induction of both ATP and NP-Y was markedly reduced in the serum of aged animals, when compared to their younger counterparts, while induction of VMA was not affected by age. In spite of these changes, serum levels of TNFα and IL-10 were strongly hyper induced and delayed in aged rats. The results suggest that during aging there is a dysregulation in sympathetic neurotransmitter regulatory mechanisms, and this might play a role in the impairment of the inflammatory response. PMID:18973771

  6. Evaluating Weathering of Food Packaging Polyethylene-Nano-clay Composites: Release of Nanoparticles and their Impacts.

    PubMed

    Han, Changseok; Zhao, Amy; Varughese, Eunice; Sahle-Demessie, E

    2018-01-01

    Nano-fillers are increasingly incorporated into polymeric materials to improve the mechanical, barrier or other matrix properties of nanocomposites used for consumer and industrial applications. However, over the life cycle, these nanocomposites could degrade due to exposure to environmental conditions, resulting in the release of embedded nanomaterials from the polymer matrix into the environment. This paper presents a rigorous study on the degradation and the release of nanomaterials from food packaging composites. Films of nano-clay-loaded low-density polyethylene (LDPE) composite for food packaging applications were prepared with the spherilene technology and exposed to accelerated weathering of ultraviolet (UV) irradiation or low concentration of ozone at 40 °C. The changes in the structural, surface morphology, chemical and physical properties of the films during accelerated weathering were investigated. Qualitative and quantitative changes in properties of pristine and aged materials and the release of nano-clay proceeded slowly until 130 hr irradiation and then accelerated afterward resulting complete degradation. Although nano-clay increased the stability of LDPE and improved thermal and barrier properties, they accelerated the UV oxidation of LDPE. With increasing exposure to UV, the surface roughness, chemiluminescence index, and carbonyl index of the samples increased while decreasing the intensity of the wide-angle X-ray diffraction pattern. Nano-clay particles with sizes ranging from 2-8 nm were released from UV and ozone weathered composite. The concentrations of released nanoparticles increased with an increase in aging time. Various toxicity tests, including reactive oxygen species generation and cell activity/viability were also performed on the released nano-clay and clay polymer. The released nano-clays basically did not show toxicity. Our combined results demonstrated the degradation properties of nano-clay particle-embedded LDPE composites

  7. The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

    PubMed

    Hodgman, Michael; Holland, Michael G; Englich, Ulrich; Wojcik, Susan M; Grant, William D; Leitner, Erich

    2016-12-01

    Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

  8. Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells.

    PubMed Central

    Kuijpers, G A; Vergara, L A; Calvo, S; Yadid, G

    1994-01-01

    1. Strychnine, which is known as a potent and selective antagonist of the inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultured adrenal chromaffin cells in a concentration-dependent (1-100 microM) manner. At 10 microM nicotine, the IC50 value for strychnine is approximately 30 microM. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca2+ concentration. 2. The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K+ concentration, histamine or angiotensin II. 3. Strychnine competes with nicotine in its effect, but not modify the apparent positive cooperatively of the nicotine binding sites. In the absence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory action of strychnine on this release. 4. These results suggest that strychnine interacts with the agonist binding site of the nicotinic acetylcholine receptor in chromaffin cells, thus exerting a pharmacological effect independently of the glycine receptor. PMID:7834198

  9. Systemic administration of WIN 55,212-2 increases norepinephrine release in the rat frontal cortex.

    PubMed

    Oropeza, V C; Page, M E; Van Bockstaele, E J

    2005-06-07

    Cannabinoid agonists modulate a variety of behavioral functions by activating cannabinoid receptors that are widely distributed throughout the central nervous system. In the present study, norepinephrine efflux was assessed in the frontal cortex of rats that received a systemic administration of the cannabinoid agonist, WIN 55,212-2. The synthetic cannabinoid agonist dose-dependently increased the release of norepinephrine in this brain region. Pretreatment with the cannabinoid receptor antagonist, SR 141716A, blocked the increase in norepinephrine release. To identify sites of cellular activation, immunocytochemical detection of c-Fos was combined with detection of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in the brainstem nucleus locus coeruleus (LC), a region that is the sole source of norepinephrine to the frontal cortex. Systemic administration of WIN 55,212-2 significantly increased the number of c-Fos immunoreactive cells within TH-containing neurons in the LC compared to vehicle-treated rats. Pretreatment with SR 141716A inhibited the WIN 55,212-2 induced c-Fos expression, while the antagonist alone did not affect c-Fos expression. Taken together, these data indicate that systemically administered cannabinoid agonists stimulate norepinephrine release in the frontal cortex by activating noradrenergic neurons in the coeruleo-frontal cortex pathway. These effects may partially underlie changes in attention, arousal and anxiety observed following exposure to cannabis-based drugs.

  10. On Solar Wind Origin and Acceleration: Measurements from ACE

    NASA Astrophysics Data System (ADS)

    Stakhiv, Mark; Lepri, Susan T.; Landi, Enrico; Tracy, Patrick; Zurbuchen, Thomas H.

    2016-10-01

    The origin and acceleration of the solar wind are still debated. In this paper, we search for signatures of the source region and acceleration mechanism of the solar wind in the plasma properties measured in situ by the Advanced Composition Explorer spacecraft. Using the elemental abundances as a proxy for the source region and the differential velocity and ion temperature ratios as a proxy for the acceleration mechanism, we are able to identify signatures pointing toward possible source regions and acceleration mechanisms. We find that the fast solar wind in the ecliptic plane is the same as that observed from the polar regions and is consistent with wave acceleration and coronal-hole origin. We also find that the slow wind is composed of two components: one similar to the fast solar wind (with slower velocity) and the other likely originating from closed magnetic loops. Both components of the slow solar wind show signatures of wave acceleration. From these findings, we draw a scenario that envisions two types of wind, with different source regions and release mechanisms, but the same wave acceleration mechanism.

  11. Dissemination and support of ARGUS for accelerator applications

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

    Not Available

    The ARGUS code is a three-dimensional code system for simulating for interactions between charged particles, electric and magnetic fields, and complex structure. It is a system of modules that share common utilities for grid and structure input, data handling, memory management, diagnostics, and other specialized functions. The code includes the fields due to the space charge and current density of the particles to achieve a self-consistent treatment of the particle dynamics. The physic modules in ARGUS include three-dimensional field solvers for electrostatics and electromagnetics, a three-dimensional electromagnetic frequency-domain module, a full particle-in-cell (PIC) simulation module, and a steady-state PIC model.more » These are described in the Appendix to this report. This project has a primary mission of developing the capabilities of ARGUS in accelerator modeling of release to the accelerator design community. Five major activities are being pursued in parallel during the first year of the project. To improve the code and/or add new modules that provide capabilities needed for accelerator design. To produce a User's Guide that documents the use of the code for all users. To release the code and the User's Guide to accelerator laboratories for their own use, and to obtain feed-back from the. To build an interactive user interface for setting up ARGUS calculations. To explore the use of ARGUS on high-power workstation platforms.« less

  12. Hot spots and dark current in advanced plasma wakefield accelerators

    DOE PAGES

    Manahan, G. G.; Deng, A.; Karger, O.; ...

    2016-01-29

    Dark current can spoil witness bunch beam quality and acceleration efficiency in particle beam-driven plasma wakefield accelerators. In advanced schemes, hot spots generated by the drive beam or the wakefield can release electrons from higher ionization threshold levels in the plasma media. Likewise, these electrons may be trapped inside the plasma wake and will then accumulate dark current, which is generally detrimental for a clear and unspoiled plasma acceleration process. The strategies for generating clean and robust, dark current free plasma wake cavities are devised and analyzed, and crucial aspects for experimental realization of such optimized scenarios are discussed.

  13. Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor β2.

    PubMed

    Long, Qiqi; Liu, Xishi; Qi, Qiuming; Guo, Sun-Wei

    2016-11-01

    (a non-specific ADRB agonist), respectively. In all three experiments, the bodyweight and hotplate latency were evaluated before sacrifice 14 days after the induction. In all experimentations, the lesion weight was evaluated and the harvested ectopic endometrial tissue samples were subjected to immunohistochemistry analysis of vascular endothelial growth factor (VEGF), CD31-positive microvessels, proliferating cell nuclear antigen (PCNA), phosphorylated CREB, ADRB1, ADRB2, ADRB3, adrenergic receptor α1 (ADRA1) and ADRA2. Exposure to chronic stress accelerated the development of endometriosis and exacerbated the endometriosis-associated generalized hyperalgesia. This promotional effect is likely to be mediated through the systemic activation of the sympatho-adreno-medullary (SAM) axis, which results in subsequent release of catecholamines. The surging catecholamines may activate ADRB2 and CREB, yielding increased angiogenesis and cellular proliferation in ectopic endometrium in mice with induced endometriosis. In addition, β adrenergic receptor blockade completely abolished the promotional effect of chronic stress, likely through suppression of ADRB2 and CREB activation, thus suppressing angiogenesis and proliferation. Moreover, a non-specific adrenergic β agonist and a specific adrenergic β2 agonist, but not non-specific adrenergic α agonist, acted similarly to chronic stress, accelerating the development of endometriosis and exacerbating the generalized hyperalgesia in mice with pre-existing endometriosis. NA. This study is limited by the use of immunohistochemistry analyses only and the lack of molecular data. The present study provides the experimental evidence that chronic stress can promote the development of endometriosis through the activation of ADRB2. Given ADRB2 is also expressed in human endometriosis and appears to be functional, and in light of recent awareness that adrenergic signaling plays critical roles in tumorigenesis, it is likely that

  14. Accelerated Seismic Release and Related Aspects of Seismicity Patterns on Earthquake Faults

    NASA Astrophysics Data System (ADS)

    Ben-Zion, Y.; Lyakhovsky, V.

    Observational studies indicate that large earthquakes are sometimes preceded by phases of accelerated seismic release (ASR) characterized by cumulative Benioff strain following a power law time-to-failure relation with a term (tf-t)m, where tf is the failure time of the large event and observed values of m are close to 0.3. We discuss properties of ASR and related aspects of seismicity patterns associated with several theoretical frameworks. The subcritical crack growth approach developed to describe deformation on a crack prior to the occurrence of dynamic rupture predicts great variability and low asymptotic values of the exponent m that are not compatible with observed ASR phases. Statistical physics studies assuming that system-size failures in a deforming region correspond to critical phase transitions predict establishment of long-range correlations of dynamic variables and power-law statistics before large events. Using stress and earthquake histories simulated by the model of Ben-Zion (1996) for a discrete fault with quenched heterogeneities in a 3-D elastic half space, we show that large model earthquakes are associated with nonrepeating cyclical establishment and destruction of long-range stress correlations, accompanied by nonstationary cumulative Benioff strain release. We then analyze results associated with a regional lithospheric model consisting of a seismogenic upper crust governed by the damage rheology of Lyakhovskyet al. (1997) over a viscoelastic substrate. We demonstrate analytically for a simplified 1-D case that the employed damage rheology leads to a singular power-law equation for strain proportional to (tf-t)-1/3, and a nonsingular power-law relation for cumulative Benioff strain proportional to (tf-t)1/3. A simple approximate generalization of the latter for regional cumulative Benioff strain is obtained by adding to the result a linear function of time representing a stationary background release. To go beyond the analytical

  15. [The effects of perioperative continuous administration of mivazerol on early postoperative hemodynamics and plasma catecholamines after major surgery].

    PubMed

    Apitzsch, H; Olthoff, D; Thieme, V; Vetter, B; Wiegel, M

    2000-08-01

    During and after surgical procedures a strong activation of the sympatho-adrenergic system is common with correlation to adverse cardiac outcome. Several drugs (alpha 2-adrenoceptor-agonists, beta blockers) are discussed to prevent this reaction. The new alpha 2-adrenoceptor-agonist mivazerol with marked specificity for alpha 2-adrenergic receptors may be suitable for this indication. The aim of the present study was to investigate the effects of perioperative continuous administration of mivazerol on plasma catecholamines, body temperature and calculated haemodynamic parameters in the early postoperative period in cardiac risk patients undergoing non-cardiac surgery. 36 patients with known coronary heart disease or risk factors for coronary heart disease scheduled for elective abdominal or vascular surgery were included in the study. Patients received either mivazerol (n = 18) or placebo (n = 18) [initial dose 4 micrograms kg-1 for 10 minutes before induction of anaesthesia, followed by a continuous infusion of 1.5 micrograms kg-1 h-1 intraoperatively and for as long as 72 h after surgery] in a double-blinded, randomized manner. Blood pressure, heart rate and body temperature were measured every 10 minutes until 240 minutes after arrival at the ICU. During 240 minutes after arrival at the ICU measured parameters (CVP, PAP, PCWP, SaO2, SvO2, CO), calculated parameters (CI, SVR, PVR, VO2) and plasma catecholamines were measured at defined time intervalls. The plasma concentrations of epinephrine and norepinephrine and the heart rate were significantly lower in the mivazerol group in the study period. Regarding blood pressure and body temperature there were no differences between the groups. At some measuring points preload was higher in the mivazerol group, but there were no differences between the groups for measured (SaO2, SvO2, CO) and calculated (CI, SVR, PVR, VO2) cardiorespiratory parameters. The incidence of shivering, nausea and vomiting were similar in both

  16. Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis

    NASA Astrophysics Data System (ADS)

    Li, Li; Peng, Xiaozhong; Qin, Yongbao; Wang, Renchong; Tang, Jingli; Cui, Xu; Wang, Ting; Liu, Wenlong; Pan, Haobo; Li, Bing

    2017-03-01

    By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.

  17. Exercise capacity is associated with endothelin-1 release during emotional excitement in coronary artery disease patients.

    PubMed

    Tulppo, Mikko P; Piira, Olli-Pekka; Hautala, Arto J; Kiviniemi, Antti M; Miettinen, Johanna A; Huikuri, Heikki V

    2014-08-01

    Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are increased and heart rate variability [SD of normal to normal R-R intervals (SDNN)] decreased during emotional excitement, but individual responses vary. We tested the hypothesis that exercise capacity is associated with physiological responses caused by real-life emotional excitement. We measured the plasma levels of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice hockey spectators (n = 51; age, 59 ± 9 years) with stable coronary artery disease (CAD) at baseline and during the Finnish National Ice Hockey League's final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test and left ventricular ejection fraction (LVEF) were measured on a separate day. ET-1 response from baseline to emotional excitement correlated with maximal METs (r = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were entered the model as independent variables to explain ET-1 response. This model explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly correlated with ET-1 response (β = -0.45; partial correlation r = -0.43; P = 0.002), followed by BMI (β = -0.31; partial correlation r = -0.31; P = 0.033) and LVEF (β = -0.30; partial correlation r = -0.33; P = 0.023). Exercise capacity may protect against further cardiovascular events in CAD patients, because it is associated with reduced ET-1 release during emotional excitement. Copyright © 2014 the American Physiological Society.

  18. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

    PubMed

    Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; Del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

    2016-05-01

    Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Acceleration of robust "biotube" vascular graft fabrication by in-body tissue architecture technology using a novel eosin Y-releasing mold.

    PubMed

    Nakayama, Yasuhide; Tsujinaka, Takahiro

    2014-02-01

    A novel eosin Y-releasing mold was designed to accelerate the fabrication of in vivo tissue engineered autologous vascular prosthetic tissues, called the "biotubes." The mold was prepared by addition of an aqueous solution of eosin Y (1∼6 w/v%) to the agar gel (0.3%), which was attached to the luminal surface of the microporous acrylate tube (diameter, 5 mm; length, 28 mm; pore size, 0.5 mmϕ). The eosin Y release period was controlled by the number of pores (3∼160). On embedding the molds into dorsal, subcutaneous pouches of rats for 1 week, completely encapsulated biotubes, mainly consisting of collagen, with thick walls (418.2 ± 173.4 μm) and robust mechanical properties (elastic modulus, 956.2 ± 196.5 kPa; burst pressure 5850 ± 2383 mmHg) were formed. These values were, respectively, more than 4.3, 3.8, and 5.6 times greater than the corresponding controls (acrylate rods). The high elastic modulus of the biotubes was obtained even with a small number of micropores (3), and a low concentration of eosin Y (1%) within a very short embedding period (5 days), irrespective of rat weights. This innovative method for rapid production of vascular grafts with thick walls and robust mechanical properties may be adaptable for the sub-emergency clinical use of biotubes in regenerative medicine. Copyright © 2013 Wiley Periodicals, Inc.

  20. [Hypertension, catecholamine hypersecretion and potential for metastasis: recent progress in the pathophysiology and genetics of pheochromocytoma and paraganglioma].

    PubMed

    Plouin, Pierre-François; Amar, Laurence; Gimenez-Roqueplo, Anne-paule

    2015-01-01

    Pheochromocytomas and paragangliomas are catecholamine-secreting tumors usually associated with arterial hypertension. They can contribute to acute cardiovascular events. Ten to 15 percent of tumors are metastatic. Autosomal dominant gene alterations are present in more than a third of cases. The secretory phenotype and the risk of malignancy are driven by the presence of gene mutations, specifically in the subunits of succinate dehydrogenase. Recent advances in genomics have clinical implications for family screening, biological follow-up, prediction of the risk of recurrence, and therapeutic options in cases with malignant recurrence.

  1. The principle of phase stability and the accelerator program at Berkeley, 1945--1954

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

    Lofgren, E.J.

    1994-07-01

    The discovery of the Principle of Phase Stability by Vladimir Veksler and Edwin McMillian and the end of the war released a surge of accelerator activity at the Lawrence Berkeley Laboratory (then The University of California Radiation Laboratory). Six accelerators incorporating the Principle of Phase Stability were built in the period 1945--1954.

  2. Particle acceleration at a reconnecting magnetic separator

    NASA Astrophysics Data System (ADS)

    Threlfall, J.; Neukirch, T.; Parnell, C. E.; Eradat Oskoui, S.

    2015-02-01

    Context. While the exact acceleration mechanism of energetic particles during solar flares is (as yet) unknown, magnetic reconnection plays a key role both in the release of stored magnetic energy of the solar corona and the magnetic restructuring during a flare. Recent work has shown that special field lines, called separators, are common sites of reconnection in 3D numerical experiments. To date, 3D separator reconnection sites have received little attention as particle accelerators. Aims: We investigate the effectiveness of separator reconnection as a particle acceleration mechanism for electrons and protons. Methods: We study the particle acceleration using a relativistic guiding-centre particle code in a time-dependent kinematic model of magnetic reconnection at a separator. Results: The effect upon particle behaviour of initial position, pitch angle, and initial kinetic energy are examined in detail, both for specific (single) particle examples and for large distributions of initial conditions. The separator reconnection model contains several free parameters, and we study the effect of changing these parameters upon particle acceleration, in particular in view of the final particle energy ranges that agree with observed energy spectra.

  3. The cyanogenic syndrome in rubber tree Hevea brasiliensis: tissue-damage-dependent activation of linamarase and hydroxynitrile lyase accelerates hydrogen cyanide release

    PubMed Central

    Kadow, Daniel; Voß, Karsten; Selmar, Dirk; Lieberei, Reinhard

    2012-01-01

    Background and Aims The release of hydrogen cyanide (HCN) from injured plant tissue affects multiple ecological interactions. Plant-derived HCN can act as a defence against herbivores and also plays an important role in plant–pathogen interactions. Crucial for activity as a feeding deterrent is the amount of HCN generated per unit time, referred to as cyanogenic capacity (HCNc). Strong intraspecific variation in HCNc has been observed among cyanogenic plants. This variation, in addition to genotypic variability (e.g. in Trifolium repens), can result from modifications in the expression level of the enzymes involved in either cyanogenic precursor formation or HCN release (as seen in Sorghum bicolor and Phaseolus lunatus). Thus, a modification or modulation of HCNc in reaction to the environment can only be achieved from one to the next generation when under genetic control and within days or hours when transcriptional regulations are involved. In the present study, it is shown that in rubber tree (Hevea brasiliensis) HCNc is modulated by post-translational activity regulation of the key enzymes for cyanide release. Methods Linamarase (LIN) and hydroxynitrile lyase (HNL) activity was determined by colorimetric assays utilizing dissociation of the substrates p-nitrophenyl-β-d-glucopyranoside and acetone cyanohydrin, respectively. Key Results In rubber tree leaves, LIN and HNL show up to ten-fold increased activity in response to tissue damage. This enzyme activation occurs within seconds and results in accelerated HCN formation. It is restricted to the damaged leaf area and depends on the severity of tissue damage. Conclusions LIN and HNL activation (in contrast to genetic and transcriptional regulations) allows an immediate, local and damage type-dependent modulation of the cyanogenic response. Accordingly, this post-translational activation plays a decisive role in the defence of H. brasiliensis against herbivores as well as pathogens and may allow more flexible

  4. Imidacloprid, a neonicotinoid insecticide, facilitates tyrosine hydroxylase transcription and phenylethanolamine N-methyltransferase mRNA expression to enhance catecholamine synthesis and its nicotine-evoked elevation in PC12D cells.

    PubMed

    Kawahata, Ichiro; Yamakuni, Tohru

    2018-02-01

    Imidacloprid is a neonicotinoid insecticide acting as an agonist of nicotinic acetylcholine receptors (nAChRs) in the target insects. However, questions about the safety to mammals, including human have emerged. Overactivation of mammalian peripheral catecholaminergic systems leads to onset of tachycardia, hypertension, vomiting, etc., which have been observed in acutely imidacloprid-poisoned patients as well. Physiological activation of the nAChRs is known to drive catecholamine biosynthesis and secretion in mammalian adrenal chromaffin cells. Yet, the impacts of imidacloprid on the catecholaminergic function of the chromaffin cells remain to be evaluated. In this study using PC12D cells, a catecholaminergic cell line derived from the medulla chromaffin-cell tumors of rat adrenal gland, we examined whether imidacloprid itself could impact the catecholamine-synthesizing ability. Imidacloprid alone did facilitate tyrosine hydroxylase (TH) transcription via activation of α3β4 nAChR and the α7 subunit-comprising receptor. The insecticide showed the TH transcription-facilitating ability at the concentrations of 3 and 30 μM, at which acetylcholine is known to produce physiological responses, including catecholamine secretion through the nAChRs in adrenal chromaffin cells. The insecticide-facilitated TH transcription was also dependent on PKA- and RhoA-mediated signaling pathways. The insecticide coincidentally raised levels of TH and phenylethanolamine N-methyltransferase (PNMT) mRNA, and as a consequence, increased catecholamine production, although the efficacy of the neonicotinoid was lesser than that of nicotine, indicating its partial agonist-like action. Intriguingly, in cultured rat adrenal chromaffin cells, imidacloprid did increase levels of TH and PNMT protein. When the chromaffin cells were treated with nicotine in the presence of the insecticide, nicotine-elevated adrenaline production was enhanced due to facilitation of nicotine-increased TH and PNMT

  5. Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

    PubMed

    Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

    2001-01-01

    A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

  6. Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

    PubMed

    Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

    2007-10-01

    In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

  7. ON SOLAR WIND ORIGIN AND ACCELERATION: MEASUREMENTS FROM ACE

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

    Stakhiv, Mark; Lepri, Susan T.; Landi, Enrico

    The origin and acceleration of the solar wind are still debated. In this paper, we search for signatures of the source region and acceleration mechanism of the solar wind in the plasma properties measured in situ by the Advanced Composition Explorer spacecraft. Using the elemental abundances as a proxy for the source region and the differential velocity and ion temperature ratios as a proxy for the acceleration mechanism, we are able to identify signatures pointing toward possible source regions and acceleration mechanisms. We find that the fast solar wind in the ecliptic plane is the same as that observed frommore » the polar regions and is consistent with wave acceleration and coronal-hole origin. We also find that the slow wind is composed of two components: one similar to the fast solar wind (with slower velocity) and the other likely originating from closed magnetic loops. Both components of the slow solar wind show signatures of wave acceleration. From these findings, we draw a scenario that envisions two types of wind, with different source regions and release mechanisms, but the same wave acceleration mechanism.« less

  8. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

    PubMed

    Bunzow, J R; Sonders, M S; Arttamangkul, S; Harrison, L M; Zhang, G; Quigley, D I; Darland, T; Suchland, K L; Pasumamula, S; Kennedy, J L; Olson, S B; Magenis, R E; Amara, S G; Grandy, D K

    2001-12-01

    The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

  9. N2-fixing red alder indirectly accelerates ecosystem nitrogen cycling

    USGS Publications Warehouse

    Perakis, Steven S.; Matkins, Joselin J.; Hibbs, David E.

    2012-01-01

    Symbiotic N2-fixing tree species can accelerate ecosystem N dynamics through decomposition via direct pathways by producing readily decomposed leaf litter and increasing N supply to decomposers, as well as via indirect pathways by increasing tissue and detrital N in non-fixing vegetation. To evaluate the relative importance of these pathways, we compared three-year decomposition and N dynamics of N2-fixing red alder leaf litter (2.34 %N) to both low-N (0.68 %N) and high-N (1.21 %N) litter of non-fixing Douglas-fir, and decomposed each litter source in four forests dominated by either red alder or Douglas-fir. We also used experimental N fertilization of decomposition plots to assess elevated N availability as a potential mechanism of N2-fixer effects on litter mass loss and N dynamics. Direct effects of N2-fixing red alder on decomposition occurred primarily as faster N release from red alder than Douglas-fir litter, but direct increases in N supply to decomposers via fertilization did not stimulate decomposition of any litter. Fixed N indirectly influenced detrital dynamics by increasing Douglas-fir tissue and litter N concentrations, which accelerated litter N release without accelerating mass loss. By increasing soil N, tissue N, and the rate of N release from litter of non-fixers, we conclude that N2-fixing vegetation can indirectly foster plant-soil feedbacks that contribute to the persistence of elevated N availability in terrestrial ecosystems.

  10. Perioperative Management of Severe Hypertension during Laparoscopic Surgery for Pheochromocytoma

    PubMed Central

    Erdoğan, Mehmet Ali; Uçar, Muharrem; Özkan, Ahmet Selim; Özgül, Ülkü; Durmuş, Mahmut

    2016-01-01

    Phaeochromocytoma is a catecholamine-secreting vascular tumour that is derived from chromaffin cell. Lethal cardiovascular complications, such as serious hypertension, myocardial infarction and aortic dissection, may occur because of uncontrolled catecholamine release. Each stage of anaesthesia management has vital importance because of this destructive catecholamine secretion that may occur during induction, perioperative stage and surgical manipulation. In this study, we report regarding the preoperative preparation and severe, persistent hypertension attack management with a combination of α-adrenergic blockade, β-adrenergic blockade, sodium nitroprusside and remifentanil in a patient who underwent laparoscopic surgery for phaeochromocytoma. PMID:27366556

  11. A painful pulsatile abdominal mass in a young man with elevated blood pressures: an unusual presentation of phaeochromocytoma.

    PubMed

    Lee, B M K; Ti, L K

    2002-08-01

    We report an unusual presentation of phaeochromocytoma in a young man with a painful, pulsatile abdominal mass and elevated blood pressures. This led to a delay in diagnosis and resulted in the administration of triggers of catecholamine release, possibly causing a catecholamine surge. This caused the development of catecholamine-induced cardiomyopathy and multiple organ failure, requiring inotropic and ventilatory support, intra-aortic balloon pump and dialysis. Fortunately, his condition reversed with supportive treatment and alpha-adrenergic blockade. This illustrates the importance of having a high index of suspicion of phaeochromocytoma, especially in young patients with elevated blood pressures.

  12. Stress hyperglycaemia as a result of a catecholamine producing tumour in an infant.

    PubMed

    de Grauw, Anne Mariëtte; Mul, Dick; van Noesel, Max M; Buddingh, Emilie P

    2015-09-04

    Hyperglycaemia commonly occurs in children presenting at the emergency department. In the absence of diabetic symptoms, this stress-related hyperglycaemia is considered a benign condition. We present a malignant cause of hyperglycaemia in an 11-month-old girl with concomitant symptoms of a neuroendocrine malignancy. One month earlier, she had undergone an episode of stress-related hyperglycaemia concurrent with fever during an upper respiratory tract infection. Current glucose level was 234 mg/dL (13 mmol/L) and the glycosylated haemoglobin level was 44 mmol/mol (6.2%) without metabolic acidosis. We observed periods of hyperglycaemia, sweating, flushing, hypertension and tachypnoea. Urinalysis showed high amounts of catecholamine intermediates. Abdominal ultrasound revealed a mass originating in the right adrenal gland. Histology confirmed the diagnosis of neuroblastoma. Hyperglycaemia in this patient was the first presenting symptom of a metabolically active neuroblastoma. 2015 BMJ Publishing Group Ltd.

  13. Mechanism of action of chromogranin A on catecholamine release: molecular modeling of the catestatin region reveals a β-strand/loop/β-strand structure secured by hydrophobic interactions and predictive of activity

    PubMed Central

    Tsigelny, Igor; Mahata, Sushil K.; Taupenot, Laurent; Preece, Nicholas E.; Mahata, Manjula; Khan, Imran; Parmer, Robert J.; O’Connor, Daniel T.

    2009-01-01

    A novel fragment of chromogranin A, known as ‘catestatin’ (bovine chromogranin A344–364), inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist, and may therefore constitute an endogenous autocrine feedback regulator of sympathoadrenal activity. To characterize how this activity depends on the peptide’s structure, we searched for common 3-dimensional motifs for this primary structure or its homologs. Catestatin’s primary structure bore significant (29–35.5% identity, general alignment score 44–57) sequence homology to fragment sequences within three homologs of known 3-dimensional structures, based on solved X-ray crystals: 8FAB, 1PKM, and 2IG2. Each of these sequences exists in nature as a β-strand/loop/β-strand structure, stabilized by hydrophobic interactions between the β-strands. The catestatin structure was stable during molecular dynamics simulations. The catestatin loop contains three Arg residues, whose electropositive side chains form the terminus of the structure, and give rise to substantial uncompensated charge asymmetry in the molecule. A hydrophobic moment plot revealed that catestatin is the only segment of chromogranin A predicted to contain amphiphilic β-strand. Circular dichroism in the far ultraviolet showed substantial (63%) β-sheet structure, especially in a hydrophobic environment. Alanine-substitution mutants of catestatin established a crucial role for the three central arginine residues in the loop (Arg351, Arg353, and Arg358), though not for two arginine residues in the strand region toward the amino-terminus. [125I]Catestatin bound to Torpedo membranes at a site other than the nicotinic agonist binding site. When the catestatin structure was ‘docked’ with the extracellular domain of the Torpedo nicotinic cholinergic receptor, it interacted principally with the β and δ subunits, in a relatively hydrophobic region of the cation

  14. Hydroxylation increases the neurotoxic potential of BDE-47 to affect exocytosis and calcium homeostasis in PC12 cells.

    PubMed

    Dingemans, Milou M L; de Groot, Aart; van Kleef, Regina G D M; Bergman, Ake; van den Berg, Martin; Vijverberg, Henk P M; Westerink, Remco H S

    2008-05-01

    Oxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants. Our objective was to investigate the effects of a hydroxylated metabolite of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells. We measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively. Acute exposure of PC12 cells to 6-OH-BDE-47 (5 microM) induced vesicular catecholamine release. Catecholamine release coincided with a transient increase in [Ca2+]i, which was observed shortly after the onset of exposure to 6-OH-BDE-47 (120 microM). An additional late increase in [Ca2+]i was often observed at > or =1 microM 6-OH-BDE-47. The initial transient increase was absent in cells exposed to the parent compound BDE-47, whereas the late increase was observed only at 20 microM. Using the mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and thapsigargin to empty intracellular Ca2+ stores, we found that the initial increase originates from emptying of the endoplasmic reticulum and consequent influx of extracellular Ca2+, whereas the late increase originates primarily from mitochondria. The hydroxylated metabolite 6-OH-BDE-47 is more potent in disturbing Ca2+ homeostasis and neurotransmitter release than the parent compound BDE-47. The present findings indicate that bioactivation by oxidative metabolism adds considerably to the neurotoxic potential of PBDEs. Additionally, based on the observed mechanism of action, a cumulative neurotoxic effect of PBDEs and ortho-substituted polychlorinated biphenyls on [Ca2+]i cannot be ruled out.

  15. Analysis of 14C-bearing compounds released by the corrosion of irradiated steel using accelerator mass spectrometry.

    PubMed

    Cvetković, B Z; Salazar, G; Kunz, D; Szidat, S; Wieland, E

    2018-06-25

    The combination of ion chromatography (IC) with accelerator mass spectrometry (AMS) was developed to determine the speciation of 14C-(radiocarbon) bearing organic compounds in the femto to pico molar concentration range. The development of this compound-specific radiocarbon analysis (CSRA) of carboxylic acids is reported and the application of the method on a leaching solution from neutron-irradiated steel is demonstrated. The background and the dynamic range of the AMS-based method were quantified. On using 14C-labelled standards, the measurements demonstrate the repeatability of the analytical method and the reproducible recovery of the main target carboxylic acids (i.e., acetate, formate, malonate, and oxalate). The detection limit was determined to be in the mid fmol 14C per L level while the dynamic range of the analytical method covers three orders of magnitude from the low fmol to the mid pmol 14C per L level. Cross contamination was found to be negligible during IC fractionation and was accounted for during eluate processing and 14C detection by AMS. The 14C-bearing carboxylates released from an irradiated steel nut into an alkaline leaching solution were analysed using the CSRA-based analytical method with the aim to check the applicability of the approach and develop appropriate sample preparation. The concentrations of 14C-bearing formate and acetate, the main organic corrosion products, were at a low pmol 14C per L level for convenient dimensions of the alkaline leaching experiment which demonstrates that compound-specific 14C AMS is an extremely sensitive analytical method for analysing 14C-bearing compounds. The content of total organic 14C in solution (TO14C) determined by the direct measurement of an aliquot of the leaching solution agrees well with the sum of the 14C concentrations of the individual carboxylates within the uncertainty of the data. Furthermore, the TO14C content is in good agreement with the calculated value using the corrosion rate

  16. Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats.

    PubMed

    Yogeeta, Surinder Kumar; Raghavendran, Hanumantha Rao Balaji; Gnanapragasam, Arunachalam; Subhashini, Rajakannu; Devaki, Thiruvengadam

    2006-10-27

    Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.

  17. Effects of endotoxin on monoamine metabolism in the rat.

    NASA Technical Reports Server (NTRS)

    Pohorecky, L. A.; Wurtman, R. J.; Taam, D.; Fine, J.

    1972-01-01

    Examination of effects of administered endotoxin on catecholamine metabolism in the rat brain, sympathetic neurons, and adrenal medulla. It is found that endotoxin, administered intraperitoneally, lowers the norepinephrine content in peripheral sympathetic neurons and the brain, and the catecholamine content in the adrenal medulla. It also accelerates the disappearance of H3-norepinephrine from all these tissues. It is therefore suggested that the effects of endotoxin on body temperature may be mediated in part by central non-adrenergic neurons.

  18. Observed form and action of the magnetic energy release in flares

    NASA Technical Reports Server (NTRS)

    Machado, Marcos E.; Moore, Ronald L.

    1986-01-01

    The observable spatio-temporal characteristics of the energy release in flares and their association with the magnetic environment and tracers of field dynamics are reviewed. The observations indicate that impulsive phase manifestations, like particle acceleration, may be related to the formation of neutral sheets at the interface between interacting bipoles, but that the site for the bulk of the energy release is within closed loops rather than at the interaction site.

  19. Natural ageing process accelerates the release of Ag from functional textile in various exposure scenarios

    PubMed Central

    Ding, Dahu; Chen, Lulu; Dong, Shaowei; Cai, Hao; Chen, Jifei; Jiang, Canlan; Cai, Tianming

    2016-01-01

    Natural ageing process occurs throughout the life cycle of textile products, which may possess influences on the release behavior of additives such as silver nanoparticles (Ag NPs). In this study, we assessed the releasability of Ag NPs from a Ag NPs functionalized textile in five different exposure scenarios (i.e. tap water (TW), pond water (PW), rain water (RW), artificial sweat (AS), and detergent solution (DS) along with deionized water (DW) as reference), which were very likely to occur throughout the life cycle of the textile. For the pristine textile, although the most remarkable release was found in DW (6–15 μg Ag/g textile), the highest release rate was found in RW (around 7 μg Ag/(g textile·h)). After ageing treatment, the total released Ag could be increased by 75.7~386.0% in DW, AS and DS. Morphological analysis clearly showed that the Ag NPs were isolated from the surface of the textile fibre due to the ageing treatment. This study provides useful information for risk assessment of nano-enhanced textile products. PMID:27869136

  20. Natural ageing process accelerates the release of Ag from functional textile in various exposure scenarios

    NASA Astrophysics Data System (ADS)

    Ding, Dahu; Chen, Lulu; Dong, Shaowei; Cai, Hao; Chen, Jifei; Jiang, Canlan; Cai, Tianming

    2016-11-01

    Natural ageing process occurs throughout the life cycle of textile products, which may possess influences on the release behavior of additives such as silver nanoparticles (Ag NPs). In this study, we assessed the releasability of Ag NPs from a Ag NPs functionalized textile in five different exposure scenarios (i.e. tap water (TW), pond water (PW), rain water (RW), artificial sweat (AS), and detergent solution (DS) along with deionized water (DW) as reference), which were very likely to occur throughout the life cycle of the textile. For the pristine textile, although the most remarkable release was found in DW (6-15 μg Ag/g textile), the highest release rate was found in RW (around 7 μg Ag/(g textile·h)). After ageing treatment, the total released Ag could be increased by 75.7~386.0% in DW, AS and DS. Morphological analysis clearly showed that the Ag NPs were isolated from the surface of the textile fibre due to the ageing treatment. This study provides useful information for risk assessment of nano-enhanced textile products.

  1. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.

    PubMed

    Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J M; Yeo, Robin; Zhang, Yue; Huynh, Frank K; Ilkayeva, Olga R; Hirschey, Matthew D; Grant, Ana R; Mair, William B

    2015-02-26

    Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal

    PubMed Central

    Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J.M.; Yeo, Robin; Zhang, Yue; Huynh, Frank K.; Ilkayeva, Olga R.; Hirschey, Matthew D.; Grant, Ana R.; Mair, William B.

    2015-01-01

    SUMMARY Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell-nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging. PMID:25723162

  3. Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment.

    PubMed

    Fedeli, Donatella; Carloni, Manuel; Nasuti, Cinzia; Gambini, Anna; Scocco, Vitangelo; Gabbianelli, Rosita

    2013-09-01

    The aim of this study is to gain more knowledge on the impact of early life pesticide exposure on premature aging. The effect of a low dose of the insecticide permethrin administered to rats during early life (1/50 LD50, from 6th to 21st day of life) was analyzed by measuring some metabolites in plasma and urine of 500-day-old animals. Significant differences in early life treated rats compared to the control group were found in the plasma levels of Ca(++), Na(+), 25-hydroxy-vitamin D, adrenaline, noradrenaline, nitric oxide, cholesterol and urea while in urine only Na(+) content was different. These results add information on the impact of permethrin during the neonatal period, supporting the evidence that early life environmental exposure to xenobiotics has long-term effects, inducing modifications in adulthood that can be revealed by the analysis of some macroelements, metabolites and catecholamines in plasma, when rats are 500 days old. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Using terlipressin in a pediatric patient with septic shock resistant to catecholamines

    PubMed Central

    Erdogan, Seher; Bosnak, Mehmet

    2017-01-01

    Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock. PMID:29270582

  5. The TiPS/TINS lecture. Catecholamines: from gene regulation to neuropsychiatric disorders.

    PubMed

    Mallet, J

    1996-04-01

    In addition to their ability to change the electrical properties of neurones, evidence suggests that neurotransmitters are able to alter the cell's metabolism. Transmitter phenotype is labile and expression might be regulated, during development, by the cellular environment of neurones. The study of a key enzyme in the synthesis of catecholamines, tyrosine hydroxylase (TH), has provided clues about these adaptive responses. This enzyme has a large molecular diversity, resulting from the differential splicing of its mRNA, which is tissue-specific and might result in long-term changes in activity of the enzyme and, therefore, in the availability of neurotransmitter at various synapses. The presence of different DNA sequences at the TH locus confers susceptibility to various disorders of the brain, including manic-depressive illness and schizophrenia. Indeed, an association between a rare variant allele of the gene encoding TH and the occurrence of schizophrenia has been found in several populations. New techniques being developed to treat diseases such as Parkinson's disease involve various gene therapies, including a method of transferring genes directly into nerve cells using an adenovirus-based system.

  6. The TiPS/TINS Lecture. Catecholamines: from gene regulation to neuropsychiatric disorders.

    PubMed

    Mallet, J

    1996-05-01

    In addition to their ability to change the electrical properties of neurons, evidence suggests that neurotransmitters are able to alter the cell's metabolism. Transmitter phenotype is labile and expression might be regulated, during development, by the cellular environment of neurons. The study of a key enzyme in the synthesis of catecholamines, tyrosine hydroxylase (TH), has provided clues about these adaptive responses. This enzyme has a large molecular diversity, resulting from the differential splicing of its mRNA, which is tissue-specific and might result in long-term changes in activity of the enzyme and, therefore, in the availability of neurotransmitter at various synapses. The presence of different DNA sequences at the TH locus confers susceptibility to various disorders of the brain, including manic-depressive illness and schizophrenia. Indeed, an association between a rare variant allele of the gene encoding TH and the occurrence of schizophrenia has been found in several populations. New techniques being developed to treat diseases such as Parkinson's disease involve various gene therapies, including a method of transferring genes directly into nerve cells using an adenovirus-based system.

  7. Using terlipressin in a pediatric patient with septic shock resistant to catecholamines.

    PubMed

    Erdogan, Seher; Bosnak, Mehmet

    2017-01-01

    Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock.

  8. Wide-Open: Accelerating public data release by automating detection of overdue datasets

    PubMed Central

    Poon, Hoifung; Howe, Bill

    2017-01-01

    Open data is a vital pillar of open science and a key enabler for reproducibility, data reuse, and novel discoveries. Enforcement of open-data policies, however, largely relies on manual efforts, which invariably lag behind the increasingly automated generation of biological data. To address this problem, we developed a general approach to automatically identify datasets overdue for public release by applying text mining to identify dataset references in published articles and parse query results from repositories to determine if the datasets remain private. We demonstrate the effectiveness of this approach on 2 popular National Center for Biotechnology Information (NCBI) repositories: Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA). Our Wide-Open system identified a large number of overdue datasets, which spurred administrators to respond directly by releasing 400 datasets in one week. PMID:28594819

  9. Wide-Open: Accelerating public data release by automating detection of overdue datasets.

    PubMed

    Grechkin, Maxim; Poon, Hoifung; Howe, Bill

    2017-06-01

    Open data is a vital pillar of open science and a key enabler for reproducibility, data reuse, and novel discoveries. Enforcement of open-data policies, however, largely relies on manual efforts, which invariably lag behind the increasingly automated generation of biological data. To address this problem, we developed a general approach to automatically identify datasets overdue for public release by applying text mining to identify dataset references in published articles and parse query results from repositories to determine if the datasets remain private. We demonstrate the effectiveness of this approach on 2 popular National Center for Biotechnology Information (NCBI) repositories: Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA). Our Wide-Open system identified a large number of overdue datasets, which spurred administrators to respond directly by releasing 400 datasets in one week.

  10. Increased GAD67 mRNA levels are correlated with in vivo GABA synthesis in the MPTP-treated catecholamine-depleted goldfish brain.

    PubMed

    Hibbert, Benjamin; Fung, Irene; McAuley, Rebecca; Larivière, Katherine; MacNeil, Brian; Bafi-Yeboa, Nana; Livesey, John; Trudeau, Vance

    2004-09-28

    The role of catecholamine neuronal input on GABAergic activity in the hypothalamus, telencephalon, optic tectum, and cerebellum was investigated in early recrudescent female goldfish (Carassius auratus). A new quantitative technique was developed and validated, permitting concomitant quantification and correlational analysis of glutamic acid decarboxylase 65 (GAD65), GAD67, and GAD3 mRNA levels and in vivo GABA synthesis. Catecholamine depletion was achieved by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 microg/g body weight) and dopamine (DA) depletion verified by HPLC. Endogenous GABA levels were increased by intraperitoneal administration of gamma-vinyl GABA (GVG; 300 microg/g body weight), an inhibitor of the GABA catabolic enzyme GABA transaminase. Treatment with MPTP resulted in a greater than twofold increase in GABA synthesis rate in the optic tectum and telencephalon. The increase in GABA synthesis rate was highly correlated with an increase in GAD67, but not GAD65 or GAD3 mRNA levels. These results suggest that catecholaminergic input exerts inhibitory effects on GABA synthesis rates through the modulation of GAD67 in the optic tectum and telencephalon. Together with previously published observations in rodents and primates, it is suggested that catecholaminergic control of GABA synthesis must have evolved more than 200 million years ago, before the emergence of the teleost fishes.

  11. Microchip-based Integration of Cell Immobilization, Electrophoresis, Post-column Derivatization, and Fluorescence Detection for Monitoring the Release of Dopamine from PC 12 Cells

    PubMed Central

    Li, Michelle W.; Martin, R. Scott

    2008-01-01

    In this paper, we describe the fabrication and evaluation of a multilayer microchip device that can be used to quantitatively measure the amount of catecholamines released from PC 12 cells immobilized within the same device. This approach allows immobilized cells to be stimulated on-chip and, through rapid actuation of integrated microvalves, the products released from the cells are repeatedly injected into the electrophoresis portion of the microchip, where the analytes are separated based upon mass and charge and detected through post-column derivatization and fluorescence detection. Following optimization of the post-column derivatization detection scheme (using naphthalene-2,3-dicarboxaldehyde and 2-β-mercaptoethanol), off-chip cell stimulation experiments were performed to demonstrate the ability of this device to detect dopamine from a population of PC 12 cells. The final 3-dimensional device that integrates an immobilized PC 12 cell reactor with the bilayer continuous flow sampling/electrophoresis microchip was used to continuously monitor the on-chip stimulated release of dopamine from PC 12 cells. Similar dopamine release was seen when stimulating on-chip versus off-chip yet the on-chip immobilization studies could be carried out with 500 times fewer cells in a much reduced volume. While this paper is focused on PC 12 cells and neurotransmitter analysis, the final device is a general analytical tool that is amenable to immobilization of a variety of cell lines and analysis of various released analytes by electrophoretic means. PMID:18810283

  12. Neonatal overfeeding increases capacity for catecholamine biosynthesis from the adrenal gland acutely and long-term in the male rat.

    PubMed

    Sominsky, Luba; Ong, Lin Kooi; Ziko, Ilvana; Dickson, Phillip W; Spencer, Sarah J

    2018-07-15

    A poor nutritional environment during early development has long been known to increase disease susceptibility later in life. We have previously shown that rats that are overfed as neonates (i.e. suckled in small litters (4 pups) relative to control conditions (12 pups)) show dysregulated hypothalamic-pituitary-adrenal axis responses to immune stress in adulthood, particularly due to an altered capacity of the adrenal to respond to an immune challenge. Here we hypothesised that neonatal overfeeding similarly affects the sympathomedullary system, testing this by investigating the biochemical function of tyrosine hydroxylase (TH), the first rate-limiting enzyme in the catecholamine synthesis. We also examined changes in adrenal expression of the leptin receptor and in mitogen-activated protein kinase (MAPK) signalling. During the neonatal period, we saw age-dependent changes in TH activity and phosphorylation, with neonatal overfeeding stimulating increased adrenal TH specific activity at postnatal days 7 and 14, along with a compensatory reduction in total TH protein levels. This increased TH activity was maintained into adulthood where neonatally overfed rats exhibited increased adrenal responsiveness 30 min after an immune challenge with lipopolysaccharide, evident in a concomitant increase in TH protein levels and specific activity. Neonatal overfeeding significantly reduced the expression of the leptin receptor in neonatal adrenals at postnatal day 7 and in adult adrenals, but did not affect MAPK signalling. These data suggest neonatal overfeeding alters the capacity of the adrenal to synthesise catecholamines, both acutely and long term, and these effects may be independent of leptin signalling. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Investigation of the aerothermodynamics of hypervelocity reacting flows in the ram accelerator

    NASA Technical Reports Server (NTRS)

    Hertzberg, A.; Bruckner, A. P.; Mattick, A. T.; Knowlen, C.

    1992-01-01

    New diagnostic techniques for measuring the high pressure flow fields associated with high velocity ram accelerator propulsive modes was experimentally investigated. Individual propulsive modes are distinguished by their operating Mach number range and the manner in which the combustion process is initiated and stabilized. Operation of the thermally choked ram accelerator mode begins by injecting the projectile into the accelerator tube at a prescribed entrance velocity by means of a conventional light gas gun. A specially designed obturator, which is used to seal the bore of the gun, plays a key role in the ignition of the propellant gases in the subsonic combustion mode of the ram accelerator. Once ignited, the combustion process travels with the projectile and releases enough heat to thermally choke the flow within several tube diameters behind it, thereby stabilizing a high pressure zone on the rear of the projectile. When the accelerating projectile approaches the Chapman-Jouguet detonation speed of the propellant mixture, the combustion region is observed to move up onto the afterbody of the projectile as the pressure field evolves to a distinctively different form that implies the presence of supersonic combustion processes. Eventually, a high enough Mach number is reached that the ram effect is sufficient to cause the combustion process to occur entirely on the body. Propulsive cycles utilizing on-body heat release can be established either by continuously accelerating the projectile in a single propellant mixture from low initial in-tube Mach numbers (M less than 4) or by injecting the projectile at a speed above the propellant's Chapman-Jouguet detonation speed. The results of experimental and theoretical explorations of ram accelerator gas dynamic phenomena and the effectiveness of the new diagnostic techniques are presented in this report.

  14. UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans

    PubMed Central

    Hu, Zhitao; Tong, Xia-Jing; Kaplan, Joshua M

    2013-01-01

    Synaptic transmission consists of fast and slow components of neurotransmitter release. Here we show that these components are mediated by distinct exocytic proteins. The Caenorhabditis elegans unc-13 gene is required for SV exocytosis, and encodes long and short isoforms (UNC-13L and S). Fast release was mediated by UNC-13L, whereas slow release required both UNC-13 proteins and was inhibited by Tomosyn. The spatial location of each protein correlated with its effect. Proteins adjacent to the dense projection mediated fast release, while those controlling slow release were more distal or diffuse. Two UNC-13L domains accelerated release. C2A, which binds RIM (a protein associated with calcium channels), anchored UNC-13 at active zones and shortened the latency of release. A calmodulin binding site accelerated release but had little effect on UNC-13’s spatial localization. These results suggest that UNC-13L, UNC-13S, and Tomosyn form a molecular code that dictates the timing of neurotransmitter release. DOI: http://dx.doi.org/10.7554/eLife.00967.001 PMID:23951547

  15. Trigger, an active release experiment that stimulated auroral particle precipitation and wave emissions

    NASA Technical Reports Server (NTRS)

    Holmgren, G.; Bostroem, R.; Kelley, M. C.; Kintner, P. M.; Lundin, R.; Fahleson, U. V.; Bering, E. A.; Sheldon, W. R.

    1979-01-01

    The experiment design, including a description of the diagnostic and chemical release payload, and the general results are given for an auroral process simulation experiment. A drastic increase of the field aligned charged particle flux was observed over the approximate energy range 10 eV to more than 300 keV, starting about 150 ms after the release and lasting about one second. The is evidence of a second particle burst, starting one second after the release and lasting for tens of seconds, and evidence for a periodic train of particle bursts occurring with a 7.7 second period from 40 to 130 seconds after the release. A transient electric field pulse of 200 mv/m appeared just before the particle flux increase started. Electrostatic wave emissions around 2 kHz, as well as a delayed perturbation of the E-region below the plasma cloud were also observed. Some of the particle observations are interpreted in terms of field aligned electrostatic acceleration a few hundred kilometers above the injected plasma cloud. It is suggested that the acceleration electric field was created by an instability driven by field aligned currents originating in the plasma cloud.

  16. CRRES: The combined release and radiation effects satellite program directory

    NASA Technical Reports Server (NTRS)

    Layman, Laura D.; Miller, George P.

    1992-01-01

    As a result of natural processes, plasma clouds are often injected into the magnetosphere. These chemical releases can be used to study many aspects of such injections. When a dense plasma is injected into the inner magnetosphere, it is expected to take up the motion of the ambient plasma. However, it has been observed in previous releases at moderate altitudes that the cloud preserved its momentum for some time following the release and that parts of the cloud peeled off from the main cloud presumable due to the action of an instability. As one moves outward into the magnetosphere, the mirror force becomes less dominant and the initial conditions following a release are dominated by the formation of a diamagnetic cavity since the initial plasma pressure from the injected Ba ions is greater than the magnetic field energy density. A previous high-altitude release (31,300 km) showed this to be the case initially, but at later times there was evidence for acceleration of the Ba plasma to velocities corresponding to 60,000 K. This effect is not explained. This series of experiments is therefore designed to inject plasma clouds into the magnetosphere under widely varying conditions of magnetic field strength and ambient plasma density. In this way the coupling of injected clouds to the ambient plasma and magnetic field, the formation of striations due to instabilities, and possible heating and acceleration of the injected Ba plasma can be studied over a wide range of magnetosphere parameters. Adding to the scientific yield will be the availability of measurements for the DOD/SPACERAD instruments which can monitor plasma parameters, electric and magnetic fields, and waves before, during and after the releases.

  17. Investigations of turbulent motions and particle acceleration in solar flares

    NASA Technical Reports Server (NTRS)

    Jakimiec, J.; Fludra, A.; Lemen, J. R.; Dennis, B. R.; Sylwester, J.

    1986-01-01

    Investigations of X-raya spectra of solar flares show that intense random (turbulent) motions are present in hot flare plasma. Here it is argued that the turbulent motions are of great importance for flare development. They can efficiently enhance flare energy release and accelerate particles to high energies.

  18. Electron heating and acceleration during magnetic reconnection

    NASA Astrophysics Data System (ADS)

    Dahlin, Joel

    2017-10-01

    Magnetic reconnection is thought to be an important driver of energetic particles in a variety of astrophysical phenomena such as solar flares and magnetospheric storms. However, the observed fraction of energy imparted to a nonthermal component can vary widely in different regimes. We use kinetic particle-in-cell (PIC) simulations to demonstrate the important role of the non-reversing (guide) field in controlling the efficiency of electron acceleration in collisionless reconnection. In reconnection where the guide field is smaller than the reconnecting component, the dominant electron accelerator is a Fermi-type mechanism that preferentially energizes the most energetic particles. In strong guide field reconnection, the field-line contraction that drives the Fermi mechanism becomes weak. Instead, parallel electric fields are primarily responsible for driving electron heating but are ineffective in driving the energetic component of the spectrum. Three-dimensional simulations reveal that the stochastic magnetic field that develops during 3D guide field reconnection plays a vital role in particle acceleration and transport. The reconnection outflows that drive Fermi acceleration also expel accelerating particles from energization regions. In 2D reconnection, electrons are trapped in island cores and acceleration ceases, whereas in 3D the stochastic magnetic field enables energetic electrons to leak out of islands and freely sample regions of energy release. A finite guide field is required to break initial 2D symmetry and facilitate escape from island structures. We show that reconnection with a guide field comparable to the reconnecting field generates the greatest number of energetic electrons, a regime where both (a) the Fermi mechanism is an efficient driver and (b) energetic electrons may freely access acceleration sites. These results have important implications for electron acceleration in solar flares and reconnection-driven dissipation in turbulence.

  19. An investigation of the mechanism of release of the amphoteric drug amoxycillin from poly(D,L-lactide-co-glycolide) matrices.

    PubMed

    Mollo, A Rosario; Corrigan, Owen I

    2002-01-01

    Amoxycillin-poly (D,L-lactide-co-glycolide) (PLGA) compacts were prepared by direct compression of both powder mixtures or films in a pre-heated press. Release profiles generally showed two phases separated by an induction period. Thus, both diffusion and polymer degradation mechanisms were involved in drug release, the relative importance of each depending on processing type and drug loading. Drug release parameters for each phase were determined. The fraction of total drug released, in the initial release phase, increased with drug loading and was much larger for compressed physical mixtures than for compressed composites prepared from co-evaporate films. Comparison of the polymer mass loss profiles of drug-loaded and drug-free discs indicated that the presence of the amphoteric drug amoxycillin had little impact on the polymer degradation rate, in contrast to the marked acceleration previously reported for basic drugs. Significant drug degradation occurred and was associated with release at later times. Release data was fitted to an equation accounting for degradation of the drug on release and suggested accelerated amoxycillin degradation during the polymer degradation controlled release phase, consistent with changes in pH in the microenvironment of the eroding compact.

  20. On-line preconcentration of fluorescent derivatives of catecholamines in cerebrospinal fluid using flow-gated capillary electrophoresis.

    PubMed

    Zhang, Qiyang; Gong, Maojun

    2016-06-10

    Flow-gated capillary electrophoresis (CE) coupled with microdialysis has become an important tool for in vivo bioanalytical measurements because it is capable of performing rapid and efficient separations of complex biological mixtures thus enabling high temporal resolution in chemical monitoring. However, the limit of detection (LOD) is often limited to a micro- or nano-molar range while many important target analytes have picomolar or sub-nanomolar levels in brain and other tissues. To enhance the capability of flow-gated CE for catecholamine detection, a novel and simple on-line sample preconcentration method was developed exclusively for fluorescent derivatives of catecholamines that were fluorogenically derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide. The effective preconcentration coupled with the sensitive laser-induced fluorescence (LIF) detection lowered the LOD down to 20pM for norepinephrine (NE) and 50pM for dopamine (DA) at 3-fold of S/N ratio, and the signal enhancement was estimated to be over 100-fold relative to normal injection when standard analytes were dissolved in artificial cerebrospinal fluid (aCSF). The basic focusing principle is novel since the sample plug contains borate while the background electrolyte (BGE) is void of borate. This strategy took advantage of the complexation between diols and borate, through which one negative charge was added to the complex entity. The sample derivatization mixture was electrokinetically injected into a capillary via the flow-gated injection, and then NE and DA derivatives were selectively focused to a narrow zone by the reversible complexation. Separation of NE and DA derivatives was executed by incoming surfactants of cholate and deoxycholate mixed in the front BGE plug. This on-line preconcentration method was finally applied to the detection of DA in rat cerebrospinal fluid (CSF) via microdialysis and on-line derivatization. It is anticipated that the method would

  1. Parallel theoretical study of the two components of the prompt fission neutrons: Dynamically released at scission and evaporated from fully accelerated fragments

    NASA Astrophysics Data System (ADS)

    Carjan, Nicolae; Rizea, Margarit; Talou, Patrick

    2017-09-01

    Prompt fission neutrons (PFN) angular and energy distributions for the reaction 235U(nth,f) are calculated as a function of the mass asymmetry of the fission fragments using two extreme assumptions: 1) PFN are released during the neck rupture due to the diabatic coupling between the neutron degree of freedom and the rapidly changing neutron-nucleus potential. These unbound neutrons are faster than the separation of the nascent fragments and most of them leave the fissioning system in few 10-21 sec. i.e., at the begining of the acceleration phase. Surrounding the fissioning nucleus by a sphere one can calculate the radial component of the neutron current density. Its time integral gives the angular distribution with respect to the fission axis. The average energy of each emitted neutron is also calculated using the unbound part of each neutron wave packet. The distribution of these average energies gives the general trends of the PFN spectrum: the slope, the range and the average value. 2) PFN are evaporated from fully accelerated, fully equilibrated fission fragments. To follow the de-excitation of these fragments via neutron and γ-ray sequential emissions, a Monte Carlo sampling of the initial conditions and a Hauser-Feshbach statistical approach is used. Recording at each step the emission probability, the energy and the angle of each evaporated neutron one can construct the PFN energy and the PFN angular distribution in the laboratory system. The predictions of these two methods are finally compared with recent experimental results obtained for a given fragment mass ratio.

  2. Capsaicin-sensitive sensory neurons are involved in the plasma catecholamine response of rats to selective stressors.

    PubMed Central

    Zhou, X F; Livett, B G

    1991-01-01

    1. The effect of capsaicin pre-treatment on adrenal catecholamine (CA) secretion in response to stress is controversial. In earlier experiments performed under pentobarbitone anaesthesia, the release of CA in response to stress was complicated by the effects of the barbiturate anaesthesia. 2. In the present study we have used conscious freely moving rats with indwelling cannulae to study the effect of neonatal capsaicin pre-treatment on the plasma CA response to different types of stressors (swimming stress, hypovolaemic stress, immobilization stress and cold stress). 3. After swimming for 20 min, plasma noradrenaline (NA) levels increased by 8-fold and adrenaline by 2-fold in control rats. The increase in plasma NA levels in the capsaicin group was attenuated at 10 min of swimming compared with the vehicle group (P < 0.05). 4. With hypovolaemic stress, there were no differences in plasma CA levels, blood pressure and heart rate between the capsaicin group and the vehicle group. There were also no differences in plasma CA levels after immobilization stress between the two groups. 5. With cold stress, plasma NA levels increased 5-fold and adrenaline levels by 3-fold over basal at 45 min in the vehicle pre-treated rats. This increase was not observed in the capsaicin group. 6. Immunoreactive substance P was depleted by only 68% in the splanchnic nerve following capsaicin pre-treatment. If the remaining 32% was biologically active substance P then it could account for the maintenance of the response to hypovolaemic and immobilization stress. However, it might be possible that the responses to hypovolaemic and immobilization stresses could be attenuated if a more complete depletion were achieved. 7. These results in conscious rats indicate that capsaicin-sensitive sensory neurons are required for plasma CA response to selective stressors. They are required for CA output in response to cold stress and to the early phase of swimming stress, but not to hypovolaemic stress

  3. Large-scale particle acceleration by magnetic reconnection during solar flares

    NASA Astrophysics Data System (ADS)

    Li, X.; Guo, F.; Li, H.; Li, G.; Li, S.

    2017-12-01

    Magnetic reconnection that triggers explosive magnetic energy release has been widely invoked to explain the large-scale particle acceleration during solar flares. While great efforts have been spent in studying the acceleration mechanism in small-scale kinetic simulations, there have been rare studies that make predictions to acceleration in the large scale comparable to the flare reconnection region. Here we present a new arrangement to study this problem. We solve the large-scale energetic-particle transport equation in the fluid velocity and magnetic fields from high-Lundquist-number MHD simulations of reconnection layers. This approach is based on examining the dominant acceleration mechanism and pitch-angle scattering in kinetic simulations. Due to the fluid compression in reconnection outflows and merging magnetic islands, particles are accelerated to high energies and develop power-law energy distributions. We find that the acceleration efficiency and power-law index depend critically on upstream plasma beta and the magnitude of guide field (the magnetic field component perpendicular to the reconnecting component) as they influence the compressibility of the reconnection layer. We also find that the accelerated high-energy particles are mostly concentrated in large magnetic islands, making the islands a source of energetic particles and high-energy emissions. These findings may provide explanations for acceleration process in large-scale magnetic reconnection during solar flares and the temporal and spatial emission properties observed in different flare events.

  4. Assessment of bisphenol-A release from orthodontic adhesives.

    PubMed

    Eliades, Theodore; Hiskia, Anastasia; Eliades, George; Athanasiou, Athanasios E

    2007-01-01

    The aim of this study was to quantitatively characterize the bisphenol-A (BPA) released from orthodontic adhesives after artificial accelerated aging. A chemically cured, no-mix adhesive and a visible light-cured adhesive were bonded to 40 stainless steel brackets divided in 2 groups of 20 brackets each. In total, 3 series of specimens were prepared for each adhesive-bracket group. All specimens were immersed in alcohol to induce accelerated aging. Samples of eluent removed from each group at 1 day and at 1, 3, and 5 weeks after aging were processed with high-pressure liquid chromatography; all assays were performed in triplicate, and the results were averaged. No trace of BPA was identified for either adhesive across all time intervals, implying that, if present, the amount of BPA did not exceed the detection limit of the analytical technique (0.1 ppm or 0.1 microg/L). BPA release from light-cured or chemically cured, no-mix adhesives did not reach the 0.1 ppm level. Estrogenicity assays are required to clarify the potential estrogenicity of adhesives, whereas formulation of benzoic ring-free, high molecular weight monomers might eliminate the concerns associated with the use of Bis-GMA.

  5. Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women.

    PubMed

    Komesaroff, P A; Esler, M D; Sudhir, K

    1999-02-01

    Estrogens are reported to provide protection against the development of cardiovascular disease in women, but the mechanisms underlying these effects are not well defined. We hypothesized that estrogen might affect the hormonal responses to stress. We therefore studied cortisol, ACTH, epinephrine, norepinephrine, and norepinephrine spillover and hemodynamic responses to a 10-min mental arithmetic test in 12 perimenopausal women randomized to 8 weeks of estrogen supplementation (estradiol valerate, 2 mg daily; n = 7) or placebo (n = 5). Total body and forearm norepinephrine spillover were measured by radiotracer methodology. After supplementation with estradiol, the increases in both systolic and diastolic blood pressure in response to mental stress were reduced, and cortisol, ACTH, plasma epinephrine and norepinephrine, and total body norepinephrine spillover responses to stress were significantly attenuated (P < 0.05 in each case). Forearm norepinephrine spillover was unchanged by estrogen, and there was no change in any of the responses after placebo. We conclude that estrogen supplementation in perimenopausal women attenuates blood pressure, glucocorticoid, and catecholamine responses to psychological stress.

  6. Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

    PubMed

    Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

    2014-10-10

    Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  8. Determination of Nitrogen, Phosphorus, and Potassium Release Rates of Slow- and Controlled-Release Fertilizers: Single-Laboratory Validation, First Action 2015.15.

    PubMed

    Thiex, Nancy

    2016-01-01

    A previously validated method for the determination of nitrogen release patterns of slow- and controlled-release fertilizers (SRFs and CRFs, respectively) was submitted to the Expert Review Panel (ERP) for Fertilizers for consideration of First Action Official Method(SM) status. The ERP evaluated the single-laboratory validation results and recommended the method for First Action Official Method status and provided recommendations for achieving Final Action. The 180 day soil incubation-column leaching technique was demonstrated to be a robust and reliable method for characterizing N release patterns from SRFs and CRFs. The method was reproducible, and the results were only slightly affected by variations in environmental factors such as microbial activity, soil moisture, temperature, and texture. The release of P and K were also studied, but at fewer replications than for N. Optimization experiments on the accelerated 74 h extraction method indicated that temperature was the only factor found to substantially influence nutrient-release rates from the materials studied, and an optimized extraction profile was established as follows: 2 h at 25°C, 2 h at 50°C, 20 h at 55°C, and 50 h at 60°C.

  9. Acceleration through passive destabilization: protein folding in a weak hydrophobic environment

    NASA Astrophysics Data System (ADS)

    Jewett, Andrew; Baumketner, Andrij; Shea, Joan-Emma

    2004-03-01

    The GroEL chaperonin is a biomolecule which assists the folding of an extremely diverse range of proteins in Eubacteria. Some proteins undergo many rounds of ATP-regulated binding and dissociation from GroEL/ES before folding. It has been proposed that transient stress from ATP-regulated binding and release from GroEL/ES frees frustrated proteins from misfolded conformations. However recent evidence suggests that chaperonin-accelerated protein folding can take place entirely within a mutated GroEL+ES cavity that is unable to open and release the protein. Using molecular dynamics, we demonstrate that static confinement within a weakly hydrophobic (attractive) cavity (similar to the interior of the cavity formed by the GroEL+ES complex) is sufficient to significantly accelerate the folding of a highly frustrated protein-like heteropolymer. Our frustrated molecule benifits kinetically from a static hydrophobic environment that destabilizes misfolded conformations. This may shed light on the mechanisms used by other chaperones which do not depend on ATP.

  10. Stochastic Particle Acceleration in Impulsive Solar Flares

    NASA Technical Reports Server (NTRS)

    Miller, James A.

    2001-01-01

    The acceleration of a huge number of electrons and ions to relativistic energies over timescales ranging from several seconds to several tens of seconds is the fundamental problem in high-energy solar physics. The cascading turbulence model we have developed has been shown previously (e.g., Miller 2000; Miller & Roberts 1995; Miner, LaRosa, & Moore 1996) to account for all the bulk features (such as acceleration timescales, fluxes, total number of energetic particles, and maximum energies) of electron and proton acceleration in impulsive solar flares. While the simulation of this acceleration process is involved, the essential idea of the model is quite simple, and consists of just a few parts: 1. During the primary flare energy release phase, we assume that low-amplitude MHD Alfven and fast mode waves are excited at long wavelengths, say comparable to the size of the event (although the results are actually insensitive to this initial wavelength). While an assumption, this appears reasonable in light of the likely highly turbulent nature of the flare. 2. These waves then cascade in a Kolmogorov-like fashion to smaller wavelengths (e.g., Verma et al. 1996), forming a power-law spectral density in wavenumber space through the inertial range. 3. When the mean wavenumber of the fast mode waves has increased sufficiently, the transit-time acceleration rate (Miller 1997) for superAlfvenic electrons can overcome Coulomb energy losses, and these electrons are accelerated out of the thermal distribution and to relativistic energies (Miller et al. 1996). As the Alfven waves cascade to higher wavenumbers, they can cyclotron resonate with progressively lower energy protons. Eventually, they will resonate with protons in the tail of the thermal distribution, which will then be accelerated to relativistic energies as well (Miller & Roberts 1995). Hence, both ions and electrons are stochastically accelerated, albeit by different mechanisms and different waves. 4. When the

  11. Influence of paints formulations on nanoparticles release during their life cycle

    NASA Astrophysics Data System (ADS)

    Fiorentino, Brice; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine

    2015-03-01

    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO2 NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM-EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO2 addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm3. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a "safe-by-design" product.

  12. Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks

    PubMed Central

    Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

    2014-01-01

    A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic–phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits. PMID:24723897

  13. Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks.

    PubMed

    Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

    2014-01-01

    A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.

  14. Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

    PubMed

    Allababidi, S; Shah, J C

    1998-06-01

    than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.

  15. ARE THERE TWO DISTINCT SOLAR ENERGETIC PARTICLE RELEASES IN THE 2012 MAY 17 GROUND LEVEL ENHANCEMENT EVENT?

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

    Ding, Liu-Guan; Jiang, Yong; Li, Gang, E-mail: gang.li@uah.edu

    We examine ion release times in the solar vicinity for the 2012 May 17 Ground Level Enhancement event using the velocity dispersion analysis method. In situ energetic proton data from Solar and Heliospheric Observatory (SOHO)/Energetic and Relativistic Nuclei and Electron and Geostationary Operational Environmental Satellite are used. We find two distinct releases of Solar Energetic Particles (SEPs) near the Sun, separated by ∼40 minutes. From soft X-ray observations, we find that the first release coincides with the solar flare eruption: the release starts from the flare onset and ends near the peak of the soft X-ray; type-III radio bursts alsomore » occur when the release starts. A type II radio burst may also start at the begining of the release. However, the associated Coronal Mass Ejection (CME) only has a height of 0.08R{sub s} from extrapolation of SOHO/LASCO data. At the start of the second release, the CME propagates to more than 8.4R{sub s} in height, and there are signatures of an enhanced type II radio burst. The time-integrated spectra for the two releases differ. The spectrum for the second release shows the common double-power-law feature of gradual SEP events. The spectrum for the first release does not resemble power laws because there is considerable modulation at lower energies. Based on our analysis, we suggest that SEPs of the first release were dominated by particles accelerated at the flare, and those of the second release were dominated by particles accelerated at the associated CME-driven shock. Our study may be important to understand certain extreme SEP events.« less

  16. Biocompatible Poly(catecholamine)-Film Electrode for Potentiometric Cell Sensing.

    PubMed

    Kajisa, Taira; Yanagimoto, Yoshiyuki; Saito, Akiko; Sakata, Toshiya

    2018-02-23

    Surface-coated poly(catecholamine) (pCA) films have attracted attention as biomaterial interfaces owing to their biocompatible and physicochemical characteristics. In this paper, we report that pCA-film-coated electrodes are useful for potentiometric biosensing devices. Four different types of pCA film, l-dopa, dopamine, norepinephrine, and epinephrine, with thicknesses in the range of 7-27 nm were electropolymerized by oxidation on Au electrodes by using cyclic voltammetry. By using the pCA-film electrodes, the pH responsivities were found to be 39.3-47.7 mV/pH within the pH range of 1.68 to 10.01 on the basis of the equilibrium reaction with hydrogen ions and the functional groups of the pCAs. The pCA films suppressed nonspecific signals generated by other ions (Na + , K + , Ca 2+ ) and proteins such as albumin. Thus, the pCA-film electrodes can be used in pH-sensitive and pH-selective biosensors. HeLa cells were cultivated on the surface of the pCA-film electrodes to monitor cellular activities. The surface potential of the pCA-film electrodes changed markedly because of cellular activity; therefore, the change in the hydrogen ion concentration around the cell/pCA-film interface could be monitored in real time. This was caused by carbon dioxide or lactic acid that is generated by cellular respiration and dissolves in the culture medium, resulting in the change of hydrogen concentration. pCA-film electrodes are suitable for use in biocompatible and pH-responsive biosensors, enabling the more selective detection of biological phenomena.

  17. Piezoelectric detection of ion pairs between sulphonate and catecholamines for flow injection analysis of pharmaceutical preparations.

    PubMed

    Mo, Z; Long, X; Zhang, M

    1999-03-01

    Fundamentals of ion-pair flow injection with piezoelectric detection were investigated experimentally and theoretically for the adsorption of dodecyl phenylsulfonate and interfacial ion-pair formation with epinephrine and l-dopa on silver electrode of quartz crystal microbalance. The influences of sulfonate concentration and operating parameters on the frequency response were demonstrated and provided the possibility for the discriminating determination of mixtures. The selected system of ion-pair flow injection with piezoelectric detection was applied to the determination of epinephrine and l-dopa. Calibration curves were linear in ranges 4.00-850 and 3.50-730 mug ml(-1), with detection limits of 1.22 and 1.05 mug ml(-1) and sampling frequencies of 120 samples h(-1), for epinephrine and l-dopa, respectively. The method has been satisfactorily applied to the determination of catecholamines in pharmaceutical preparations.

  18. Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder.

    PubMed

    Lin, Chen-Cheng; Tung, Che-Se; Lin, Pin-Hsuan; Huang, Chuen-Lin; Liu, Yia-Ping

    2016-09-01

    Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  19. Turbulence, Magnetic Reconnection in Turbulent Fluids and Energetic Particle Acceleration

    NASA Astrophysics Data System (ADS)

    Lazarian, A.; Vlahos, L.; Kowal, G.; Yan, H.; Beresnyak, A.; de Gouveia Dal Pino, E. M.

    2012-11-01

    Turbulence is ubiquitous in astrophysics. It radically changes many astrophysical phenomena, in particular, the propagation and acceleration of cosmic rays. We present the modern understanding of compressible magnetohydrodynamic (MHD) turbulence, in particular its decomposition into Alfvén, slow and fast modes, discuss the density structure of turbulent subsonic and supersonic media, as well as other relevant regimes of astrophysical turbulence. All this information is essential for understanding the energetic particle acceleration that we discuss further in the review. For instance, we show how fast and slow modes accelerate energetic particles through the second order Fermi acceleration, while density fluctuations generate magnetic fields in pre-shock regions enabling the first order Fermi acceleration of high energy cosmic rays. Very importantly, however, the first order Fermi cosmic ray acceleration is also possible in sites of magnetic reconnection. In the presence of turbulence this reconnection gets fast and we present numerical evidence supporting the predictions of the Lazarian and Vishniac (Astrophys. J. 517:700-718, 1999) model of fast reconnection. The efficiency of this process suggests that magnetic reconnection can release substantial amounts of energy in short periods of time. As the particle tracing numerical simulations show that the particles can be efficiently accelerated during the reconnection, we argue that the process of magnetic reconnection may be much more important for particle acceleration than it is currently accepted. In particular, we discuss the acceleration arising from reconnection as a possible origin of the anomalous cosmic rays measured by Voyagers as well as the origin cosmic ray excess in the direction of Heliotail.

  20. High-performance Liquid Chromatography Measured Metabolites of Endogenous Catecholamines and Their Relations to Chronic Kidney Disease and High Blood Pressure in Heart Transplant Recipients.

    PubMed

    Wasilewski, G; Przybylowski, P; Wilusz, M; Sztefko, K; Janik, Ł; Koc-Żórawska, E; Malyszko, J

    2016-06-01

    Patients after solid organ transplantation, especially heart and kidneys, are prone to be hypertensive. Recently chronic kidney disease and renalase metabolism of endogenous catecholamines are thought to make major contribution to the pathogenesis of hypertension. We analyzed 75 heart recipients (80% male, 20% female), medium age 54.9 years (range, 25-75) at 0.5 to 22 years after heart transplantation (median, 10.74). Diagnosis of hypertension was made on the basis of ambulatory blood pressure monitoring. Complete blood count, urea, creatinine, estimated glomerular filtration rate (eGFR), renalase in serum, and levels of metanefrine, normetanefrine, and 3-metoxytyramine in 24-hour urine collection calculated with a high-performance liquid chromatography were recorded. Urine endogenous catecholamine metabolites were estimated according to creatinine clearance. Normetanefrine was correlated with age (r = 0.27; P < .05), urea (r = 0.64; P < .01), creatinine (r = 0.6; P < .01), eGFR (r = -0.51; P < .01), renalase (r = 0.5; P < .01), and diastolic blood pressure (r = 0.26; P < .05). Metanefrine was correlated with urea (r = 0.43; P < .01), creatinine (0.32; P < .01), eGFR (r = -0.4; P < .01), renalase (r = 0.34; P < .05), height (r = -0.26; P < .05), weight (r = -0.23; P < .05), and time after heart transplantation (r = 0.27; P < .05). 3-Metoxytyramine was correlated with urea (r = 0.43; P < .01), creatinine (r = 0.32; P < .01), and the eGFR (r = -0.24; P < .05). Creatinine was correlated with age (r = 0.36; P < .01), diastolic blood pressure (r = 0.26; P < .05), time after heart transplantation (r = 0.24; P < .05), and renalase (r = 0.69; P < .01). Systolic blood pressure was correlated with proteinuria (r = 0.26; P < .05). Chronic kidney disease and concomitant hypertension are the most prevalent comorbidities in the population of heart transplant recipients. Urine catecholamine metabolites were related to kidney

  1. Metal release and speciation of released chromium from a biomedical CoCrMo alloy into simulated physiologically relevant solutions.

    PubMed

    Hedberg, Yolanda; Odnevall Wallinder, Inger

    2014-05-01

    The objective of this study was to investigate the extent of released Co, Cr(III), Cr(VI), and Mo from a biomedical high-carbon CoCrMo alloy exposed in phosphate-buffered saline (PBS), without and with the addition of 10 µM H2 O2 (PBS + H2 O2 ), and 10 g L(-1) bovine serum albumin (PBS + BSA) for time periods up to 28 days. Comparative studies were made on AISI 316L for the longest time period. No Cr(VI) release was observed for any of the alloys in either PBS or PBS + H2 O2 at open-circuit potential (no applied potential). However, at applied potentials (0.7 V vs. Ag/AgCl), Cr was primarily released as Cr(VI). Co was preferentially released from the CoCrMo alloy at no applied potential. As a consequence, Cr was enriched in the utmost surface oxide reducing the extent of metal release over time. This passivation effect was accelerated in PBS + H2 O2 . As previously reported for 316L, BSA may also enhance metal release from CoCrMo. However, this was not possible to verify due to the precipitation of metal-protein complexes with reduced metal concentrations in solution as a consequence. This was particularly important for Co-BSA complexes after sufficient time and resulted in an underestimation of metals in solution. Copyright © 2013 Wiley Periodicals, Inc.

  2. Mineral stimulation of subsurface microorganisms: release of limiting nutrients from silicates

    USGS Publications Warehouse

    Roger, Jennifer Roberts; Bennett, Philip C.

    2004-01-01

    Microorganisms play an important role in the weathering of silicate minerals in many subsurface environments, but an unanswered question is whether the mineral plays an important role in the microbial ecology. Silicate minerals often contain nutrients necessary for microbial growth, but whether the microbial community benefits from their release during weathering is unclear. In this study, we used field and laboratory approaches to investigate microbial interactions with minerals and glasses containing beneficial nutrients and metals. Field experiments from a petroleum-contaminated aquifer, where silicate weathering is substantially accelerated in the contaminated zone, revealed that phosphorus (P) and iron (Fe)-bearing silicate glasses were preferentially colonized and weathered, while glasses without these elements were typically barren of colonizing microorganisms, corroborating previous studies using feldspars. In laboratory studies, we investigated microbial weathering of silicates and the release of nutrients using a model ligand-promoted pathway. A metal-chelating organic ligand 3,4 dihydroxybenzoic acid (3,4 DHBA) was used as a source of chelated ferric iron, and a carbon source, to investigate mineral weathering rate and microbial metabolism.In the investigated aquifer, we hypothesize that microbes produce organic ligands to chelate metals, particularly Fe, for metabolic processes and also form stable complexes with Al and occasionally with Si. Further, the concentration of these ligands is apparently sufficient near an attached microorganism to destroy the silicate framework while releasing the nutrient of interest. In microcosms containing silicates and glasses with trace phosphate mineral inclusions, microbial biomass increased, indicating that the microbial community can use silicate-bound phosphate inclusions. The addition of a native microbial consortium to microcosms containing silicates or glasses with iron oxide inclusions correlated to

  3. Catecholamines alter the intrinsic variability of cortical population activity and perception

    PubMed Central

    Avramiea, Arthur-Ervin; Nolte, Guido; Engel, Andreas K.; Linkenkaer-Hansen, Klaus; Donner, Tobias H.

    2018-01-01

    The ascending modulatory systems of the brain stem are powerful regulators of global brain state. Disturbances of these systems are implicated in several major neuropsychiatric disorders. Yet, how these systems interact with specific neural computations in the cerebral cortex to shape perception, cognition, and behavior remains poorly understood. Here, we probed into the effect of two such systems, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems, on an important aspect of cortical computation: its intrinsic variability. To this end, we combined placebo-controlled pharmacological intervention in humans, recordings of cortical population activity using magnetoencephalography (MEG), and psychophysical measurements of the perception of ambiguous visual input. A low-dose catecholaminergic, but not cholinergic, manipulation altered the rate of spontaneous perceptual fluctuations as well as the temporal structure of “scale-free” population activity of large swaths of the visual and parietal cortices. Computational analyses indicate that both effects were consistent with an increase in excitatory relative to inhibitory activity in the cortical areas underlying visual perceptual inference. We propose that catecholamines regulate the variability of perception and cognition through dynamically changing the cortical excitation–inhibition ratio. The combined readout of fluctuations in perception and cortical activity we established here may prove useful as an efficient and easily accessible marker of altered cortical computation in neuropsychiatric disorders. PMID:29420565

  4. Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre-existing gastric ulcers.

    PubMed

    Magierowski, Marcin; Magierowska, Katarzyna; Hubalewska-Mazgaj, Magdalena; Sliwowski, Zbigniew; Ginter, Grzegorz; Pajdo, Robert; Chmura, Anna; Kwiecien, Slawomir; Brzozowski, Tomasz

    2017-10-01

    Carbon monoxide (CO), a gaseous mediator produced by haem oxygenases (HOs), has been shown to prevent stress-, ethanol-, aspirin- and alendronate-induced gastric damage; however, its role in gastric ulcer healing has not been fully elucidated. We investigated whether CO released from tricarbonyldichlororuthenium (II) dimer (CORM-2) can affect gastric ulcer healing and determined the mechanisms involved in this healing action. Gastric ulcers were induced in Wistar rats by serosal application of acetic acid. Animals received 9 days of treatment with RuCl 3 [2.5 mg·kg -1 intragastrically (i.g.)], haemin (5 mg·kg -1 i.g.), CORM-2 (0.1-10 mg·kg -1 i.g.) administered alone or with zinc protoporphyrin IX (ZnPP, 10 mg·kg -1 i.g.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 mg·kg -1 i.g.), N G -nitro-l-arginine (l-NNA, 15 mg·kg -1 i.g.), indomethacin (5 mg·kg -1 i.g.) or glibenclamide (10 mg·kg -1 i.g.). Gastric ulcer area and gastric blood flow (GBF) were assessed planimetrically, microscopically and by laser flowmeter respectively. Gastric mRNA/protein expressions of EGF, EGF receptors, VEGFA, HOs, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), COX-2, hypoxia-inducible factor (HIF)-1α and pro-inflammatory iNOS, IL-1β and TNF-α were determined by real-time PCR or Western blots. CORM-2 and haemin but not RuCl 3 or ZnPP decreased ulcer size while increasing GBF. These effects were reduced by ODQ, indomethacin, l-NNA and glibenclamide. CORM-2 significantly decreased the expression of pro-inflammatory markers, Nrf2/HO1 and HIF-1α, and up-regulated EGF. CO released from CORM-2 or endogenously produced by the HO1/Nrf2 pathway accelerates gastric ulcer healing via an increase in GBF, an up-regulation in EGF expression and down-regulation of the inflammatory response. © 2017 The British Pharmacological Society.

  5. Natural and technologic hazardous material releases during and after natural disasters: a review.

    PubMed

    Young, Stacy; Balluz, Lina; Malilay, Josephine

    2004-04-25

    Natural disasters may be powerful and prominent mechanisms of direct and indirect hazardous material (hazmat) releases. Hazardous materials that are released as the result of a technologic malfunction precipitated by a natural event are referred to as natural-technologic or na-tech events. Na-tech events pose unique environmental and human hazards. Disaster-associated hazardous material releases are of concern, given increases in population density and accelerating industrial development in areas subject to natural disasters. These trends increase the probability of catastrophic future disasters and the potential for mass human exposure to hazardous materials released during disasters. This systematic review summarizes direct and indirect disaster-associated releases, as well as environmental contamination and adverse human health effects that have resulted from natural disaster-related hazmat incidents. Thorough examination of historic disaster-related hazmat releases can be used to identify future threats and improve mitigation and prevention efforts.

  6. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  7. Catecholamine excretion rates in relation to life-styles in the male population of Otmoor, Oxfordshire.

    PubMed

    Reynolds, V; Jenner, D A; Palmer, C D; Harrison, G A

    1981-01-01

    The paper gives the results of the number of analyses of aspects of life-style and dietary patterns of members of the Otmoor population, in relation to their catecholamine excretion rates. The data reported here are restricted to males. Feelings of boredom were associated with low adrenaline excretion rates. Reported physical tiredness was associated with low adrenaline levels, while mental tiredness seems to be related to high adrenaline levels. People who regarded themselves as having a competitive personality, as being faced by a large number of life challenges, as having to meet self-set deadlines, as choosing to focus on more than one task at the same time, or as being under time pressure had high rates. Cigarette smoking and coffee consumption were related to high adrenaline excretion rates. Taken together these variables can explain 16-20% of variance in adrenaline excretion. Smoking and coffee consumption are of primary importance. The results of similar analyses of noradrenaline are reported.

  8. Release and Degradation of Microencapsulated Spinosad and Emamectin Benzoate.

    PubMed

    Huang, Bin Bin; Zhang, Shao Fei; Chen, Peng Hao; Wu, Gang

    2017-09-07

    The dynamics of release and degradation of the microencapsulation formulation containing spinosad (SP) and emamectin benzoate (EM) were evaluated in the present study. SP and EM were microencapsulated using biodegradable poly-lactic acid (PLA) as the wall material. Their release from and degradation within the prepared SP and EM microspheres (SP-EM-microspheres) were studied. It was found that the encapsulation significantly prolonged the insecticide release. The release could be further extended if the external aqueous phase was pre-saturated with the insecticides and the microspheres were additionally coated with gelatin. On the other hand, increasing the water content of the emulsion or the hydrophilic polycaprolactone (PCL) content in the PLA/PCL mixture accelerated the release. Due to the photolysis and hydrolysis of SP and EM by sunlight, the toxicity of the non-encapsulated insecticides in water declined continuously from 0 through the 9 th day (d), and dissipated in 13 d. In contrast, an aqueous suspension containing 5% SP-EM-microspheres maintained a mostly constant toxicity to Plutella xylostella for 17 d. The biodegradable SP-EM-microspheres showed significantly higher long-term toxicity to P. xylostella due to lower release, reduced photolysis and hydrolysis of the encapsulated insecticides, which were affected by the varied preparation conditions.

  9. Meltable magnetic biocomposites for controlled release

    NASA Astrophysics Data System (ADS)

    Müller, R.; Zhou, M.; Dellith, A.; Liebert, T.; Heinze, T.

    2017-06-01

    New biocompatible composites with adjustable melting point in the range of 30-140 °C, consisting of magnetite nanoparticles embedded into a matrix of meltable dextran fatty acid ester are presented which can be softened under an induced alternating magnetic field (AMF). The chosen thermoplastic magnetic composites have a melting range close to human body temperature and can be easily shaped into disk or coating film under melting. The composite disks were loaded with green fluorescent protein (GFP) as a model protein. Controlled release of the protein was realized with high frequent alternating magnetic field of 20 kA/m at 400 kHz. These results showed that under an AMF the release of GFP from magnetic composite was accelerated compared to the control sample without exposure to AMF. Furthermore a texturing of particles in the polymer matrix by a static magnetic field was investigated.

  10. Beyond injection: Trojan horse underdense photocathode plasma wakefield acceleration

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

    Hidding, B.; Rosenzweig, J. B.; Xi, Y.

    2012-12-21

    An overview on the underlying principles of the hybrid plasma wakefield acceleration scheme dubbed 'Trojan Horse' acceleration is given. The concept is based on laser-controlled release of electrons directly into a particle-beam-driven plasma blowout, paving the way for controlled, shapeable electron bunches with ultralow emittance and ultrahigh brightness. Combining the virtues of a low-ionization-threshold underdense photocathode with the GV/m-scale electric fields of a practically dephasing-free beam-driven plasma blowout, this constitutes a 4th generation electron acceleration scheme. It is applicable as a beam brightness transformer for electron bunches from LWFA and PWFA systems alike. At FACET, the proof-of-concept experiment 'E-210: Trojanmore » Horse Plasma Wakefield Acceleration' has recently been approved and is in preparation. At the same time, various LWFA facilities are currently considered to host experiments aiming at stabilizing and boosting the electron bunch output quality via a trojan horse afterburner stage. Since normalized emittance and brightness can be improved by many orders of magnitude, the scheme is an ideal candidate for light sources such as free-electron-lasers and those based on Thomson scattering and betatron radiation alike.« less

  11. Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

    PubMed

    Meyer, Hajo; Winkler, Felix; Kunz, Peter; Schmidt, Annette M; Hamacher, Alexandra; Kassack, Matthias U; Janiak, Christoph

    2015-12-07

    Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min

  12. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

    PubMed Central

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  13. Demonstrations that the Solar Wind Is Not Accelerated by Waves

    NASA Technical Reports Server (NTRS)

    Roberts, Aaron

    2008-01-01

    The present work uses both observations and theoretical considerations to show that hydromagnetic waves cannot produce the acceleration of the fast solar wind and the related heating of the open solar corona. Waves do exist, and can play a role in the differential heating and acceleration of minor ions, but their amplitudes are not sufficient to power the wind, as demonstrated by extrapolation of magnetic spectra from Helios and Ulysses observations. Dissipation mechanisms invoked to circumvent this conclusion cannot be effective for a variety of reasons. In particular, turbulence does not play a strong role in the corona as shown by both observations of coronal striations and theoretical considerations of line-tying to a nonturbulent photosphere, nonlocality of interactions, and the nature of the kinetic dissipation. In the absence of wave heating and acceleration, the chromosphere and transition region become the natural source of open coronal energization. We suggest a variant of the 'velocity filtration' approach in which the emergence and complex churning of the magnetic flux in the chromosphere and transition region continuously and ubiquitously produces the nonthermal distributions required. These particles are then released by magnetic carpet reconnection at a wide range of scales and produce the wind as described in kinetic approaches. Since the carpet reconnection is not the main source of the energization of the plasma, there is no expectation of an observable release of energy in nanoflares.

  14. Particle acceleration in a complex solar active region modelled by a Cellular automata model

    NASA Astrophysics Data System (ADS)

    Dauphin, C.; Vilmer, N.; Anastasiadis, A.

    2004-12-01

    The models of cellular automat allowed to reproduce successfully several statistical properties of the solar flares. We use a cellular automat model based on the concept of self-organised critical system to model the evolution of the magnetic energy released in an eruptive active area. Each burst of magnetic energy released is assimilated to a process of magnetic reconnection. We will thus generate several current layers (RCS) where the particles are accelerated by a direct electric field. We calculate the energy gain of the particles (ions and electrons) for various types of magnetic configuration. We calculate the distribution function of the kinetic energy of the particles after their interactions with a given number of RCS for each type of configurations. We show that the relative efficiency of the acceleration of the electrons and the ions depends on the selected configuration.

  15. Acute catecholamine cardiomyopathy in patients with phaeochromocytoma or functional paraganglioma.

    PubMed

    Giavarini, Alessandra; Chedid, Antoine; Bobrie, Guillaume; Plouin, Pierre-François; Hagège, Albert; Amar, Laurence

    2013-10-01

    Phaeochromocytomas and paragangliomas (PPGL) can cause acute catecholamine cardiomyopathy (ACC). We assessed the prevalence of ACC and compared the presentation of cases with and without ACC in a large series of PPGL. Single centre retrospective study. Hypertension Unit, University Hospital, Paris. 140 consecutive patients with PPGL, referred from January 2003 to September 2012. Left ventricular ejection fraction (LVEF), perioperative mortality. Fifteen patients (11%) had suffered an ACC, occurring in 14 cases before the diagnosis of PPGL. Precipitating factors were identified in 11 cases. Twelve patients presented with acute pulmonary oedema, including 10 with cardiogenic shock, requiring life support in eight cases. Seven patients (five with pulmonary oedema) presented with acute chest pain and cardiac dysfunction. Electrocardiographic abnormalities were present in 14 cases: ST segment elevation or pathological Q waves, ST segment depression, and/or diffuse T wave inversion. Six patients displayed classical (apical ballooning) or inverted (basal/mid ventricular stunning) takotsubo-like cardiomyopathy. Coronary arteries were always normal on angiography. In patients with ACC, median LVEF rose from 30% (IQR 23-33%) during ACC to 71% (50-72%) before surgery (n=11, p<0.001). Median LVEF before PPGL surgery was 65% (51-72%) and 65% (60-70%) in patients with and without a history of ACC, respectively (not significant). PPGL may present as ACC in 11% of cases, excluding patients dying from undiagnosed tumours. Left ventricular dysfunction is usually reversible before surgery. PPGL should be suspected in patients with acute heart failure without evidence of valvular or coronary artery disease.

  16. Effects of aeolian erosion on microbial release from solids.

    NASA Technical Reports Server (NTRS)

    Gustan, E. A.; Olson, R. L.; Taylor, D. M.; Green, R. H.

    1972-01-01

    This study was initiated to determine the percentage of spores that would be expected to be released from the interior of solid materials by aeolian erosion on a planetary surface. Methyl methacrylate and Eccobond disks were fabricated so that each disk contained approximately 40,000 Bacillus subtilis var. niger spores. The disks were placed in a specially designed sandblasting device and eroded. Exposure periods of 0.5, 2 and 24 hours were investigated using filtered air to accelerate the sand. A series of tests was also conducted for a 0.5 hour period using carbon dioxide. Examination of the erosion products showed that less than 1% of the spores originally contained in the solids was released by aeolian erosion.

  17. Prompt acceleration of ions by oblique turbulent shocks in solar flares

    NASA Technical Reports Server (NTRS)

    Decker, R. B.; Vlahos, L.

    1985-01-01

    Solar flares often accelerate ions and electrons to relativistic energies. The details of the acceleration process are not well understood, but until recently the main trend was to divide the acceleration process into two phases. During the first phase elctrons and ions are heated and accelerated up to several hundreds of keV simultaneously with the energy release. These mildly relativistic electrons interact with the ambient plasma and magnetic fields and generate hard X-ray and radio radiation. The second phase, usually delayed from the first by several minutes, is responsible for accelerating ions and electrons to relativistic energies. Relativistic electrons and ions interact with the solar atmosphere or escape from the Sun and generate gamma ray continuum, gamma ray line emission, neutron emission or are detected in space by spacecraft. In several flares the second phase is coincident with the start of a type 2 radio burst that is believed to be the signature of a shock wave. Observations from the Solar Maximum Mission spacecraft have shown, for the first time, that several flares accelerate particles to all energies nearly simultaneously. These results posed a new theoretical problem: How fast are shocks and magnetohydrodynamic turbulence formed and how quickly can they accelerate ions to 50 MeV in the lower corona? This problem is discussed.

  18. Effects of acupuncture on peripheral T lymphocyte subpopulation and amounts of cerebral catecholamines in mice.

    PubMed

    Okumura, M; Toriizuka, K; Iijima, K; Haruyama, K; Ishino, S; Cyong, J C

    1999-01-01

    The aim of this study was to investigate the effects of acupuncture on peripheral lymphocyte subpopulations and cerebral catecholamines. In order to examine the effects of acupuncture, two experiments were performed. Experiment 1: Eighteen female mice (strain; C57BL/6) at the age of 7 weeks were divided three groups, (a) sham operated (control; n=6), (b) ovariectomized (OVX; n=6), and (c) ovariectomized and stimulated by subcutaneous needles on acupuncture point, Shenshu (BL23) at the both sides of the back for 20 days (OVX+Acu; n=6). These animals were sacrificed at 20 days after needle insertion, and the splenic lymphoid cells were examined by two-color flow cytometry, using monoclonal antibodies (mAb) to the cell surface antigens, CD3, CD4, CD8a and NK1.1 (CD56). In the ovariectomized (OVX) group, the peripheral CD4/CD8 ratio was significantly increased and the ratio of natural killer (NK) cells (CD3-NK1.1+; CD3 negative, NK1.1 positive) to T lymphocytes was decreased compared to the sham control group. In the ovariectomized with needle insertion (OVX+Acu) group, the CD4/CD8 ratio was reduced, but the NK cells ratio was not changed compared to the OVX group. Experiment 2: To investigate the acute effects of subcutaneous needle insertion, male C57BL/6 mice (7 weeks old) were used (n=6, each group). The acupuncture points Shen-shu (BL23) on the backs of the male mice were also stimulated by subcutaneous needles for 3 and 7 days. As a result, the CD4/CD8 ratio was significantly decreased at day 3 and day 7, compared to the control group. On the other hand the NK cells ratio and activated T-cells were increased at day 7. The mitogenic activities in the splenic lymphocytes were also increased by acupuncture stimulation at day 3. Catecholamine contents in the hippocampus were measured by high performance liquid chromatography with the electro-chemical detector (ECD-HPLC) method. No significant change was observed in either dopamine contents or norepinephrine; however

  19. Energy dissipation on ion-accelerator grids during high-voltage breakdown

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

    Menon, M.M.; Ponte, N.S.

    1981-01-01

    The effects of stored energy in the system capacitance across the accelerator grids during high voltage vacuum breakdown are examined. Measurements were made of the current flow and the energy deposition on the grids during breakdown. It is shown that only a portion (less than or equal to 40 J) of the total stored energy (congruent to 100 J) is actually dissipated on the grids. Most of the energy is released during the formation phase of the vacuum arc and is deposited primarily on the most positive grid. Certain abnormal situations led to energy depositions of about 200 J onmore » the grid, but the ion accelerator endured them without exhibiting any deterioration in performance.« less

  20. Modeling the Acceleration of Global Surface Temperture

    NASA Astrophysics Data System (ADS)

    Jones, B.

    2017-12-01

    A mathematical projection focusing on the changing rate of acceleration of Global Surface Temperatures. Using historical trajectory and informed expert near-term prediction, it is possible to extend this further forward drawing a reference arc of acceleration. Presented here is an example of this technique based on data found in the Summary of Findings of A New Estimate of the Average Earth Surface Land Temperature Spanning 1753 to 2011 and that same team's stated prediction to 2050. With this, we can project a curve showing future acceleration: Decade (midpoint) Change in Global Land Temp Degrees C Known Slope Projected Trend 1755 0.000 1955 0.600 0.0030 2005 1.500 0.0051 2045 3.000 0.0375 2095 5.485 0.0497 2145 8.895 0.0682 2195 13.488 0.0919 Observations: Slopes are getting steeper and doing so faster in an "acceleration of the acceleration" or an "arc of acceleration". This is consistent with the non-linear accelerating feedback loops of global warming. Such projected temperatures threaten human civilization and human life. This `thumbnail' projection is consistent with the other long term predictions based on anthropogenic greenhouse gases. This projection is low when compared to those whose forecasts include greenhouse gases released from thawing permafrost and clathrate hydrates. A reference line: This curve should be considered a point of reference. In the near term and absent significant drawdown of greenhouse gases, my "bet" for this AGU session is that future temperatures will generally be above this reference curve. For example, the decade ending 2020 - more than 1.9C and the decade ending 2030 - more than 2.3C - again measured from the 1750 start point. *Caveat: The long term curve and prediction assumes that mankind does not move quickly away from high cost fossil fuels and does not invent, mobilize and take actions drawing down greenhouse gases. Those seeking a comprehensive action plan are directed to drawdown.org

  1. A bench-scale assessment for phosphorus release control of sediment by an oxygen-releasing compound (ORC).

    PubMed

    Yang, Jie; Lin, Feng K; Yang, Lei; Hua, Dan Y

    2015-01-01

    The effects of oxygen-releasing compound (ORC) on the control of phosphorus (P) release as well as the spatial and temporal distribution of P fractions in sediment were studied through a bench-scale test. An ORC with an extended oxygen-releasing capacity was prepared. The results of the oxygen-releasing test showed that the ORC provided a prolonged period of oxygen release with a highly effective oxygen content of 60.6% when compared with powdery CaO2. In the bench-scale test, an ORC dose of 180 g·m(-2) provided a higher inhibition efficiency for P release within 50 days. With the application of the ORC, the dissolved oxygen (DO) concentration and redox potential (ORP) of the overlying water were notably improved, and the dissolved total phosphorus (DTP) was maintained below 0.689 mg·L(-1) compared to 2.906 mg·L(-1) without the ORC treatment. According to the P fractions distribution, the summation of all detectable P fractions in each sediment layer exhibited an enhanced accumulation tendency with the application of ORC. Higher phosphorus retention efficiencies were observed in the second and third layers of sediment from days 10 to 20 with the ORC. Phosphorus was trapped mainly in the form of iron bound P (Fe-P) and organically bound P (O-P) in sediment with the ORC, whereas the effects of the ORC on exchangeable P (EX-P), apatite-associated P (A-P) and detrital P (De-P) in the sediment sample were not significant. The microbial activities of the sediment samples demonstrated that both the dehydrogenase activity (DHA) and alkaline phosphatase activity (APA) in the upper sediment layer increased with the ORC treatment, which indicated that the mineralization of P was accelerated and the microbial biomass was increased. As the accumulation of P suppressed the release of P, the sediment exhibited an increased P retention efficiency with the application of the ORC.

  2. Change in energy expenditure and brain and adrenal content of catecholamines in rats during muscular loading and hypokinesia

    NASA Technical Reports Server (NTRS)

    Rozanova, V. D.; Savkiv, T. G.; Khodorova, N. A.

    1980-01-01

    In male 1-7 month old rats, the growth and the protein content of skeletal muscles were higher than in female rats while the O2 consumption and the heart rate were lower. This is combined with reduction of the thyroid gland weight and of catecholamine content in adrenals at the age of 7 months. The development of male and female rats (1-7 month) under conditions of systematic muscular loads increases the growth tempo and protein of skeletal muscles and intensifies the degree of reduction of energy expenditure and the heart rate. This is accomplished by the greater reduction of relative weight of the thyroid gland and, at the age of 7 months, by reduction of the noradrenaline content in the brainstem. Hypodynamic conditions have the exact opposite effect.

  3. Influence of age and splanchnic nerve on the action of melatonin in the adrenomedullary catecholamine content and blood glucose level in the avian group.

    PubMed

    Mahata, S K; Mandal, A; Ghosh, A

    1988-01-01

    A single intraperitoneal (IP) melatonin injection (0.5 mg/100 g body wt.) caused an increase in norepinephrine (NE) fluorescence and elevation of NE content in newly-hatched pigeons (Columba livia), but a reduction of NE fluorescence and depletion of NE content in the adrenal medulla of newly-hatched crows (Corvus splendens) after 0.5 h of treatment. In contrast, in adults melatonin caused increase in NE fluorescence and elevation of NE content only in the parakeet (Psittacula krameri). Half an hour of IP melatonin treatment (0.5 mg/100 g body wt.) induced release of epinephrine (E) from the adrenal medulla of newly-hatched pigeon and parakeet. In contrast, in the adults melatonin caused more than a two-fold increase in E in the pigeon, and a significant increase in the crow. Single IP melatonin injection (0.5 mg/100 g body wt.) caused hypoglycemia in the newly-hatched parakeet and adult pigeon, and hyperglycemia in newly-hatched pigeon after 0.5 h of treatment. Melatonin failed to regulate glucose homoeostasis in newly-hatched and adult crow. Splanchnic denervation of the left adrenal gland was performed in the adult pigeon. The right adrenal served as the innervated gland. Melatonin-induced modulation of catecholamines following a single IP injection (0.5 mg/100 g body wt.) revealed significant increases in NE fluorescence and NE content at 4 and 12 h after treatment in the denervated gland only, which gradually approached normal levels 9 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Increased release of norepinephrine and dopamine from canine kidney during bilateral carotid occlusion

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

    Bradley, T.; Hjemdahl, P.; DiBona, G.F.

    1987-02-01

    The renal overflow of norepinephrine (NE) and dopamine (DA) to plasma from the innervated kidney was studied at rest and during sympathetic nervous system activation by bilateral carotid artery occlusion (BCO) in vagotomized dogs under barbiturate or barbiturate/nitrous oxide anesthesia. BCO elevated arterial pressure and the arterial plasma concentration of NE, DA, and epinephrine (Epi). Renal vascular resistance (renal arterial pressure kept constant) increased by 15 +/- 7% and the net renal venous outflows (renal veno-arterial concentration difference x renal plasma flow) of NE and DA were enhanced. To obtain more correct estimates of the renal contribution to the renalmore » venous catecholamine outflow, they corrected for the renal extraction of arterial catecholamines, assessed as the extractions of (/sup 3/H)NE, (/sup 3/H)DA, or endogenous Epi. The (/sup 3/H)NE corrected renal NE overflow to plasma increased from 144 +/- 40 to 243 +/- 64 pmol-min/sup -1/ during BCO, which, when compared with a previous study of the (/sup 3/H)NE corrected renal NE overflow to plasma evoked by electrical renal nerve stimulation, corresponds to a 40% increase in nerve impulse frequency from approx. 0.6 Hz. If the renal catecholamine extraction was not taken into account the effect of BCO was underestimated. The renal DA overflow to plasma was about one-fifth of the NE overflow both at rest and during BCO, indicating that there was no preferential activation of noradrenergic or putative dopaminergic nerves by BCO.« less

  5. Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy.

    PubMed

    Hori, Hikaru; Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Igata, Ryohei; Konishi, Yuki; Nakamura, Jun

    2017-08-01

    Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

  6. EXTENT AND MAGNITUDE OF CATECHOLAMINE SURGE IN PEDIATRIC BURNED PATIENTS

    PubMed Central

    Kulp, Gabriela A; Herndon, David N.; Lee, Jong O.; Suman, Oscar E.; Jeschke, Marc G

    2009-01-01

    Increased catecholamine (CA) levels after severe burn are associated with stress, inflammation, hypermetabolism and impaired immune function. The CA secretion profiles in burned patients are not well described. Mechanisms, duration and extent of CA surge are unknown. The purpose of this large unicenter study was to evaluate the extent and magnitude of CA surge following severe burn in pediatric patients. Patients admitted between 1996 and 2008 were enrolled in this study. Twenty-four-hour urine collections were performed during acute hospitalization and up to 2 years post burn. Results from the samples collected from 12 normal, healthy volunteers were compared with the data from the burned patients. Relevant demographic and clinical information was obtained from Medical Records. Student’s t-test and one way ANOVA were used to analyze the data where appropriate. Significance was accepted at p<0.05. Four-hundred thirteen patients were enrolled in this study, 17 patients died during acute hospitalization. Burn caused a marked stress and inflammatory response, indicated by massive tachycardia and elevated pro-inflammatory cytokines. In burned patients, CA levels are consistently and significantly modulated after burn when compared to the levels in normal, healthy volunteers. CA levels were significantly higher in males compared to females, correlated with burn size in burns over 40% and were increased in older children. There were differences over time in survivors vs. non-survivors, with CA levels significantly higher in non-survivors at 2 time points. Inflammatory cytokines show a similar profile during the study period. Our study gives clinicians a useful insight into the extent and magnitude of CA elevation to better design treatment strategies. PMID:20407405

  7. Nonhydrolytic sol-gel approach to facile creation of surface-bonded zirconia organic-inorganic hybrid coatings for sample preparation. Ι. Capillary microextraction of catecholamine neurotransmitters.

    PubMed

    Alhendal, Abdullah; Mengis, Stephanie; Matthews, Jacob; Malik, Abdul

    2016-10-14

    Nonhydrolytic sol-gel (NHSG) route was used for the creation of novel zirconia-polypropylene oxide (ZrO 2 -PPO) sol-gel hybrid sorbents in the form of surface coatings for the extraction and preconcentration of catecholamine neurotransmitters and molecules structurally related to their deaminated metabolites. In comparison to other sorbents made of inorganic transition metal oxides, the presented hybrid organic-inorganic sorbents facilitated reversible sorption properties that allowed for efficient desorption of the extracted analytes by LC-MS compatible mobile phases. The presented sol-gel hybrid sorbents effectively overcame the major drawbacks of traditional silica- or polymer-based sorbents by providing superior pH stability (pH range: 0-14), and a variety of intermolecular interactions. Nonaqueous sol-gel treatment of PPO with ZrCl 4 was employed for the derivatization of the terminal hydroxyl groups on PPO, providing zirconium trichloride-containing end groups characterized by enhanced sol-gel reactivity. NHSG ZrO 2 -PPO sorbent provided excellent microextraction performance for catecholamines, low detection limits (5.6-9.6pM), high run-to-run reproducibility (RSD 0.6-5.1%), high desorption efficiency (95.0-99.5%) and high enrichment factors (∼1480-2650) for dopamine and epinephrine, respectively, extracted from synthetic urine samples. The presented sol-gel sorbents provided effective alternative to conventional extraction media providing unique physicochemical characteristics and excellent extraction capability. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Highly magneto-responsive multilayer microcapsules for controlled release of insulin.

    PubMed

    Zheng, Chunli; Ding, Yafei; Liu, Xiaoqing; Wu, Yunkai; Ge, Liang

    2014-11-20

    In this study, magneto-responsive polyelectrolyte multilayer microcapsules were successfully prepared by the formation of shell with biocompatible iron oxide nanoparticles (Fe₃O₄ NPs) and polyallylamine hydrochloride (PAH) by layer-by-layer (LbL) self-assembly technique. The self-assembled microcapsules were characterized by SEM, TEM and zeta-potential analyzer. According to the pH sensitivity of the microcapsule membrane permeability, insulin was encapsulated, with the encapsulation efficiency of 92.08±5.57%. The in vitro release behavior in an external alternating magnetic field indicated that once the magnetic field was applied, the drug release was greatly accelerated. In addition, according to the observed pulse release upon cyclic on-off operations of magnetic field, it could be assumed that the magneto-responsive microcapsules had an excellent "switching on" effect, which might be attributed to the rearrangement of shell structure caused by magnetic nanoparticles twisting and polyelectrolyte chains shaking, hence the increase of microcapsule membrane permeability and the enhancement of insulin release. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice.

    PubMed

    Reyes, Ricardo; Rodríguez, Jose Antonio; Orbe, Josune; Arnau, María Rosa; Évora, Carmen; Delgado, Araceli

    2018-11-01

    The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control. Encapsulation efficiency was assessed and in vivo release kinetics of BMP-2 and MMP10 were examined over 14 days. Histological analyses were used to analyze bone formation after four and eight weeks. Combination with MMP10 (30 ng) significantly enhanced BMP-2 (600 ng)-mediated osteogenesis, as confirmed by the increase in percentage of bone fill (p < .05) at four weeks. Moreover, it also increased mineral apposition rate (p < .05), measured by double labeling with tetracycline and calceine. MMP10 accelerates bone repair by enhancing BMP-2-promoted bone healing and improving the mineralization rate. In conclusion combination of MMP10 and BMP-2 may become a promising strategy for repair and regeneration of bone defects.

  10. Acid-Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release.

    PubMed

    Mao, Dake; Liang, Yajun; Liu, Yamin; Zhou, Xianhao; Ma, Jiaqi; Jiang, Biao; Liu, Jia; Ma, Da

    2017-10-02

    Stimuli-responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition properties of CB[n]-type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Thermodynamic and kinetic analysis of the reaction between biological catecholamines and chlorinated methylperoxy radicals

    NASA Astrophysics Data System (ADS)

    Dimić, Dušan S.; Milenković, Dejan A.; Marković, Jasmina M. Dimitrić; Marković, Zoran S.

    2018-05-01

    The antiradical potency of catecholamines (dopamine, epinephrine, norepinephrine, L-DOPA), metabolites of dopamine (homovanillic acid, 3-methoxytyramine and 3,4-dihydroxyphenylacetic acid) and catechol towards substituted methylperoxy radicals is investigated. The thermodynamic parameters, together with the kinetic approach, are used to determine the most probable mechanism of action. The natural bond orbital and quantum theory of atoms in molecules are utilised to explain the highest reactivity of trichloromethylperoxy radical. The preferred mechanism is dependent both on the thermodynamic and kinetic parameters . The number of chlorine atoms on radical, the presence of intra-molecular hydrogen bond and number of hydroxy groups attached to the aromatic ring significantly influence the mechanism. The results suggest that sequential proton loss electron transfer (SPLET) is the most probable for reaction with methylperoxy and hydrogen atom transfer (HAT) for reaction with trichloromethylperoxy radicals, with a gradual transition between SPLET and HAT for other two radicals. Due to the significant deprotonation of molecules containing the carboxyl group, the respective anions are also investigated. The HAT and SPLET mechanisms are highly competitive in reaction with MP radical, while the dominant mechanism towards chlorinated radicals is HAT. The reactions in methanol and benzene are also discussed.

  12. Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

    PubMed

    Jepma, Marieke; Murphy, Peter R; Nassar, Matthew R; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

    2016-10-01

    Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

  13. Catecholaminergic Regulation of Learning Rate in a Dynamic Environment

    PubMed Central

    Jepma, Marieke; Nassar, Matthew R.; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

    2016-01-01

    Adaptive behavior in a changing world requires flexibly adapting one’s rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the ‘learning rate’). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG—an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex—predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables—capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief—on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants’ baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change. PMID:27792728

  14. Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest.

    PubMed

    Li, Duan; Mabrouk, Omar S; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J; Mathur, Abhay; Crooks, Charles P; Kennedy, Robert T; Wang, Michael M; Ghanbari, Hamid; Borjigin, Jimo

    2015-04-21

    The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain-heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain's autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain.

  15. Successful desensitization to Gonadotropin-releasing hormone analogue Triptorelin Acetate using a sustained-release depot preparation.

    PubMed

    Chan Ng, Pauline; Huang, Chiung-Hui; Rajakulendran, Mohana; Tan, Michelle Meiling; Wang, Ping Ping; Tay, Lei Qiu; Goh, Siok Ying; Shek, Lynette Pei-Chi; Tham, Elizabeth Huiwen

    2018-05-29

    Gonadotropin-releasing hormone (GnRH) analogues are commonly used in pediatric patients in the treatment of central precocious puberty 1 . GnRH analogues suppress the secretion of gonadotropins and sex hormones, preventing progression to advanced puberty and reduced final adult height secondary to accelerated fusion of growth plates. GnRH analogues are also used in adults for treatment of endometriosis 2 and prostatic cancer 3 . Hypersensitivity reactions to GnRH analogues are exceedingly rare 4-6 and to date, we are unaware of any desensitization protocols for GnRH hypersensitivity in the literature or used in clinical practice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Effects of perch access on physiological parameters in caged White Leghorn pullets

    USDA-ARS?s Scientific Manuscript database

    The neuroendocrine system controls animals' adaptability to their environments by releasing psychotropic compounds such as catecholamines [epinephrine (EP), norepinephrine (NE), and dopamine (DA)], corticosterone (CORT), and serotonin (5-HT). Changes of these neuroendocrine compounds have been used ...

  17. Brain catechol synthesis - Control by brain tyrosine concentration

    NASA Technical Reports Server (NTRS)

    Wurtman, R. J.; Larin, F.; Mostafapour, S.; Fernstrom, J. D.

    1974-01-01

    Brain catechol synthesis was estimated by measuring the rate at which brain dopa levels rose following decarboxylase inhibition. Dopa accumulation was accelerated by tyrosine administration, and decreased by treatments that lowered brain tyrosine concentrations (for example, intraperitoneal tryptophan, leucine, or parachlorophenylalanine). A low dose of phenylalanine elevated brain tyrosine without accelerating dopa synthesis. Our findings raise the possibility that nutritional and endocrine factors might influence brain catecholamine synthesis by controlling the availability of tyrosine.

  18. First muon acceleration using a radio-frequency accelerator

    NASA Astrophysics Data System (ADS)

    Bae, S.; Choi, H.; Choi, S.; Fukao, Y.; Futatsukawa, K.; Hasegawa, K.; Iijima, T.; Iinuma, H.; Ishida, K.; Kawamura, N.; Kim, B.; Kitamura, R.; Ko, H. S.; Kondo, Y.; Li, S.; Mibe, T.; Miyake, Y.; Morishita, T.; Nakazawa, Y.; Otani, M.; Razuvaev, G. P.; Saito, N.; Shimomura, K.; Sue, Y.; Won, E.; Yamazaki, T.

    2018-05-01

    Muons have been accelerated by using a radio-frequency accelerator for the first time. Negative muonium atoms (Mu- ), which are bound states of positive muons (μ+) and two electrons, are generated from μ+'s through the electron capture process in an aluminum degrader. The generated Mu- 's are initially electrostatically accelerated and injected into a radio-frequency quadrupole linac (RFQ). In the RFQ, the Mu- 's are accelerated to 89 keV. The accelerated Mu- 's are identified by momentum measurement and time of flight. This compact muon linac opens the door to various muon accelerator applications including particle physics measurements and the construction of a transmission muon microscope.

  19. Permanent alterations in catecholamine concentrations in discrete areas of brain in the offspring of rats treated with methylamphetamine and chlorpromazine

    PubMed Central

    Tonge, Sally R.

    1973-01-01

    Methylamphetamine hydrochloride (80 mg/l.) and/or chlorpromazine hydrochloride (200 mg/l.) have been administered in the drinking water of female Wistar rats during pregnancy and suckling. The offspring were weaned at 21 days and thereafter received no drugs. Nine months later, male offspring were killed and noradrenaline and normetanephrine concentrations were determined in eight discrete areas of the brains: neocortex, hippocampus, striatum, thalamus, hypothalamus, corpora quadrigemina, pons/medulla, and amygdala region. Both drugs appeared to have permanently altered catecholamine concentrations in several areas of the brain. There was evidence of antagonism between the effects of the two drugs in the hippocampus, striatum, thalamus, and corpora quadrigemina, where the individual drugs produced altered noradrenaline concentrations but a combination of the two had no effect. PMID:4722052

  20. Particle injection and acceleration at earth's bow shock - Comparison of upstream and downstream events

    NASA Technical Reports Server (NTRS)

    Ellison, Donald C.; Moebius, Eberhard; Paschmann, Goetz

    1990-01-01

    The injection and acceleration of thermal solar wind ions at the quasi-parallel earth's bow shock during radial interplanetary magnetic field conditions is investigated. Active Magnetospheric Particle Tracer Explorers/Ion Release Module satellite observations of complete proton spectra, and of heavy ion spectra above 10 keV/Q, made on September 12, 1984 near the nose of the shock, are presented and compared to the predictions of a Monte Carlo shock simulation which includes diffusive shock acceleration. It is found that the spectral observations are in good agreement with the predictions of the simulation when it is assumed that all accelerated ions originate in the solar wind and are injected into the acceleration mechanism by thermal leakage from the downstream plasma. The efficiency, which is determined directly from the downstream observations, is high, with at least 15 percent of the solar wind energy flux going into accelerated particles. The comparisons allow constraints to be placed on the rigidity dependence of the scattering mean free path and suggest that the upstream solar wind must be slowed substantially by backstreaming accelerated ions prior to undergoing a sharp transition in the viscous subshock.

  1. A Discussion of SY-101 Crust Gas Retention and Release Mechanisms

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

    SD Rassat; PA Gauglitz; SM Caley

    1999-02-23

    The flammable gas hazard in Hanford waste tanks was made an issue by the behavior of double-shell Tank (DST) 241-SY-101 (SY-101). Shortly after SY-101 was filled in 1980, the waste level began rising periodically, due to the generation and retention of gases within the slurry, and then suddenly dropping as the gases were released. An intensive study of the tank's behavior revealed that these episodic releases posed a safety hazard because the released gas was flammable, and, in some cases, the volume of gas released was sufficient to exceed the lower flammability limit (LFL) in the tank headspace (Allemann etmore » al. 1993). A mixer pump was installed in SY-101 in late 1993 to prevent gases from building up in the settled solids layer, and the large episodic gas releases have since ceased (Allemann et al. 1994; Stewart et al. 1994; Brewster et al. 1995). However, the surface level of SY-101 has been increasing since at least 1995, and in recent months the level growth has shown significant and unexpected acceleration. Based on a number of observations and measurements, including data from the void fraction instrument (VFI), we have concluded that the level growth is caused largely by increased gas retention in the floating crust. In September 1998, the crust contained between about 21 and 43% void based on VFI measurements (Stewart et al. 1998). Accordingly, it is important to understand the dominant mechanisms of gas retention, why the gas retention is increasing, and whether the accelerating level increase will continue, diminish or even reverse. It is expected that the retained gas in the crust is flammable, with hydrogen as a major constituent. This gas inventory would pose a flammable gas hazard if it were to release suddenly. In May 1997, the mechanisms of bubble retention and release from crust material were the subject of a workshop. The evaluation of the crust and potential hazards assumed a more typical void of roughly 15% gas. It could be similar to

  2. Comparing Solar-Flare Acceleration of >-20 MeV Protons and Electrons Above Various Energies

    NASA Technical Reports Server (NTRS)

    Shih, Albert Y.

    2010-01-01

    A large fraction (up to tens of percent) of the energy released in solar flares goes into accelerated ions and electrons, and studies indicate that these two populations have comparable energy content. RHESSI observations have shown a striking close linear correlation between the 2.223 MeV neutron-capture gamma-ray line and electron bremsstrahlung emission >300 keV, indicating that the flare acceleration of >^20 MeV protons and >300 keV electrons is roughly proportional over >3 orders of magnitude in fluence. We show that the correlations of neutron-capture line fluence with GOES class or with bremsstrahlung emission at lower energies show deviations from proportionality, primarily for flares with lower fluences. From analyzing thirteen flares, we demonstrate that there appear to be two classes of flares with high-energy acceleration: flares that exhibit only proportional acceleration of ions and electrons down to 50 keV and flares that have an additional soft, low-energy bremsstrahlung component, suggesting two separate populations of accelerated electrons. We use RHESSI spectroscopy and imaging to investigate a number of these flares in detail.

  3. Astressin B, a corticotropin-releasing hormone receptor antagonist, accelerates the return to normal luteal function after an inflammatory-like stress challenge in the rhesus monkey.

    PubMed

    Xiao, Ennian; Xia-Zhang, Linna; Vulliemoz, Nicolas; Rivier, Jean; Ferin, Michel

    2007-02-01

    Endogenous release of CRH in stress has been associated with a dysfunctional reproductive endocrine axis. In the rhesus monkey, an inflammatory-like stress challenge in the luteal phase decreases luteal secretory function. Here, we tested the effectiveness of astressin B, a nonspecific CRH receptor antagonist, in constraining the deleterious impact of a 10-d lipopolysaccharide (LPS) challenge on the menstrual cycle. Two protocols were carried out in nine animals. In the first, the animals, after showing two normal consecutive control cycles, were injected daily for 10 days with LPS (75-125 mug/d) during the luteal phase of the cycle. The animals were followed through the two postchallenge cycles. The second protocol, carried out in the following year, was identical with protocol 1, except that the animals were treated with astressin B (0.45 mg/kg) 1 h before each daily LPS challenge during the luteal phase. Blood samples were obtained daily to document cyclic hormones levels. The LPS challenge significantly decreased luteal progesterone and LH release during the challenge cycle. Inhibition of luteal progesterone extended to the two successive postchallenge cycles. Astressin B treatment prevented luteal LH but not luteal progesterone decrease during the treatment cycle and restored normal progesterone secretion during the two posttreatment cycles. We conclude that the deleterious impact of a short-term inflammatory stress challenge on luteal function is far longer than the stress period itself. Systemic administration of astressin B accelerates the return to normal luteal function, presumably by restoring normal neuroendocrine regulation of gonadotropin secretion.

  4. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  5. On Quantizing Ride Comfort and Allowable Accelerations

    DTIC Science & Technology

    1976-07-01

    UnImited and approved for Public release. ,.Io. 7 D5Xt4WX.AX..JL.1.X.1LJ -’a~ft IF I.,, I. ’W No 1 -0.U /cM Report) MAR 3 19M0 III. SUPPLEMENTARY NOTES...vehicle’s habitability for a given tive. This is for three main reasons: acceleration-time history. These indices are: Mankind is very variable, and even an...though the limits may not be entirely "correct" in an absolute sense,.e ~utIY* review the l~steryof an analogousawL I Hey~ f .,B 7 -tisom e To better

  6. Released advance reproduction of white and red fir. . . growth, damage, mortality

    Treesearch

    Donald T. Gordon

    1973-01-01

    Advance reproduction of white fir and red fir released by cutting overmature over-story was studied at the Swain Mountain Experimental Forest in northern California, at 6,300 feet elevation. Seedling and sapling height growth before logging was only 0.1-0.2 foot per year. Five years after cutting, seedling and sapling height growth had accelerated to about 0.5 to 0.8...

  7. The effect of platform switching on the levels of metal ion release from different implant–abutment couples

    PubMed Central

    Alrabeah, Ghada O; Knowles, Jonathan C; Petridis, Haralampos

    2016-01-01

    The improved peri-implant bone response demonstrated by platform switching may be the result of reduced amounts of metal ions released to the surrounding tissues. The aim of this study was to compare the levels of metal ions released from platform-matched and platform-switched implant–abutment couples as a result of accelerated corrosion. Thirty-six titanium alloy (Ti-6Al-4V) and cobalt–chrome alloy abutments were coupled with titanium cylinders forming either platform-switched or platform-matched groups (n=6). In addition, 18 unconnected samples served as controls. The specimens were subjected to accelerated corrosion by static immersion in 1% lactic acid for 1 week. The amount of metal ions ion of each test tube was measured using inductively coupled plasma mass spectrometry. Scanning electron microscope (SEM) images and energy dispersive spectroscopy X-ray analyses were performed pre- and post-immersion to assess corrosion at the interface. The platform-matched groups demonstrated higher ion release for vanadium, aluminium, cobalt, chrome, and molybdenum compared with the platform-switched groups (P<0.05). Titanium was the highest element to be released regardless of abutment size or connection (P<0.05). SEM images showed pitting corrosion prominent on the outer borders of the implant and abutment platform surfaces. In conclusion, implant–abutment couples underwent an active corrosion process resulting in metal ions release into the surrounding environment. The highest amount of metal ions released was recorded for the platform-matched groups, suggesting that platform-switching concept has a positive effect in reducing the levels of metal ion release from the implant–abutment couples. PMID:27357323

  8. Acceleration Modes and Transitions in Pulsed Plasma Accelerators

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Greve, Christine M.

    2018-01-01

    Pulsed plasma accelerators typically operate by storing energy in a capacitor bank and then discharging this energy through a gas, ionizing and accelerating it through the Lorentz body force. Two plasma accelerator types employing this general scheme have typically been studied: the gas-fed pulsed plasma thruster and the quasi-steady magnetoplasmadynamic (MPD) accelerator. The gas-fed pulsed plasma accelerator is generally represented as a completely transient device discharging in approximately 1-10 microseconds. When the capacitor bank is discharged through the gas, a current sheet forms at the breech of the thruster and propagates forward under a j (current density) by B (magnetic field) body force, entraining propellant it encounters. This process is sometimes referred to as detonation-mode acceleration because the current sheet representation approximates that of a strong shock propagating through the gas. Acceleration of the initial current sheet ceases when either the current sheet reaches the end of the device and is ejected or when the current in the circuit reverses, striking a new current sheet at the breech and depriving the initial sheet of additional acceleration. In the quasi-steady MPD accelerator, the pulse is lengthened to approximately 1 millisecond or longer and maintained at an approximately constant level during discharge. The time over which the transient phenomena experienced during startup typically occur is short relative to the overall discharge time, which is now long enough for the plasma to assume a relatively steady-state configuration. The ionized gas flows through a stationary current channel in a manner that is sometimes referred to as the deflagration-mode of operation. The plasma experiences electromagnetic acceleration as it flows through the current channel towards the exit of the device. A device that had a short pulse length but appeared to operate in a plasma acceleration regime different from the gas-fed pulsed plasma

  9. Membrane Potential Controls the Efficacy of Catecholamine-induced β1-Adrenoceptor Activity*

    PubMed Central

    Birk, Alexandra; Rinne, Andreas; Bünemann, Moritz

    2015-01-01

    G protein-coupled receptors (GPCRs) are membrane-located proteins and, therefore, are exposed to changes in membrane potential (VM) in excitable tissues. These changes have been shown to alter receptor activation of certain Gi-and Gq-coupled GPCRs. By means of a combination of whole-cell patch-clamp and Förster resonance energy transfer (FRET) in single cells, we demonstrate that the activation of the Gs-coupled β1-adrenoreceptor (β1-AR) by the catecholamines isoprenaline (Iso) and adrenaline (Adr) is regulated by VM. This voltage-dependence is also transmitted to G protein and arrestin 3 signaling. Voltage-dependence of β2-AR activation, however, was weak compared with β1-AR voltage-dependence. Drug efficacy is a major target of β1-AR voltage-dependence as depolarization attenuated receptor activation, even under saturating concentrations of agonists, with significantly faster kinetics than the deactivation upon agonist withdrawal. Also the efficacy of the endogenous full agonist adrenaline was reduced by depolarization. This is a unique finding since reports of natural full agonists at other voltage-dependent GPCRs only show alterations in affinity during depolarization. Based on a Boltzmann function fit to the relationship of VM and receptor-arrestin 3 interaction we determined the voltage-dependence with highest sensitivity in the physiological range of membrane potential. Our data suggest that under physiological conditions voltage regulates the activity of agonist-occupied β1-adrenoceptors on a very fast time scale. PMID:26408198

  10. Dormancy release and flowering time in Ziziphus jujuba Mill., a "direct flowering" fruit tree, has a facultative requirement for chilling.

    PubMed

    Meir, Michal; Ransbotyn, Vanessa; Raveh, Eran; Barak, Simon; Tel-Zur, Noemi; Zaccai, Michele

    2016-03-15

    In deciduous fruit trees, the effect of chilling on flowering has mostly been investigated in the "indirect flowering" group, characterized by a period of rest between flower bud formation and blooming. In the present study, we explored the effects of chilling and chilling deprivation on the flowering of Ziziphus jujuba, a temperate deciduous fruit tree belonging to the "direct flowering" group, in which flower bud differentiation, blooming and fruit development occur after dormancy release, during a single growing season. Dormancy release, vegetative growth and flowering time in Z. jujuba cv. Ben-Li were assessed following several treatments of chilling. Chilling treatments quantitatively decreased the timing of vegetative bud dormancy release, thereby accelerating flowering, but had no effect on the time from dormancy release to flowering. Trees grown at a constant temperature of 25°C, without chilling, broke dormancy and flowered, indicating the facultative character of chilling in this species. We measured the expression of Z. jujuba LFY and AP1 homologues (ZjLFY and ZjAP1). Chilling decreased ZjLFY expression in dormant vegetative buds but had no effect on ZjAP1expression, which reached peak expression before dormancy release and at anthesis. In conclusion, chilling is not obligatory for dormancy release of Z. jujuba cv. Ben-Li vegetative buds. However, the exposure to chilling during dormancy does accelerate vegetative bud dormancy release and flowering. Copyright © 2016 Elsevier GmbH. All rights reserved.

  11. Evaluation of particles released from single-wall carbon nanotube/polymer composites with or without thermal aging by an accelerated abrasion test.

    PubMed

    Jiang, Lin; Kondo, Akira; Shigeta, Masahiro; Endoh, Shigehisa; Uejima, Mitsugu; Ogura, Isamu; Naito, Makio

    2014-01-01

    To provide data required for assessing the environmental health and safety risks of nanocomposites, abrasion-induced particle release from single-wall carbon nanotube (SWCNT)/polymer composites with or without thermal aging were evaluated by a shot blast system. First, overall composite weight loss (i.e., overall particle release) as a result of shot blasting was measured. Incorporating 5 wt% SWCNTs in polystyrene (PS) matrix was observed to reduce overall particle release by approximately 30% compared with pure PS. Heat treatment of the 5 wt% SWCNT/PS composites at 100°C for 10 days induced very slight change in overall particle release due to shot blasting. However, heat treatment at 350°C for 1 hr greatly deteriorated the abrasion resistance of the composites, enhancing overall particle release. Second, to verify the existence and form of SWCNTs released from the composites, released particles were observed by electron microscopy. Micron-sized particles with protruding SWCNTs and submicron-sized SWCNT clusters were observed in the particles released from the composites. Heat treatment of the composites at 350°C for 1 hr enhanced SWCNT release, which mainly formed clusters or rope-like bundles.

  12. Controlled drug release by polymer dissolution. II: Enzyme-mediated delivery device.

    PubMed

    Heller, J; Trescony, P V

    1979-07-01

    A novel, closed-loop drug delivery system was developed where the presence or absence of an external compound controls drug delivery from a bioerodible polymer. In the described delivery system, hydrocortisone was incorporated into a n-hexyl half-ester of a methyl vinyl ehter-maleic anhydride copolymer, and the polymer-drug mixture was fabricated into disks. These disks were then coated with a hydrogel containing immobilized urease. In a medium of constant pH and in the absence of external urea, the hydrocortisone release was that normally expected for that polymer at the given pH. With external urea, ammonium bicarbonate and ammonium hydroxide were generated within the hydrogel, which accelerated polymer erosion and drug release. The drug delivery rate increase was proportional to the amount of external urea and was reversible; that is, when external urea was removed, the drug release rate gradually returned to its original value.

  13. Release behavior of uranium in uranium mill tailings under environmental conditions.

    PubMed

    Liu, Bo; Peng, Tongjiang; Sun, Hongjuan; Yue, Huanjuan

    2017-05-01

    Uranium contamination is observed in sedimentary geochemical environments, but the geochemical and mineralogical processes that control uranium release from sediment are not fully appreciated. Identification of how sediments and water influence the release and migration of uranium is critical to improve the prevention of uranium contamination in soil and groundwater. To understand the process of uranium release and migration from uranium mill tailings under water chemistry conditions, uranium mill tailing samples from northwest China were investigated with batch leaching experiments. Results showed that water played an important role in uranium release from the tailing minerals. The uranium release was clearly influenced by contact time, liquid-solid ratio, particle size, and pH under water chemistry conditions. Longer contact time, higher liquid content, and extreme pH were all not conducive to the stabilization of uranium and accelerated the uranium release from the tailing mineral to the solution. The values of pH were found to significantly influence the extent and mechanisms of uranium release from minerals to water. Uranium release was monitored by a number of interactive processes, including dissolution of uranium-bearing minerals, uranium desorption from mineral surfaces, and formation of aqueous uranium complexes. Considering the impact of contact time, liquid-solid ratio, particle size, and pH on uranium release from uranium mill tailings, reducing the water content, decreasing the porosity of tailing dumps and controlling the pH of tailings were the key factors for prevention and management of environmental pollution in areas near uranium mines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Understanding projectile acceleration.

    PubMed

    Hecht, H; Bertamini, M

    2000-04-01

    Throwing and catching balls or other objects is a generally highly practiced skill; however, conceptual as well as perceptual understanding of the mechanics that underlie this skill is surprisingly poor. In 5 experiments, we investigated conceptual and perceptual understanding of simple ballistic motion. Paper-and-pencil tests revealed that up to half of all participants mistakenly believed that a ball would continue to accelerate after it left the thrower's hand. Observers also showed a remarkable tolerance for anomalous trajectory shapes. Perceptual judgments based on graphics animations replicated these erroneous beliefs for shallow release angles. Observers' tolerance for anomalies tended to decrease with their distance from the actor. The findings are at odds with claims of the naive physics literature that liken intuitive understanding to Aristotelian or medieval physics theories. Instead, observers seem to project their intentions to the ball itself (externalization) or even feel that they have power over the ball when it is still close.

  15. Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells.

    PubMed

    Lenis, Yasser Y; Wang, Xiaoqiu; Tang, Wanjin; Wu, Guoyao; Bazer, Fuller W

    2016-10-01

    Embryonic survival requires histotrophic nutrition, including molecules secreted or transported into the uterine lumen by uterine epithelia. L-Arginine (Arg) is a common substrate for synthesis of nitric oxide, ornithine, proline, glutamate, creatinine, urea, polyamines and agmatine. Agmatine (Agm) is a product of arginine decarboxylation and it is a substrate for agmatinase for synthesis of putrescine and other polyamines in the ovine conceptus. Polyamines are essential for conceptus development. Therefore, this study compared effects of Arg and Agm on the behavior of ovine trophectoderm (oTr1) cells cultured in vitro. Arg, but not Agm, increased proliferation and migration of oTr1 cells, but neither Arg nor Agm affected cell adhesion. The total amount of IFNT in culture medium of oTr1 cells was increased by Arg, but Agm increased the IFNT production per oTr1 cell. Arg and Agm plus Arg decreased secretion of dopamine and norepinephrine by oTr1 cells. Agm upregulates expression of mRNAs SLC7A1, agmatinase and OAZ2 while the combination of Arg and Agm decreased expression of mRNAs for ODC1, SLC7A1, OAZ1 and OAZ3 by oTr1 cells. Although Agm does not stimulate proliferation, migration or adhesion of oTr1 cells or their secretion of catecholamines, Agm did increase transcription of SLC7A1, agmatinase and OAZ2 genes which would increase the capacity of oTr1 cells to produce polyamines. Collectively, our findings suggest a role for Arg and Agm in the regulation of transport of basic amino acids (including Arg), polyamine synthesis, and secretion of catecholamines by oTr1 cells.

  16. Transient shock and myocardial impairment caused by phaeochromocytoma crisis.

    PubMed Central

    Shaw, T R; Rafferty, P; Tait, G W

    1987-01-01

    A patient admitted to hospital after injury to the abdomen was found to have transient hypertension which was followed by profound hypotension. ST elevation developed and extensive myocardial akinesia was seen at echocardiography, but coronary angiograms at this stage were normal. After treatment with intravenous fluids and dopamine he progressively recovered normal cardiac function. A partly necrotic catecholamine secreting tumour was later removed from the abdomen and it is likely that a kick to the abdomen had damaged the tumour and the consequent release of catecholamine had triggered a phaeochromocytoma crisis. Images Fig 1 Fig 2 PMID:3814455

  17. Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest

    PubMed Central

    Li, Duan; Mabrouk, Omar S.; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J.; Mathur, Abhay; Crooks, Charles P.; Kennedy, Robert T.; Wang, Michael M.; Ghanbari, Hamid; Borjigin, Jimo

    2015-01-01

    The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain–heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain’s autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain. PMID:25848007

  18. Studies of Particle Acceleration, Transport and Radiation in Impulsive Phase of Solar Flares

    NASA Technical Reports Server (NTRS)

    Petrosian, Vahe

    2005-01-01

    Solar activity and its most prominent aspect, the solar flares, have considerable influence on terrestrial and space weather. Solar flares also provide a suitable laboratory for the investigation of many plasma and high energy processes important in the magnetosphere of the Earth and many other space and astrophysical situations. Hence, progress in understanding of flares will have considerable scientific and societal impact. The primary goal of this grant is the understanding of two of the most important problems of solar flare physics, namely the determination of the energy release mechanism and how this energy accelerates particles. This is done through comparison of the observations with theoretical models, starting from observations and gradually proceeding to theoretically more complex situations as the lower foundations of our understanding are secured. It is generally agreed that the source of the flare energy is the annihilation of magnetic fields by the reconnection process. Exactly how this energy is released or how it is dissipated remains controversial. Moreover, the exact mechanism of the acceleration of the particles is still a matter of debate. Data from many spacecrafts and ground based instruments obtained over the past decades have given us some clues. Theoretical analyses of these data have led to the standard thick target model (STT) where most of the released energy goes into an (assumed) power law spectrum of accelerated particles, and where all the observed radiations are the consequence of the interaction of these particles with the flare plasma. However, some theoretical arguments, and more importantly some new observations, have led us to believe that the above picture is not complete. It appears that plasma turbulence plays a more prominent role than suspected previously, and that it is the most likely agent for accelerating particles. The model we have developed is based on production of a high level of plasma waves and turbulence in

  19. 78 FR 21996 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69341; File No. SR-NASDAQ-2013-048] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval of a Proposed Rule... in a Limit State or Straddle State, and unlike normal circumstances, may not be a true reflection of...

  20. Matching native electrical stimulation by graded chemical stimulation in isolated mouse adrenal chromaffin cells.

    PubMed

    Fulop, Tiberiu; Smith, Corey

    2007-11-30

    Adrenal chromaffin cells release multiple transmitters in response to sympathetic stimulation. Modest cell firing, matching sympathetic tone, releases small freely soluble catecholamines. Elevated electrical firing rates matching input under sympathetic stress results in release of catecholamines as well as semi-soluble vaso- and neuro-active peptides packaged within the dense core of the secretory granule. This activity-dependent differential transmitter release has been shown to rely on a mechanistic shift in the mode of exocytosis through the regulated dilation of the secretory fusion pore between granule and cell surface membranes. However, biochemical description of the mechanism regulating fusion pore dilation remains elusive. In the experimental setting, electrical stimulation designed to mimic sympathetic input, is achieved through single-cell voltage-clamp. While precise, this approach is incompatible with biochemical and proteomic analysis, both of which require large sample sizes. We address this limitation in the current study. We describe a bulk chemical stimulation paradigm calibrated to match defined electrical activity. We utilize calcium and single-cell amperometric measurements to match extracellular potassium concentrations to physiological electrical stimulation under sympathetic tone as well as acute stress conditions. This approach provides larger samples of uniformly stimulated cells for determining molecular players in activity-dependent differential transmitter release from adrenal chromaffin cells.

  1. Microwave-Accelerated Method for Ultra-Rapid Extraction of Neisseria gonorrhoeae DNA for Downstream Detection

    PubMed Central

    Melendez, Johan H.; Santaus, Tonya M.; Brinsley, Gregory; Kiang, Daniel; Mali, Buddha; Hardick, Justin; Gaydos, Charlotte A.; Geddes, Chris D.

    2016-01-01

    Nucleic acid-based detection of gonorrhea infections typically require a two-step process involving isolation of the nucleic acid, followed by the detection of the genomic target often involving PCR-based approaches. In an effort to improve on current detection approaches, we have developed a unique two-step microwave-accelerated approach for rapid extraction and detection of Neisseria gonorrhoeae (GC) DNA. Our approach is based on the use of highly-focused microwave radiation to rapidly lyse bacterial cells, release, and subsequently fragment microbial DNA. The DNA target is then detected by a process known as microwave-accelerated metal-enhanced fluorescence (MAMEF), an ultra-sensitive direct DNA detection analytical technique. In the present study, we show that highly focused microwaves at 2.45 GHz, using 12.3 mm gold film equilateral triangles, are able to rapidly lyse both bacteria cells and fragment DNA in a time- and microwave power-dependent manner. Detection of the extracted DNA can be performed by MAMEF, without the need for DNA amplification in less than 10 minutes total time or by other PCR-based approaches. Collectively, the use of a microwave-accelerated method for the release and detection of DNA represents a significant step forward towards the development of a point-of-care (POC) platform for detection of gonorrhea infections. PMID:27325503

  2. Microwave-accelerated method for ultra-rapid extraction of Neisseria gonorrhoeae DNA for downstream detection.

    PubMed

    Melendez, Johan H; Santaus, Tonya M; Brinsley, Gregory; Kiang, Daniel; Mali, Buddha; Hardick, Justin; Gaydos, Charlotte A; Geddes, Chris D

    2016-10-01

    Nucleic acid-based detection of gonorrhea infections typically require a two-step process involving isolation of the nucleic acid, followed by detection of the genomic target often involving polymerase chain reaction (PCR)-based approaches. In an effort to improve on current detection approaches, we have developed a unique two-step microwave-accelerated approach for rapid extraction and detection of Neisseria gonorrhoeae (gonorrhea, GC) DNA. Our approach is based on the use of highly focused microwave radiation to rapidly lyse bacterial cells, release, and subsequently fragment microbial DNA. The DNA target is then detected by a process known as microwave-accelerated metal-enhanced fluorescence (MAMEF), an ultra-sensitive direct DNA detection analytical technique. In the current study, we show that highly focused microwaves at 2.45 GHz, using 12.3-mm gold film equilateral triangles, are able to rapidly lyse both bacteria cells and fragment DNA in a time- and microwave power-dependent manner. Detection of the extracted DNA can be performed by MAMEF, without the need for DNA amplification, in less than 10 min total time or by other PCR-based approaches. Collectively, the use of a microwave-accelerated method for the release and detection of DNA represents a significant step forward toward the development of a point-of-care (POC) platform for detection of gonorrhea infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Covariant Uniform Acceleration

    NASA Astrophysics Data System (ADS)

    Friedman, Yaakov; Scarr, Tzvi

    2013-04-01

    We derive a 4D covariant Relativistic Dynamics Equation. This equation canonically extends the 3D relativistic dynamics equation , where F is the 3D force and p = m0γv is the 3D relativistic momentum. The standard 4D equation is only partially covariant. To achieve full Lorentz covariance, we replace the four-force F by a rank 2 antisymmetric tensor acting on the four-velocity. By taking this tensor to be constant, we obtain a covariant definition of uniformly accelerated motion. This solves a problem of Einstein and Planck. We compute explicit solutions for uniformly accelerated motion. The solutions are divided into four Lorentz-invariant types: null, linear, rotational, and general. For null acceleration, the worldline is cubic in the time. Linear acceleration covariantly extends 1D hyperbolic motion, while rotational acceleration covariantly extends pure rotational motion. We use Generalized Fermi-Walker transport to construct a uniformly accelerated family of inertial frames which are instantaneously comoving to a uniformly accelerated observer. We explain the connection between our approach and that of Mashhoon. We show that our solutions of uniformly accelerated motion have constant acceleration in the comoving frame. Assuming the Weak Hypothesis of Locality, we obtain local spacetime transformations from a uniformly accelerated frame K' to an inertial frame K. The spacetime transformations between two uniformly accelerated frames with the same acceleration are Lorentz. We compute the metric at an arbitrary point of a uniformly accelerated frame. We obtain velocity and acceleration transformations from a uniformly accelerated system K' to an inertial frame K. We introduce the 4D velocity, an adaptation of Horwitz and Piron s notion of "off-shell." We derive the general formula for the time dilation between accelerated clocks. We obtain a formula for the angular velocity of a uniformly accelerated object. Every rest point of K' is uniformly accelerated, and

  4. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

    PubMed

    Missaghi, Shahrzad; Young, Cara; Fegely, Kurt; Rajabi-Siahboomi, Ali R

    2010-02-01

    Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months. All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

  5. Analyzing radial acceleration with a smartphone acceleration sensor

    NASA Astrophysics Data System (ADS)

    Vogt, Patrik; Kuhn, Jochen

    2013-03-01

    This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

  6. Ultrasound stimulated release of gallic acid from chitin hydrogel matrix.

    PubMed

    Jiang, Huixin; Kobayashi, Takaomi

    2017-06-01

    Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0-30W at 43kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25mg/cm 3 ) and chitin concentrations (0.1, 0.5, and 1wt%) on the release behaviors were recorded under 43kHz US exposure at 30W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74μg/mL·min was obtained from 0.54mg/cm 3 of GA-loaded hydrogel fabricated from a 0.1wt% chitin mixture solution under 43kHz US exposure at 30W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Catecholaminergic systems in stress: structural and molecular genetic approaches.

    PubMed

    Kvetnansky, Richard; Sabban, Esther L; Palkovits, Miklos

    2009-04-01

    Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct

  8. Community Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

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

    Spentzouris, P.; /Fermilab; Cary, J.

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessarymore » accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors. ComPASS is in the first year of executing its plan to develop the next-generation HPC accelerator modeling tools. ComPASS aims to develop an integrated simulation environment that will utilize existing and new accelerator physics modules with petascale capabilities, by employing modern computing and solver technologies. The ComPASS vision is to deliver to accelerator scientists a virtual accelerator and virtual prototyping modeling environment, with the necessary multiphysics, multiscale capabilities. The plan for this development includes delivering accelerator modeling applications appropriate for each stage of the ComPASS software evolution. Such applications are already being used to address challenging problems in accelerator design and optimization. The Com

  9. Effect of Orion Post-Touchdown Parachute Release Time on Vehicle Rollover

    NASA Technical Reports Server (NTRS)

    Lawrence, Charles; Georgiadis, Nicholas J.; Littell, Justin

    2008-01-01

    The effects that the Orion parachutes have on the vehicle response once the vehicle lands on the ground are examined in this report. A concern with the Orion landing is that structural accelerations will cause vehicle and/or crew injuries or that the vehicle may roll over. The parachute effects are thought to have the potential of pulling the vehicle over during conditions such as higher winds or in some cases stabilizing the vehicle by preventing its motions after touchdown. A collection of representative landing conditions is used to assess the post-touchdown parachute release effect, and it was determined that, in general, there is no significant advantage or disadvantage to releasing the parachutes past the time when the vehicle touches ground. For landing conditions when there is a high horizontal wind, retaining the parachutes has a detrimental effect on vehicle rollover because the drag force on the parachutes pulls the vehicle over. Under this condition, some form of automated parachute release should be a requirement given that an attached parachute may cause the vehicle to roll over. An automated system would ensure that the release occur within 0.50 sec of touchdown (time when parachute regains tension), which is not enough time for a crew-operated manual release.

  10. The Awful Truth About Zero-Gravity: Space Acceleration Measurement System; Orbital Acceleration Research Experiment

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Earth's gravity holds the Shuttle in orbit, as it does satellites and the Moon. The apparent weightlessness experienced by astronauts and experiments on the Shuttle is a balancing act, the result of free-fall, or continuously falling around Earth. An easy way to visualize what is happening is with a thought experiment that Sir Isaac Newton did in 1686. Newton envisioned a mountain extending above Earth's atmosphere so that friction with the air would be eliminated. He imagined a cannon atop the mountain and aimed parallel to the ground. Firing the cannon propels the cannonball forward. At the same time, Earth's gravity pulls the cannonball down to the surface and eventual impact. Newton visualized using enough powder to just balance gravity so the cannonball would circle the Earth. Like the cannonball, objects orbiting Earth are in continuous free-fall, and it appears that gravity has been eliminated. Yet, that appearance is deceiving. Activities aboard the Shuttle generate a range of accelerations that have effects similar to those of gravity. The crew works and exercises. The main data relay antenna quivers 17 times per second to prevent 'stiction,' where parts stick then release with a jerk. Cooling pumps, air fans, and other systems add vibration. And traces of Earth's atmosphere, even 200 miles up, drag on the Shuttle. While imperceptible to us, these vibrations can have a profound impact on the commercial research and scientific experiments aboard the Shuttle. Measuring these forces is necessary so that researchers and scientists can see what may have affected their experiments when analyzing data. On STS-107 this service is provided by the Space Acceleration Measurement System for Free Flyers (SAMS-FF) and the Orbital Acceleration Research Experiment (OARE). Precision data from these two instruments will help scientists analyze data from their experiments and eliminate outside influences from the phenomena they are studying during the mission.

  11. IDM release behavior and surface characteristics of the novel Cu/IDM/LDPE nanocomposite for intrauterine device.

    PubMed

    Yang, Zhihong; Xie, Changsheng; Xiang, Hua; Feng, Jinqing; Xia, Xianping; Cai, Shuizhou

    2009-03-01

    Copper/indomethacin/low-density polyethylene (Cu/IDM/LDPE) nanocomposite was prepared as a novel material for intra-uterine device (IUD). IDM release profile of the nanocomposite was investigated by using spectrophotometer. The results show that IDM release rate of Cu/IDM/LDPE nanocomposite is higher in simulated uterine solution than that in methanol, confirming that the release process of IDM is dominated mainly by pore diffusion. The decrease in copper particle size and the increase in copper mass content all accelerate IDM release, indicating that IDM release rate can be adjusted by changing copper loading or copper particle size. The surface of the incubated nanocomposite was characterized by X-ray diffraction, scanning electron microscopy and energy dispersive X-ray microanalysis. A few deposits composed of P, Cl, Ca, Cu and O were observed on the nanocomposite surface, which may be related to the presence of IDM particles with large particle size.

  12. Release from ISOLDE molten metal targets under pulsed proton beam conditions

    NASA Astrophysics Data System (ADS)

    Lettry, J.; Catherall, R.; Cyvoct, G.; Evensen, A. H. M.; Lindroos, M.; Jonsson, O. C.; Kugler, E.; Schindl, K.; Ravn, H.; Wildner, E.; Drumm, P.; Obert, J.; Putaux, J. C.; Sauvage, J.

    1996-04-01

    By moving the ISOLDE mass separators from the 600 MeV Synchrocyclotron (SC) to the 1 GeV Proton-Synchrotron-Booster (PS) the instantaneous energy density of the proton beam went up by 3 orders of magnitude. The developments of the molten metal target units and the optimization of the PS proton beam to cope with the effects of the thermal shocks induced by the proton beam are described. The energy density of the PS proton beam was reduced by spatial defocusing and time staggered extraction of the four PS-accelerators. The release from lanthanum, lead and tin targets is discussed for different settings of the proton beam and compared to the release observed at ISOLDE-SC. The yields of Hg isotopes are presented.

  13. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

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

    Siemann, R.H.; /SLAC

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  14. Commnity Petascale Project for Accelerator Science And Simulation: Advancing Computational Science for Future Accelerators And Accelerator Technologies

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

    Spentzouris, Panagiotis; /Fermilab; Cary, John

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessarymore » accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors.« less

  15. Rapid acceleration leads to rapid weakening in earthquake-like laboratory experiments

    USGS Publications Warehouse

    Chang, Jefferson C.; Lockner, David A.; Reches, Z.

    2012-01-01

    After nucleation, a large earthquake propagates as an expanding rupture front along a fault. This front activates countless fault patches that slip by consuming energy stored in Earth’s crust. We simulated the slip of a fault patch by rapidly loading an experimental fault with energy stored in a spinning flywheel. The spontaneous evolution of strength, acceleration, and velocity indicates that our experiments are proxies of fault-patch behavior during earthquakes of moment magnitude (Mw) = 4 to 8. We show that seismically determined earthquake parameters (e.g., displacement, velocity, magnitude, or fracture energy) can be used to estimate the intensity of the energy release during an earthquake. Our experiments further indicate that high acceleration imposed by the earthquake’s rupture front quickens dynamic weakening by intense wear of the fault zone.

  16. Tyrosine administration enhances dopamine synthesis and release in light-activated rat retina

    NASA Technical Reports Server (NTRS)

    Gibson, C. J.; Watkins, C. J.; Wurtman, R. J.

    1983-01-01

    Exposure of dark-adapted albino rats to light (350 lux) significantly elevated retinal levels of the dopamine metabolite dihydroxyphenyl acetic acid during the next hour; their return to a dark environment caused dihydroxyphenyl acetic acid levels to fall. Retinal dopamine levels were increased slightly by light exposure, suggesting that the increase in dihydroxyphenyl acetic acid reflected accelerated dopamine synthesis. Administration of tyrosine (100 mg/kg, i.p.) further elevated retinal dihydroxyphenyl acetic acid among light-exposed animals, but failed to affect dopamine release among animals in the dark. These observations show that a physiological stimulus - light exposure - can cause catecholaminergic neurons to become tyrosine-dependent; they also suggest that food consumption may affect neurotransmitter release within the retina.

  17. Influences of graded dose of melatonin on the levels of blood glucose and adrenal catecholamines in male roseringed parakeets (Psittacula krameri ) under different photoperiods.

    PubMed

    Maitra, S K; Dey, M; Dutta, S; Bhattacharya, S; Dey, R; Sengupta, A

    2000-12-01

    Effects of daily evening (just before the onset of darkness in a 24 h light dark cycle) administration of graded doses (25, 50, or 100 microg/100 g body wt./day for 30 days) of melatonin on the concentrations of blood glucose and adrenal catecholamines were studied in sexually active male roseringed parakeets under natural (NP; approximately 12L: 12D) and artificial long (LP; 16L: 8D) and short (SP; 8L: 16D) photoperiods. Blood samples and adrenal glands were collected from each bird during the mid-day on the following day of the last treatment. The concentrations of glucose in blood and epinephrine (E) and norepinephrine (NE) in the adrenals were measured. The results of the study indicated that exogenous melatonin induces hypo- or hyperglycemia depending on the dose of hormone administered as well as to the length of photoperiod to which birds were exposed. The levels of E and NE in the adrenals were shown also to vary in relation to photoperiod and the dose of melatonin administered. But the nature of the influence of melatonin becomes different under altered photoperiodic conditions. It appears that short photoperiods are more effective than long photoperiods as a modulator of glycemic and adrenal catecholaminergic responses to exogenous melatonin. A statistically significant correlation between the levels of blood glucose and that of E and NE in the adrenals was found in the control birds, but not in the melatonin treated birds. The results suggested that the responses of blood glucose and adrenal catecholamines to the treatment with melatonin in the roseringed parakeets may not be dependent on each other.

  18. Projectile Combustion Effects on Ram Accelerator Performance

    NASA Astrophysics Data System (ADS)

    Chitale, Saarth Anjali

    University of Washington Abstract Projectile Combustion Effects on Ram Accelerator Performance Saarth Anjali Chitale Chair of the Supervisory Committee: Prof. Carl Knowlen William E. Boeing Department of Aeronautics and Astronautics The ram accelerator facility at the University of Washington is used to propel projectiles at supersonic velocities. This concept is similar to an air-breathing ramjet engine in that sub-caliber projectiles, shaped like the ramjet engine center-body, are shot through smooth-bore steel-walled tubes having an internal diameter of 38 mm. The ram accelerator propulsive cycles operate between Mach 2 to 10 and have the potential to accelerate projectile to velocities greater than 8 km/s. The theoretical thrust versus Mach number characteristics can be obtained using knowledge of gas dynamics and thermodynamics that goes into the design of the ram accelerator. The corresponding velocity versus distance profiles obtained from the test runs at the University of Washington, however, are often not consistent with the theoretical predictions after the projectiles reach in-tube Mach numbers greater than 4. The experimental velocities are typically greater than the expected theoretical predictions; which has led to the proposition that the combustion process may be moving up onto the projectile. An alternative explanation for higher than predicted thrust, which is explored here, is that the performance differences can be attributed to the ablation of the projectile body which results in molten metal being added to the flow of the gaseous combustible mixture around the projectile. This molten metal is assumed to mix uniformly and react with the gaseous propellant; thereby enhancing the propellant energy release and altering the predicted thrust-Mach characteristics. This theory predicts at what Mach number the projectile will first experience enhanced thrust and the corresponding velocity-distance profile. Preliminary results are in good agreement

  19. Functional poly(ε-caprolactone)/chitosan dressings with nitric oxide-releasing property improve wound healing.

    PubMed

    Zhou, Xin; Wang, He; Zhang, Jimin; Li, Xuemei; Wu, Yifan; Wei, Yongzhen; Ji, Shenglu; Kong, Deling; Zhao, Qiang

    2017-05-01

    Wound healing dressings are increasingly needed clinically due to the large number of skin damage annually. Nitric oxide (NO) plays a key role in promoting wound healing, thus biomaterials with NO-releasing property receive increasing attention as ideal wound dressing. In present study, we prepared a novel functional wound dressing by combining electrospun poly(ε-caprolactone) (PCL) nonwoven mat with chitosan-based NO-releasing biomaterials (CS-NO). As-prepared PCL/CS-NO dressing released NO sustainably under the physiological conditions, which was controlled by the catalysis of β-galactosidase. In vivo wound healing characteristics were further evaluated on full-thickness cutaneous wounds in mice. Results showed that PCL/CS-NO wound dressings remarkably accelerated wound healing process through enhancing re-epithelialization and granulation formation and effectively improved the organization of regenerated tissues including epidermal-dermal junction, which could be ascribed to the pro-angiogenesis, immunomodulation, and enhanced collagen synthesis provided by the sustained release of NO. Therefore, PCL/CS-NO may be a promising candidate for wound dressings, especially for the chronic wound caused by the ischemia. Serious skin damage caused by trauma, surgery, burn or chronic disease has become one of the most serious clinical problems. Therefore, there is an increasing demand for ideal wound dressing that can improve wound healing. Due to the vital role of nitric oxide (NO), we developed a novel functional wound dressing by combining electrospun polycaprolactone (PCL) mat with NO-releasing biomaterial (CS-NO). The sustained release of NO from PCL/CS-NO demonstrated positive effects on wound healing, including pro-angiogenesis, immunomodulation, and enhanced collagen synthesis. Hence, wound healing process was remarkably accelerated and the organization of regenerated tissues was effectively improved as well. Taken together, PCL/CS-NO dressing may be a promising

  20. Group dynamics and catecholamines during long-duration confinement in an isolated environment

    NASA Technical Reports Server (NTRS)

    Kraft, Norbert O.; Lyons, Terence J.; Binder, Heidi

    2003-01-01

    INTRODUCTION: The objectives of this study were to investigate possible relationships between catecholamine excretion and long-duration confinement in an isolated environment. METHODS: Stays of long duration were made by Group I (n = 4, all Russian, weeks 1-34), Group II (n = 4, mixed nationality, weeks 3-18), and Group III (n = 4, mixed nationality, weeks 22-38); other groups joined the residents for 1-wk intervals at weeks #13, #19, and #33. Data were collected from Groups I and III. RESULTS: In both Group I and Group III, the daily epinephrine excretion was significantly elevated during and after confinement compared with the pre-isolation baseline (p < 0.05), but remained mostly within normal limits during the experiment. During isolation, epinephrine excretion was significantly higher, compared with other weeks in isolation, during weeks #19 and #27 for Group I, and during week #30 for Group III. In both Group I and Group II, norepinephrine excretion increased significantly during and after isolation (p < 0.05) and was above the normal range. The daily norepinephrine excretion was significantly higher (p < 0.05) in Group I during weeks #12, #13, and #27, and during week #30 for Group III. DISCUSSION: Epinephrine excretion generally remained in the normal range. However, occasional elevations occurred due to psychological stress, which apparently correlate with changes in group dynamics. Norepinephrine excretion was above the normal range and was correlated with social events. These results suggest that to ensure optimum crew performance, entire crews along with their visiting crews should be selected collectively, rather than individually.

  1. IMPULSIVE ACCELERATION OF CORONAL MASS EJECTIONS. II. RELATION TO SOFT X-RAY FLARES AND FILAMENT ERUPTIONS

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

    Bein, B. M.; Berkebile-Stoiser, S.; Veronig, A. M.

    2012-08-10

    Using high time cadence images from the STEREO EUVI, COR1, and COR2 instruments, we derived detailed kinematics of the main acceleration stage for a sample of 95 coronal mass ejections (CMEs) in comparison with associated flares and filament eruptions. We found that CMEs associated with flares reveal on average significantly higher peak accelerations and lower acceleration phase durations, initiation heights, and heights, at which they reach their peak velocities and peak accelerations. This means that CMEs that are associated with flares are characterized by higher and more impulsive accelerations and originate from lower in the corona where the magnetic fieldmore » is stronger. For CMEs that are associated with filament eruptions we found only for the CME peak acceleration significantly lower values than for events that were not associated with filament eruptions. The flare rise time was found to be positively correlated with the CME acceleration duration and negatively correlated with the CME peak acceleration. For the majority of the events the CME acceleration starts before the flare onset (for 75% of the events) and the CME acceleration ends after the soft X-ray (SXR) peak time (for 77% of the events). In {approx}60% of the events, the time difference between the peak time of the flare SXR flux derivative and the peak time of the CME acceleration is smaller than {+-}5 minutes, which hints at a feedback relationship between the CME acceleration and the energy release in the associated flare due to magnetic reconnection.« less

  2. 78 FR 22001 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69344; File No. SR-Phlx-2013-29] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a Proposed Rule Change... not be a true reflection of the value of the series being quoted. In response to these concerns, the...

  3. Dissemination and support of ARGUS for accelerator applications. Technical progress report, April 24, 1991--January 20, 1992

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

    Not Available

    The ARGUS code is a three-dimensional code system for simulating for interactions between charged particles, electric and magnetic fields, and complex structure. It is a system of modules that share common utilities for grid and structure input, data handling, memory management, diagnostics, and other specialized functions. The code includes the fields due to the space charge and current density of the particles to achieve a self-consistent treatment of the particle dynamics. The physic modules in ARGUS include three-dimensional field solvers for electrostatics and electromagnetics, a three-dimensional electromagnetic frequency-domain module, a full particle-in-cell (PIC) simulation module, and a steady-state PIC model.more » These are described in the Appendix to this report. This project has a primary mission of developing the capabilities of ARGUS in accelerator modeling of release to the accelerator design community. Five major activities are being pursued in parallel during the first year of the project. To improve the code and/or add new modules that provide capabilities needed for accelerator design. To produce a User`s Guide that documents the use of the code for all users. To release the code and the User`s Guide to accelerator laboratories for their own use, and to obtain feed-back from the. To build an interactive user interface for setting up ARGUS calculations. To explore the use of ARGUS on high-power workstation platforms.« less

  4. Fermilab | Tevatron | Accelerator

    Science.gov Websites

    Leading accelerator technology Accelerator complex Illinois Accelerator Research Center Fermilab temperature. They were used to transfer particles from one part of the Fermilab accelerator complex to another center ring of Fermilab's accelerator complex. Before the Tevatron shut down, it had three primary

  5. Oral controlled release optimization of pellets prepared by extrusion-spheronization processing.

    PubMed

    Bianchini, R; Vecchio, C

    1989-06-01

    Controlled release high dosage forms of a typical drug such as Indobufen were prepared as multiple-unit doses by employing extrusion-spheronization processing and subsequently film coating operations. The effects of drug particle size, drug/binder ratio, extruder screen size and preparation reproducibility on the physical properties of the spherical granules were evaluated. Controlled release optimization was obtained on the same granules by coating with polymeric membranes of different thickness consisting of water-soluble and insoluble substances. Film coating was applied from an organic solution using pan coating technique. The drug diffusion is allowed by dissolution of part of the membrane leaving small channels of the polymer coat. Further preparations were conducted to evaluate coatings applied from aqueous dispersion (pseudolatex) using air suspension coating technique. In this system the drug diffusion is governed by the intrinsic pore network of the membrane. The most promising preparations having the desired in vitro release, were metered into hard capsules to obtain the drug unit dosage. Accelerated stability tests were carried out to assess the influence of time and the other storage parameters on the drug release profile.

  6. Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia

    PubMed Central

    Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

    2015-01-01

    Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. PMID:25713330

  7. Distinguishing splanchnic nerve and chromaffin cell stimulation in mouse adrenal slices with fast-scan cyclic voltammetry

    PubMed Central

    Walsh, Paul L.; Petrovic, Jelena

    2011-01-01

    Electrical stimulation is an indispensible tool in studying electrically excitable tissues in neurobiology and neuroendocrinology. In this work, the consequences of high-intensity electrical stimulation on the release of catecholamines from adrenal gland slices were examined with fast-scan cyclic voltammetry at carbon fiber microelectrodes. A biphasic signal, consisting of a fast and slow phase, was observed when electrical stimulations typically used in tissue slices (10 Hz, 350 μA biphasic, 2.0 ms/phase pulse width) were applied to bipolar tungsten-stimulating electrodes. This signal was found to be stimulation dependent, and the slow phase of the signal was abolished when smaller (≤250 μA) and shorter (1 ms/phase) stimulations were used. The slow phase of the biphasic signal was found to be tetrodotoxin and hexamethonium independent, while the fast phase was greatly reduced using these pharmacological agents. Two different types of calcium responses were observed, where the fast phase was abolished by perfusion with a low-calcium buffer while both the fast and slow phases could be modulated when Ca2+ was completely excluded from the solution using EGTA. Perfusion with nifedipine resulted in the reduction of the slow catecholamine release to 29% of the original signal, while the fast phase was only decreased to 74% of predrug values. From these results, it was determined that high-intensity stimulations of the adrenal medulla result in depolarizing not only the splanchnic nerves, but also the chromaffin cells themselves resulting in a biphasic catecholamine release. PMID:21048165

  8. Piezoelectric particle accelerator

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

    Kemp, Mark A.; Jongewaard, Erik N.; Haase, Andrew A.

    2017-08-29

    A particle accelerator is provided that includes a piezoelectric accelerator element, where the piezoelectric accelerator element includes a hollow cylindrical shape, and an input transducer, where the input transducer is disposed to provide an input signal to the piezoelectric accelerator element, where the input signal induces a mechanical excitation of the piezoelectric accelerator element, where the mechanical excitation is capable of generating a piezoelectric electric field proximal to an axis of the cylindrical shape, where the piezoelectric accelerator is configured to accelerate a charged particle longitudinally along the axis of the cylindrical shape according to the piezoelectric electric field.

  9. Oral administration of quercetin is unable to protect against isoproterenol cardiotoxicity.

    PubMed

    Ríha, Michal; Vopršalová, Marie; Pilařová, Veronika; Semecký, Vladimír; Holečková, Magdalena; Vávrová, Jaroslava; Palicka, Vladimir; Filipský, Tomáš; Hrdina, Radomír; Nováková, Lucie; Mladěnka, Přemysl

    2014-09-01

    Catecholamines are endogenous amines that participate in the maintenance of cardiovascular system homeostasis. However, excessive release or exogenous administration of catecholamines is cardiotoxic. The synthetic catecholamine, isoprenaline (isoproterenol, ISO), with non-selective β-agonistic activity has been used as a viable model of acute myocardial toxicity for many years. Since the pathophysiology of ISO-cardiotoxicity is complex, the aim of this study was to elucidate the effect of oral quercetin pretreatment on myocardial ISO toxicity. Wistar-Han rats were randomly divided into four groups: solvent or quercetin administered orally by gavage in a dose of 10 mg kg(-1) daily for 7 days were followed by s.c. water for injection or ISO in a dose of 100 mg kg(-1). Haemodynamic, ECG and biochemical parameters were measured; effects on blood vessels and myocardial histology were assessed, and accompanying pharmacokinetic analysis was performed. Quercetin was unable to protect the cardiovascular system against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T release, QRS-T junction elevation and histological impairment). The sole positive effect of quercetin on catecholamine-induced cardiotoxicity was the normalization of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO-treated animals, but it decreased the same parameter in the control animals. Accompanying pharmacokinetic analysis showed absorption of quercetin and its metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In conclusion, a daily oral dose of 10 mg kg(-1) of quercetin for 7 days did not ameliorate acute ISO-cardiovascular toxicity in rats despite minor positive cardiovascular effects.

  10. EDITORIAL: Laser and plasma accelerators Laser and plasma accelerators

    NASA Astrophysics Data System (ADS)

    Bingham, Robert

    2009-02-01

    This special issue on laser and plasma accelerators illustrates the rapid advancement and diverse applications of laser and plasma accelerators. Plasma is an attractive medium for particle acceleration because of the high electric field it can sustain, with studies of acceleration processes remaining one of the most important areas of research in both laboratory and astrophysical plasmas. The rapid advance in laser and accelerator technology has led to the development of terawatt and petawatt laser systems with ultra-high intensities and short sub-picosecond pulses, which are used to generate wakefields in plasma. Recent successes include the demonstration by several groups in 2004 of quasi-monoenergetic electron beams by wakefields in the bubble regime with the GeV energy barrier being reached in 2006, and the energy doubling of the SLAC high-energy electron beam from 42 to 85 GeV. The electron beams generated by the laser plasma driven wakefields have good spatial quality with energies ranging from MeV to GeV. A unique feature is that they are ultra-short bunches with simulations showing that they can be as short as a few femtoseconds with low-energy spread, making these beams ideal for a variety of applications ranging from novel high-brightness radiation sources for medicine, material science and ultrafast time-resolved radiobiology or chemistry. Laser driven ion acceleration experiments have also made significant advances over the last few years with applications in laser fusion, nuclear physics and medicine. Attention is focused on the possibility of producing quasi-mono-energetic ions with energies ranging from hundreds of MeV to GeV per nucleon. New acceleration mechanisms are being studied, including ion acceleration from ultra-thin foils and direct laser acceleration. The application of wakefields or beat waves in other areas of science such as astrophysics and particle physics is beginning to take off, such as the study of cosmic accelerators considered

  11. Encapsulation of Ethylene Gas into Granular Cold-Water-Soluble Starch: Structure and Release Kinetics.

    PubMed

    Shi, Linfan; Fu, Xiong; Tan, Chin Ping; Huang, Qiang; Zhang, Bin

    2017-03-15

    Ethylene gas was introduced into granular cold-water-soluble (GCWS) starches using a solid encapsulation method. The morphological and structural properties of the novel inclusion complexes (ICs) were characterized using scanning electron microscopy, X-ray diffractometry, and Raman spectroscopy. The V-type single helix of GCWS starches was formed through controlled gelatinization and ethanol precipitation and was approved to host ethylene gas. The controlled release characteristics of ICs were also investigated at various temperature and relative humidity conditions. Avrami's equation was fitted to understand the release kinetics and showed that the release of ethylene from the ICs was accelerated by increasing temperature or RH and was decelerated by increased degree of amylose polymerization. The IC of Hylon-7 had the highest ethylene concentration (31.8%, w/w) among the five starches, and the IC of normal potato starch showed the best controlled release characteristics. As a renewable and inexpensive material, GCWS starch is a desirable solid encapsulation matrix with potential in agricultural and food applications.

  12. Exploring Non-Thermal Radiofrequency Bioeffects for Novel Military Applications

    DTIC Science & Technology

    2006-11-30

    catecholamine release, using cultured adrenal chromaffin cells as an i,i vitro model system, and on skeletal muscle contraction , using intact skeletal...characterization and construction of a waveguide-based exposure system for monitoring skeletal muscle contraction during exposure to 0.75-1 GHz RF

  13. Tonic control of kisspeptin release in prepubertal monkeys: implications to the mechanism of puberty onset.

    PubMed

    Kurian, Joseph R; Keen, Kim L; Guerriero, Kathryn A; Terasawa, Ei

    2012-07-01

    Previously we have shown that a reduction in γ-amino butyric acid (GABA) inhibition is critical for the mechanism initiating puberty onset because chronic infusion of the GABA(A) receptor antagonist, bicuculline, significantly increased GnRH release and accelerated the timing of menarche and first ovulation in female rhesus monkeys. Because previous studies in our laboratory indicate that in prepubertal female monkeys, kisspeptin release in the medial basal hypothalamus is low, whereas kisspeptin-10 can stimulate GnRH release, we hypothesized that a low level of kisspeptin release prior to puberty onset is due to tonic GABA inhibition. To test this hypothesis we examined the effects of bicuculline infusion on kisspeptin release using a microdialysis method. We found that bicuculline at 1 μM dramatically stimulates kisspeptin release in the medial basal hypothalamus of prepubertal monkeys but had little effect on kisspeptin release in midpubertal monkeys. We further examined whether bicuculline-induced GnRH release is blocked by the presence of the kisspeptin antagonist, peptide 234. We found that inhibition of kisspeptin signaling blocked the bicuculline-induced stimulation of GnRH release, suggesting that kisspeptin neurons may relay inhibitory GABA signals to GnRH neurons. This implies that a reduction in tonic GABA inhibition of GnRH release is, at least in part, mediated through kisspeptin neurons.

  14. 18F-Labelled catecholamine type radiopharmaceuticals in the diagnosis of neurodegenerative diseases and neuroendocrine tumours: approaches to synthesis and development prospects

    NASA Astrophysics Data System (ADS)

    Vatsadze, S. Z.; Eremina, O. E.; Veselova, I. A.; Kalmykov, S. N.; Nenajdenko, V. G.

    2018-04-01

    The pathogenesis of many socially significant diseases such as neurodegenerative dementias and neuroendocrine tumours involves imbalance of neurotransmitters. Among the known neuroimaging methods, positron emission tomography (PET) is the most perfect and informative technique for diagnosing these diseases. The potential of PET is largely determined by the inventory of available radiopharmaceuticals, that is, biologically active molecules containing short-lived nuclides with positron decay. This review gives a systematic account of the application of fluorine-18-labelled catecholamine type radiopharmaceuticals in clinical investigations of the sympathetic and central nervous systems. The methods for the synthesis of these agents and existing problems are considered. The material is arranged according to the mechanisms of reactions that underlie the synthetic approaches: electrophilic, nucleophilic and metal-catalyzed reactions. The bibliography includes 198 references.

  15. 78 FR 21982 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69343; File No. SR-BX-2013-026] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Granting Accelerated Approval of a Proposed Rule Change To Adopt... not be a true reflection of the value of the series being quoted. In response to these concerns, the...

  16. Observational and Theoretical Challenges to Wave or Turbulence Accelerations of the Fast Solar Wind

    NASA Technical Reports Server (NTRS)

    Roberts, D. Aaron

    2008-01-01

    We use both observations and theoretical considerations to show that hydromagnetic waves or turbulence cannot produce the acceleration of the fast solar wind and the related heating of the open solar corona. Waves do exist as shown by Hinode and other observations, and can play a role in the differential heating and acceleration of minor ions but their amplitudes are not sufficient to power the wind, as demonstrated by extrapolation of magnetic spectra from Helios and Ulysses observations. Dissipation mechanisms invoked to circumvent this conclusion cannot be effective for a variety of reasons. In particular, turbulence does not play a strong role in the corona as shown by both eclipse observations of coronal striations and theoretical considerations of line-tying to a nonturbulent photosphere, nonlocality of interactions, and the nature of kinetic dissipation. In the absence of wave heating and acceleration, the chromosphere and transition region become the natural source of open coronal energization. We suggest a variant of the velocity filtration approach in which the emergence and complex churning of the magnetic flux in the chromosphere and transition region continuously and ubiquitously produces the nonthermal distributions required. These particles are then released by magnetic carpet reconnection at a wide range of scales and produce the wind as described in kinetic approaches. Since the carpet reconnection is not the main source of the energization of the plasma, there is no expectation of an observable release of energy in nanoflares.

  17. Synthesis of amphiphilic alternating polyesters with oligo(ethylene glycol) side chains and potential use for sustained release drug delivery.

    PubMed

    Wang, Wei; Ding, Jianxun; Xiao, Chunsheng; Tang, Zhaohui; Li, Di; Chen, Jie; Zhuang, Xiuli; Chen, Xuesi

    2011-07-11

    Novel amphiphilic alternating polyesters, poly((N-phthaloyl-l-glutamic anhydride)-co-(2-(2-(2-methoxyethoxy)ethoxy)methyl)oxirane) (P(PGA-co-ME(2)MO)), were synthesized by alternating copolymerization of PGA and ME(2)MO. The structures of the synthesized polyesters were characterized by (1)H NMR, (13)C NMR, FT-IR, and GPC analyses. Because of the presence of oligo(ethylene glycol) (OEG) side chains, the polyesters could self-assemble into thermosensitive micelles. Dynamic light scattering (DLS) showed that these micelles underwent thermoinduced size decrease without intermicellar aggregation. In vitro methyl thiazolyl tetrazolium (MTT) assay demonstrated that the polyesters were biocompatible to Henrietta Lacks (HeLa) cells, rendering their potential for drug delivery applications. Two hydrophobic drugs, rifampin and doxorubicin (DOX), were loaded into the polyester micelles and observed to be released in a zero-order sustained manner. The sustained release could be accelerated in lower pH or in the presence of proteinase K, due to the degradation of the polyester under these conditions. Remarkably, in vitro cell experiments showed that the polyester micelles accomplished fast release of DOX inside cells and higher anticancer efficacy as compared with the free DOX. With enhanced stability during circulation condition and accelerated drug release at the target sites (e.g., low pH or enzyme presence), these novel polyesters with amphiphilic structures are promising to be used in sustained release drug delivery systems.

  18. Source-to-accelerator quadrupole matching section for a compact linear accelerator

    NASA Astrophysics Data System (ADS)

    Seidl, P. A.; Persaud, A.; Ghiorso, W.; Ji, Q.; Waldron, W. L.; Lal, A.; Vinayakumar, K. B.; Schenkel, T.

    2018-05-01

    Recently, we presented a new approach for a compact radio-frequency (RF) accelerator structure and demonstrated the functionality of the individual components: acceleration units and focusing elements. In this paper, we combine these units to form a working accelerator structure: a matching section between the ion source extraction grids and the RF-acceleration unit and electrostatic focusing quadrupoles between successive acceleration units. The matching section consists of six electrostatic quadrupoles (ESQs) fabricated using 3D-printing techniques. The matching section enables us to capture more beam current and to match the beam envelope to conditions for stable transport in an acceleration lattice. We present data from an integrated accelerator consisting of the source, matching section, and an ESQ doublet sandwiched between two RF-acceleration units.

  19. Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

    PubMed

    Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

    2015-01-01

    Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

  20. Oxalic acid pretreatment of rice straw particles and loblolly pine chips : release of hemicellulosic carbohydrates

    Treesearch

    Xianjun Li; Zhiyong Cai; Eric Horn; Jerrold E. Winandy

    2011-01-01

    This study was conducted to evaluate the effect of oxalic acid (OA) pretreatment on carbohydrates released from rice straw particles and wood chips. The results showed that OA treatment accelerated carbohydrates extraction from rice straw particles and wood chips. OA pretreatment dramatically increased the amount of carbohydrates extracted, up to 24 times for wood...

  1. The effect of preoperative magnesium supplementation on blood catecholamine concentrations in patients undergoing CABG.

    PubMed

    Pasternak, K; Dabrowski, W; Dobija, J; Wrońskal, J; Rzecki, Z; Biernacka, J

    2006-06-01

    It is well known that magnesium (Mg) plays an important role in many physiological processes such as regulation of blood catecholamine concentrations, particularly epinephrine (E) and norepinephrine (NE). The complex character of extracorporeal circulation (ECC) with intraoperative normovolemic haemodilution (NH) may alter blood Mg levels, which is likely to result in disorders of E and NE. The aim of this study was to analyze the influence of preoperative Mg supplementation on E and NE in patients undergoing CABG. Forty male patients undergoing CABG under general anaesthesia were included. Patients were randomly divided into two groups: A--the patients receiving pre-operative magnesium supplementation and B--patients without pre-operative magnesium supplementation. The Mg, E and NE blood concentrations were measured in five stages: 1) before anesthesia after the radial artery cannulation, 2) during NH and ECC, 3) immediately after surgery, 4) in the morning of the 1st postoperative day, 5) in the morning of the 2nd postoperative day. The Mg levels were determined by spectrophotometric methods, E and NE were measured by radioimmunoassay methods. The CABG caused a decrease of Mg and an increase of E and NE in both groups, but the changes were significantly higher in group B. 1) CABG causes a decrease of Mg and an increase of E and NE; 2) Preoperative, oral supplementation of Mg substantially reduces intra- and postoperative disorders.

  2. Release of PCBs from Silvretta glacier (Switzerland) investigated in lake sediments and meltwater.

    PubMed

    Pavlova, P A; Zennegg, M; Anselmetti, F S; Schmid, P; Bogdal, C; Steinlin, C; Jäggi, M; Schwikowski, M

    2016-06-01

    This study is part of our investigations about the release of persistent organic pollutants from melting Alpine glaciers and the relevance of the glaciers as secondary sources of legacy pollutants. Here, we studied the melt-related release of polychlorinated biphenyls (PCBs) in proglacial lakes and glacier streams of the catchment of the Silvretta glacier, located in the Swiss Alps. To explore a spatial and temporal distribution of chemicals in glacier melt, we combined two approaches: (1) analysing a sediment record as an archive of past remobilization and (2) passive water sampling to capture the current release of PCBs during melt period. In addition, we determined PCBs in a non-glacier-fed stream as a reference for the background pollutant level in the area. The PCBs in the sediment core from the Silvretta lake generally complied with trends of PCB emissions into the environment. Elevated concentrations during the most recent ten years, comparable in level with times of the highest atmospheric input, were attributed to accelerated melting of the glacier. This interpretation is supported by the detected PCB fractionation pattern towards heavier, less volatile congeners, and by increased activity concentrations of the radioactive tracer (137)Cs in this part of the sediment core. In contrast, PCB concentrations were not elevated in the stream water, since no significant difference between pollutant concentrations in the glacier-fed and the non-glacier-fed streams was detected. In stream water, no current decrease of the PCBs with distance from the glacier was observed. Thus, according to our data, an influence of PCBs release due to accelerated glacier melt was only detected in the proglacial lake, but not in the other compartments of the Silvretta catchment.

  3. Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

    PubMed

    Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

    2015-06-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

  4. Effects of dorsal hippocampus catecholamine depletion on paired-associates learning and place learning in rats.

    PubMed

    Roschlau, Corinna; Hauber, Wolfgang

    2017-04-14

    Growing evidence suggests that the catecholamine (CA) neurotransmitters dopamine and noradrenaline support hippocampus-mediated learning and memory. However, little is known to date about which forms of hippocampus-mediated spatial learning are modulated by CA signaling in the hippocampus. Therefore, in the current study we examined the effects of 6-hydroxydopamine-induced CA depletion in the dorsal hippocampus on two prominent forms of hippocampus-based spatial learning, that is learning of object-location associations (paired-associates learning) as well as learning and choosing actions based on a representation of the context (place learning). Results show that rats with CA depletion of the dorsal hippocampus were able to learn object-location associations in an automated touch screen paired-associates learning (PAL) task. One possibility to explain this negative result is that object-location learning as tested in the touchscreen PAL task seems to require relatively little hippocampal processing. Results further show that in rats with CA depletion of the dorsal hippocampus the use of a response strategy was facilitated in a T-maze spatial learning task. We suspect that impaired hippocampus CA signaling may attenuate hippocampus-based place learning and favor dorsolateral striatum-based response learning. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Cardiac catecholamines in rats fed copper deficient or copper adequate diets containing fructose or starch

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

    Scholfield, D.J.; Fields, M.; Beal, T.

    1989-02-09

    The symptoms of copper (Cu) deficiency are known to be more severe when rats are fed a diet with fructose (F) as the principal carbohydrate. Mortality, in males, due to cardiac abnormalities usually occurs after five weeks of a 62% F, 0.6 ppm Cu deficient diet. These effects are not observed if cornstarch (CS) is the carbohydrate (CHO) source. Studies with F containing diets have shown increased catecholamine (C) turnover rates while diets deficient in Cu result in decreased norepinephrine (N) levels in tissues. Dopamine B-hydroxylase (EC 1.14.17.1) is a Cu dependent enzyme which catalyzes the conversion of dopamine (D)more » to N. An experiment was designed to investigate the effects of CHO and dietary Cu on levels of three C in cardiac tissue. Thirty-two male and female Sprague-Dawley rats were fed Cu deficient or adequate diets with 60% of calories from F or CS for 6 weeks. N, epinephrine (E) and D were measured by HPLC. Statistical analysis indicates that Cu deficiency tends to decrease N levels, while having the reverse effect on E. D did not appear to change. These findings indicate that Cu deficiency but not dietary CHO can affect the concentration of N and E in rat cardiac tissue.« less

  6. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

    PubMed Central

    Govindasamy, Parthasarathy; Kesavan, Bhaskar Reddy; Narasimha, Jayaveera Korlakunta

    2013-01-01

    Objective To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite® Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84% and FB16 released 99.01% of drug in 140 min. Conclusions The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine. PMID:24093793

  7. Experimental Study on Ice Forming Process of Cryogenic Liquid Releasing underwater

    NASA Astrophysics Data System (ADS)

    Zhang, Bin; Wu, Wanqing; Zhang, Xingdong; Zhang, Yi; Zhang, Chuanlin; Zhang, Haoran; Wang, Peng

    2017-11-01

    Cryogenic liquid releasing into water would be a process combines hyperactive boiling with ice forming. There are still few researches on the experimental study on the environmental conditions for deciding ice forming speed and liquid surviving state. In this paper, to advance our understanding of ice forming deciding factors in the process of LN2 releasing underwater, a visualization experimental system is built. The results show that the pressure difference significantly influences the ice forming speed and liquid surviving distance, which is observed by the experiment and theoretically analysed by Kelvin-Helmholtz instability. Adding nucleating agent is helpful to provide ice nucleus which can accelerate the ice forming speed. Water flowing has some effect on changing pressure difference, which can affect the ice forming speed and liquid surviving distance.

  8. Time Variation of the Distance Separating Bomb and Dive Bomber Subsequent to Bomb Release

    NASA Technical Reports Server (NTRS)

    Mathews, Charles W.

    1952-01-01

    A study has been made of the variation of the distance separating bomb and aircraft with time after release as applied to dive-bombing operations, Separation distances determined from this study are presented in terms of two variables only, dive angle and maximum airplane accelerometer reading; the values of separation distance include the effects of delay in initiation of the pull-out and lag in attainment of the maximum normal acceleration.Contains analysis and calculations of the separation distances between bomb and dive bomber following bomb release, Separation distances as determined by the dive angle and the maximum airplane accelerometer reading are presented in a single chart.

  9. Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

    PubMed

    Warren, W B; Gurewitsch, E D; Goland, R S

    1995-02-01

    We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

  10. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  11. Detection of the Acceleration Site in a Solar Flare

    NASA Astrophysics Data System (ADS)

    Fleishman, Gregory D.; Kontar, E. P.; Nita, G. M.; Gary, D. E.

    2011-05-01

    We report the observation of an unusual cold, tenuous solar flare (ApJL, v. 731, p. L19, 2011), which reveals itself via numerous and prominent non-thermal manifestations, while lacking any noticeable thermal emission signature. RHESSI hard X-rays and 0.1-18 GHz radio data from OVSA and Phoenix-2 show copious electron acceleration (1035 electrons per second above 10 keV) typical for GOES M-class flares with electrons energies up to 100 keV, but GOES temperatures not exceeding 6.1 MK. The HXR footpoints and coronal radio sources belong, supposedly, to a single magnetic loop, which departs strongly from the corresponding potential loop (obtained from a photospheric extrapolation) in agreement with the apparent need of a non-potential magnetic field structure to produce a flare. The imaging, temporal, and spectral characteristics of the flare have led us to a firm conclusion that the bulk of the microwave continuum emission from this flare was produced directly in the acceleration region. We found that the electron acceleration efficiency is very high in the flare, so almost all available thermal electrons are eventually accelerated. However, given a relatively small flaring volume and rather low thermal density at the flaring loop, the total energy release turned out to be insufficient for a significant heating of the coronal plasma or for a prominent chromospheric response giving rise to chromospheric evaporation. Some sort of stochastic acceleration process is needed to account for an approximately energy-independent lifetime of about 3 s for the electrons in the acceleration region. This work was supported in part by NSF grants AGS-0961867, AST-0908344, and NASA grants NNX10AF27G and NNX11AB49G to New Jersey Institute of Technology. This work was supported by a UK STFC rolling grant, STFC/PPARC Advanced Fellowship, and the Leverhulme Trust, UK. Financial support by the European Commission through the SOLAIRE and HESPE Networks is gratefully acknowledged.

  12. Exploring the correlation between the sequence composition of the nucleotide binding G5 loop of the FeoB GTPase domain (NFeoB) and intrinsic rate of GDP release.

    PubMed

    Guilfoyle, Amy P; Deshpande, Chandrika N; Schenk, Gerhard; Maher, Megan J; Jormakka, Mika

    2014-12-12

    GDP release from GTPases is usually extremely slow and is in general assisted by external factors, such as association with guanine exchange factors or membrane-embedded GPCRs (G protein-coupled receptors), which accelerate the release of GDP by several orders of magnitude. Intrinsic factors can also play a significant role; a single amino acid substitution in one of the guanine nucleotide recognition motifs, G5, results in a drastically altered GDP release rate, indicating that the sequence composition of this motif plays an important role in spontaneous GDP release. In the present study, we used the GTPase domain from EcNFeoB (Escherichia coli FeoB) as a model and applied biochemical and structural approaches to evaluate the role of all the individual residues in the G5 loop. Our study confirms that several of the residues in the G5 motif have an important role in the intrinsic affinity and release of GDP. In particular, a T151A mutant (third residue of the G5 loop) leads to a reduced nucleotide affinity and provokes a drastically accelerated dissociation of GDP.

  13. Accelerations in Flight

    NASA Technical Reports Server (NTRS)

    Doolittle, J H

    1925-01-01

    This work on accelerometry was done at McCook Field for the purpose of continuing the work done by other investigators and obtaining the accelerations which occur when a high-speed pursuit airplane is subjected to the more common maneuvers. The accelerations obtained in suddenly pulling out of a dive with well-balanced elevators are shown to be within 3 or 4 per cent of the theoretically possible accelerations. The maximum acceleration which a pilot can withstand depends upon the length of time the acceleration is continued. It is shown that he experiences no difficulty under the instantaneous accelerations as high as 7.8 G., but when under accelerations in excess of 4.5 G., continued for several seconds, he quickly loses his faculties.

  14. In Situ Oxalic Acid Injection to Accelerate Arsenic Remediation at a Superfund Site in New Jersey.

    PubMed

    Wovkulich, Karen; Stute, Martin; Mailloux, Brian J; Keimowitz, Alison R; Ross, James; Bostick, Benjamin; Sun, Jing; Chillrud, Steven N

    2014-09-25

    Arsenic is a prevalent contaminant at a large number of US Superfund sites; establishing techniques that accelerate As remediation could benefit many sites. Hundreds of tons of As were released into the environment by the Vineland Chemical Co. in southern New Jersey during its manufacturing lifetime (1949-1994), resulting in extensive contamination of surface and subsurface soils and sediments, groundwater, and the downstream watershed. Despite substantial intervention at this Superfund site, sufficient aquifer cleanup could require many decades if based on traditional pump and treat technologies only. Laboratory column experiments have suggested that oxalic acid addition to contaminated aquifer solids could promote significant As release from the solid phase. To evaluate the potential of chemical additions to increase As release in situ and boost treatment efficiency, a forced gradient pilot scale study was conducted on the Vineland site. During spring/summer 2009, oxalic acid and bromide tracer were injected into a small portion (~50 m 2 ) of the site for 3 months. Groundwater samples indicate that introduction of oxalic acid led to increased As release. Between 2.9 and 3.6 kg of As were removed from the sampled wells as a result of the oxalic acid treatment during the 3-month injection. A comparison of As concentrations on sediment cores collected before and after treatment and analyzed using X-ray fluorescence spectroscopy suggested reduction in As concentrations of ~36% (median difference) to 48% (mean difference). While further study is necessary, the addition of oxalic acid shows potential for accelerating treatment of a highly contaminated site and decreasing the As remediation time-scale.

  15. Catecholamine transport in isolated lung parenchyma of pig

    PubMed Central

    Goldie, Roy G.; Paterson, James W.

    1982-01-01

    1 Lung parenchyma strips of the pig incubated at 37°C with [3H]-(-)-noradrenaline ([3H]-NA) or [3H]-(±)-isoprenaline ([3H]-Iso), accumulated radioactivity via saturable, high affinity uptake processes. Apparent saturation constants (Km) for [3H]-NA and [3H]-Iso were 1.34 × 10-6 M and 1.63 × 10-6 M respectively, while apparent transport maxima (Vmax) were 4.86 and 1.63 × 10-9 mol min-1 g-1 respectively. 2 Cellular accumulation of radioactivity from radiolabelled catecholamines was greatly reduced by lowering the temperature to 7°C, pretreatment with ouabain (100 μM), phentolamine (15 μM) or phenoxybenzamine (80 μM). However, accumulation of radioactivity derived from (3H]-NA was inhibited selectively by cocaine (10 μM) and desipramine (1 μM), while normetanephrine (80 μM) and 3-O-methylisoprenaline (50 μM) caused much greater reductions in cellular radioactivity from [3H]-Iso than from (3H]-NA. Taken together with information from kinetic studies, the results indicate that these amines are transported by separate uptake processes. 3 Cocaine (50 μM) which selectively reduced [3H]-NA transport, had no significant effect on the sensitivity (EC50) of isolated parenchyma lung strips of the pig to the contractile effects of cumulative concentrations of NA. The catechol-O-methyl transferase (COMT) inhibitor, U-0521 (60 μM), also failed to alter the potency of NA, while normetanephrine (80 μM) caused a 2 fold decrease in potency. 4 Phentolamine (15 μM), which reduced the cellular accumulation of radioactivity derived from [3H]-Iso by 64%, caused a small potentiation of Iso-induced relaxations of porcine lung strips. Normetanephrine (80 μM) and 3-O-methylisoprenaline (50 μM), which also depressed the accumulation of cellular radioactivity from [3H]-Iso by > 50%, caused rightward shifts in Iso concentration-effect curves as a result of β-adrenoceptor blockade. In sharp contrast, cortisol (80 μM) and U-0521 (60 μM), which caused smaller reductions in the

  16. ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

    PubMed

    Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

    1999-01-01

    The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

  17. Three-dimensional entertainment as a novel cause of takotsubo cardiomyopathy.

    PubMed

    Taylor, Montoya; Amin, Anish; Bush, Charles

    2011-11-01

    Takotsubo cardiomyopathy (TC) is an uncommon entity. It is known to occur in the setting of extreme catecholamine release and results in left ventricular dysfunction without evidence of angiographically definable coronary artery disease. There have been no published reports of TC occurring with visual stimuli, specifically 3-dimensional (3D) entertainment. We present a 55-year-old woman who presented to her primary care physician's office with extreme palpitations, nausea, vomiting, and malaise <48 hours after watching a 3D action movie at her local theater. Her electrocardiogram demonstrated ST elevations in aVL and V1, prolonged QTc interval, and T-wave inversions in leads I, II, aVL, and V2-V6. Coronary angiography revealed angiographically normal vessels, elevated left ventricular filling pressures, and decreased ejection fraction with a pattern of apical ballooning. The presumed final diagnosis was TC, likely due to visual-auditory-triggered catecholamine release causing impaired coronary microcirculation. © 2011 Wiley Periodicals, Inc.

  18. Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.

    PubMed

    Weigel, Marianne; Hahner, Stefanie; Sherlock, Mark; Agha, Amar; Behan, Lucy Ann; Stewart, Paul M; Arlt, Wiebke; Beier, Daniela; Frey, Kathrin; Zopf, Kathrin; Quinkler, Marcus

    2017-04-01

    Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet. Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone. Pharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40-20-0 mg, in nine patients with ACC and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (SAI) on three different hydrocortisone regimens and ten healthy males were included. Serum cortisol and plasma ACTH were measured by chemiluminescent enzyme immunoassay, and CBG by RIA, followed by calculation of free cortisol. Calculated free serum cortisol levels after 40 mg immediate release hydrocortisone in ACC patients (46 ± 14 nmol/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with SAI (64 ± 16 nmol/l) or to the physiological morning free cortisol levels in healthy subjects (31 ± 5 nmol/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in ACC patients were significantly lower (12 ± 3 nmol/l; P = 0·03) resulting in a generally lower AUC (98 ± 21 vs 149 ± 37 nmol h/l; P = 0·02). 40-20-0 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with ACC receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment. © 2017 John Wiley & Sons Ltd.

  19. Collisionless shock formation and the prompt acceleration of solar flare ions

    NASA Technical Reports Server (NTRS)

    Cargill, P. J.; Goodrich, C. C.; Vlahos, L.

    1988-01-01

    The formation mechanisms of collisionless shocks in solar flare plasmas are investigated. The priamry flare energy release is assumed to arise in the coronal portion of a flare loop as many small regions or 'hot spots' where the plasma beta locally exceeds unity. One dimensional hybrid numerical simulations show that the expansion of these 'hot spots' in a direction either perpendicular or oblique to the ambient magnetic field gives rise to collisionless shocks in a few Omega(i), where Omega(i) is the local ion cyclotron frequency. For solar parameters, this is less than 1 second. The local shocks are then subsequently able to accelerate particles to 10 MeV in less than 1 second by a combined drift-diffusive process. The formation mechanism may also give rise to energetic ions of 100 keV in the shock vicinity. The presence of these energetic ions is due either to ion heating or ion beam instabilities and they may act as a seed population for further acceleration. The prompt acceleration of ions inferred from the Gamma Ray Spectrometer on the Solar Maximum Mission can thus be explained by this mechanism.

  20. The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity.

    PubMed

    Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur

    2017-01-05

    The 5-HT 1A/1B -receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT 1A/1B -receptor activation decreases impulsive choice, but increases impulsive action. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Compact Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Foster, John E.

    2004-01-01

    A plasma accelerator has been conceived for both material-processing and spacecraft-propulsion applications. This accelerator generates and accelerates ions within a very small volume. Because of its compactness, this accelerator could be nearly ideal for primary or station-keeping propulsion for spacecraft having masses between 1 and 20 kg. Because this accelerator is designed to generate beams of ions having energies between 50 and 200 eV, it could also be used for surface modification or activation of thin films.

  2. Microelectromechanical acceleration-sensing apparatus

    DOEpatents

    Lee, Robb M [Albuquerque, NM; Shul, Randy J [Albuquerque, NM; Polosky, Marc A [Albuquerque, NM; Hoke, Darren A [Albuquerque, NM; Vernon, George E [Rio Rancho, NM

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  3. SHORT ACCELERATION TIMES FROM SUPERDIFFUSIVE SHOCK ACCELERATION IN THE HELIOSPHERE

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

    Perri, S.; Zimbardo, G., E-mail: silvia.perri@fis.unical.it

    2015-12-10

    The analysis of time profiles of particles accelerated at interplanetary shocks allows particle transport properties to be inferred. The frequently observed power-law decay upstream, indeed, implies a superdiffusive particle transport when the level of magnetic field variance does not change as the time interval from the shock front increases. In this context, a superdiffusive shock acceleration (SSA) theory has been developed, allowing us to make predictions of the acceleration times. In this work we estimate for a number of interplanetary shocks, including the solar wind termination shock, the acceleration times for energetic protons in the framework of SSA and wemore » compare the results with the acceleration times predicted by standard diffusive shock acceleration. The acceleration times due to SSA are found to be much shorter than in the classical model, and also shorter than the interplanetary shock lifetimes. This decrease of the acceleration times is due to the scale-free nature of the particle displacements in the framework of superdiffusion. Indeed, very long displacements are possible, increasing the probability for particles far from the front of the shock to return, and short displacements have a high probability of occurrence, increasing the chances for particles close to the front to cross the shock many times.« less

  4. MABE multibeam accelerator

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

    Hasti, D.E.; Ramirez, J.J.; Coleman, P.D.

    1985-01-01

    The Megamp Accelerator and Beam Experiment (MABE) was the technology development testbed for the multiple beam, linear induction accelerator approach for Hermes III, a new 20 MeV, 0.8 MA, 40 ns accelerator being developed at Sandia for gamma-ray simulation. Experimental studies of a high-current, single-beam accelerator (8 MeV, 80 kA), and a nine-beam injector (1.4 MeV, 25 kA/beam) have been completed, and experiments on a nine-beam linear induction accelerator are in progress. A two-beam linear induction accelerator is designed and will be built as a gamma-ray simulator to be used in parallel with Hermes III. The MABE pulsed power systemmore » and accelerator for the multiple beam experiments is described. Results from these experiments and the two-beam design are discussed. 11 refs., 6 figs.« less

  5. Ignition of the Pegasus rocket moments after release from the B-52 signaled acceleration of the X-43

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The first X-43A hypersonic research aircraft and its modified Pegasus booster rocket were carried aloft by NASA's NB-52B carrier aircraft from Dryden Flight Research Center at Edwards Air Force Base, Calif., on June 2, 2001 for the first of three high-speed free flight attempts. About an hour and 15 minutes later the Pegasus booster was released from the B-52 to accelerate the X-43A to its intended speed of Mach 7. Before this could be achieved, the combined Pegasus and X-43A 'stack' lost control about eight seconds after ignition of the Pegasus rocket motor. The mission was terminated and explosive charges ensured the Pegasus and X-43A fell into the Pacific Ocean in a cleared Navy range area. A NASA investigation board is being assembled to determine the cause of the incident. Work continues on two other X-43A vehicles, the first of which could fly by late 2001. Central to the X-43A program is its integration of an air-breathing 'scramjet' engine that could enable a variety of high-speed aerospace craft, and promote cost-effective access to space. The 12-foot, unpiloted research vehicle was developed and built for NASA by MicroCraft Inc., Tullahoma, Tenn. The booster was built by Orbital Sciences Corp. at Chandler, Ariz. The X-43A flights are the first actual flight tests of an aircraft powered by a scramjet engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). Some 90 minutes after takeoff, the Pegasus will launch from a B-52, rocketing the X-43A to Mach 7 at 95,000 feet altitude, or Mach 10 at 105,000 feet altitude. The X-43A will be powered by its revolutionary air-breathing supersonic-combustion ramjet or 'scramjet' engine. The X-43A will then fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments as it descends until it splashes into the Pacific Ocean.

  6. Increase in swimming endurance capacity of mice by capsaicin-induced adrenal catecholamine secretion.

    PubMed

    Kim, K M; Kawada, T; Ishihara, K; Inoue, K; Fushiki, T

    1997-10-01

    Increase in endurance swimming capacity caused by capsaicin (CAP), a pungent component of red pepper, -induced increase of fat metabolism in mice was investigated using an adjustable-current water pool. The mice administered CAP via a stomach tube, showed longer swimming time until exhaustion than the control group of mice, in a dose-dependent manner. The maximal effect was observed at a dose of 10 mg/kg while more than 15 mg/kg had no effect. The increase of endurance was observed only when CAP was administered two hours before swimming. After the administration of CAP, the serum glucose concentration rapidly increased and then decreased within 60 min, while the concentration of serum-free fatty acids gradually increased through 3 hours. The residual glycogen concentration of the gastrocnemius muscle after 30 min of swimming was significantly higher in the CAP-administered mice than in control mice, suggesting that use of the serum free fatty acids spared muscle glycogen consumption. The serum adrenaline concentration significantly increased with twin peaks at 30 min and two hours after administration of CAP. An experiment using adrenalectomized mice was done to confirm that the effect of CAP is due to increased energy metabolism through the secretion of adrenaline from the adrenal gland. The swimming endurance capacity of the adrenalectomized mice was not increased by CAP administration, although adrenaline injection induced a 58% increase in the endurance time. These results suggest that the increase of swimming endurance induced by CAP in mice is caused by an increase in fatty acid utilization due to CAP-induced adrenal catecholamine secretion.

  7. Does cattle grazing of dual-purpose wheat accelerate the rate of stubble decomposition and nutrients released

    USDA-ARS?s Scientific Manuscript database

    Decomposition and nutrient release of winter annual forages in integrated crop-livestock systems could be affected by the resultant alterations in structure and quality of residues caused by grazing, but little information is available to test this hypothesis. Information on residue dynamics is need...

  8. 77 FR 3829 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66192; File No. SR-NYSEArca-2012-02] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Order Granting Accelerated Approval of a Proposed Rule Amendments to NYSE Arca Rule 9.4 and NYSE Equities Inc. Rules 5.3(d) and 9.4 Relating to Discretionary Proxy Voting on Executive...

  9. Probing electron acceleration and x-ray emission in laser-plasma accelerators

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

    Thaury, C.; Ta Phuoc, K.; Corde, S.

    2013-06-15

    While laser-plasma accelerators have demonstrated a strong potential in the acceleration of electrons up to giga-electronvolt energies, few experimental tools for studying the acceleration physics have been developed. In this paper, we demonstrate a method for probing the acceleration process. A second laser beam, propagating perpendicular to the main beam, is focused on the gas jet few nanosecond before the main beam creates the accelerating plasma wave. This second beam is intense enough to ionize the gas and form a density depletion, which will locally inhibit the acceleration. The position of the density depletion is scanned along the interaction lengthmore » to probe the electron injection and acceleration, and the betatron X-ray emission. To illustrate the potential of the method, the variation of the injection position with the plasma density is studied.« less

  10. Investigating glide snow avalanche release using seismic monitoring in combination with time-lapse photography

    NASA Astrophysics Data System (ADS)

    van Herwijnen, Alec; Failletaz, Jerome; Berhod, Nicole; Mitterer, Christoph

    2013-04-01

    Glide avalanches occur when the entire snowpack glides over the ground until an avalanche releases. These avalanches are difficult to forecast since the gliding process can take place over a few hours up to several weeks or months. The presence of liquid water at the interface between the snow cover and the ground surface is of primary importance as it reduces frictional support. Glide avalanches are often preceded by the opening of a tensile crack in the snow cover, called a glide crack. Past research has shown that glide crack opening accelerates prior to avalanche release. During the winter of 2012-2013, we monitored glide crack expansion using time-lapse photography in combination with a seismic sensor and two heat flux sensors on a slope with well documented glide avalanche activity in the Eastern Swiss Alps above Davos, Switzerland. To track changes in glide rates, the number of dark pixels in an area around the glide crack is counted in each image. Using this technique, we observed an increase in glide rates prior to avalanche release. Since the field site is located very close to the town of Davos, the seismic data was very noisy. Nevertheless, the accelerated snow gliding observed in the time-lapse images coincided with increased seismic activity. Overall, these results show that a combination of time-lapse photography with seismic monitoring could provide valuable insight into glide avalanche release. Recordings of the heat flux plates show that the energy input from the soil is fairly small and constant throughout the observed period. The results suggest that ground heat flux is a minor contributor to the water production at the snow-soil interface. Instead, the presence of water at the base of the snowpack is probably due to a strong hydraulic pressure gradient at the snow-soil interface.

  11. Hydrogen release from 800 MeV proton-irradiated tungsten

    NASA Astrophysics Data System (ADS)

    Oliver, B. M.; Venhaus, T. J.; Causey, R. A.; Garner, F. A.; Maloy, S. A.

    2002-12-01

    Tungsten irradiated in spallation neutron sources, such as those proposed for the accelerator production of tritium (APT) project, will contain large quantities of generated helium and hydrogen gas. Tungsten used in proposed fusion reactors will also be exposed to neutrons, and the generated protium will be accompanied by deuterium and tritium diffusing in from the plasma-facing surface. The release kinetics of these gases during various off-normal scenarios involving loss of coolant and after heat-induced rises in temperature are of particular interest for both applications. To determine the release kinetics of hydrogen from tungsten, tungsten rods irradiated with 800 MeV protons in the Los Alamos Neutron Science Center (LANSCE) to high exposures as part of the APT project have been examined. Hydrogen evolution from the tungsten has been measured using a dedicated mass-spectrometer system by subjecting the specimens to an essentially linear temperature ramp from ˜300 to ˜1500 K. Release profiles are compared with predictions obtained using the Tritium Migration Analysis Program (TMAP4). The measurements show that for high proton doses, the majority of the hydrogen is released gradually, starting at about 900 K and reaching a maximum at about 1400 K, where it drops fairly rapidly. Comparisons with TMAP show quite reasonable agreement using a trap energy of 1.4 eV and a trap density of ˜7%. There is a small additional release fraction occurring at ˜550 K, which is believed to be associated with low-energy trapping at or near the surface, and, therefore, was not included in the bulk TMAP model.

  12. Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling

    PubMed Central

    Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

    2016-01-01

    An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties. PMID:27610147

  13. Nitric oxide-releasing chitosan film for enhanced antibacterial and in vivo wound-healing efficacy.

    PubMed

    Kim, Jong Oh; Noh, Jin-Ki; Thapa, Raj Kumar; Hasan, Nurhasni; Choi, Moonjeong; Kim, Jeong Hwan; Lee, Joon-Hee; Ku, Sae Kwang; Yoo, Jin-Wook

    2015-08-01

    Nitric oxide (NO) is a promising therapeutic agent with antibacterial and wound-healing properties. However, the gaseous state and short half-life of NO necessitate a formulation that can control its storage and release. In this study, we developed NO-releasing films (CS/NO film) composed of chitosan (CS) and S-nitrosoglutathione (GSNO) as a NO donor. Thermal analysis demonstrated molecular dispersion of GSNO in the films. In vitro release study revealed that NO release from CS/NO films followed Korsmeyer-Peppas model with Fickian diffusion kinetics. Moreover, the CS/NO film showed a stronger antibacterial activity against Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) than the CS film. Further, the CS/NO film accelerated wound healing and epithelialization in a rat model of full-thickness wounds as compared to the CS film. Histopathological studies revealed that CS/NO films favorably enhanced the re-epithelialization and reconstruction of wounded skin. Therefore, our results suggest that CS/NO films could be a suitable formulation for treating full-thickness wounds. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Social-emotional characteristics of gifted accelerated and non-accelerated students in the Netherlands.

    PubMed

    Hoogeveen, Lianne; van Hell, Janet G; Verhoeven, Ludo

    2012-12-01

    In the studies of acceleration conducted so far a multidimensional perspective has largely been neglected. No attempt has been made to relate social-emotional characteristics of accelerated versus non-accelerated students in perspective of environmental factors. In this study, social-emotional characteristics of accelerated gifted students in the Netherlands were examined in relation to personal and environmental factors. Self-concept and social contacts of accelerated (n = 148) and non-accelerated (n = 55) gifted students, aged 4 to 27 (M = 11.22, SD = 4.27) were measured. Self-concept and social contacts of accelerated and non-accelerated gifted students were measured using a questionnaire and a diary, and parents of these students evaluated their behavioural characteristics. Gender and birth order were studied as personal factors and grade, classroom, teachers' gender, teaching experience, and the quality of parent-school contact as environmental factors. The results showed minimal differences in the social-emotional characteristics of accelerated and non-accelerated gifted students. The few differences we found favoured the accelerated students. We also found that multiple grade skipping does not have negative effects on social-emotional characteristics, and that long-term effects of acceleration tend to be positive. As regards the possible modulation of personal and environmental factors, we merely found an impact of such factors in the non-accelerated group. The results of this study strongly suggest that social-emotional characteristics of accelerated gifted students and non-accelerated gifted students are largely similar. These results thus do not support worries expressed by teachers about the acceleration of gifted students. Our findings parallel the outcomes of earlier studies in the United States and Germany in that we observed that acceleration does not harm gifted students, not even in the case of multiple grade skipping. On the contrary, there is a

  15. Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

    PubMed

    Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

    2016-07-01

    Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Regulation of Episodic Growth Hormone Secretion by the Central Epinephrine System

    PubMed Central

    Terry, L. Cass; Crowley, W. R.; Johnson, M. D.

    1982-01-01

    Catecholamines are postulated to regulate growth hormone (GH) secretion by their influence on the release of two hypothalamic substances, somatostatin, which inhibits GH release, and GH-releasing factor, as yet unidentified. Extensive pharmacologic studies in man and animals indicate a stimulatory effect of central norepinephrine and dopamine on GH, but the function of epiphephrine (EPI) is uncertain. Furthermore, many of the agents used to study the role of catecholamines in GH regulation are not selective in that they affect adrenergic as well as nor-adrenergic and/or dopaminergic neurotransmission. In the present investigation, central nervous system (CNS) EPI biosynthesis was selectively interrupted with the specific norepinephrine N-methyltransferase inhibitors, SK & F 64139 (Smith, Kline & French Laboratories) and LY 78335, (Eli Lilly & Co. Research Laboratories) and the effects of central EPI depletion on episodic GH secretion in the chronically cannulated rat model were determined. Inhibition of CNS EPI synthesis with SK & F 64139 caused complete suppression of episodic GH secretion and concomitantly reduced the EPI level in the hypothalamus without affecting dopamine or norepinephrine. Administration of LY 78335 produced similar effects on pulsatile GH. Morphine-induced, but not clonidine-induced, GH release also was blocked by SK & F 64139. These results indicate that (a) the central EPI system has a major stimulatory function in episodic GH release, (b) morphine-induced GH release is mediated by the central EPI system, and (c) clonidine stimulates GH release by activation of postsynaptic α-adrenergic receptors. Drugs that affect CNS adrenergic systems have a potential role in the diagnosis and treatment of disorders of GH secretion. PMID:7054231

  17. Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.

    PubMed

    Gao, Xiao-Ming; Moore, Xiao-Lei; Liu, Yang; Wang, Xin-Yu; Han, Li-Ping; Su, Yidan; Tsai, Alan; Xu, Qi; Zhang, Ming; Lambert, Gavin W; Kiriazis, Helen; Gao, Wei; Dart, Anthony M; Du, Xiao-Jun

    2016-07-01

    Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  18. Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration

    NASA Technical Reports Server (NTRS)

    Mills, P. J.; Meck, J. V.; Waters, W. W.; D'Aunno, D.; Ziegler, M. G.

    2001-01-01

    OBJECTIVE: The objective of this study was to determine the effects of spaceflight duration on immune cells and their relationship to catecholamine levels. METHODS: Eleven astronauts who flew aboard five different US Space Shuttle flights ranging in duration from 4 to 16 days were studied before launch and after landing. RESULTS: Consistent with prior studies, spaceflight was associated with a significant increase in the number of circulating white blood cells (p <.01), including neutrophils (p <.01), monocytes (p <.05), CD3+CD4+ T-helper cells (p <.05), and CD19+ B cells (p <.01). In contrast, the number of CD3-CD16+56+ natural killer cells was decreased (p <.01). Plasma norepinephrine levels were increased at landing (p <.01) and were significantly correlated with the number of white blood cells (p <.01), neutrophils (p <.01), monocytes (p <.01), and B cells (p <.01). Astronauts who were in space for approximately 1 week showed a significantly larger increase on landing in plasma norepinephrine (p =.02) and epinephrine (p =.03) levels, as well as number of circulating CD3+CD4+ T-helper cells (p <.05) and CD3+CD8+ T-cytotoxic cells (p <.05) as compared with astronauts in space for approximately 2 weeks. CONCLUSIONS: The data suggest that the stress of spaceflight and landing may lead to a sympathetic nervous system-mediated redistribution of circulating leukocytes, an effect potentially attenuated after longer missions.

  19. Evidence of soluble microbial products accelerating chloramine decay in nitrifying bulk water samples.

    PubMed

    Bal Krishna, K C; Sathasivan, Arumugam; Chandra Sarker, Dipok

    2012-09-01

    The discovery of a microbially derived soluble product that accelerates chloramine decay is described. Nitrifying bacteria are believed to be wholly responsible for rapid chloramine loss in drinking water systems. However, a recent investigation showed that an unidentified soluble agent significantly accelerated chloramine decay. The agent was suspected to be either natural organic matter (NOM) or soluble microbial products (SMPs). A laboratory scale reactor was fed chloraminated reverse osmosis (RO) treated water to eliminate the interference from NOM. Once nitrification had set in, experiments were conducted on the reactor and feed waters to determine the identity of the component. The study showed the presence of SMPs released by microbes in severely nitrified waters. Further experiments proved that the SMPs significantly accelerated chloramine decay, probably through catalytic reaction. Moreover, application of common protein denaturing techniques stopped the reaction implying that the compound responsible was likely to be a protein. This significant finding will pave the way for better control of chloramine in the distribution systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Modelling the Interaction of Catecholamines with the α1A Adrenoceptor Towards a Ligand-induced Receptor Structure

    NASA Astrophysics Data System (ADS)

    Kinsella, Gemma K.; Rozas, Isabel; Watson, Graeme W.

    2005-06-01

    Adrenoceptors are members of the important G protein coupled receptor family for which the detailed mechanism of activation remains unclear. In this study, we have combined docking and molecular dynamics simulations to model the ligand induced effect on an homology derived human α1A adrenoceptor. Analysis of agonist/α1A adrenoceptor complex interactions focused on the role of the charged amine group, the aromatic ring, the N-methyl group of adrenaline, the beta hydroxyl group and the catechol meta and para hydroxyl groups of the catecholamines. The most critical interactions for the binding of the agonists are consistent with many earlier reports and our study suggests new residues possibly involved in the agonist-binding site, namely Thr-174 and Cys-176. We further observe a number of structural changes that occur upon agonist binding including a movement of TM-V away from TM-III and a change in the interactions of Asp-123 of the conserved DRY motif. This may cause Arg-124 to move out of the TM helical bundle and change the orientation of residues in IC-II and IC-III, allowing for increased affinity of coupling to the G-protein.